Search Results (18,780)

Background: Endometriosis is a chronic, estrogen-dependent inflammatory disease affecting up to 10% of women of reproductive age. It substantially impacts quality of life (QoL) through pelvic pain, infertility, and psychological distress. Increasing attention has been directed toward patient-reported outcomes and validated QoL instruments, which are essential for understanding the burden of disease and guiding individualized management. Materials and Methods: We performed a narrative review of the literature published in the last five years in PubMed, Scopus, Web of Science, and Cochrane Library, focusing on validated QoL instruments, fertility indices, and clinical outcomes after minimally invasive surgery (MIS) for deep infiltrating endometriosis (DIE). Discussions: The most widely used QoL instruments are the Endometriosis Health Profile-30 (EHP-30), Short Form-36 (SF-36), and EQ-5D, each providing multidimensional evaluation across physical, psychological, and social domains. Fertility-related prognosis is assessed with the Endometriosis Fertility Index (EFI), while staging of disease severity relies on rASRM and #ENZIAN classifications. Evidence from comparative and cohort studies suggests that both laparoscopic and robotic MIS can improve QoL and reproductive outcomes; however, the magnitude of benefit varies across studies, patient phenotypes, and follow-up periods. Conclusions: MIS is an increasingly used therapeutic option for DIE, with growing evidence of improvement in pain and QoL, but current data remain heterogeneous and do not uniformly support superiority over other approaches. Routine incorporation of validated QoL instruments and fertility indices into both clinical practice and research is essential to better stratify patients, support shared decision-making, and optimize long-term outcomes. Full article

STC2 (stanniocalcin 2) controls calcium (Ca²⁺) homeostasis in human platelets and other cell lines. The regulation of intracellular Ca²⁺ homeostasis is crucial for platelet activation; thus, the alteration in intracellular Ca²⁺ concentration or the mechanism involved in its regulation has been proposed to underlie some thrombotic disorders. Our previous studies evidenced that the knockdown of STC2 altered murine platelet activation; furthermore, a reduction in STC2 expression resulted in enhanced Ca²⁺ homeostasis in diabetic patients and, therefore, would contribute to the prothrombotic condition as a hallmark of diabetes mellitus type 2 (DM2). In this study, we examine a possible link between the expression of stanniocalcins (STCs) and different thrombotic events in humans. The expression of STCs was determined by Western blotting (WB); meanwhile, the analysis of protein interaction and phosphorylation was performed by completing a previous immunoprecipitation protocol (IP) of the proteins of interest. Thus, our results from patients with stroke/ictus presented a clear reduction in STC2 expression in their platelets, finding less STC2 content in the youngest thrombotic patients. Furthermore, acetyl-salicylic acid (ASA) administration reversed the decrease in the expression of STC2 in patients who did not suffer additional thrombotic episodes, as evidenced by the longitudinal analysis of up to 10 years of follow-up. Additionally, the increase in STC2 phosphorylation at the serine residues revealed increased activity of STC2 in thrombotic patients. Finally, we suggest that store-operated Ca²⁺ entry (SOCE) is over-activated in patients suffering from stroke/ictus, as revealed by the increase in the STIM1/Orai1 interaction found under resting conditions and, further, because MEG-01 cells transfected with siRNA STC2 to evoke artificial reduction in the STC2 expression presented an increased SOCE with respect to the control cells transfected with siRNA A. Conversely, the expression of the non-capacitative Ca²⁺ channels, Orai3 and TRPC6, was found to be reduced in patients with stroke. Altogether, our data allow us to conclude that STC2 represents a promising marker of stroke/ictus in thrombotic patients. Full article

Cystic fibrosis (CF) is an autosomal recessive genetic condition affecting nearly 1 in 4000 newborns. Early diagnosis and treatment have been shown to improve the care of individuals with CF, which is enhanced through newborn screening (NBS). The state of Florida has been performing CF NBS since 2007, and in 2022, Florida implemented enhanced next generation sequencing (NGS). The goal of this change was to identify individuals from under-represented racial and ethnic groups, who may have rare or de novo variants. NBS screening for CF involved a first tier with immunoreactive trypsinogen (IRT) ≥ 50 or the top 4% of daily specimens, whichever is lower, reflexing to a second tier. As of 2022, the second tier has evolved to an expanded sequence with an Agena 74-variant panel. Single variants would then reflex to the third tier utilizing NGS. NGS is able to confirm what is detected in second-tier testing, adding variants not included in the Agena panel, and refining the TG replications for Poly-T variants to determine pathogenicity of 5T results. When there is a variant of varying clinical consequence between the two databases, the most conservative classification is selected. Individuals with variants would then be referred to one of the contracted CF NBS referral centers for confirmatory sweat chloride testing (sweat). With implementation of NGS, referrals nearly tripled in 2022–2024, with 538 referrals in 2019; 485 in 2020; and 805 in 2021; followed by 1223 referrals made in 2022; 1146 in 2023; and 1294 in 2024. In 2022–2024, 71% of referrals to the contracted NBS CF referral centers were for single variant results, and no cases of CF were identified from these referrals. The number of CF cases remained about the same, ranging from 23 to 40 through the years 2019–2024. The number of CRMS/CFSPID cases, however, tripled going from 10 to 12 in 2019–2022 to over 100 in 2024. The reason for this change seems to be related to complex heterozygous genetic variants as opposed to abnormal sweat. Implementation of NGS for CF in Florida led to a significant increase in the identification of CFTR variants which affected all aspects of the NBS CF process, from an increased workload on the NBS laboratory and follow-up staff, to an increase in referrals to the NBS CF referral centers. The majority of referrals were for single-variant results, which meant the infants had a very low likelihood of having CF. It is recommended that when an algorithm involving NGS is utilized, one should verify that there are appropriate processes for sweat, including the manner in which single-variant CF results are handled, avoiding unnecessary healthcare utilization. Full article

Nuts are nutrient-rich foods that help reduce the risk of coronary heart disease (CHD), but their potential contamination with aflatoxins (AFs) may increase the risk of liver cancer. In this study, the European Benefit–Risk Analysis for Foods (BRAFO) framework was used to evaluate both the health risks and benefits of nut consumption among Chinese adults. Based on the actual consumption patterns of nuts among the Chinese population, the current consumption level was set as the reference scenario (4.66 g/day), and three alternative scenarios were simulated with a daily nut consumption of 10, 20, and 30 g, respectively. Dose–response relationships were established using a two-stage dose–response analysis for nut consumption and CHD risk, and a one-stage dose–response analysis for aflatoxin B1 (AFB1) exposure and liver cancer risk. A Monte Carlo probabilistic model quantified the CHD prevention benefits and liver cancer risks associated with AF exposure. Disability-Adjusted Life Year (DALY) analysis indicated net health benefits in all scenarios, with nut consumptions of 10, 20, and 30 g/day reducing DALYs per 100,000 population by 104.39, 143.63, and 181.47 in men, and by 58.79, 81.29, and 102.94 in women, respectively. A nut consumption of 10 g/day was recommended for Chinese adults, considering both health benefits and the risk of AF exposure. This study presents the first application of the BRAFO framework to evaluate the net health effect of nut consumption in a Chinese population, filling a critical gap in the risk–benefit assessment of nut consumption. Full article

Students with autism spectrum disorder (ASD) often face difficulties in solving arithmetic word problems, particularly in transitioning from informal counting strategies to more efficient methods based on number facts and formal operations. This study examined the development of problem-solving strategies in a single student with ASD and intellectual disability across two sequential single-case experiments using multiple baseline designs. Study 1 (age 13 years 9 months; 17 sessions) employed Modified Schema-Based Instruction (MSBI) to teach addition and subtraction change problems, while Study 2 (age 14 years 10 months; 18 sessions) utilized the Conceptual Model-based Problem Solving (COMPS) approach for multiplication and division equal-group problems. Success was defined as both correctness of the response and correctly identifying the required operation. Results indicated that the student’s performance improved in all problem types in both studies, with maintenance observed 8 weeks after Study 1 and 5 weeks after Study 2. Instruction effects generalized to two-step addition and subtraction problems in Study 1, and to two-step addition and multiplication problems in Study 2. The findings indicate that both MSBI and COMPS facilitated the student’s shift from informal strategies to efficient operation-based problem solving. Implications for practice include the need for individualized reinforcements, careful adaptation of instruction, and providing teachers with a variety of problems and knowledge of these teaching methods to support students with ASD in developing advanced problem-solving skills. Full article

Despite the ongoing electromobility revolution in urban areas, fleet managers still prefer combustion engines over electric vehicles. Fleet electrification can deliver tangible benefits not only for the urban environment but also for the company itself. However, this requires a robust economic and technical analysis approach. This study assesses the technical and economic viability of integrating electric vehicle (EV) fleets into the Turkish manual frequency recovery reserve (mFRR) market. Using a life-cycle costing (LCC) framework, three operational scenarios are modeled: Baseline (leased EVs without V2G), V2G+ (leased EVs with aggregator-based mFRR), and High Utilization (owned EVs with full V2G integration and increased rental activity). The baseline scenario assumes a net cost of USD 142,500 over 10 years, excluding revenue share. V2G+ reduces this amount to USD 137,000, generating an annual income of approximately USD 4400 from its share of the frequency reserve. A high utilization scenario, combining V2G with ownership and higher rental income, reduces the net LCC to USD 125,500 and generates over USD 12,000 annually, reaching breakeven around year 7. Sensitivity analyses show that the financial profitability of the system is significantly influenced by EV purchase prices, aggregator fees, mFRR capacity payments, and vehicle utilization rates. Adding a 30–50% solar-powered charging enclosure further reduces operating costs by up to USD 21,500, demonstrating the synergistic potential of integrating V2G and distributed photovoltaics. These results influence not only the priorities for electrifying the urban vehicle fleet, but also smart city regulations in the area of energy management, through the development of bidirectional charging standards and pilot implementation of V2G in emerging markets such as Turkey. Full article

Background: Oscillating hyperglycemia (glycemic variability) and vitamin D deficiency each damage the retinal microvasculature, yet their combined effect on sight-threatening proliferative diabetic retinopathy (PDR) is uncertain. Objective: To determine whether high GV and severe vitamin D deficiency independently, and additively, associate with retinal neovascularization in adults with diabetes. Materials and Methods: We conducted a cross-sectional study between January 2025 and June 2025 in 58 adults with diabetes at Constanța County Emergency Hospital, Romania. GV was classified as high (coefficient of variation > 36% or SMBG-SD > 50 mg/dL) or low. Serum 25-hydroxy-vitamin D [25(OH)D] was measured; severe deficiency < 10 ng/mL. Dilated funduscopy graded retinopathy as non-proliferative (NPDR) or proliferative (PDR). Multivariable logistic regression adjusted for HbA1c, diabetes duration, BMI, smoking, triglycerides and therapy. Results: From 58 adults (mean ± SD 59 ± 11 years), high GV characterized 29/58 participants (50%). Severe vitamin D deficiency was more frequent in the GV-high group (45% vs. 31%). PDR prevalence was 48% in GV-high and 31% in GV-low patients. After adjustment, high GV (adjusted OR 2.31, 95% CI 1.05–5.09) and severe vitamin D deficiency (OR 2.04, 95% CI 0.98–4.25) each predicted PDR. Concomitant exposure to both stressors conferred 3.9-fold higher odds of PDR (OR 3.88, 95% CI 1.35–11.1). No interaction term reached significance (p = 0.21), indicating additive effects. Conclusions: High GV and severe vitamin D deficiency independently and additively associate with PDR. Screening for both parameters may enhance risk stratification of PDR. Within adults with diabetes, high glycemic variability and severe vitamin D deficiency were each associated with higher odds of PDR after adjustment for HbA1c, diabetes duration, BMI, smoking, triglycerides, and treatment pattern; their effects appeared additive rather than multiplicative. These findings reflect associations within diabetes and do not imply that vitamin D deficiency produces retinopathy in euglycemic individuals. Full article

Background/Objectives: Increased screen time partially replaces social interaction, physical activity, and outdoor play in kindergarten children, leading to a risk of decreased cognitive, emotional, and motor skills. Children with high motor skills are more likely to have access to challenging joint activities that promote their cognitive and emotional development. This study examines the moderating role of motor competence in the relationship between executive function skills and emotion comprehension. Methods: A sample of 220 kindergarten children (101 girls, 119 boys) completed the NEPSY-II subtests and the ‘Dimensional Change Card Sort’ tool for executive function skills assessment, the Movement Assessment Battery for Children—Second Edition (MABC-2) for motor competence, and the Test of Emotion Comprehension (TEC) for emotion comprehension. Executive function skills and motor competence were assessed when children were in their penultimate year of kindergarten (children were aged on average 5 years 10 months), and emotion comprehension was assessed one year later, when children were in their final year of kindergarten. When children were in their penultimate year of kindergarten, caregivers also reported on children’s passive and active screen time, maternal education, and family income, which were used as control variables. Results: For girls, motor competence moderated the relationship between cognitive flexibility and later emotion comprehension. High motor competence amplified this relationship (B = 0.171; SE = 0.066; 95% CI [0.041, 0.302]; p = 0.011). For boys, there were no significant moderation effects. Conclusions: High motor competence can improve emotion comprehension in kindergarten girls. Emotional development may benefit from effective shared motor interventions for children. Full article

Background/Objectives: The clinical management of adolescent idiopathic scoliosis (AIS) is hindered by the inability to accurately predict curve progression. Although skeletal maturity and the initial Cobb angle are established predictors of progression, their combined predictive accuracy remains limited. This study aimed to develop a robust and interpretable artificial intelligence (AI) system using deep learning (DL) models to predict the progression of scoliosis using only standing frontal radiographs. Methods: We conducted a multicenter study involving 542 patients with AIS. After excluding 52 borderline progression cases (6–9° progression in the Cobb angle), 294 and 196 patients were assigned to progression (≥10° increase) and non-progression (≤5° increase) groups, respectively, considering a 2-year follow-up. Frontal whole spinal radiographs were preprocessed using histogram equalization and divided into two regions of interest (ROIs) (ROI 1, skull base–femoral head; ROI 2, C7–iliac crest). Six pretrained DL models, including convolutional neural networks (CNNs) and transformer-based models, were trained on the radiograph images. Gradient-weighted class activation mapping (Grad-CAM) was further performed for model interpretation. Results: Ensemble models outperformed individual ones, with the average ensemble model achieving area under the curve (AUC) values of 0.769 for ROI 1 and 0.755 for ROI 2. Grad-CAM revealed that the CNNs tended to focus on the local curve apex, whereas the transformer-based models demonstrated global attention across the spine, ribs, and pelvis. Models trained on ROI 2 performed comparably with respect to those using ROI 1, supporting the feasibility of image standardization without a loss of accuracy. Conclusions: This study establishes the clinical potential of transformer-based DL models for predicting the progression of scoliosis using only plain radiographs. Our multicenter approach, high AUC values, and interpretable architectures support the integration of AI into clinical decision-making for the early treatment of AIS. Full article

Background: Pain is one of the most common complaints among all age groups. Adult patients can express pain more clearly. Unfortunately, pediatric patients cannot perform this. This study aimed to assess the extent of knowledge of healthcare providers regarding acute pediatric pain management. Methods: A cross-sectional study was conducted utilizing the modified Knowledge and Attitude Survey Regarding Pain (KASRP) questionnaire through face-to-face interviews. The modified version included 34 questions (24 true/false questions and 10 MCQs). This study targeted anesthesiologists, pediatricians, and pediatric nurses through interviews. Demographic and educational data were analyzed as factors affecting the results of the KASRP questionnaire. The total score was classified as poor, fair, or good. Results: A total of 137 participants were enrolled in this study. The mean age was 31.8 years, and of the participants, 62.8% were women, 30.0% were anesthesia physicians, 25.5% were pediatric physicians, and 44.5% were pediatric nurses. The participants scored an average of 20.7 out of 34. Performance was categorized as poor, fair, or good, with 22.6%, 64.2% and 13.2% of participants falling into each category, respectively. The mean score of correct responses was higher for anesthesiologists (p = 0.0001). Specialists achieved higher mean scores than residents. Completion of pediatric pain management courses and the use of assessment tools were linked to higher performance. Conclusions: Pediatric nurses achieved lower scores for knowledge of acute pediatric pain management than physicians. Anesthesiologists achieved the highest score, probably because of their training in pain management. All healthcare providers should attend pain management courses. Full article

The surface properties of composite resin restorative materials are critical for the esthetics and longevity of restorations. This in vitro study evaluated the microhardness change and surface roughness change in four resin composites recommended for anterior restorations after two aging simulations: thermal cycling (10,000 cycles) and one year of water storage. Ten specimens (n = 10) were prepared for each material. After baseline measurements, samples were subjected to one of the aging procedures, and surface properties were reassessed. For microhardness change (∆H), significant differences were observed among materials under both thermal cycling (p = 0.001) and water storage (p = 0.001). Omnichroma–thermal cycling showed a greater decrease than G-ænial Anterior (p = 0.028) and Clearfil Majesty ES-2 (p = 0.001), while Optishade–thermal cycling decreased more than Clearfil Majesty ES-2 (p = 0.015). In water storage, Omnichroma exhibited a greater decrease than Optishade (p = 0.042) and Clearfil Majesty ES-2 (p = 0.001), and G-ænial Anterior decreased more than Clearfil Majesty ES-2 (p = 0.026). Optishade and Clearfil Majesty ES-2 showed significantly greater decreases after thermal cycling than water storage, while Omnichroma and G-ænial Anterior showed no difference. For the change in surface roughness (∆R), significant differences were also found (p = 0.001). In thermal cycling, Optishade exhibited the lowest increase, while G-ænial Anterior showed the highest. In water storage, G-ænial Anterior again had the highest increase, significantly greater than all others (p = 0.001). For all materials, ∆R values were significantly higher after thermal cycling compared with those in water storage (p = 0.001). These results demonstrate that both composite type and aging method influence long-term surface properties. Overall, thermal cycling exerted more detrimental effects than water storage. Full article

This research determines the techno-economic feasibility of valorizing as biofertilizer the nitrogen (N) and the phosphorus (P) from a municipal wastewater effluent using the microalgae Scenedesmus sp., contributing to phosphorus recycling, resource optimization, and diminishing eutrophication by capturing 74% of N, 97% of P, and 41% of chemical oxygen demand in effluents. The inoculum was conditioned in 20 L photobioreactors by weekly harvesting and refilling at room temperature (25 °C day, 12 °C night) with a 12:12 photoperiod and 4 L/min atmospheric air bubbling. The improved operational conditions were obtained using a Box–Behnken experimental design, establishing that 70% wastewater concentration (vol./vol.), 4.5% nutrient addition, and 3 days’ harvesting time were the best conditions. The estimated biomass production was 176 tons/year, and this represents a maximum net present value of 1.5 MUSD for a 6.8 Ha plant, capturing 10% of municipal wastewater effluent, which serves 64000 inhabitants. The representative operational costs (OPEX) were 32% for utilities, 30% labor costs, and 25% for raw materials, and the required capital expenditures (CAPEX) were 11 MUSD and are related to photobioreactors (64%) and land (21%). The findings demonstrate the potential of microalgae-based systems as a feasible and profitable approach to wastewater valorization, while also highlighting the need for scale-up validation and integration with existing treatment infrastructures, where land requirements and photobioreactor installation will be relevant for financial feasibility. Full article

Background and Clinical Significance: In gastric cancer, splenic metastases are found in less than 7% of cases and are usually associated with other systemic secondary determinations; much more rarely, they represent the sole secondary determination of the malignant disease. Case presentation: In this paper, we present the case of a 64-year-old patient who underwent curative surgery for gastric adenocarcinoma 10 months ago and, during oncological monitoring, was diagnosed with a splenic tumor formation with intense metabolic activity on PET-CT examination, raising suspicion of splenic metastases. The medical team observed an increase in carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, and Cluster of Differentiation (CD) 276 values, along with a slight decrease in Dickkopf Related Protein 3 (DKK 3). Considering that the spleen was the only site of secondary localization of the malignant disease, the patient underwent laparoscopic splenectomy with histopathological confirmation of the presence of gastric adenocarcinoma. There are no signs of loco-regional or distant recurrence 15 months postoperatively. In patients with radical excision of gastric cancer who present only with splenic metastases, splenectomy is indicated and is associated with good disease-free survival. If other secondary manifestations of malignant gastric disease are identified or suspected, chemotherapy treatment and the wait-and-see approach are recommended, as the patient does not have a real benefit from splenectomy. Until now, there is no standard protocol for the diagnostic and therapeutic management of patients with gastric cancer and metachronous splenic metastases; thus, the development of a decision-making scheme for these situations is necessary. Conclusions: The multidisciplinary approach, including the tumor board and an infectious disease specialist, are important steps in the effective management of these cases. The role of new biological markers such as CD 276 and DKK 3 for assessing the progression of malignant disease could constitute a new direction for research. Full article

This study proposes an integrated framework for the optimal sizing of off-grid hybrid energy systems, combining photovoltaic panels, wind turbines, battery storage, a diesel generator, and an inverter. The methodology uniquely integrates long-term meteorological forecasting through a hybrid approach based on the Discrete Wavelet Transform and Long Short-Term Memory networks, together with metaheuristic optimization techniques (Particle Swarm Optimization and Genetic Algorithm), to minimize the system’s total annual cost. A case study was conducted in Guanambi, Brazil, using ten years (2012–2021) of hourly data on wind speed, solar irradiance, and ambient temperature. Forecasting results show that the hybrid Discrete Wavelet Transform–Long Short-Term Memory model outperforms the conventional Long Short-Term Memory approach, reducing error metrics and improving predictive accuracy. In the optimization stage, Particle Swarm Optimization consistently achieved lower costs and more stable convergence compared to the Genetic Algorithm. The optimal configuration comprised 450 photovoltaic panels, 10 wind turbines, 66 lithium iron phosphate battery, and 1 diesel generator, yielding a total annual cost of $105,381.17, a cost of energy of $0.1243/kWh, and minimal diesel dependence ($8825.89 annually). The proposed framework demonstrates robustness, economic viability, and applicability for providing sustainable and reliable electricity in isolated regions with high renewable energy potential. Full article

Background and Objectives: Ixekizumab is a human monoclonal antibody targeting interleukin-17A, approved for the treatment of moderate-to-severe plaque psoriasis. Given its demonstrated efficacy and safety in clinical trials, this study aimed to evaluate the real-world drug survival of Ixekizumab and identify clinical predictors of treatment discontinuation. Materials and Methods: A retrospective, observational, hospital-based study was conducted in the Department of Dermatology at the Central University Hospital of Asturias (HUCA). Patients with moderate-to-severe plaque psoriasis who initiated treatment with Ixekizumab (Taltz^®) between 8 June 2017 and 10 October 2024, were included. Demographic data, comorbidities, age at disease onset, family history, PASI score, and previous treatments were recorded. Drug survival was assessed using Kaplan–Meier survival curves and the log-rank test. Predictors of discontinuation were analyzed using univariate and multivariate Cox proportional hazards models. Results: A total of 103 patients (55.3% women) were included. Drug survival rates were 85% at one year, 73% at two years, and 61% at four years, with a mean treatment duration of 52.5 months (95% CI: 46.01–58.99). Multivariate analysis showed that patients under the age of 65 had a significantly higher risk of treatment discontinuation (hazard ratio: 1.813; p < 0.05). The most common reason for discontinuation was secondary treatment failure (45.16%). Ixekizumab demonstrated sustained drug survival in a real-world setting, with rates falling within the mid-to-upper range reported in the literature. Older age (>65 years) was associated with greater treatment persistence, highlighting a potential influence of age on long-term therapeutic adherence. Full article