Search Results (561)

Background: Polycystic ovary syndrome (PCOS) is characterized by substantial inter-individual variability in ovarian sensitivity to recombinant follicle-stimulating hormone (rFSH) during controlled ovarian stimulation (COS). Clinically applicable tools for personalized dosing in this population remain limited. Methods: This retrospective single-center study (2013–2024) analyzed 369 PCOS patients undergoing GnRH antagonist protocols who achieved optimal ovarian responses (10–20 oocytes with at least 40% of follicles ≥ 16 mm in diameter on trigger day). The final retrospective dataset was randomly split into modeling (n = 258) and validation (n = 111) groups. A multivariate linear regression model incorporating age, BMI, basal FSH, basal LH, AMH, and AFC was developed to estimate the average daily rFSH dose. Model performance was evaluated using correlation analysis, prediction error metrics, and calibration assessment. Results: Age, BMI, and basal FSH were positively associated with average daily rFSH dose, whereas basal LH, AMH, and AFC were negatively associated. The model explained 40.4% of the variability in average daily rFSH dose. In the modeling cohort, 77.9% of estimated doses fell within ±20% of the observed values, with a moderate correlation between predicted and observed doses (ρ = 0.646). In the validation cohort, 67.6% of estimates met the predefined accuracy threshold (ρ = 0.676). Calibration analyses demonstrated robust agreement between predicted and observed doses. Conclusions: By integrating endocrine markers, ovarian reserve indicators, and clinical characteristics, this study provides a practical example of personalized medicine in COS in women with PCOS. The internally validated approach may support individualized rFSH dosing during COS and serve as a basis for future development of decision support tools in this specific population. Full article

Background: Genetic causes of growth failure should be suspected in patients born small for gestational age (SGA) who fail to show postnatal catch-up growth, present with severe short stature (SS), and exhibit a poor or absent response to growth hormone (rhGH) therapy. Mutations in the insulin-like growth factor 1 receptor (IGF1R) gene are associated with impaired growth, intrauterine growth restriction (IUGR), low birth weight and/or length, and postnatal SS. Case Description: A 9-year-old boy, born SGA for birth length, was evaluated for severe SS. Common causes of SS were excluded. At 9 years and 7 months of age, his height was 112.6 cm (−3.99 SDS), weight 18 kg (−3.79 SDS), and BMI 14.2 kg/m² (−1.8 SDS); pubertal development was Tanner stage 1. The target height was 158 cm (−2.62 SDS). Bone age was delayed by approximately one year compared with chronological age. Serum IGF-1 levels were within the upper-normal range for age. GH therapy (0.035 mg/kg/day) was initiated due to the lack of catch-up growth in an SGA subject. After three years of treatment, the height gain was only 0.5 SDS. IGF-1 levels showed a transient treatment-related increase, followed by persistent normalization during ongoing therapy. Next-generation sequencing (NGS) analysis identified novel heterozygous paternal nonsense variant in the IGF1R gene: c.3498C>G (p.Tyr1166Ter). At 12 years of age, impaired fasting glucose and reduced glucose tolerance were detected; consequently, it was decided to discontinue rhGH therapy, also in light of the IGF1R mutation and the lack of height recovery. Conclusions: This case underlines the critical role of genetic testing in the evaluation of patients born SGA. The coexistence of SGA status and an IGF1R gene mutation may provide a clear explanation for both the poor response to rhGH therapy and the increased risk of alterations in glucose metabolism. An extensive narrative review of the literature on growth outcomes and glucose metabolism abnormalities during GH treatment in SGA patients carrying IGF1R variants was also performed. Full article

Background: Recombinant human growth hormone (rhGH) replacement therapy, administered to children with growth hormone deficiency (GHD), exerts pleiotropic effects on growth, metabolism, and tissue functions. Extracellular vesicles (EVs) are emerging mediators of inter-organ communication, but the effects of rhGH therapy on EV release in humans have not yet been investigated. Methods: In a preliminary prospective clinical study, children with GHD (n = 10; F/M = 5/5; age: 11.0 ± 2.7 years) were treated with rhGH for 6 months. Plasma samples were collected at baseline (T0) and after treatment (T6) to characterize the size distribution and tissue-derived composition of circulating EVs. Total EVs and EV subpopulations derived from monocytes/macrophages (CD14+), adipose tissue (FABP+), skeletal muscle (SCG+), endothelium (CD62E+), and platelets (CD42A+) were analyzed. Clinical, auxological/auxometric, and biochemical/metabolic parameters were assessed in parallel. Statistical methods included longitudinal analyses, interaction models, and adjustments for relevant covariates, including insulin-like growth factor 1 (IGF-1) and osteocalcin. Results: After 6 months of rhGH therapy, significant improvements in height velocity (cm/year and SDS) were observed, accompanied by increased circulating IGF-1 and osteocalcin levels. Hormone therapy induced no size-dependent changes in (total) EVs. Significant increases in CD14+ and FABP+ EVs were observed after treatment, without affecting the other tissue-derived EVs. Interaction analyses revealed that children with more severe GHD exhibited a stronger vesiculogenic response to rhGH. Furthermore, specific tissue-derived EVs were associated with metabolic/biochemical and auxological/auxometric parameters, including lipids, insulin resistance, and growth-related measures. Conclusions: When administered for six months, rhGH therapy seems to selectively change tissue-derived composition of circulating EVs in GHD children, particularly those derived from immune cells and adipose tissue. These preliminary findings suggest that EVs might represent an adjunctive component of GH-dependent inter-organ communication and might serve as biomarkers of treatment response and disease severity in pediatric endocrinology. Full article

Concrete is accelerating its transition towards green and low-carbon development, but its performance throughout its entire life cycle is significantly influenced by environmental changes, which remains a key technical challenge currently faced. The effects of early-age concrete tensile damage on thermal conductivity and moisture transport properties, as well as their coupling mechanism, remain unclear, leading to severe cracking. To explore the cracking mechanism of early-age concrete under the coupled conditions of environment and damage and to evaluate its performance throughout its lifecycle, this article conducts comparative experiments on the performance of concrete under high temperature, varying humidity, and damage conditions in the early age stage. The variation law of temperature, humidity, and strain of concrete is studied, and the evolution of microstructure and composition of concrete is explored. The response of porosity to ambient humidity exhibits opposite trends between restrained and unrestrained specimens, with rates of change of +0.0353%/RH and −0.0245%/RH, respectively. Furthermore, the study identified a critical turning point in ambient relative humidity (50% RH), which significantly alters the degree of hydration (Ca/Si ratio) of the concrete. The research results may provide theoretical and technical support for cracking risk assessment and crack control throughout the entire life cycle of concrete thin-walled structures. Full article

Background and Objectives: Stroke is a leading cause of long-term disability in older adults, who often face persistent motor, cognitive, and functional challenges. Conventional stroke rehabilitation programs often involve highly repetitive motor tasks, which may reduce patient motivation and contribute to suboptimal adherence over time. Virtual reality (VR) offers an engaging alternative; however, much of the existing research has focused on specialized rehabilitation-oriented VR systems rather than off-the-shelf commercial platforms. This study evaluated older stroke survivors’ acceptance, tolerability, and lived experiences of a short VR-based rehabilitation session using a commercial game on a commercial wearable VR system. Methods: A single-session convergent mixed-methods design was employed. Thirteen community-dwelling older stroke survivors (mean age 79.2 ± 7.1 years; 9 males, 4 female) completed a 15 min VR session using a commercial wearable VR system. The Technology Acceptance Model (TAM) questionnaire and Simulator Sickness Questionnaire (SSQ) assessed acceptance and tolerability, while semi-structured interviews explored lived experiences. Qualitative data were thematically analyzed. Results: Participants reported high acceptance across all TAM domains (overall M = 4.35 ± 0.79, scale 1–5). Enjoyment/intention to use was rated highest (M = 4.77 ± 0.42), while perceived usefulness was lowest (M = 4.15 ± 0.77). VR was well tolerated: the SSQ total score was 17.38 ± 1.73, with most symptoms rated at the mild level only. Exploratory Spearman correlations revealed a significant positive association between age and SSQ total score (r_h = +0.568, p = 0.043). Thematic analysis identified five themes: (1) usability and accessibility; (2) therapeutic value; (3) engagement and motivation; (4) social and clinical support; and (5) physical and cognitive demands. Conclusions: A commercial wearable VR system was found to be acceptable, safe, and engaging for older stroke survivors. With supervision and therapeutic framing, it may serve as a motivating adjunct to conventional rehabilitation. Full article

Background/Objective: Coffee is the most highly consumed beverage worldwide, and coffee drinkers exhibit decreased mortality and protection from aging-related diseases. This study investigates the role of orphan nuclear receptor 4A1 (NR4A1) in mediating the effects of brewed coffee and the major polyphenolic and polyhydroxy compounds in brewed coffee and also in determining their binding to NR4A1. Methods: The interactions of brewed coffee and several of the major individual compounds in brewed coffee with the ligand-binding domain of NR4A1 were determined using a fluorescent binding assay. For specific compounds, binding was also carried out by surface plasmon resonance, and molecular docking studies were also performed. NR4A1-responsive Rh30 cancer cells were used as models to determine NR4A1-dependent transactivation, cell growth inhibition and inhibition of specific gene products, and in some studies, knockdown of NR4A1 by RNA interference was also determined. Inhibition of lipopolysaccharide-induced IkBα by key polyphenolics was also investigated in RAW264.7 macrophages. Results: Brewed coffee and several polyphenolics, including caffeic acid, ferulic acid, chlorogenic acid, p-coumaric acid, several cinnamic acid derivatives, kahweol, and cafestrol, bound NR4A1 in binding assays, and most Kd values were <10 µM. Brewed coffee and the major polyphenolics inhibited growth of NR4A1-responsive Rh30 cells, and this was attenuated in NR4A1-deficient Rh30 cells. These same compounds also exhibited NR4A1-dependent effects on transactivation and gene product responses in Rh30 and RAW264.7 macrophages and exhibited inverse NR4A1 agonist activity. In contrast, the NR4A1-dependent activity of caffeine and quinic acid was highly variable, suggesting that they are selective NR4A1 ligands. Conclusions: The results of this study demonstrate that brewed coffee and its major polyphenolics and polyhydroxy constituents are NR4A1 ligands and that NR4A1 may play an important role in the health-protective effects of coffee. These results, coupled with recent studies, indicate that NR4A1 and its ligands may play an important role in diet and health. Full article

The aim of this work is to prepare and characterize a composite adsorbent comprising the hydrophilic ionic liquid 1-ethyl-3-methylimidazolium acetate [EMIM-Ac] composite supported on mesoporous silica gel for application in adsorption heat storage systems. Water adsorption/desorption isotherms were measured gravimetrically at T = 40, 50, 70 °C across a relative humidity (RH) range of 0–0.8, demonstrating a high adsorption capacity (up to 0.71 g/g at 50 °C and RH = 0.8, for a 50 wt % [EMIM-Ac] loading). Full process reversibility and negligible ad/desorption hysteresis were also verified. Thermal stability of the prepared silica/[EMIM-Ac] composites was confirmed up to approximately T = 200 °C. Structural stability of samples subjected to repeated ad/desorption aging cycles was verified via FT-IR, High-Resolution Solid-State NMR, and Time-Domain NMR spectroscopy. Finally, the thermodynamic analysis based on adsorption experimental data indicated that the silica/[EMIM-Ac] composite is highly suitable for adsorption heat storage, providing a volumetric density of 600–920 MJ/m³ at regeneration temperatures below 100 °C. Full article

This work investigates the reciprocal adhesion of Polybenzoxazole (PBO) and silicon nitride (SiN) with a focus on the combined effects of surface chemistry and environmental conditions, i.e., temperature (T) and relative humidity (RH). A set of six samples, including standard and silicon-rich SiN substrates treated with oxygen (O₂) or carbon tetrafluoride (CF₄) plasma, was fabricated and characterized by AFM, XPS, and TEM/EDX to quantify surface roughness and interfacial chemical modifications. Adhesion with PBO was then assessed through nanoindentation both in situ, during ambient control, and ex situ, after aging in a climatic chamber. Compared to PBO adhesion with as-deposited standard and silicon-rich SiN, O₂ plasma treatment was shown to improve adhesion by 13% and 24%, respectively, whereas CF₄ plasma treatment was still beneficial but more limited, improving adhesion by 8% for both substrates. The different effects were ascribed to the formation of a surface oxide layer after O₂ plasma, enhancing chemical affinity and substantially equalizing the adhesion on the two SiN substrates, while CF₄ plasma was impacting adhesion by reducing the substrates’ activity and, thus, increasing the efficiency of the PBO curing procedure. Notably, the adhesion loss with increasing dew point of the ambient (dependent on temperature and relative humidity) was observed across all samples regardless of surface treatment, reinforcing the critical role of absorbed moisture on polymeric film adhesion. However, this trend was observed for all samples only for in situ testing, with a loss of 25% in the critical load of delamination for the most critical environment, while ex situ tests showed a marked recovery of adhesion properties, leading to measurements no longer reflecting the actual state of the samples inside the altered environment. The results presented in this paper highlight the effect of substrate preparation on the adhesion of an organic compound and a substantial difference in environmental control methods for adhesion testing, providing an alternative approach to classical aging treatments and subsequent characterization for qualifying polymer/inorganic interfaces exposed to stressful operational conditions. Full article

Objective: Individuals with reactive hypoglycemia (RH) may be more likely to develop obesity and type 2 diabetes, but the ability to identify RH has been hampered by the lack of clear criteria. This study used calculus-based curve parameters from a mixed macronutrient liquid meal test (MMTT) to define RH in men and women with obesity. Methods: A total of 69 non-diabetic adults aged 35 ± 8.3 years with obesity (BMI 32.3 ± 4.2 kg/m²) underwent a 4 h MMTT to define RH, and an intravenous glucose tolerance test (IVGTT) to characterize RH (via insulin sensitivity, the acute insulin response to glucose (AIRg), insulin clearance, and the disposition index). Perceived hunger and fullness were assessed by visual analog scale. Results: RH was defined using curve properties of the MMTT. A total of 19 of the 69 participants had a reactive hypoglycemic response to the MMTT. Glucose AUC and nadir were lower, timing of glucose nadir was earlier, and insulin sensitivity was higher in RH compared to non-RH. Sex (female) and race (AA) were significant predictors of RH presence. Conclusions: Among individuals with obesity, RH is characterized by greater sensitivity to insulin and greater disposition index. We introduce a novel and reproducible method to define RH using curve-based criteria from a mixed meal test integrated with gold-standard IVGTT-derived outcomes. Full article

Standard maturity methods for concrete monitoring rely primarily on temperature history, often neglecting the influence of internal relative humidity (RH) on hydration kinetics and self-desiccation risks. Continuous in situ monitoring of internal RH remains a challenge due to the high cost, proprietary nature, and lack of reproducibility of existing solutions. This study evaluates a low-cost, open-source embedded sensor array designed to characterize early-age curing behavior through trend-based monitoring—defined here as the evaluation of ensemble consistency and repeatability rather than absolute metrological traceability. The prototype system, based on SHT31 sensors controlled by an ESP32 microcontroller, was embedded in high-performance concrete cylinders (f′c = 45 MPa) to capture the exothermic hydration peak and the equilibration of internal humidity. Results demonstrate that while the sensor encapsulation introduced a geometric disturbance that reduced compressive strength by approximately 25%—a limitation requiring mitigation in structural applications—the system successfully captured reproducible curing transitions. The proposed framework provides an accessible tool for experimental research into internal curing conditions, offering a digital complement to traditional surface-based quality control. Full article

Rare earth elements (REEs) and technology-related trace elements are increasingly used in modern products and processes, but biomonitoring data in healthy children and adolescents remain scarce; scalp hair provides a practical, integrative matrix for assessing multi-element patterns over time. Scalp hair collected in April–May 2001 from children (6–9 years; n = 120) and adolescents (13–16 years; n = 97) living in Alcalá de Henares (Spain) was retrieved from archival storage and analysed in 2025 using a single QA/QC-controlled ICP–MS workflow. Seven REEs (Ce, La, Pr, Nd, Gd, Er, and Y) and nine technology-related trace elements (Bi, Sb, Th, U, Pd, Pt, Rh, Ir, and Rb) were quantified after rigorous decontamination; left-censored data were treated using Kaplan–Meier, regression on order statistics, and maximum-likelihood approaches, and population reference values were derived as percentile-based upper limits (P95, 95% CI). In children, REEs were frequently detected and showed strong within-suite covariation, with medians in the low ng g⁻¹ range (e.g., Ce ≈ 0.011 µg g⁻¹; La ≈ 0.007 µg g⁻¹), whereas in adolescents, most REEs were near reporting limits. Sb and U were ubiquitous in both age groups, while platinum-group elements were largely undetected. Shale-normalised REE patterns were subparallel across normalisers, La/Ce anomalies were centred below unity, and weak soil–hair correlations suggested multiple microenvironmental exposure pathways. These data provide a robust pre-diffusion baseline for REE metals in European youth, offering a benchmark for future urban exposome assessments. Full article

Current international standards (EN 12004; SI 4004) are testing ceramic tile adhesives under post-cure thermal aging. However, the standards omit UV radiation exposure during the fresh-adhesive phase. This research investigated three commercial polymer-modified cement adhesives (C2TE, C2TE-S2, C2T) bonding porcelain stoneware tiles under simulated Eastern Mediterranean and desert conditions. Three commercial adhesives were exposed during the initial (uncured) period to elevated temperature (30 °C), humidity variation (40–65% RH), and UV radiation (295–365 nm, 1.5–2.0 mW/cm²) for 20 min, followed by 28 days of curing. Pull-off testing and scanning electron microscopy, combined with quantitative directionality analysis, were used to characterize the mechanical performance and microstructural degradation. UV exposure of adhesives during tiling working time caused a drop of mean bond strength from 1.77 to 0.26 MPa (85% reduction) compared with 1.77 to 0.64 MPa (36% reduction) under hot-arid conditions. Microstructural analysis of the hardened pull-off adhesives revealed that exposure of the fresh adhesive to UV radiation causes thinning and degradation of the interfacial layer (15–40 µm), leading to a drop in macroscopic strength. In contrast, hot-arid exposure induces adhesive bulk cracking while preserving interface integrity. Fracture surface directionality (goodness parameter), crack density, and delamination percentage together distinguish interface failure from adhesive bulk degradation and provide a forecast of long-term durability. This combined SEM-mechanical approach identified critical gaps in testing protocols and enables evidence-based adhesive selection, as current EN 12004 classifications based solely on mechanical properties prove insufficient. Full article

Prior research has offered substantial evidence for letter transposition effect in word reading, yet studies in logographic languages such as Chinese are scarce and have largely focused on adults. This study aimed to determine whether second-grade children show character transposition effect impact in recognizing two-character Chinese words and to examine potential differences between the left and right visual fields corresponding to the two cerebral hemispheres. A lexical decision task was used across two experiments. Experiment 1 tested 56 second graders and manipulated three stimulus types—normal words, Transposed pseudo-words, and Substituted pseudo-words—to verify the presence of the effect. Experiment 2 recruited an independent sample of 97 second graders and applied a lateralized presentation paradigm, presenting stimuli to either the right or left visual field (RVF/LVF), which project to the left and right hemispheres (LH/RH), respectively, to assess hemispheric differences. Experiment 1 revealed a significant character transposition effect among second-grade children. Experiment 2 showed no significant differences in the magnitude of the effect between the two visual fields. These findings provide new developmental evidence for Chinese word reading and important implications for theories of position encoding. Future studies should trace its developmental trajectory across a wider age range and diverse learning contexts. Full article

As coastal ultra-deep mine shafts advance to greater depths, shaft lining concrete may experience sustained humid–hot conditions. Elevated temperature is induced by geothermal heat and early-age hydration heat, while high humidity is maintained in water-rich underground environments, which can compromise long-term performance. Such late-age deterioration may increase maintenance demand and pose safety concerns for ultra-deep shaft construction and long-term service. This study experimentally evaluates a high-strength shaft lining concrete designed with a composite cementitious system and cured at 40, 60, and 80 °C (95% RH) for 30–180 days, considering the engineering scenario of the 2500 m shaft at the Sanshan Island Gold Mine. The selected temperature range was determined based on in situ temperature monitoring in the target shaft. P-wave velocity measurements and uniaxial compression tests were conducted, while acoustic emission (AE) monitoring and energy evolution analysis were used to interpret damage progression. P-wave velocity decreased with curing temperature, with the most pronounced reduction at 80 °C. Compressive strength increased at early ages and then declined at later ages; by 180 d, the strength loss relative to the peak level is more pronounced at higher temperatures. AE results show four typical damage stages, with activity increasingly concentrated near peak stress as temperature and age increase. AF–RA analysis indicates tensile cracking dominates, with a slight increase in shear-related events at higher curing temperatures and longer ages. Energy analysis further confirms that most input energy is stored as elastic strain energy prior to peak stress, and higher curing temperatures increase the proportion of input energy stored elastically, implying a higher tendency toward brittle failure. These results suggest optimizing curing regimes and toughness-enhancement strategies for durable shaft infrastructure. Full article

Background: Delayed or non-union fractures comprise 5–10% of cases, indicating the need for biologic interventions. Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a potent osteoinductive agent; yet, collagen carrier-based uncontrolled release causes adverse events. We evaluated the safety and efficacy of a hydroxyapatite (HA) carrier-based rhBMP-2 delivery system for acute traumatic upper and lower fractures exhibiting bone defects. Methods: This prospective, multicenter, single-arm clinical trial enrolled 90 patients who underwent surgery using a hydroxyapatite (HA) carrier-based rhBMP-2 delivery system (Novosis^TM). Radiographically validated union at 6 and 12 months post-surgery and treatment success (union without additional surgery) were used to assess efficacy. The incidence, type, and severity of all device-related adverse events during follow-up were monitored by investigators to evaluate safety. Results: Of the 90 patients enrolled, 81 were included in the full analysis set. The mean age was 58.5 years, and 18.6% (15/81) had open fractures. At 6 months post-surgery, radiographically validated union was achieved in 81.5% (66/81) of patients, increasing to 96.2% (77/81) at 12 months after surgery. Treatment success was 95.0% (76/81). Adverse events were rare (1/81, 1.2%). No ectopic ossification, systemic complications, or severe inflammatory responses were observed. Conclusions: HA-based rhBMP-2 intervention demonstrated favorable union rates and safety with minimal complications in acute upper and lower fractures with bone defects. The biocompatibility and controlled-release properties of HA likely improved efficacy and reduced complications. Results should be interpreted as feasibility data from a heterogeneous case series without a control group. Larger randomized controlled comparative trials are warranted for optimal dosing and evaluating efficacy and cost-effectiveness. Full article