Search Results (7,951)

Background: Single-agent pembrolizumab represents a standard of care in the first-line treatment of patients with metastatic non-small cell lung cancer (mNSCLC) with a programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) of ≥50%. Real-world evidence is of increasing importance in oncology, as clinical trial inclusion criteria may not be truly reflective of the patient population seen in daily clinical practice. Methods: We performed a prospective–retrospective single-center study including 121 patients who received pembrolizumab as a first-line therapy for mNSCLC with a PD-L1 TPS ≥ 50%. Our aims were to make a comparison with published clinical trial results by assessing the efficacy and safety of pembrolizumab monotherapy in our population. We collected patient demographics, clinical characteristics of the disease, and treatment outcomes, including efficacy and safety. Results: A total of 121 patients were included, with a median follow-up of 40.77 months. The median progression-free survival in the real world (rwPFS) was 20.73 months (95% CI 12.24–29.22), and the median overall survival (OS) was 29.30 months (95% CI 16.57–42.04). Immune-mediated adverse events (irAEs) occurred in 42% of patients, with serious events (grade 3 or more) occurring in 12%. ECOG PS 2, male gender, squamous histology, pleural and visceral metastases, and treatment with corticosteroids prior to initiation of pembrolizumab were found to be negative predictors for overall survival, while the occurrence of irAEs was the predictor of longer survival. Conclusions: This study provides further real-world insights into the efficacy of pembrolizumab in a heterogeneous patient population with advanced NSCLC in a single center in Serbia. It also confirmed the value of good ECOS PS and the occurrence of irAEs as predictors of favorable outcomes. Full article

Compared to the traditional unidirectional power supply system, the bidirectional traction power supply system in an electrified railway offers advantages like improved traction voltage and reduced energy losses, making it more suitable for steep gradient routes. However, its increased electrical complexity necessitates advanced catenary-rail short-circuit fault calculations and relay protection calibration. This paper proposes a fault calibration approach based on deriving electrical quantities with fault distance in the railway bidirectional traction grid system. A multi-loop circuit modeling method is used to accurately model the traction grid system and impedance parameters, incorporating real loop circuits formed by the grid transmission and return conductors for the first time. The approach is validated through real-life experiments on a Chinese railway line. A case study of a direct power supply system with a return cable is used to derive electrical quantities. Faults are categorized into two sections: between the substation and the parallel station (PS), and between the PS and the section post (SP). For each section, electrical quantities are derived under unidirectional substation excitation, and the results are superimposed to obtain fault distance variation curves for currents and voltages of substation, PS, SP, and Thévenin impedance. Finally, a calibration strategy for relay protection is presented. Full article

Siliceous dolomite is developed at the top of the fourth member of Dengying Formation in Penglai gas field, Sichuan Province, and can be used as a good cap rock to seal oil and gas. In this study, based on post-stack seismic data mining and optimization, sensitive logging curve analysis is found to be the optimal prediction method, subdividing small layers to finely characterize thin-layer siliceous dolomite. It is found that the navigation-pyramid two-stage classification seismic data and the waveform indication simulation method based on RXO parameters have a good recognition effect on the characterization of thin-layer siliceous dolomite. Studies have shown that faults can provide ascending channels for deep silicon-rich hydrothermal fluids, resulting in the development of siliceous dolomite mostly near the fault zone. The siliceous dolomite in the upper sub-member of the fourth member of Dengying Formation in Penglai area mainly develops two sets of siliceous dolomite in the vertical direction, and the lower siliceous rock develops on a larger scale. In the lateral direction, it is mainly distributed in the JT1-PS7-P8-PS9 well area in the north, in a continuous sheet shape. In the south, the development scale of siliceous dolomite is small and distributed in the shape of a strip. Full article

A pivotal food crop in arid and semi-arid zones, proso millet boasts remarkable economic value, making the breeding of stable high-yield varieties critical for industrial sustainability. This study employed a randomized complete block design to conduct a two-year multi-environment trial on nine new varieties across six representative spring-sown test regions in China. Analytical tools, including additive main effects and multiplicative interaction (AMMI) biplots, AMMI stability values (ASV), genotype and genotype × environment (GGE) models, and genotype by yield–trait (GYT) biplots were utilized to assess genotype–environment (G × E) interactions and screen superior genotypes. AMMI variance analysis showed extremely significant effects of genotype, environment, and G × E on yield traits (p < 0.01). G × E principal component analysis identified JS8, PS3, PS6, and PM4 as dominant genotypes. Based on ASV indices, varietal stability rankings were PS5 > YS13 > JS8 > PS3 > PS6 > PM4 > others. GGE analysis indicated PM4 had the broadest adaptability across tested environments, while JS15 exhibited specific adaptability in Datong. Huairen and Shuozhou were validated as ideal testing environments via an ideal environment plot. GYT biplots further confirmed that YS13, JS15, PS3, and PM4 excelled in comprehensive yield–trait combinations. These findings offer a scientific foundation for ecological adaptability evaluation, breeding material selection, and commercial variety promotion. Full article

The increasing presence of microplastics (MPs) and nanoplastics (NPs) in environmental matrices presents substantial analytical challenges due to their small size and chemical diversity. This study introduces a novel enzymatic biosensor based on the Surface Plasmon Resonance (SPR) platform for the sensitive detection of MPs and NPs, utilizing laccase as the recognition element. Standard plastic particles, including polystyrene (PS, 0.1 µm), polymethyl methacrylate (PMMA, 1.0 µm and 100 µm), and polyethylene (PE, 34–50 µm), were analyzed using SPR angular interrogation along with a fixed-angle scheme. The angular approach revealed a clear relationship between the resonance angle, particle size, and refractive index, while the fixed-angle method, combined with immobilized laccase, facilitated specific detection through enzyme/substrate interactions. The analytical parameters showed detection limits ranging from 7.5 × 10⁻⁴ µg/mL (PE, 34–50 µm) to 253.2 µg/mL (PMMA, 1 µm), with significant differences based on polymer type and enzymatic affinity. Application of the biosensor to real rainwater samples collected from two regions in Mexico (Tula and Molango) confirmed its functionality, although performance varied depending on matrix composition, exhibiting inhibition in samples with high manganese (Mn²⁺), chromium (Cr²⁺), and zinc (Zn²⁺) content. Despite these limitations, the sensor achieved a 113% recovery rate in Tula rainwater, demonstrating its potential for straightforward in situ environmental monitoring. This study highlights the capabilities of laccase-based SPR biosensors in enhancing microplastic detection and underscores the necessity of considering matrix effects for real-world applications. Full article

Metal–organic frameworks (MOFs) and their derivatives have emerged as promising candidates for separator engineering in lithium–sulfur batteries (LSBs). This is attributed to their structural tunability, high porosity, and chemical versatility. Despite their potential, challenges such as lithium polysulfide (LiPS) shuttling, sluggish redox kinetics, and poor interfacial stability still hinder the practical deployment of LSBs. This review examines recent advances in MOF- and MOF derivative-based materials for separator modification, focusing on design strategies, functional mechanisms, and electrochemical performance. Pristine MOFs are classified into the following three key structural tuning strategies: control of the pore microenvironment, engineering of metal sites, and enhancement of electrical conductivity. Meanwhile, MOF derivatives are examined using compositional categories to highlight their distinct chemical characteristics and catalytic functionalities for LiPS regulation. Key findings demonstrate that these materials can effectively suppress polysulfide migration, accelerate LiPS redox reactions, and improve lithium-ion transport across the separator. The review also identifies remaining challenges and suggests future perspectives for bridging material-level innovations with system-level applications. Overall, MOF-based separator materials represent a versatile and impactful approach for advancing the electrochemical performance and stability of next-generation LSBs. Full article

Polypropylene (PP) dielectric capacitors are crucial for electronics and electric power systems due to their high power density. However, their relatively low energy density limits their practical application in energy storage devices, presenting a long-standing challenge. Montmorillonite (MMT), a natural phyllosilicate mineral abundantly found on earth, features a two-dimensional nanosheet structure and excellent insulating properties. MMT nanosheets have shown promise in enhancing the breakdown strength and energy storage capability of PP dielectric, but compatibility issues with the PP matrix remain a challenge. In this study, we propose a novel surface modification strategy in which polystyrene (PS)-capped MMT (PCM) nanosheets are synthesized through a polymerization–dissolution process. The modified PCM nanosheets demonstrate improved compatibility and are well dispersed within the PP matrix. Optimal loading of the PCM nanosheets effectively dissipate charge energy and hinder the growth of electric trees in the PP matrix. As a result, the PP nanocomposite with 0.2 wt% PCM nanosheets exhibits an enhanced breakdown strength of 619 MV m⁻¹ and a discharged energy density of 4.23 J cm⁻³, with an energy storage efficiency exceeding 90%. These findings provide a promising strategy for the development of high-energy-density dielectric capacitors in an economical manner. Full article

A novel structure–functional-integrated particle featuring dual micromechanical interlocking property with resin matrix was constructed through surface modification of urchin-like serried hydroxyapatite (UHA) in this work, and the effect of this modification strategy on physicochemical and biological properties of dental resin composite was also investigated. A porous silica coating layer was anchored onto UHA surface via a simple template method in an oil−water biphase reaction system, and the coating time had a prominent effect on the coating thickness and morphology-structure of the particle. When these particles with different porous silica coating thickness were used as fillers for dental resin composite, results showed that UHA/PS5 (porous silica coating reaction time: 5 h) exhibited the optimal 3D urchin-like structure and a desirable porous silica coating thickness. Additionally, UHA/PS5 formed the best dual physical micromechanical interlocking structure when mixing with resin matrix, making the dental resin composites presented the desirable matrix/filler interfacial bonding, and the excellent physicochemical–biological properties, especially for flexural strength and water sorption-solubility. In vitro remineralization and cellular biological properties confirmed that the coating layer did not compromise their remineralization activity. The use of UHA/PSx provides a promising approach to develop strong, durable, and biocompatible DRCs. Full article

In this paper, we design a new type of terahertz orbital angular momentum (OAM) optical fiber with excellent transmission characteristics over a wide frequency range. Within the 0.8–1.8 THz frequency band, it shows stable support for transmission of the fifth-order OAM mode. Its dispersion control effect is excellent; it maintains the confinement loss of most modes at the extremely low level of 10⁻¹⁰ dB/m; its maximum dispersion is only 5.57 ps/THz/cm; and its effective mode field area is greater than 1.11 × 10⁻⁷ m². These characteristics jointly endow this optical fiber with broad application prospects and significant research value in the field of terahertz communication. With the continuous advancement of technology in this field, this optical fiber is expected to become a key component when building efficient, reliable, and large-capacity communication systems. Full article

Background/Objectives: Copovidone (polyvinylpyrrolidone-vinyl acetate copolymer, PVP/VA) is a widely used pharmaceutical excipient with various applications in drug formulation. In hot melt extrusion (HME), PVP/VA is an approved carrier material for the production of amorphous solid dispersions (ASDs) by embedding drugs on a molecular level. This study investigates the properties and processability of two copovidone grades—Plasdone™ S-630 (PS-630) and the novel Plasdone™ S-630 Ultra (PS-630U)—to assess their suitability as ASD carrier materials. Methods: The thermal and physicochemical characteristics of both polymers were evaluated, focusing on glass transition temperature and polymer melt rheology. The process performance in HME was investigated on small-scale as well as in production-scale extrusion. The two model drugs itraconazole and griseofulvin were used to examine drug dissolution and degradation during HME via in-line UV-vis spectroscopy. Results: When comparing both polymers, PS-630U offers various advantages due to the improved powder feeding behavior and reduced yellowing of extruded products while maintaining similar melt properties and drug compatibility compared to PS-630. Conclusions: These findings support the use of PS-630U as an optimized copovidone grade for ASD manufacturing, facilitating improved processing characteristics and best product qualities without the requirement of significant formulation adjustments. Full article

Purpose: To investigate the therapeutic potential of inducible pluripotent stem cell (hiPSC)-based vascular repair, we evaluated two vascular reparative cell populations, CD34⁺ cells derived from hiPSC (hiPSC-CD34⁺) and endothelial colony forming cells (ECFCs) derived from hiPSC (iPS-ECFCs), alone and in combination, in a type 2 diabetic (db/db) mouse model of DR. Methods: hiPSC-CD34⁺ cells (1 × 10⁴) or iPSC- ECFCs (1 × 10⁵) alone or in combination (1.1 × 10⁵) were injected into the vitreous of immunosuppressed db/db mice with six months of established diabetes. One month post-injection, mice underwent electroretinography (ERG) and optical coherence tomography (OCT) to evaluate functional and structural retinal recovery with iPSC administration. Immunohistochemistry (IHC) was used to assess recruitment and incorporation of cells into the retinal vasculature. Retinas from the experimental groups were analyzed using Functional Proteomics via Reverse Phase Protein Array (RPPA). Results: Functional assessment via ERG demonstrated significant improvements in retinal response in the diabetic cohorts treated with either hiPSC-derived CD34⁺ cells or hiPSC-ECFCs. Retinal thickness, assessed by OCT, was restored to near-nondiabetic levels in mice treated with hiPSC-CD34⁺ cells alone and the combination group, whereas hiPSC-ECFCs alone did not significantly affect retinal thickness. One month following intravitreal injection, hiPSC-CD34⁺ cells were localized to perivascular regions, whereas hiPSC-ECFCs were observed to integrate directly into the retinal vasculature. RPPA analysis revealed interaction-significant changes, and this was interpreted as a combination-specific, non-additive host responses (m⁶A, PI3K–AKT–mTOR, glycolysis, endothelial junction pathways). Conclusions: The studies support that injection of hiPSC-CD34⁺ cells and hiPSC-ECFCs, both individually and in combination, showed benefit; however, iPSC combination-specific effects were identified by measurement of retinal thickness and by RPPA. Full article

Background/Objectives: Many cancer survivors continue to experience persistent symptoms such as pain, fatigue, and depression. Exercise and increasing physical activity (PA) are recommended as methods that can help alleviate these symptoms. However, maintaining regular exercise can be difficult due to the challenge of maintaining motivation. This secondary analysis uses data from a randomized controlled pilot study that examines the feasibility of the technology-enhanced combined exercise and other nonpharmacological interventions, such as the TEHEplus program, in managing symptoms. The program used mobile technologies and sent weekly physical performance reports to maintain engagement. In this study, we aimed to examine the impact of weekly physical performance reports on daily symptoms and PA and explored characteristics as moderators. Methods: This secondary analysis included participants who completed the 12-week TEHEplus program. Daily data of steps (PA), sleep duration, and symptoms (rated on a 4-point scale) were collected for 84 days. Mixed-effects and lagged regression models were used to assess the impact of weekly physical performance reports and the moderating effects of baseline characteristics. Results: Seventy-seven survivors of solid tumor cancer (mean age, 59.79, SD = 12.17) were analyzed. During this 84-day period, participants reported a reduction in low energy (B = −0.003, p = 0.004). Step counts increased by an average of 141 steps immediately after each weekly report (B = 140.857, p = 0.027). An increase of 5000 steps on the prior day was related to decreasing pain (B = −0.047, p < 0.001) and fatigue/low energy (B = −0.082, p < 0.001). Two additional hours of prior-night sleep worsened pain (B = 0.029, p = 0.001) and fatigue/low energy (B = 0.027, p = 0.002). Gender, employment, race, caregiver, and type of treatments moderate the relationship between daily PA, sleep (B = −0.131~0.078, p_s < 0.05). Conclusions: Weekly physical performance reports promoted PA, which possibly led to self-reported improvement of symptoms. Higher PA was associated with better self-report symptoms, but longer sleep duration was associated with worsened symptoms, suggesting the need for future studies. The moderating effects suggested that tailoring interventions to individual profiles may enhance the program’s effectiveness. Full article

This study, based on the Decomposed Theory of Planned Behavior (DTPB), constructs and validates a systematic model to explore the key drivers influencing consumers’ continuous usage intention of sustainable Ready-to-Drink (RTD) beverage packaging. The model includes perceived value and social normative paths, introducing perceived sustainability (PS) and perceived value fit (PVF) as moderators to reveal the role of contextual perceptions in green consumption decision-making. Empirical results show that all conventional path hypotheses (H1–H6) are supported. Among the moderating effect hypotheses, H7b, H9a, and H10c are not supported, while the rest hold. Theoretical implications include the following: Perceived Usefulness (PU) and Perceived Enjoyment (PE) significantly and positively influence consumer satisfaction (SA), consistent with the Expectation Confirmation Model (ECM). Both external influence (EI) and interpersonal influence (II) significantly enhance subjective norms (SN), aligning with TPB theory. Self-efficacy (SE) and facilitating conditions (FA) positively affect perceived behavioral control (PBC), consistent with the DTPB model. Satisfaction, subjective norms, and perceived behavioral control significantly predict continuous usage intention (UI), with satisfaction showing the strongest effect, highlighting the importance of positive initial experiences for green behavior continuation. Full article

A novel skin test for an in vivo assessment of SARS-CoV-2-specific T-cell immunity was developed using CoronaDermPS, a multiepitope recombinant polypeptide encompassing MHC II–binding CD4+ T-cell epitopes of the SARS-CoV-2 structural proteins (S, E, M) and full length nucleocapsid (N). In silico epitope prediction and modeling guided antigen design, which was expressed in Escherichia coli, was purified (>95% purity) and formulated for intradermal administration. Preclinical evaluation in guinea pigs, mice, and rhesus macaques demonstrated a robust delayed type hypersensitivity (DTH) response at optimal doses (10–75 µg), with no acute or chronic toxicity, mutagenicity, or adverse effects on reproductive organs. An integrated clinical analysis included 374 volunteers stratified by vaccination status (EpiVacCorona, Gam-COVID-Vac, CoviVac) prior to COVID-19 infection (Wuhan/Alpha, Delta, Omicron variants), and SARS-CoV-2–naïve controls. Safety assessments across phase I–II trials recorded 477 adverse events, of which >88% were mild and self-limiting; no severe or anaphylactic reactions occurred. DTH responses were measured at 24 h, 72 h, and 144 h post-injection by papule and hyperemia measurements. Overall, 282/374 participants (75.4%) exhibited a positive skin test. Receiver operating characteristic analysis yielded an overall AUC of 0.825 (95% CI: 0.726–0.924), sensitivity 79.5% (95% CI: 75.1–83.3%), and specificity 85.5% (95% CI: 81.8–88.7%), with comparable diagnostic accuracy across vaccine, and variant subgroups (AUC range 0.782–0.870). CoronaDerm-PS–based skin testing offers a simple, reproducible, and low-cost method for qualitative evaluation of T-cell–mediated immunity to SARS-CoV-2, independent of specialized laboratory equipment (Eurasian Patent No. 047119). Its high safety profile and consistent performance across diverse cohorts support its utility for mass screening and monitoring of cellular immune protection following infection or vaccination. Full article

Background: Problematic Internet gaming (PIG), considered an early stage of Internet gaming addiction (IGA), has become increasingly prevalent among adolescents. This study focused on deviant peer affiliation (DPA) and hedonic gaming experience (HGE) as key mediators and examined four psychosocial risk factors closely related to them: interpersonal incompetence (II), perceived stress (PS), frustration (FR), and emotional loneliness (EL). Specifically, the study investigated how these four psychosocial risk factors influence adolescents’ DPA, HGE, and PIG, and whether DPA and HGE mediate these relationships. Methods: Based on existing validated scales, we developed a questionnaire to measure these seven constructs (II, PS, FR, IC, DPA, HGE, and PIG), proposed 14 hypotheses, and collected 214 valid responses from adolescents. Structural equation modeling (SEM) was used to test the hypothesized model. Findings: The results showed that all 14 hypotheses were supported. Specifically, interpersonal incompetence significantly predicted perceived stress; stress led to frustration; and frustration, in turn, contributed to emotional loneliness. Furthermore, all four psychosocial risk factors significantly predicted deviant peer affiliation, hedonic gaming experience, and ultimately, problematic Internet gaming among adolescents. Both DPA and HGE mediated the effects of psychosocial risk factors on adolescent problematic Internet gaming (PIG), with the model explaining moderate-to-high variance. This study highlights the importance of segmenting adolescents into more specific subgroups based on the distinct developmental pathways leading to PIG. Implications: Understanding the step-by-step mechanisms and psychological drivers of different adolescent subtypes can provide a more solid foundation for early identification and targeted intervention efforts. Full article