Search Results (7,438)

Presbyopia is a ubiquitous age-related condition characterized by reduced near focusing ability due to lenticular stiffening. Pharmacologic agents such as pilocarpine have re-emerged as a less-invasive treatment option by inducing miosis and thereby enhancing depth of focus. However, the optimal pharmacologically induced pupil size that balances improved near vision with sufficient retinal illuminance remains undetermined. In this work, we present for the first time a direct integration of advanced theoretical modeling with a systematic synthesis of clinical trial outcomes to define the optimal target pupil size for pharmacologic presbyopia correction. We modeled visual performance using the Visual Strehl Ratio of the Optical Transfer Function (VSOTF) and convolved images of optotypes across a range of pupil diameters from 1.5 mm to 3.5 mm. This combined optical–clinical approach allowed us to quantitatively compare modeled image quality and depth of focus predictions with real-world clinical efficacy data from pilocarpine-based interventions. Simulations showed that smaller pupil sizes (1.5–2.5 mm) significantly extended depth of focus compared to standard multifocal optics while maintaining image quality within acceptable limits. These findings align with clinical trials of pilocarpine formulations, which commonly achieve post-treatment pupil diameters in the 2.0–2.5 mm range and are associated with clinically meaningful gains in near vision. Our analysis uniquely demonstrates that these clinically achieved pupil sizes closely match the theoretically optimal 2.0–3.0 mm range identified in our modeling, strengthening the evidence base for drug design and patient selection. These results reinforce the role of pharmacologically controlled pupil size as a central target in presbyopia management. By explicitly linking predictive optical modeling with aggregated clinical outcomes, we introduce a novel framework to guide future pharmacologic development strategies and refine clinical counseling in the emerging era of presbyopia therapeutics. Full article

Predictive maintenance of railroads is essential to prevent costly disruptions. A critical aspect of this maintenance is ensuring the integrity of the pantograph-catenary system, where copper alloy wires experience continuous friction and wear. The degradation rate and condition of these wires are vital factors in planning maintenance activities. Current wear rate prediction methods are largely theoretical and often inaccurate, overlooking essential contextual details. Additionally, wire condition data frequently show inaccuracies and inconsistencies in spatial and temporal resolution, complicating the feasibility of using data-driven approaches. This research investigates a data-driven framework to accurately predict wear rates, emphasizing data processing and optimized data use. A dataset spanning nine years of Dutch railway infrastructure measurements is used, employing various machine learning techniques to determine the most effective approach. Findings indicate that, in 95% of cases, average wire thickness can be predicted with a precision of ±0.12 mm over a four-year period. This study advances the field by proposing a framework that addresses measurement errors, a common challenge in sensor-based assessments, making data-driven maintenance a more reliable option. Full article

Background/Objectives: Endovascular treatment has become the primary treatment for intracranial aneurysms, yet direct bypass surgery remains an option in selected cases where standard approaches fail. This study aims to evaluate the role, indications, and outcomes of bypass surgery for intracranial aneurysm management in the current endovascular era. Methods: A single-center retrospective analysis was conducted on consecutive cases who underwent direct intracranial bypass surgery for intracranial aneurysms between 2015 and 2024. Data on demographics, aneurysm characteristics, indications, bypass type, patency, and clinical outcomes (using the modified Rankin Scale) were collected. Results: Of the 101 bypasses performed between 2015 and 2025, 25 were used for complex aneurysm cases. Intracranial bypass was necessary in as many as 5% of all microsurgical aneurysm repairs in 2023 and 10% in 2024. Bypass surgery was indicated in young patients with complex aneurysms not amenable to endovascular therapy (45%) and in 20% of the cases for recanalized aneurysms after previous endovascular repair. Intraoperative and postoperative bypass patency was confirmed for all patients except one case due to ongoing malignant brain swelling after an ongoing infarction. At follow-up, 87% of patients, with both ruptured and unruptured aneurysms, had a good outcome (mRS ≤ 2), and all patients had a patent bypass. Permanent morbidity was observed in 5% and procedure-related mortality in 0%. Conclusions: While bypass surgery constitutes a minority of intracranial aneurysm treatment by volume, its role in intracranial aneurysm repair is crucial and relevant in response to the evolving complexity of aneurysms. Further refinement of techniques is necessary. Full article

With the increasing demand for urban rail transit capacity, shield tunneling has become the predominant method for constructing underground metro systems in densely populated cities. However, the spatial interaction between shield tunnels and adjacent retaining structures poses significant engineering challenges, potentially leading to excessive ground settlement, structural deformation, and even stability failure. This study systematically investigates the deformation behavior and associated risks of retaining systems during adjacent shield tunnel construction. An orthogonal multi-factor analysis was conducted to evaluate the effects of grouting pressure, grout stiffness, and overlying soil properties on maximum surface settlement. Results show that soil cohesion and grouting pressure are the most influential parameters, jointly accounting for over 72% of the variance in settlement response. Based on the numerical findings, a Bayesian network model was developed to assess construction risk, integrating expert judgment and field monitoring data to quantify the conditional probability of deformation-induced failure. The model identifies key risk sources such as geological variability, groundwater instability, shield steering correction, segmental lining quality, and site construction management. Furthermore, the effectiveness and cost-efficiency of various grouting reinforcement strategies were evaluated. The results show that top grouting increases the reinforcement efficiency to 34.7%, offering the best performance in terms of both settlement control and economic benefit. Sidewall grouting yields an efficiency of approximately 30.2%, while invert grouting shows limited effectiveness, with an efficiency of only 11.6%, making it the least favorable option in terms of both technical and economic considerations. This research provides both practical guidance and theoretical insight for risk-informed shield tunneling design and management in complex urban environments. Full article

Background: The Induced Membrane Technique (IMT), commonly known as the Masquelet Technique (MT), has shown promising results in the reconstruction of bone defects caused by osteomyelitis. However, it is not a standardized surgical protocol but a treatment concept that has undergone various modifications, often yielding heterogeneous outcomes. Methods: This retrospective, single-center clinical cohort study included 49 patients treated with the Bone Block Technique (BBT) between 2013 and 2019 for bone defects resulting from osteomyelitis. The primary outcomes were time to bone healing, reinfection rate, and time to full weight-bearing. Additionally, infectious disease parameters, surgical site complications (SSCs), and epidemiological data were evaluated. Results: Data from 49 patients (mean age: 51 years, range: 17.6–76.9; 28.6% female) were analyzed, with a mean follow-up of 6.1 years (range: 4–10.5). The average bone defect length was 4.2 cm (range: 2.1–8.4 cm), predominantly involving the lower extremity. Primary bone consolidation was achieved in 93%, and secondary consolidation (requiring additional surgery) in 7%. Revision surgery due to recurrent infection was necessary in 16.6% of cases. The average time to full weight-bearing was 101.3 days. Conclusions: The BBT, as a modified approach based on the original IMT, represents a viable and reproducible option for bone defect reconstruction. When applied in accordance with the principles of the Diamond Concept, this technique facilitates reliable primary consolidation with a low complication rate. Full article

Background: Pediatric tracheostomy decisions are challenging for clinicians and parents, especially when a child’s survival/neurodevelopmental outcome is uncertain. Better understanding of parents’ values over the decision period is crucial for clinical decision-making. Objective: To describe parents’ values during tracheostomy decision-making for their critically ill child and to identify opportunities to improve parent–clinician shared decision-making (SDM). Methods: We thematically analyzed 12 semi-structured interviews with parents who recently faced a tracheostomy decision for their critically ill child. Three study team members with qualitative expertise reviewed the transcripts, identifying key topics independently. A codebook was developed, and data were coded. Key research questions guided analysis, with findings iteratively reviewed by the study team. Results: We identified parents’ values at the three time points: when the decision was introduced, during their deliberations of it, and when the ultimate decision was made. Initially, parents resisted tracheostomy because it threatens normalcy. They valued proof of a need for tracheostomy and information with certainty. As certainty for tracheostomy increased over time, parents’ hope focused on reversibility of tracheostomy and improvement in normalcy compared to current status. They concurrently worried about practical issues such as emergencies, home care, and finances. Key considerations driving the final decision included best interest of the child, perceived benefits of tracheostomy compared to its downsides or other options, and potential for better quality of life and longer life. Conclusions: Parents’ dynamic values shifting with clinical uncertainty suggests opportunities to improve SDM by attending to parents’ individualized needs and managing expectations. Full article

Background: Urinary tract infections (UTIs) are among the most common bacterial infections in children, with Escherichia coli as the leading pathogen. The rise in antimicrobial resistance, particularly extended-spectrum β-lactamase (ESBL) production, complicates empirical therapy, especially in countries with limited surveillance like Romania. Methods: We conducted a retrospective study on 248 pediatric patients aged 0–17 years diagnosed with E. coli UTI and admitted to a children hospital from Bucharest, Romania, between 2022 and 2024. Data collected included clinical presentation, laboratory values, and antimicrobial susceptibility testing. Patients were divided into ESBL and non-ESBL groups, and statistical comparisons were performed using SPSS v25. Results: Infants accounted for 68.1% of cases, with male sex predominating in this group (85.3%). ESBL-producing strains were identified in 19% of patients, more frequently in males (25% vs. 13.6%, p = 0.024). While inflammatory markers (CRP, leukocytes, neutrophils) were higher in complicated infections, they were paradoxically lower in ESBL cases. Non-ESBL isolates were highly susceptible to fosfomycin, third-generation cephalosporins, nitrofurantoin, and gentamicin. ESBL isolates showed resistance to most β-lactams but retained high susceptibility to fosfomycin (100%), carbapenems (>89%), cefoxitin (89.4%), and amikacin (85.1%). Conclusions: Our findings support the use of fosfomycin, nitrofurantoin, and selected aminoglycosides as viable empirical options in pediatric UTIs. Given the substantial ESBL prevalence and resistance to commonly used oral agents, local antibiogram data should guide empirical treatment strategies to preserve antibiotic efficacy and combat resistance. Full article

In the context of the rapid development of e-commerce, the selection of optimal land plots for the construction of warehouse complexes that meet environmental, technical, and political requirements has become increasingly relevant. This task requires a comprehensive approach that accounts for a wide range of factors, including transportation accessibility, environmental conditions, geographic features, legal constraints, and more. Such an approach enhances the efficiency and sustainability of decision-making processes. This article presents a solution to the aforementioned problem that employs the use of land suitability maps generated by aggregating multiple evaluation criteria. These criteria represent the degree to which each land plot satisfies the requirements of various stakeholders and are expressed as suitability functions based on attribute values. Attributes describe different characteristics of the land plots and are represented as layers on a digital terrain map. The criteria and their corresponding attributes are classified as either quantitative or binary. Binary criteria are aggregated using the minimum operator, which filters out plots that violate any constraints by assigning them a suitability score of zero. Quantitative criteria are aggregated using the second-order Choquet integral, a method that accounts for interdependencies among criteria while maintaining computational simplicity. The criteria were developed based on statistical and environmental data obtained from an analysis of the Samara region in Russia. The resulting suitability maps are visualized as gradient maps, where land plots are categorized according to their degree of suitability—from completely unsuitable to highly suitable. This visual representation facilitates intuitive interpretation and comparison of different location options. These maps serve as an effective tool for planners and stakeholders, providing comprehensive and objective insights into the potential of land plots while incorporating all relevant factors. The proposed approach supports spatial analysis and land use planning by integrating mathematical modeling with modern information technologies to address pressing challenges in sustainable development. Full article

Background: Data on the use of dolutegravir (DTG) plus boosted darunavir (DRV/b) in people with 4-class drug-resistant HIV (4DR-PWH) are limited. This study assessed the virological effectiveness of DTG + DRV/b in this population using real-world data from the PRESTIGIO Registry. Methods: We compared three regimen groups: dual DTG + DRV/b (DODA), DTG + DRV/b plus an additional antiretroviral drug (DODA + Other), and regimens excluding DTG + DRV/b (NO-DODA). Virological failure (VF) was defined as ≥2 HIV-RNA values ≥ 50 copies/mL or 1 ≥ 1000 copies/mL. Mixed-effects logistic regression was used to assess VF, adjusting for antiretroviral therapy (ART) duration, age, number of fully active drugs, sex at birth, and nadir CD4+. Individuals could switch regimens during follow-up. Results: Among 249 4DR-PWH (median follow-up: 8.7 years), 844 ART regimens were analyzed: 72 (8.5%) DODA, 264 (31.3%) DODA + Other, and 508 (60.2%) NO-DODA. Compared to NO-DODA, the odds of VF were 77% and 35.9% lower with DODA and DODA + Other, respectively. Notably, in the DODA group, DTG and DRV/b were fully active in only 63.9% and 47.2% of the cases, respectively. Conclusions: DTG + DRV/b regimens were associated with a significantly lower risk of virological failure, even when drug activity was partial. This strategy remains a valuable option for managing multi-drug-resistant HIV. Full article

Linezolid (LNZ) is a synthetic oxazolidinone antibiotic that inhibits bacterial protein synthesis through binding to ribosomal RNA, also preventing the assembly of the initiation complex during translation. It is one of the last-line therapeutic options for serious infections caused by problematic Gram-positive pathogens, including vancomycin-resistant and multidrug-resistant Enterococcus species. Data from recent large-scale studies show a 2.5-fold increase in the prevalence of clinical LNZ-resistant enterococci (LRE) over the past decade with a global detection rate of 1.1% for LNZ-resistant E. faecium (LREfm) and 2.2% for LNZ-resistant E. faecalis (LREfs). Most reported cases have originated from China, followed by South Korea and the United States. LREfm typically belongs to the high-risk clonal complex 17, whereas LREfs demonstrates a heterogeneous population structure. Mutations in the 23S rRNA and ribosomal proteins, as well as acquired resistance genes such as cfr, optrA, and poxtA are involved in the development of LNZ resistance among enterococci. Whole-genome sequencing (WGS) has been recognized as a gold standard for identifying the underlying molecular mechanisms. It exposes that numerous LRE isolates possess multiple LNZ resistance determinants and mutations, further complicating the treatment strategies. The present review article summarizes all known mutational and non-mutational LNZ resistance mechanisms and presents a global overview of WGS-based studies with emphasis on resistome analysis of clinical LREfs and LREfm isolates published in the literature during the period 2014–2025. Full article

Strongyloidosis is a parasitic disease caused by Strongyloides stercoralis, a nematode with a complex life cycle that facilitates long-term persistence within the host. The infection affects millions of people in tropical and subtropical regions and poses a particular challenge in immunocompromised individuals. Although conventional treatments, such as ivermectin and albendazole, are generally effective, emerging concerns regarding drug resistance and adverse effects have prompted the search for alternative therapeutic options. In this context, natural products—including plant extracts, bioactive phytochemicals, and nanoparticle-based formulations derived from natural sources—are emerging as promising anti-Strongyloides potential. This review summarizes recent studies on natural products with anthelmintic activity against strongyloidiasis, with emphasis on their mechanisms of action, efficacy, and future perspectives. A systematic search of the literature was conducted using terms related to Strongyloides, plant species, extracts, and bioactive compounds with nematocidal activity. Eligible studies included those reporting the activity of plants, plant extracts, and their purified metabolites against Strongyloides spp. Data were compiled into a comprehensive table including year of publication, author, plant species, active principle, application conditions, and target nematode species. The pharmacological treatment of this parasite varies according to its life cycle stage. Various biomolecules, phytoactive compounds, and novel plant-based formulations have demonstrated promising activity and may be considered both for treatment and for inclusion in control programs for strongyloidiasis. This review highlights medicinal plants and phytochemicals with ethnopharmacological background and experimentally validated activity against Strongyloides spp., integrating evidence from in vitro, in vivo, and experimental models, as well as clinical trials. Full article

Background/Objectives: Recurrent meningiomas remain difficult to manage due to the absence of effective systemic therapies and comparatively high treatment failure rates, particularly in high-grade tumors. Stereotactic radiosurgery (SRS) offers a minimally-invasive and precise option, particularly for tumors in surgically complex locations. However, the risks associated with re-irradiation, and recent changes in the WHO classification of CNS tumors highlight the need for more personalized and strategic treatment approaches. This systematic review evaluates the safety, efficacy, and clinical considerations for use of SRS for recurrent meningiomas. Methods: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic literature search was conducted using the PubMed, Scopus, and Web of Science databases for studies reporting outcomes of SRS in recurrent, pathologically confirmed intracranial meningiomas. Studies were excluded if they were commentaries, reviews, case reports with fewer than three cases, or had inaccessible full text. The quality and risk of bias of the included studies were assessed using the modified Newcastle-Ottawa Scale. Data on patient and tumor characteristics, SRS treatment parameters, clinical outcomes, adverse effects, and statistical analysis results were extracted. Results: Sixteen studies were included. For WHO Grade I tumors, 3- to 5-year progression-free survival (PFS) ranged from 85% to 100%. Grade II meningiomas demonstrated more variable outcomes, with 3-year PFS ranging from 23% to 100%. Grade III tumors had consistently poorer outcomes, with reported 1-year and 2-year PFS rates as low as 0% and 46%, respectively. SRS performed after surgery alone was associated with superior outcomes, with local control rates of 79% to 100% and 5-year PFS ranging from 40.4% to 91%. In contrast, tumors previously treated with radiotherapy, with or without surgery, showed substantially poorer outcomes, with 3- to 5-year PFS ranging from 26% to 41% and local control rates as low as 31%. Among patients with prior radiotherapy, outcomes were particularly poor in Grade II and III recurrent tumors. Toxicity rates ranged from 3.7% to 37%, and were generally higher for patients with prior radiation. Predictors of worse PFS included prior radiation, older age, and Grade III histology. Conclusions: SRS may represent a reasonable salvage option for carefully selected patients with recurrent meningioma, particularly following surgery alone. Outcomes were notably worse in high-grade recurrent meningiomas following prior radiotherapy, emphasizing the prognostic significance of both histological grade and treatment history. Notably, the lack of molecular and genetic data in most existing studies represents a key limitation in the current literature. Future prospective studies incorporating molecular profiling may improve risk stratification and support more personalized treatment strategies. Full article

Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MS) are chronic disorders characterized by hyperglycemia. Sechium edule (S. edule) has emerged as a complementary option due to its bioactive compounds. A systematic review of preclinical and clinical studies was carried out until 25 May 2025 in the databases PubMed, Scopus, Web of Science, SciELO, and TESIUNAM. The keywords were “diabetes mellitus”, “Sechium edule”, “Squash”, “Chayote”, “hypoglycemic effect”, and “Older adults”. A total of 110 articles were found; 11 met eligibility criteria (six clinical trials and five preclinical trials). Three clinical trials met the requirements for meta-analysis. The mean difference (MD) was calculated, and data were analyzed using RevMan 5.4 software. The meta-analysis showed a statistically significant decrease in serum glucose after three months (MD = −20.56, 95% CI −29.35 to −11.77, p < 0.0001) and six months after intervention (MD = −12.96, 95% CI = −21.90 to −4.02, p = 0.004). Likewise, there was a significant decrease in glycosylated hemoglobin (HbA1c) after three months (MD = −1.12, 95% CI = −1.45, −0.78, p < 0.0001) and after six months of intervention (MD = −0.92, 95% CI = −1.13, −0.25, p = 0.002). Our findings showed that S. edule intake has a statistically significant hypoglycemic effect in older adults with T2DM or MS by decreasing serum glucose and HbA1c levels. However, the magnitude of the decrease is clinically modest, so it cannot be a substitute for pharmacological treatment. For this reason, the intake of S. edule can only be considered as a complement to pharmacological treatment. Full article

Letrozole, a third-generation aromatase inhibitor initially developed for breast cancer, has become the preferred first-line agent for ovulation induction (OI), particularly in women with polycystic ovary syndrome (PCOS). This narrative review critically evaluates the efficacy, safety, and clinical applications of letrozole across diverse infertility contexts. Compared to clomiphene citrate, letrozole is associated with higher ovulation and live birth rates, a lower risk of multiple gestation, and a more favorable endometrial environment. Its pharmacokinetics—marked by transient estrogen suppression and a short half-life—limit embryonic exposure, supporting its favorable safety profile. Emerging data from large, randomized trials and meta-analyses demonstrate no increase in congenital anomalies, miscarriage, or adverse perinatal outcomes in letrozole-conceived pregnancies. Moreover, maternal side effects are generally mild, and the risk of ovarian hyperstimulation syndrome is low. Letrozole has also shown utility in mild stimulation protocols, fertility preservation for estrogen-sensitive malignancies, and clomiphene-resistant PCOS. Key clinical strategies—such as early-cycle initiation, lowest effective dosing, and individualized monitoring—optimize therapeutic outcomes while minimizing potential risks. While long-term offspring data remain limited and mechanistic concerns persist, current evidence robustly supports letrozole as a safe and effective option for OI, balancing reproductive success with maternal–fetal safety across a range of infertility indications. Full article

This paper investigates technological pathways for the conversion of coal-fired power plants toward sustainable energy sources, using an integrated multi-criteria decision-making approach that combines Proknow-C, AHP, and PROMETHEE. Eight alternatives were identified: full conversion to natural gas, full conversion to biomass, coal and natural gas hybridization, coal and biomass hybridization, electricity and hydrogen cogeneration, coal and solar energy hybridization, post-combustion carbon capture systems, and decommissioning with subsequent reuse. The analysis combined bibliographic data (26 scientific articles and 13 patents) with surveys from 14 energy experts, using Total Decision version 1.2.1041.0 and Visual PROMETHEE version 1.1.0.0 software tools. Based on six criteria (environmental, structural, technical, technological, economic, and social), the most viable option was full conversion to natural gas (ϕ = +0.0368), followed by coal and natural gas hybridization (ϕ = +0.0257), and coal and solar hybridization (ϕ = +0.0124). These alternatives emerged as the most balanced in terms of emissions reduction, infrastructure reuse, and cost efficiency. In contrast, decommissioning (ϕ = −0.0578) and carbon capture systems (ϕ = −0.0196) were less favorable. This study proposes a structured framework for strategic energy planning that supports a just energy transition and contributes to the United Nations Sustainable Development Goals (SDGs) 7 and 13, highlighting the need for public policies that enhance the competitiveness and scalability of sustainable alternatives. Full article