Search Results (482)

Kidney transplantation is the treatment of choice for patients with end-stage kidney disease. Despite significant advances in graft survival, rejection continues to pose a major clinical challenge. Conventional monitoring tools, such as serum creatinine, donor-specific antibodies, and proteinuria, lack sensitivity and specificity for early detection of graft injury. Moreover, while biopsy remains the current gold standard for diagnosing rejection, it is prone to confounders, invasive, and associated with procedural risks. However, non-invasive novel biomarkers have emerged as promising alternatives for earlier rejection detection and improved immunosuppression management. This review focuses on the leading candidate biomarkers currently under clinical investigation, with an emphasis on their diagnostic performance, prognostic value, and potential to support personalised immunosuppressive strategies in kidney transplantation. Full article

The cornea, the transparent anterior window of the eye, critically refracts light and protects intraocular structures. Corneal pathologies, including trauma, infection, chemical injury, metabolic diseases, genetic conditions, and age-related degeneration, can lead to significant visual impairment. While penetrating keratoplasty or full-thickness corneal transplantation remains a standard and effective intervention for severe corneal dysfunction, limitations in donor tissue availability and the risk of immunogenic graft rejection necessitate alternative therapeutic strategies. Furthermore, for cases of isolated epithelial disfunction, a full-thickness cornea graft may not be required or effective. This review examines the potential of corneal epithelial constructs derived from autologous stem cells with functional barrier properties for corneal reconstruction and in vitro pharmacotoxicity testing. In this review, we delineate the current limitations of corneal transplantation, the advantages of stem cell-based approaches, and recent advances in generating engineered corneal epithelium. Finally, we address remaining technical challenges and propose future research directions aimed at clinical translation. Full article

Drosophila suzukii is an invasive pest of many fruit crops worldwide. Employing the Sterile Insect Technique (SIT) could mitigate D. suzukii population growth and crop damage. This study evaluated the efficacy of SIT on commercial fruit, by (1) validating the quality of irradiated sterile males (male mating competitiveness, courtship, and flight performance) in the laboratory, and (2) assessing population suppression and fruit damage reduction in commercial raspberry fields. Treatment with SIT was compared to the grower’s standard chemical insecticide program throughout the season. The principal metrics of efficacy were trap counts of wild adult female D. suzukii in crops and larvae per fruit during harvesting. These metrics together with monitoring of border areas allowed targeting of high-pressure areas with higher releases of sterile males, to maximise efficacy for a given release number. The sterile male D. suzukii were as competitive as their fertile non-irradiated counterparts in laboratory mating competitiveness and flight performance studies while fertility egg-to-pupae recovery was reduced by 99%. In commercial raspberry crops, season-long releases of sterile males significantly suppressed the wild D. suzukii population, compared to the grower standard control strategy; with up to 89% reduction in wild female D. suzukii and 80% decrease in numbers of larvae per harvested fruit. Additionally, relative fruit waste (i.e., percentage of harvested fruits rejected for sale) at harvest was reduced for early, mid and late harvest crops, by up to 58% compared to the grower standard control. SIT has the potential to provide an effective and sustainable strategy for managing D. suzukii in raspberries, increasing marketable yield by reducing adult populations, fruit damage and waste fruit. SIT could therefore serve as a valuable tool for integrated pest management practices in berry production systems. Full article

A recently proposed method called “controlled swelling of monolithic films” was implemented to prepare ultra-high-molecular-weight polyethylene (UHMWPE) ultrafiltration membranes. For the first time, the effect of UHMWPE molecular weight (MW) on the structure and properties of the membranes prepared via this special case of thermally induced phase separation was studied in detail. The morphology and properties of the membranes were studied using SEM, DSC, liquid–liquid displacement porometry, and standard methods for the evaluation of mechanical properties, permeance, rejection, and abrasion resistance. High-quality membranes with a tensile strength of 5.0–17.8 MPa, a mean pore size of 25–50 nm, permeance of 17–107 L m⁻² h⁻¹ bar⁻¹, rejection of model contaminant (blue dextran) of 72–98%, and great abrasion resistance can be prepared only if the MW of the polymer in the initial monolithic film is sufficiently high. The properties of the membranes can effectively be controlled by changing the MW of the polymer and the mass fraction of the latter in the swollen film. Shrinkage is responsible for the variation in the membrane properties. The membranes prepared from a higher-MW polymer are more prone to shrinking after the removal of the solvent. Shrinkage decreases before rising again and minimizes with an increase in the polymer content in the swollen film. Full article

Plant-derived vesicle-like nanoparticles (PDVLNs) are bioactive nanovesicles secreted by plant cells, emerging as a novel therapeutic tool for tissue repair and regeneration due to their low immunogenicity, intrinsic bioactivity, and potential as drug delivery carriers. This review examines PDVLNs’ biogenesis mechanisms, isolation techniques, and compositional diversity, emphasizing their roles in promoting essential regenerative processes—cell proliferation, differentiation, migration, immune modulation, and angiogenesis. We explore their therapeutic applications across multiple tissue types, including skin, bone, neural, liver, gastrointestinal, cardiovascular, and dental tissues, using both natural and engineered PDVLNs in various disease models. Compared to mammalian exosomes, PDVLNs offer advantages such as reduced immune rejection and ethical concerns, enhancing their sustainability and appeal for regenerative medicine. However, challenges in clinical translation, including scalability, standardization, and safety remain. This paper consolidates current knowledge on PDVLNs, highlighting their versatility and providing insights into engineering strategies to optimize efficacy, ultimately outlining future research directions to advance their clinical potential. Plant vesicle-like nanoparticles (PDVLNs) may become a new avenue for the treatment of tissue injury, promoting tissue repair and regeneration through their intrinsic bioactivity or as drug delivery carriers. In addition, PDVLNs can be engineered and modified to achieve better results. Full article

Background: Developing countries face significant challenges in accessing high-quality pharmaceutical products due to resource constraints, limited regulatory capacity, and market dynamics that often prioritize cost over quality. This review addresses the critical gap in regulatory frameworks that fail to ensure pharmaceutical quality equity between developed and developing nations. Objective: This comprehensive review examines a novel dual-pathway regulatory framework that leverages stringent regulatory authority (SRA) approvals, artificial intelligence-based evaluation systems, and harmonized pricing mechanisms to ensure pharmaceutical quality equity across global markets. Methods: A comprehensive systematic analysis of current regulatory challenges, proposed solutions, and implementation strategies was conducted through an extensive literature review (202 sources, 2019–2025), expert consultation on regulatory science, AI implementation in healthcare, and pharmaceutical policy development. The methodology included an analysis of regulatory precedents, an economic impact assessment, and a feasibility evaluation based on existing technological implementations. Results: The proposed framework addresses key regulatory capacity gaps through two complementary pathways: Pathway 1 enables same-batch distribution from SRA-approved products with pricing parity mechanisms. At the same time, Pathway 2 provides independent evaluation using AI-enhanced systems for differentiated products. Key components include indigenous AI development, which requires systematic implementation over 4–6 years across three distinct stages, outsourced auditing frameworks that reduce costs by 40–50%, and quality-first principles that categorically reject cost-based quality compromises. Implementation analysis demonstrates a potential for achieving a 90–95% quality standardization, accompanied by a 200–300% increase in regulatory evaluation capability. Conclusions: This framework has the potential to significantly improve pharmaceutical quality and access in developing countries while maintaining rigorous safety and efficacy standards through innovative regulatory approaches. The evidence demonstrates substantial public health benefits with projected improvements in population access (85–95% coverage), treatment success rates (90–95% efficacy), and economic benefits (USD 15–30 billion in system efficiencies), providing a compelling case for implementation that aligns with global scientific consensus and Sustainable Development Goal 3.8. Full article

Although transplantation remains the gold-standard treatment for patients with end-organ failure, lifelong adherence to immunosuppressant medication is required to prevent rejection, graft failure, and mortality. Given the increase in thoracic organ transplantation, it is crucial to better understand the associated barriers to treatment. Examining sociodemographic, transplant, healthcare access, post-transplant treatment, and patient-related psychosocial factors may help to elucidate treatment barriers that have not been previously considered in the existing literature. This single-site cross-sectional study surveyed 65 thoracic (heart and lung) transplant recipients (mean age: 62 years; 76.2% male; 72.3% White, and 21.5% Black) via phone interviews. Immunosuppressant nonadherence was found in 49.2% of participants (46.9% heart, 51.5% lung). In a four-week period, 20% of participants missed at least one dose, 40% did not take their medications on time, and 1% stopped completely. Significant correlates of nonadherence included poorer diet quality, fewer comorbidities, and maladaptive coping responses to perceived discrimination. This preliminary study highlights the importance of considering the social determinants of health—particularly post-transplant treatment and psychosocial patient-related factors—to inform post-transplant care. Addressing such variables may improve medication adherence and, subsequently, overall health outcomes. Further research with larger samples is needed to better understand the associated correlates and inform effective interventions for enhanced medication adherence. Full article

The increasing sophistication of cyberattacks on smart grid infrastructure demands advanced anomaly detection and recovery systems that balance high recall rates with acceptable precision while providing reliable data restoration capabilities. This study presents an optimized two-stage anomaly detection and recovery system combining an enhanced TimerXL detector with a DeBERTa-v3-based verification and recovery mechanism. The first stage employs an optimized increment-based detection algorithm achieving 95.0% for recall and 54.8% for precision through multidimensional analysis. The second stage leverages a modified DeBERTa-v3 architecture with comprehensive 25-dimensional feature engineering per variable to verify potential anomalies, improving the precision to 95.1% while maintaining 84.1% for recall. Key innovations include (1) a balanced loss function combining focal loss ($\alpha$ = 0.65, $\gamma$ = 1.2), Dice loss (weight = 0.5), and contrastive learning (weight = 0.03) to reduce over-rejection by 73.4%; (2) an ensemble verification strategy using multithreshold voting, achieving 91.2% accuracy; (3) optimized sample weighting prioritizing missed positives (weight = 10.0); (4) comprehensive feature extraction, including frequency domain and entropy features; and (5) integration of a generative time series model (TimER) for high-precision recovery of tampered data points. Experimental results on 2000 hourly smart grid measurements demonstrate an F1-score of 0.873 ± 0.114 for detection, representing a 51.4% improvement over ARIMA (0.576), 621% over LSTM-AE (0.121), 791% over standard Anomaly Transformer (0.098), and 904% over TimesNet (0.087). The recovery mechanism achieves remarkably precise restoration with a mean absolute error (MAE) of only 0.0055 kWh, representing a 99.91% improvement compared to traditional ARIMA models and 98.46% compared to standard Anomaly Transformer models. We also explore an alternative implementation using the Lag-LLaMA architecture, which achieves an MAE of 0.2598 kWh. The system maintains real-time capability with a 66.6 ± 7.2 ms inference time, making it suitable for operational deployment. Sensitivity analysis reveals robust performance across anomaly magnitudes (5–100 kWh), with the detection accuracy remaining above 88%. Full article

Background/Objectives: Kidney transplantation is associated with an increased risk of renal cell carcinoma (RCC). This study aimed to evaluate the outcomes of de novo RCC in kidney transplant recipients (KTRs). Methods: We retrospectively identified 50 de novo RCC cases among 4012 KTRs transplanted from 2005 to 2024. Data on patient characteristics and outcomes were collected. Propensity score matching (PSM) compared 34 localized RCC cases in KTRs with 34 non-transplant RCC cases. The statistical analyses used Kaplan–Meier estimates, the log-rank test, and the Cox regression. Results: The RCC incidence was 0.64 per 1000 person-years, with a standardized incidence ratio of 4.40 (95% CI: 3.33–5.80). In the KTR cohort, clear cell RCC was present in 42%, and papillary RCC was present in 42%. RCC developed predominantly in native kidneys (92%). UICC stage I was present in 74%. The treatment for the non-metastatic RCC was nephrectomy in the majority of cases (91%). For the metastatic RCC, 71% received a tyrosine kinase inhibitor (TKI). In the KTR cohort, the 3- and 5-year overall survival (OS) rates were 85% and 72%, respectively, with a median OS of 199 months; the synchronous metastasized (M1) patients had a median OS of 14 months. Rejection, age, advanced UICC stage, higher pT stage, clinical positive lymph nodes, M1, and higher grade were significantly associated with poor OS. The 5-year OS (96% vs. 84%, p = 0.72) and MFS (92% vs. 93%, p = 0.61) were comparable in the PSM cohort between the KTRs and the non-KTRs in the localized RCC. Conclusions: KTRs have a higher risk of RCC and present at a localized stage with comparable OS rates to non-transplant RCC patients. Adverse tumor characteristics, including synchronous metastases, significantly affect the prognosis, highlighting the need for surveillance and individualized treatment, particularly for metastatic RCC. Full article

Chimeric antigen receptor (CAR)-engineered natural killer (NK) cells are a promising platform for off-the-shelf immunotherapy due to their safety advantages over CAR-T cells, including lower risk of graft-versus-host disease, cytokine release syndrome, and neurotoxicity. However, their persistence and efficacy are limited by immunological challenges such as host T-cell-mediated rejection, NK cell fratricide, and macrophage-mediated clearance. This review summarizes gene editing strategies to overcome these barriers, including β2-microglobulin (B2M) knockout and HLA-E overexpression to evade T and NK cell attacks, CD47 overexpression to inhibit phagocytosis, and TIGIT deletion to enhance cytotoxicity. In addition, we discuss functional enhancements such as IL-15 pathway activation, KIR modulation, and transcriptional reprogramming (e.g., FOXO1 knockout) to improve persistence and antitumor activity. We also highlight the role of induced pluripotent stem cell (iPSC)-derived NK platforms, enabling standardized, scalable, and multiplex gene-edited products. Finally, we explore artificial intelligence (AI) applications in immunogenomic profiling and predictive editing to tailor NK cell therapies to patient-specific HLA/KIR/SIRPα contexts. By integrating immune evasion, functional reinforcement, and computational design, we propose a unified roadmap for next-generation CAR-NK development, supporting durable and broadly applicable cell-based therapies. Full article

This study investigates how pre-service Earth science teachers used ChatGPT in designing lessons based on the 5E instructional model and what educational opportunities and challenges emerged. As generative AI tools gain traction in education, understanding their integration into science lesson planning is increasingly important. Eight pre-service teachers from a South Korean university participated in a four-week instructional design project. They developed 5E-aligned Earth science lessons while interacting with ChatGPT for idea generation, explanation, activity development, and assessment. Data sources included lesson plans, ChatGPT interaction logs, reflective journals, and interviews. Thematic analysis was used to examine instructional uses of AI and the adaptations required during the process. Findings showed that ChatGPT supported different phases of the 5E model—providing metaphors and analogies in Engage, activity ideas in Explore, draft explanations in Explain, task prompts in Elaborate, and assessment questions in Evaluate. However, participants frequently revised or rejected AI-generated content to match inquiry goals, student readiness, and curriculum standards. The study highlights the importance of pedagogical reasoning in AI-supported lesson design. It contributes to the growing literature on teacher education and AI by offering a phase-specific view of GenAI use and underscoring the instructional mediation needed for effective application. Full article

Background: Acute cellular rejection (ACR) remains a common complication following lung transplantation and is a major risk factor for chronic lung allograft dysfunction (CLAD). Although transbronchial biopsy (TBB) is the diagnostic gold standard, it is invasive and may be contraindicated in certain patients. This study aimed to assess the diagnostic utility of combining bronchoalveolar lavage fluid (BALF) lymphocyte counts with cytokine profiling—particularly interleukin-17A (IL-17A)—in lung transplant recipients with elevated peripheral blood eosinophil (EOS) counts. Methods: We retrospectively analyzed 108 BALF and matched TBB samples from 74 lung transplant recipients with EOS counts >200 cells/μL, collected between 2014 and 2020. BALF lymphocyte percentages and levels of cytokines (IL-4, IL-6, IL-10, IL-13, IL-15, IL-17A, IFN-γ, TNF) were quantified. Associations with histologically confirmed ACR were evaluated using generalized estimating equation models. Results: ACR was diagnosed in 57% of TBB samples. BALF lymphocyte percentages were significantly higher in ACR cases (median 8% vs. 4%, p < 0.001). Each 1% increase in lymphocytes was associated with a 10% increase in the odds of ACR (OR 1.102; 95% CI 1.076–1.129). IL-17A levels were also significantly elevated in ACR (OR 1.047; 95% CI 1.003–1.092; p = 0.032), but with moderate discriminative ability (AUC = 0.629). The combination of BALF lymphocyte counts and IL-17A levels improved diagnostic performance (AUC > 0.76). Conclusions: The combined assessment of BALF lymphocyte counts and IL-17A levels in recipients with elevated EOS offers a promising non-invasive strategy to support the diagnosis of ACR. Prospective studies are needed to validate these findings and further refine personalized diagnostic approaches to ACR. Full article

This paper presents a broadband near-field probe designed for measuring the normal magnetic field ($H_z$) in radio frequency (RF) circuits operating within a frequency range of 2–8 GHz. The proposed probe uses a cost-effective 4-layer printed circuit board (PCB) structure made with an FR-4 substrate. The probe primarily consists of an $H_z$ detection unit, a broadband microstrip balun, and a coaxial-like output. The broadband balun facilitates the conversion from differential to single-ended signals, thereby enhancing the probe’s common-mode rejection capability. This design ensures that the probe achieves both cost efficiency and high broadband measurement performance. Additionally, this work investigates the feasibility of employing microstrip lines as calibration standards for the $H_z$ probe. The probe’s structural parameters and magnetic field response were initially determined through simulations, and the calibration factor was subsequently verified by calibration experiments. In practical measurements, the field distributions above a microstrip line and a low-noise amplifier (LNA) were captured. The measured field distribution of the microstrip line was compared with simulation results to verify the probe’s performance. Meanwhile, the measured field distribution of the LNA was utilized to identify the radiating components within the amplifier. Full article

This paper presents a CMOS-based optoelectronic receiver integrated circuit (CORIC) realized in a standard 180 nm CMOS technology for the applications of short-distance optical interconnects. The CORIC comprises a spatially modulated P⁺/N-well on-chip avalanche photodiode (P⁺/NW APD) for optical-to-electrical conversion, a dummy APD at the differential input for enhanced common-mode noise rejection, a cross-coupled differential transimpedance amplifier (CCD-TIA) for current-to-voltage conversion, a 3-bit continuous-time linear equalizer (CTLE) for adaptive equalization by using NMOS registers, and a $f_T$-doubler output buffer (OB). The CTLE and $f_T$-doubler OB combination not only compensates the frequency-dependent signal loss, but also provides symmetric differential output signals. Post-layout simulations of the proposed CORIC reveal a transimpedance gain of 53.2 dBΩ, a bandwidth of 4.83 GHz even with a 490 fF parasitic capacitance from the on-chip P⁺/NW APD, a dynamic range of 60 dB that handles the input photocurrents from 1 μA_pp to 1 mA_pp, and a DC power consumption of 33.7 mW from a 1.8 V supply. The CORIC chip core occupies an area of 260 × 101 μm². Full article

The standard immunosuppressive treatments in heart transplantation are calcineurin inhibitors, corticosteroids, and antimetabolite agents or inhibitors of the mammalian target of rapamycin. Pharmacogenetic studies show the impact on clinical course of genetic variability in genes that encode transporters, metabolizers, or molecular targets of immunosuppressants. The aim of this systematic review is to elucidate the role that pharmacogenetics of immunosuppressant drugs plays in clinical outcomes upon heart transplantation. PubMed, EMBASE, the Cochrane Central Register, and the Database of Abstracts of Reviews of Effects were searched without restrictions. The 64 studies analyzed followed these criteria: (1) were based on clinical data on heart transplantation patients; (2) analyzed the associations between polymorphisms and clinical response; (3) analyzed the impact of polymorphisms on immunosuppressant safety. CYP3A4/5 variants were associated with higher doses of tacrolimus, whereas POR*28 variants with lower doses—ABCB1, ABCC2, SLCO1B1, and SLC13A1—contribute to interindividual variability in drug absorption, distribution, and toxicity. An ABCC2 polymorphism (rs717620) was related to higher risk of graft rejection in pediatrics. Variations in HLA-G, TNF-α and TGF-β genes influence transplant rejection risk and immune response. Implementing pharmacogenetic screening of polymorphisms could enhance therapeutic outcomes by improving drug efficacy, reducing toxicity, and ultimately increasing heart graft survival rates. Strong evidence supports genotyping for CYP3A5 and TPMT, but further research is required for transporter genes and cytokine polymorphisms. Full article