Spinal muscular atrophy (SMA) is a genetic disorder primarily caused by mutations in the SMN1 gene, leading to motor neuron degeneration and muscle atrophy, affecting multiple organ systems. Nusinersen treatment targets gene expression and is expected to enhance the motor function of voluntary muscles in the limbs and trunk. Motor skills can be assessed through specific scales like the Revised Upper Limb Module Scale (RULM) and Hammersmith Functional Motor Scale Expanded (HFMSE). This study aims to evaluate the influence of nusinersen on the motor skills of patients with SMA Type 2 and 3 using real-world data collected over 54 months. A prospective longitudinal study was conducted on 37 SMA patients treated with nusinersen, analyzing data with R statistical software. The outcomes revealed significant improvements in motor functions, particularly in SMA Type 3 patients with higher RULM and HFSME scores. Additionally, GEE analysis identified time, type, age, and exon deletions as essential predictors of motor score improvements. The extended observation period is both a major strength and a limitation of this research, as the dropout rates could present challenges in interpretation. Variability in responses, influenced by genetic background, SMA type, and onset age, highlights the need for personalized treatment approaches.

Spinal muscular atrophy (SMA), identified over a century ago, is characterized by severe muscle wasting and early mortality. Despite its rarity, the high carrier frequency of the responsible genetic mutations and the variability in its manifestations make it a significant research focus. This prospective cross-sectional descriptive study evaluated health-related quality of life (HRQoL) across eight health domains in 43 Romanian SMA patients treated with nusinersen, using the SF-36 questionnaire to analyze influencing factors. The survey was conducted online with informed consent, and the data were analyzed using MedCalc software, employing both parametric and non-parametric statistical tests for accurate interpretation. The results revealed significant variations in HRQoL. Most patients were non-ambulatory (74.4%), reflecting SMA’s impact on mobility. Urban residents reported better outcomes, particularly in physical functioning (p = 0.014), which may be attributed to improved access to healthcare services. Younger participants (under 14), represented by proxy responses, noted better general health (p = 0.0072) and emotional well-being (p = 0.0217) compared to older participants. These findings suggest that younger patients or their proxies perceive a better health status, highlighting the need for age-specific approaches in SMA management and the potential optimistic bias associated with proxy reporting on perceived health outcomes.

Background/Objectives: Traditional histopathological classification of endometrial cancer (EC) exhibits limited prognostic precision due to interobserver variability and incomplete reflection of tumor biology. The Cancer Genome Atlas (TCGA) introduced molecular subtypes, with POLE-ultramutated tumors showing superior outcomes. This systematic review and meta-analysis assesses the prognostic impact of pathogenic/likely pathogenic POLE exonuclease-domain mutations (EDM) on survival in EC. Methods: PRISMA 2020-compliant search of PubMed, Embase, and Web of Science (2015–2025) identified 20 studies (n = 7708 EC patients; 159 POLE-mutant, 2.1%). Eligibility: Adult EC patients with POLE EDM vs. non-POLE, reporting OS/PFS/DFS/RFS/CSS hazard ratios (HR). ROBINS-I assessed bias; random-effects meta-analysis pooled multivariable HR. Results: The meta-analysis revealed a significantly reduced risk of death in POLE-mutant endometrial cancer patients, with an OS pooled hazard ratio (HR) of 0.35 (95% CI 0.21–0.58; I² = 17.9%) across eight studies. Disease control endpoints (DFS/PFS/RFS) from 10 studies showed an even more substantial benefit, with a pooled HR of 0.22 (95% CI 0.12–0.41; I² = 0%). Cancer-specific survival HRs ranged from 0.00 to 0.32 across four studies, often with zero events in POLE cohorts. ROBINS-I bias was low to moderate; heterogeneity stemmed from the comparators and stages. Conclusions: POLE-EDM confers a robust, favorable prognosis across EC stages, supporting molecular risk stratification and treatment de-escalation.

Background/Objectives: The optimal timing for orthodontic treatment in pediatric patients with malocclusion, particularly Class II discrepancies, remains a topic of ongoing clinical debate. Early treatment during the mixed dentition stage harnesses craniofacial growth potential, whereas later intervention may capitalize on pubertal growth for greater skeletal correction, especially for skeletal and airway improvements. This systematic review aimed to compare the outcomes of early versus late orthodontic treatment to assess their relative effectiveness. Methods: A systematic review was conducted in accordance with PRISMA guidelines, including randomized controlled trials and observational studies published between 2015 and 2025. Eleven studies comparing early and late treatment were analyzed, and the risk of bias was evaluated using standardized assessment tools. Results: Of the eleven studies, eight reported statistically significant improvements favoring early orthodontic intervention. Early treatment was associated with greater enhancement of maxillary and mandibular arch development, improved jaw relationships, and expanded airway dimensions. Studies utilizing headgear or other growth-modifying appliances also showed more favorable eruption patterns and alignment, underscoring the clinical relevance of early-phase management. Conclusions: Early orthodontic treatment can provide meaningful benefits in guiding skeletal growth, improving dental arch form, and enhancing treatment efficiency. These benefits were most consistently supported in skeletal and airway outcome domains. While late treatment may be suitable for some cases, personalized planning remains essential. Further large-scale, standardized longitudinal studies are needed to refine treatment-timing protocols in pediatric orthodontics.

Background and Objectives: Multiple primary malignancies involving endometrial carcinoma (EC) present complex diagnostic and management challenges. This study aimed to identify clinical, pathological, and demographic patterns among patients with EC and a second primary tumor and assess the role of comorbidities in tumor behavior. Materials and Methods: We retrospectively analyzed 35 women diagnosed with EC and a second malignancy between 2017 and 2024. We evaluated clinical variables, tumor characteristics, and comorbidities. Statistical analysis included chi-square tests, Mann–Whitney U tests, Kruskal–Wallis tests, Spearman correlations, and logistic regression. Multiple testing correction was applied using the Benjamini–Hochberg method. Results: Endometrioid EC was the most prevalent subtype (80%), most frequently associated with breast (28.5%) and colorectal cancers (11.4%). Obesity (45.7%), hypertension (62.9%), and diabetes (22.9%) were common. While univariate analysis suggested associations between comorbidities and tumor features (e.g., obesity and tumor type, ρ = 0.30, p = 0.08), no correlation remained significant after adjustment. Logistic regression identified age (OR = 0.88, CI: 0.79–0.98, p = 0.022) and obesity (OR = 0.11, CI: 0.01–0.83, p = 0.033) as independent predictors of non-endometrioid histology. Conclusions: These findings suggest that age and obesity may influence histological differentiation in EC with multiple primaries. This study suggest that age and obesity may play a role in the histological differentiation of EC in patients with multiple primary tumors. The small cohort size (n = 35) limits the statistical power and generalizability of the results; therefore, they should be regarded as exploratory and hypothesis-generating, warranting validation in larger prospective studies.

Background/Objectives: Advancements in personalized medicine have revolutionized drug delivery, enabling tailored treatments based on genetic and molecular profiles. Non-viral vectors, such as polyurethane (PU)-based systems, offer promising alternatives for gene therapy. This study develops mathematical models to analyze PU degradation, DNA/RNA release kinetics, and cellular interactions, optimizing their application in personalized therapy. Methods: This theoretical study utilized mathematical modeling and numerical simulations to analyze PU-based gene delivery, focusing on diffusion, degradation, and cellular uptake. Implemented in Python 3.9, it employed differential equation solvers and adsorption/internalization models to predict vector behavior and optimize delivery efficiency. Results: This study demonstrated that PU degrades in biological environments following first-order kinetics, ensuring a controlled and predictable release of genetic material. The Higuchi diffusion model confirmed a gradual, sustained DNA/RNA release, essential for efficient gene delivery. Simulations of PU adsorption onto cellular membranes using the Langmuir model showed saturation-dependent binding, while the endocytosis model revealed a balance between uptake and degradation. These findings highlight PU’s potential as a versatile gene delivery vector, offering controlled biodegradability, optimized release profiles, and effective cellular interaction. Conclusions: Our results confirm that PU-based vectors enable controlled biodegradability, sustained DNA/RNA release, and efficient cellular uptake. Mathematical modeling provides a framework for improving PU’s properties, enhancing transport efficiency and therapeutic potential in personalized medicine and gene therapy applications.