Search Results (437)

Background: Spinal Muscular Atrophy type 1 (SMA type 1) is a genetic neuromuscular disease that typically presents before 6 months of age and is characterized by profound hypotonia, progressive muscle weakness, and early involvement of respiratory and bulbar musculature. Swallowing impairment (dysphagia) is a hallmark of SMA type 1 and significantly contributes to morbidity. Despite the documented benefits of disease-modifying therapies (DMTs) in terms of enhanced survival and motor outcomes, their impact on swallowing remains understudied. Aim: This study aims to longitudinally characterize swallowing function in children with SMA type 1 treated with DMTs, while contextualizing these findings in relation to the patients’ current motor abilities and cognitive performance. Materials and Methods: A single-center, longitudinal, observational study was conducted at IRCCS Besta, Milan, Italy, from 2021 to 2025. Swallowing function was evaluated using four validated scales (MAS, OrSAT, FILS, and p-FOIS), while motor and cognitive functions were assessed using CHOP-INTEND and age-appropriate cognitive tests (DQ/IQ). Patients were stratified by baseline swallowing status, pharmacological therapy, and age at DMT administration. Non-parametric statistical tests were applied. Results: No statistically significant changes in swallowing function were observed over one year in the overall cohort or its subgroups, despite significant improvements in motor function. MAS/e, FILS, and p-FOIS showed moderate associations with CHOP-INTEND and DQ/IQ scores. Conclusions: Swallowing function in children with SMA type 1 remained largely stable, while motor function significantly improved over one year, regardless of baseline swallowing status, DMT type, and age at administration. These findings underscore the need for standardized, longitudinal assessments of swallowing, motor, and cognitive functions in the management of SMA type 1. Full article

Background/Objectives: Cardiometabolic risk remains a major challenge in patients with type 2 diabetes mellitus (DMT2). This study aimed to evaluate cardiovascular (CV) risk stratification using advanced glycation end-products (AGEs) measured via skin autofluorescence (SAF) and to assess the achievement of evidence-based ABC targets (HbA1c, blood pressure, low-density lipoprotein (LDL) cholesterol) in adults with DMT2 in Dalmatia. Methods: In this single-center cross-sectional study, 251 adults with DMT2 were stratified by CV risk based on SAF measured AGE levels. Clinical, biochemical, and anthropometric data were collected, including ABC goal attainment and medication use. Statistical analyses compared groups and explored predictors of ABC target achievement using regression models adjusted for clinical factors. Results: Only 17.5% of participants achieved all three ABC goals, indicating suboptimal cardiometabolic control. Those with elevated CV risk had higher hip circumference and lower diastolic blood pressure. Use of sodium-glucose cotransporter 2 (SGLT2) inhibitors was positively associated with ABC goal achievement in patients with prior CV or cerebrovascular events, while higher body mass index was negatively associated. SAF measured AGE levels correlated with cardiometabolic risk but showed no significant differences across LDL cholesterol or other traditional markers. Conclusions: SAF AGE measurement shows potential for CV risk stratification in DMT2 beyond traditional factors. The low rate of ABC goal attainment highlights the need for intensified individualized management incorporating novel biomarkers and therapeutics like SGLT2 inhibitors. Further prospective studies are needed to validate these findings and improve prevention of cardiovascular complications in DMT2. Full article

Background/Objectives: Multiple sclerosis (MS) is an autoimmune disorder affecting the central nervous system, characterised by the degradation of myelin, which results in various neurological symptoms. This study aims to utilise radiomics features to evaluate the predictive value of IVIM diffusion parameters, namely, the true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f), in relation to disability severity, assessed using the Expanded Disability Status Scale (EDSS), and mobility in patients with relapsing–remitting MS. Methods: This retrospective cross-sectional study analysed MRI data from 197 patients diagnosed with multiple sclerosis (MS). Quantitative intravoxel incoherent motion (IVIM) parameters were obtained using a 1.5 Tesla MRI scanner. Clinical information collected included age, disease duration, number of relapses, status of disease-modifying therapy (DMT), and the need for mobility assistance. Machine learning (ML) techniques, such as XGB, Random Forest, and ANN, were employed to explore the relationships between radiomic IVIM parameters and these clinical variables. Results: IVIM radiomics achieved high accuracy in lesion phenotyping. Random Forest distinguished enhancements from non-enhancing lesions with 96% accuracy and AUC = 0.99 with IVIM-f and D* maps. CNN also reached ~92% accuracy (AUC 0.97) with IVIM-f. For disability prediction, IVIM-D and D* radiomics strongly correlated with EDSS: Random Forest achieved 89% accuracy (AUC = 0.90), while CNN achieved 90% accuracy (AUC = 0.95). Mobility impairment was predicted with the highest performance—RNN achieved 96% accuracy (AUC = 0.99) across IVIM-f features. In contrast, relapse history, disease duration, and treatment status were poorly predicted (<75% accuracy). Conclusions: ML analyses of IVIM metrics provided independent predictors of functional impairment and disability in MS. Our novel approach may be used to improve diagnostic accuracy and develop personalised treatment strategies for MS patients. Full article

Pruritus (itching) is an underrecognized but often debilitating symptom in patients with central nervous system (CNS) demyelinating diseases, including multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). It is often considered a paroxysmal symptom. Although less studied than pain or spasticity, pruritus can significantly impair the quality of life. This review aims to provide a comprehensive overview of the pathophysiological mechanisms underlying pruritus in demyelinating CNS disorders, its clinical presentations, and the available treatment options. We explore the central origins of neuropathic itch, focusing on spinal cord, brainstem, and cerebral lesions, with particular emphasis on white matter involvement and spinothalamic tract dysfunction. In addition, we review pruritus triggered or exacerbated by disease-modifying therapies (DMTs) used in MS and NMOSD. Full article

The increasing environmental concerns surrounding plastic waste have intensified recycling efforts, particularly in the textile industry, where poly(ethylene terephthalate) (PET) is widely used for sustainable material production. The growing use of recycled PET (rPET) in textiles has prompted the need for reliable analytical methods to detect and quantify rPET content. This study differentiates between virgin and recycled PET by simulating mechanical recycling through five reprocessing cycles of three distinct PET grades, assessing changes in crystalline structure, intrinsic viscosity, molecular weight, and specific degradation markers. Differential Scanning Calorimetry revealed bimodal melting behaviour in reprocessed samples, while intrinsic viscosity and Gel Permeation Chromatography indicated molecular degradation. Notably, the release of dimethyl terephthalate (DMT) and dimethyl isophthalate (DMiP) was consistently observed as a function of degradation. These markers were identified and quantified using High-Performance Liquid Chromatography (HPLC) and Gas Chromatography (GC), with GC offering higher sensitivity and lower matrix interference. This study demonstrates that DMT and DMiP are robust chemical indicators of PET degradation and recycled content. This analytical approach, combining thermal, rheological, and chromatographic techniques, provides a scientifically sound and potentially cost-effective basis for traceability systems, certification protocols, and regulatory compliance in sustainable textile production. Full article

Background: Polycystic ovarian syndrome (PCOS) is a common female endocrinopathy, but its interrelations with arterial hypertension (AH) are still debatable. Therefore, the present study aims to explore the risk factors for hypertension in a large group of well-phenotyped women with PCOS. Methods: The data of 1047 Bulgarian PCOS patients diagnosed according to Rotterdam criteria in the period 2005–2022 were studied retrospectively. The risk factors for hypertension were estimated in the PCOS women with different phenotypes. Results: The prevalence of AH was 17.6% among the PCOS women, with 4.2% of them being on antihypertensive treatment. The AH prevalence was increased in women with the “classic” phenotype compared to others (18.9% vs. 12.9%, p = 0.037). The most important risk factors associated with hypertension were the presence of diabetes mellitus type 2 (DMT2), obesity, family history of AH, and age ≥ 30 years (p < 0.001). The prevalence of impaired glucose tolerance (IGT) but not impaired fasting glucose was also related to the development of AH. Conclusions: The leading independent factors associated with hypertension in PCOS patients are the presence of DMT2, IGT, obesity, family history of hypertension, and age, but not the degree of hyperandrogenism. Population-based studies, including distinct ethnic groups, are needed to reveal the pathophysiology and the optimal clinical management of AH in PCOS. Full article

Diabetes type 2 (DT2) entails significant health, economic, and productivity repercussions around the world. Poor glycaemic control, defined as an HbA1c >7.0%, has been associated with a number of complications. In spite of the large share of healthcare resources allocated to DT2 treatment, the proportion of controlled Mexican patients is among the lowest in the world (34.4%). Certain protein-encoding genetic polymorphisms involved in metformin transport may affect glycaemic control. We focused on determining the frequency of rs2289669, rs2252281, rs12943590, and rs34834489 polymorphisms in Mexican-Mestizo patients from the Tertiary Care Regional Hospital of Ixtapaluca, State of Mexico, Mexico, as well as assessing their possible association with therapeutic efficacy, as estimated through glycated haemoglobin. The individual polymorphism analysis did not reveal an association with glycaemic control; however, when combined with rs72552763 and rs622342, we found a significant positive correlation between HbA1c levels and metformin dose, which prevailed among patients carrying allelic variants of rs2289669 or rs12943590 who were also simultaneously carrying allelic variants of rs72552763 or rs622342. Patients carrying the reference allele of rs34834489 reported a significant positive correlation between HbA1c levels and metformin dose as well, regardless of their rs72552763 or rs622342 genotype. Thus, we identified alleles and allelic combinations of SLC47A1, SLC47A2, and SLC22A1 polymorphisms posing a potential glycaemic control risk in Mexican-Mestizo patients. Full article

Background and Objectives: Ofatumumab (OFA) is the first fully human anti-CD20 monoclonal antibody approved for the treatment of RRMS classified as a high-efficacy treatment agent. Real-world evidence is essential for evaluating the effectiveness and safety of OFA. Materials and Methods: A total of 184 patients (72.3% women, mean age 38 years (±10.9), 51 naïve patients and 133 after switch. Among them, 142 patients were evaluated after first 12-months of treatment according to relapse rate, neurological status expressed by Expanded Disability Status Scale (EDSS), new T2-weighted (T2-w) lesions and gadolinium-enhancing lesions (GELs) in magnetic resonance imaging (MRI), confirmed disability progression, as well as adverse events. Logistic regression identified factors associated with disease activity at ofatumumab initiation, including age, sex, disease duration, prior treatment, and baseline EDSS. Results: After the first 12 months of OFA treatment, relapses occurred in 12.0% of patients; new or enlarging T2-w lesions were observed in 12.7%; GELs in 3.5%; EDSS progression in 12.7%; and EDSS improvement in 14.2%. The No Evidence of Disease Activity-3 (NEDA-3) status was achieved in 76.1% of patients overall—75.8% in those who switched from another disease-modifying therapy (DMT), and 76.6% in treatment-naïve individuals. No significant differences were observed between the naïve and switch groups. Baseline EDSS at ofatumumab initiation was a significant predictor of relapse activity, while age was significantly associated with MRI activity (GELs) at 12 months. Conclusions: Real-world data confirmed high efficacy and safety of ofatumumab in RRMS. NEDA-3 was achieved more often than in registration trials. No efficacy differences between naïve and switch patients were observed. Full article

Indolethylamine N-methyltransferase (INMT) is a Class 1 methyltransferase responsible for N-methylation of various endogenous and exogenous compounds, including tryptamine, serotonin, and dopamine. This review aims to provide a comprehensive overview of the biological and therapeutic relevance of INMT, emphasizing the human isoform (hINMT), highlighting its structural characteristics, disease association, and recent advances in analytical strategies. Dysregulation of INMT activity has been linked to a range of pathological conditions, including neuropsychiatric disorders, neurodegeneration, and several forms of cancer. These associations are addressed by integrating current findings across disease pathophysiology, enzyme inhibition, and analytical methodologies, including both radiolabeled and non-radiolabeled in vitro assays, for measuring INMT activity. We further explored the chemical diversity of INMT inhibitors, both natural and synthetic, and highlighted key compounds with therapeutic relevance. Additionally, recent commercial assays for quantifying INMT activity are emphasized. By integrating emerging evidence from structural biology and disease pathology with inhibitor profiling and analytical technologies, this review highlights the underexplored therapeutic potential of targeting INMT and underscores its value as a promising target for drug development and therapeutic applications. Full article

Background/Objectives: Quantitative intravoxel incoherent motion (IVIM) imaging, incorporating both diffusion- and perfusion-derived metrics, offers a promising non-invasive approach for assessing tissue microstructure and clinical disability in multiple sclerosis (MS). This study aimed to investigate the correlation and predictive values of the IVIM apparent diffusion coefficient (ADC), true diffusion coefficient (D), and perfusion-derived pseudo-diffusion coefficient (D*) and perfusion fraction (f) parameters with disability status, measured using the Expanded Disability Status Scale (EDSS), in relapsing–remitting MS patients. Methods: This cross-sectional study retrospectively analyzed MRI data from 197 MS patients. Quantitative IVIM parameters were extracted from scans obtained using a 1.5 T MRI scanner. Clinical data were also obtained, including age, disease duration, number of relapses, disease-modifying therapy (DMT) status, and need for mobility assistance. Bivariate analyses were conducted to compare mean values across subgroups. Pearson correlation was used to examine associations between EDSS score and imaging/clinical variables. Multiple linear regression was applied to identify independent predictors of EDSS score. Results: The bivariate analyses revealed that ADC, D, D*, and EDSS values were higher in patients over 50 years old, those with a longer disease duration, and those who required mobility assistance. f was higher in females and DMT-treated patients, but it had no effect on EDSS score. Patients with longer disease duration and limited mobility had a higher number of MS lesions and relapses. EDSS score exhibited positive Pearson correlations with ADC, D, D*, the number of MS lesions, and the number of relapses (p-value < 0.001). In the multivariate regression analysis, only the number of MS lesions and relapses emerged as independent predictors of EDSS score (p-value < 0.001). Other variables, including ADC, D, D*, f, age, and disease duration, were not independently associated with EDSS score (p-value > 0.05). Conclusions: This study demonstrates the utility of IVIM parameters in detecting microstructural alterations associated with MS impairment. Despite relapse frequency and lesion count being the strongest predictors of EDSS score, IVIM metrics showed meaningful clinical correlations. The findings support combining IVIM biomarkers with clinical data for better disability assessment. Full article

In the realm of optical wireless communication (OWC), augmented spectral efficiency discrete multitone (ASE-DMT) has been widely recognized as a promising modulation due to its outstanding spectral efficiency and high power efficiency. However, ASE-DMT exhibits an inherently high peak-to-average power ratio (PAPR), which exacerbates error propagation and leads to a substantial transmission performance degradation in the successive interference cancellation (SIC) receiver of ASE-DMT. Therefore, a novel low-PAPR ASE-DMT scheme (LP-ASE-DMT) is proposed in the paper. Given the intricate multi-depth signal superposition of ASE-DMT, a progressive multi-level constellation extension algorithm is developed to effectively suppress the PAPR of the transmitted signal, while simultaneously achieving much lower computational complexity compared to conventional constellation extension schemes. Furthermore, a dedicated receiver architecture is designed for LP-ASE-DMT, in which a low-complexity modulo operation is employed to eliminate the impact of constellation extension without incurring significant additional receiver complexity. The effectiveness of the proposed LP-ASE-DMT scheme is validated through simulation, revealing a substantial mitigation of PAPR compared to its counterparts. This improvement notably strengthens the system’s robustness to nonlinear impairments. Consequently, LP-ASE-DMT enjoys superior performance across multiple metrics, including bit error rate (BER), power efficiency, and spectral efficiency. Full article

This study introduces a novel method for evaluating pile–soil interaction based solely on Dilatometer Test (DMT) results, enhancing and extending the established approach originally developed using Menard Pressuremeter Test (PMT) data. Currently, transfer functions utilizing DMT sounding results are in the early stages of development. Presented research fills the gap in DMT-based methods for pile design by introducing transfer functions for reversal loadings to calculate the unit shaft friction of screw displacement piles in Controlled Modulus Columns (CMC) technology. The proposed method utilizes DMT-derived soil parameters, offering a practical and accurate alternative to PMT-based models. Testing research fields were located in the Vistula Marshlands, Northern Poland. Site characterization consisted of piezocone (CPTU) and DMT soundings to characterize the soil profile and estimate soil parameters relevant for pile design. CMCs were installed and statically load tested under various loading schemes. Laboratory direct shear tests on smooth and rough soil-concrete interfaces were performed in both forward and backward directions (reversal loading) to simulate pile loading conditions. Results demonstrate improved adaptability of DMT-based transfer curves to local soil conditions and provide a reliable framework for predicting pile performance in soft soils. Proposed DMT-model returns similar ultimate bearing capacities of the pile to CPT 2012 method for first loading, simultaneously offering better agreement for reversal loading, a situation not accounted for in CPTU 2012 or most other CPT-based methods. Full article

Multiple sclerosis (MS) is a chronic, immune-mediated disorder of the central nervous system (CNS) characterized by inflammation, demyelination, axonal degeneration, and gliosis. Its pathophysiology involves a complex interplay of genetic susceptibility, environmental triggers, and immune dysregulation, ultimately leading to progressive neurodegeneration and functional decline. Although significant advances have been made in disease-modifying therapies (DMTs), many patients continue to experience disease progression and unmet therapeutic needs. Drug repurposing—the identification of new indications for existing drugs—has emerged as a promising strategy in MS research, offering a cost-effective and time-efficient alternative to traditional drug development. Several compounds originally developed for other diseases, including immunomodulatory, anti-inflammatory, and neuroprotective agents, are currently under investigation for their efficacy in MS. Repurposed agents, such as selective sphingosine-1-phosphate (S1P) receptor modulators, kinase inhibitors, and metabolic regulators, have demonstrated potential in promoting neuroprotection, modulating immune responses, and supporting remyelination in both preclinical and clinical settings. Simultaneously, artificial intelligence (AI) is transforming drug discovery and precision medicine in MS. Machine learning and deep learning models are being employed to analyze high-dimensional biomedical data, predict drug–target interactions, streamline drug repurposing workflows, and enhance therapeutic candidate selection. By integrating multiomics and neuroimaging data, AI tools facilitate the identification of novel targets and support patient stratification for individualized treatment. This review highlights recent advances in drug repurposing and discovery for MS, with a particular emphasis on the emerging role of AI in accelerating therapeutic innovation and optimizing treatment strategies. Full article

Background and Objectives: Multiple sclerosis (MS) is a chronic immune-mediated neurological disorder that primarily affects young adults and is frequently accompanied by psychiatric comorbidities such as depression and anxiety, both of which significantly diminish patients’ quality of life (QoL). This study investigated the effect of two oral disease-modifying therapies (DMTs), fingolimod and cladribine, on mental health and QoL in patients with relapsing-remitting MS (RRMS). The aim of the study was to compare levels of depression, anxiety, and health-related quality of life (HRQoL) in RRMS patients treated with fingolimod or cladribine, and to evaluate their associations with clinical and radiological parameters. Materials and Methods: Eighty RRMS patients aged 18 to 50 years with Expanded Disability Status Scale (EDSS) scores of 3.0 or less, no recent disease relapse, and no history of antidepressant use were enrolled. Forty patients were treated with fingolimod and forty with cladribine. Depression and anxiety were assessed using the Hamilton Depression Rating Scale (HDRS) and the Hamilton Anxiety Rating Scale (HARS). QoL was evaluated using the Multiple Sclerosis QoL-54 (MSQOL-54) instrument. Additional clinical data, including MRI-based lesion burden, EDSS scores, age, disease duration, and occupational status, were collected. Results: No statistically significant differences were observed between the two groups regarding HDRS and HARS scores (p > 0.05). However, patients treated with fingolimod had significantly higher scores in the Energy/Fatigue subdomain (7.55 ± 2.02 vs. 6.56 ± 2.57, p = 0.046) and Composite Mental Health (CMH) score (64.73 ± 15.01 vs. 56.00 ± 18.93, p = 0.029) compared to those treated with cladribine. No significant differences were found in the independent items of the MSQOL-54. A negative correlation was identified between total lesion load and QoL scores. Conclusions: Although fingolimod and cladribine exert comparable effects on depression and anxiety levels, fingolimod may be associated with better mental health outcomes and reduced fatigue in RRMS patients. Furthermore, lesion burden and clinical parameters such as age and EDSS score may independently influence QoL, regardless of the DMT used. Full article

DNA methylation, mediated by DNA methyltransferases (DMTs) and demethylases (DMLs), is an important epigenetic modification that maintains genomic stability and regulates gene expression in plant growth, development, and stress responses. However, a comprehensive characterization of these gene families in Populus sect. Turanga remains lacking. In this study, eight PeDMT and two PeDML genes were identified in Populus euphratica, and six PpDMT and three PpDML genes in Populus pruinosa. Phylogenetic analysis revealed that DMTs and DMLs could be classified into four and three subfamilies, respectively. The analysis of cis-acting elements indicated that the promoter regions of both DMTs and DMLs were enriched with elements responsive to growth and development, light, phytohormones, and stress. Collinearity analysis detected three segmentally duplicated gene pairs (PeDMT5/8, PeDML1/2, and PpDML2/3), suggesting potential functional diversification. Transcriptome profiling showed that several PeDMTs and PeDMLs exhibited leaf shape- and developmental stage-specific expression patterns, with PeDML1 highly expressed during early stages and in broad-ovate leaves. Whole-genome bisulfite sequencing revealed corresponding decreases in DNA methylation levels, suggesting that active demethylation may contribute to heteromorphic leaf formation. Overall, this study provides significant insights for exploring the functions and expression regulation of plant DMTs and DMLs and will contribute to future research unraveling the molecular mechanisms of epigenetic regulation in P. euphratica. Full article