Search Results (777)

Background: Steroid resistance indicates poor prognosis in pediatric nephrotic syndrome, but predictive models and risk factors for steroid-resistant nephrotic syndrome (SRNS) remain poorly understood. Methods: We searched PubMed, Embase, Scopus, CNKI, SinoMed, Wanfang, and VIP (inception to 1 March 2025) for studies developing SRNS prediction models or identifying risk factors. Odds ratios and AUC were pooled using random-effects meta-analysis. Risk of bias was assessed with PROBAST and Newcastle-Ottawa Scale. Results: Out of 2264 studies, 23 were included. Prediction models were mainly developed using logistic regression (16/17, 94.1%). The most frequently reported predictors included erythrocyte sedimentation rate and vitamin D binding protein. The reported AUC ranged from 0.75 to 0.88. Only one model had undergone external validation with an accuracy of 0.94. A total of 22 independent risk factors were identified, five of which—low birth weight, decreased urine output, hypertension, serum albumin, and serum IgM—were not in existing models. In total, 76% of model studies and 26% of risk factor analyses were at high or moderate risk of bias. Conclusions: Existing SRNS prediction models reported apparent discrimination but had a high risk of bias and very limited external validation, which substantially restricts their current clinical applicability. Several relevant risk factors remain unincorporated. Future research should prioritize rigorous model development and multi-center external validation. Full article

The global tilapia industry is threatened due to the mass die-off of farmed tilapia caused by an emerging virus, Tilapia Lake Virus (TiLV). The threat of TiLV disease demands for cost-effective diagnostics and preventive measures such as protein and antibody-based detection tools and even vaccines like protein subunit vaccines. In this study, we aimed to recombinantly express the entire S4 protein of TiLV in vitro and in vivo using an extended host-range baculovirus expression vector system (EHR-BEVS) and used the purified protein to generate polyclonal anti-S4 antibodies. The parental extended host-range ABM-eIF4E baculovirus previously developed in our laboratory was used to generate the recombinant ABM-eIF4E-S4-His baculovirus expression vector using homologous recombination and was purified through multiple rounds of plaque selection and end-point titration, eliminating the need for the use of antibiotic resistance gene selection marker. Different insect cell lines including Trichoplusia ni Hübner, 1802 larvae were infected with ABM-eIF4-S4-His to produce recombinant S4 protein. Western blotting was used to detect the recombinantly expressed S4 protein. We generated an antibiotic resistance gene-free EHR-BEV and observed the permissibility of all the insect cell lines tested including T. ni larvae to infection with the recombinant ABM-eIF4E-S4-His. Secondly, immunogenic S4 protein capable of eliciting rabbit polyclonal anti-S4 antibodies was recombinantly expressed in the infected insect cells and larvae. TiLV S4 protein was recombinantly expressed in vitro and in vivo using extended host-range ABM-eIF4E-S4-His baculovirus expression vector and was shown to induce rabbit antibody production that can recognize S4 protein supporting the potential of insect larvae as alternative biofactories in the production of recombinant TiLV protein subunit for the development of diagnostics and preventive vaccines against TiLV disease. Full article

There has been an immense concern in the healthcare industry about the globally raising rate of cardiovascular disease (CVD). As per recent WHO reports, CVD is the leading cause of disability, hospitalization and premature death. Studies indicate that oxidative stress negatively impacts the heart and vascular system, which could potentially lead to myocardial infarction, hypertension, cardiomyopathies, atherosclerosis and diabetic heart failure, highlighting its significance as a prognostic indicator in cardiovascular conditions. Nowadays, many common experimental assays are used for in-vitro and in-vivo evaluation of oxidative stress and its negative effects on the cardiovascular system. This review aims to serve as a comprehensive guide for researchers seeking to evaluate the impact of oxidative stress on DNA damage in CVD utilizing standardized methods published by leading institutions. To achieve this, we analyzed 208 relevant articles from prominent databases such as Scopus, PubMed, ScienceDirect, etc., summarizing experimental validation of oxidative stress measurements from 1955 to the present. Oxidative stress-induced DNA damage is a key driver of cardiovascular disease progression, yet experimental approaches to study it remain highly variable. This review systematically summarizes established in-vitro and in-vivo models, oxidative stress inducers, and analytical assays used in cardiovascular research. By integrating mechanistic insights with standardized methodologies, it provides a practical framework to guide model selection, improve reproducibility, and enhance translational relevance. This work serves as a concise reference for researchers investigating redox biology, cardiovascular pathology, and antioxidant-based therapeutic strategies. Full article

Precise control of mitochondrial electron transport is essential to maintain mitochondrial coupling and efficiency in ATP production. Furthermore, disruptions to ETC complex function can drive increased oxidant production, resulting in oxidative damage to the mitochondrion and bioenergetic inefficiency. This is highly relevant in the aging heart, as increased cardiac oxidative stress and mitochondrial dysfunction are hallmarks of age-related cardiovascular disease. Lysine acetylation has recently been characterized as a novel regulator of mitochondrial metabolic and bioenergetic function in the aging heart. In the present study, we investigated how lysine acetylation regulates oxidant production and redox milieu through mitochondrial acetyltransferase GCN5L1. Using a cardiac-specific GCN5L1 knockout mouse model, we observed that age-associated lipid peroxidation and semiquinone radicals were decreased with GCN5L1 KO. RNA sequencing analysis identified mitochondrial bioenergetic and respiratory pathways revolving around the respiratory chain to be enriched in the old KO group. Further, we showed the old KO group to exhibit reduced acetylation of ETC complex and antioxidant proteins, improved ETC complex and antioxidant protein activity. Overall, GCN5L1 regulates redox homeostasis in the aged heart by regulating mitochondrial ETC complex activity, oxidative stress, and mitochondrial bioenergetics. These findings identify GCN5L1 and acetylation as potential therapeutic targets in aging and age-related diseases. Full article

Background/Objective: To evaluate the reliability, diagnostic accuracy and time efficiency of an artificial intelligence (AI)-automated method (CephX) and a semiautomated method (INVIVO) for upper airway segmentation, the manual digital method (ITK-SNAP) was used as the reference standard. Methods: This retrospective study analyzed cone-beam computed tomography (CBCT) scans from 133 patients. The upper airway volume and narrowest cross-sectional area were measured via the three methods. Reliability and repeatability were assessed via the intraclass correlation coefficient (ICC). The time required for each segmentation method was also recorded and compared. Results: Both the AI-automated (ICC = 0.945) and semiautomated (ICC = 0.992) methods demonstrated excellent reliability for total volume measurements compared with the manual reference. For the narrowest area, the automated method showed excellent agreement (ICC = 0.943), whereas the semiautomated method showed good agreement (ICC = 0.868). All methods demonstrated excellent intrareader repeatability (ICC > 0.95) and high test–retest reliability. The AI-automated method was significantly more time-efficient, requiring less than 30 s per analysis, compared with 161.4 s for the semiautomated method and 336.6 s for the manual method. Conclusions: AI-automated and semiautomated segmentation methods are reliable and accurate alternatives to manual upper airway analysis. The AI-based approach offers a substantial advantage in time efficiency, making it a valuable tool for clinical practice. Full article

There has been much development of composites of calcium phosphate and polymers for use as artificial bone, with other applications still ongoing, and clarification of the in vivo absorption mechanism is considered an important perspective. In order to clarify the absorption mechanism of bioabsorbable materials used for artificial bones and bone grafts, we prepared composites of calcium phosphate and polymers and conducted in vivo experiments in experimental animals using composites as implantation samples. Two typical types of calcium phosphate, β-tricalcium phosphate (β-TCP) and unsintered hydroxyapatite (uHA), were used as calcium phosphate, and copolymers of poly-dl-lactide-co-glycolide (PDLGA) and poly-l-lactide-co-glycolide (PLGA) were used as polymers. For samples composed of PDLGA and calcium phosphates, the weight ratios of calcium phosphate were set at 40% and 10% for uHA and 40% for β-TCP (uHA(40), uHA(10) and β-TCP(40), respectively). A composite sample of PLGA and uHA was also prepared with a weight ratio of 10% uHA (uHA(10)/PLGA), intending slow degradation of the polymer matrix compared to PDLGA. The samples were implanted in the metaphysis and diaphysis region of rabbits’ femur for up to 48 weeks. In this study, positron emission tomography/X-ray computed tomography (PET/CT) was used to continuously evaluate the changes in the samples and the accumulation of cells in the animals, and histological evaluation was performed, focusing on the time of characteristic changes in the PET/CT to confirm the cell types. The results are summarized as follows: (1) the absorption mechanism of the materials used in this study was suggested to be mainly phagocytosis by macrophages; (2) the disappearance rate was faster for β-TCP(40) compared with uHA(40); and (3) uHA(10), having a lower proportion of uHA, is not prone to aggregation and exhibited a similar disappearance result to β-TCP(40). These results suggest that phagocytosis by macrophages is the dominant path in resorption of the bioresorbable materials, and the resorption period varies depending on the type of polymer. It is important to optimize the type and amount of polymers and calcium phosphate in order to achieve a degradation rate of bioresorbable materials that corresponds to the extent of damage in the healing area. Full article

Standing equine computed tomography (CT) acquisitions are susceptible to residual postural sway, which can introduce view-inconsistent motion and degrade image quality. External optical tracking based on ChArUco fiducials is a promising, low-cost strategy to enable projection-wise motion compensation, yet quantitative guidance on how camera–marker geometry affects pose-estimation performance remains limited. This CT-motivated benchtop study characterizes how the relative camera–ChArUco configuration influences both the accuracy (bias with respect to ground truth) and the precision (repeatability) of pose estimates obtained from RGB images using OpenCV ChArUco detection and reprojection-error minimization to estimate the rigid camera-to-board transformation. Controlled experiments systematically varied acquisition protocol (continuous repeated estimates at fixed pose versus cyclic repositioning), viewing angle over a wide angular range at two working distances, and camera-to-board distance over multiple depth settings. Ground truth for angular configurations was defined by a stepper-motor rotation stage, while distance ground truth was obtained by ruler measurements. Performance was summarized via mean absolute error and standard deviation across repeated measurements, complemented by variance-based statistical testing with multiple-comparison correction. Cyclic repositioning did not yield evidence of increased variability relative to continuous acquisitions, supporting view-by-view sampling. Viewing angle induced a consistent accuracy–precision trade-off for rotations: frontal views minimized mean error but exhibited higher variability, whereas oblique views reduced jitter at the expense of increased bias. Increasing working distance reduced repeatability, most prominently for depth-related components. Overall, these findings provide pre-clinical guidance for selecting camera/marker placement (moderately oblique viewpoints, limited working distance, sufficient image footprint) before in-scanner and in-vivo validation for standing equine CT motion compensation. Full article

The Norway spruce (Picea abies) is a forest resource whose by-products contain bioactive compounds such as galactoglucomannan (GGM), catechin, and epicatechin, recognized for their antioxidant and chemopreventive potential. Within a food-related valorization context, we evaluated the antiproliferative, antimetastatic, genotoxic, and antimalarial activities of the Norway spruce by-product extract (NSBE). Considering its chemical composition and multifunctional bioactive profile, NSBE is investigated for its potential application as a functional food ingredient. NSBE exhibited concentration-dependent antiproliferative and antimetastatic effects two cancer cell lines (A549 and HCT-8), reducing cell adhesion by 33.96% in A549 cells and 40.15% in HCT-8 cells, and suppressing clonogenic capacity by up to 90% and 75%, respectively. The extract preserved basal chromosomal integrity and demonstrated a cytoprotective effect at 10 µg GAE/mL, reducing cisplatin-induced genotoxicity. Additionally, in antiplasmodial assays, NSBE showed potent inhibition of two Plasmodium falciparum strains: W2 (chloroquine-resistant) and 3D7 (chloroquine-sensitive) strains, with IC₅₀ values below 3.5 µg GAE/mL. This activity was supported by a selectivity index (SI) of 13, exceeding the recommended threshold for natural antimalarial candidates. Altogether, these findings highlight the NSBE as a sustainable and multifunctional food ingredient with relevant antiproliferative and antiplasmodial properties, supporting its cytoprotective and chemopreventive potential within a functional food framework. Full article

Objectives: This study aimed to comprehensively evaluate and compare the therapeutic effects of Right Angle Maxillary Protraction Appliance (RAMPA) therapy on nasal airway volume in pediatric patients, specifically differentiated by their baseline radiological paranasal sinus status. The objective was to quantify airway volume changes (absolute and percentage) in clear and opacified sinus groups, investigate the influence of age, sex, and treatment duration on these changes, and elucidate potential differences in the underlying mechanisms of airway expansion between groups. Study Design: A retrospective comparative cohort study design was employed. This study includes a “clear sinus group” of 26 patients (mean age: 6.6 years) with radiologically clear sinuses at baseline and an “opacified sinus group” of 20 patients (mean age: 6.8 years) diagnosed with rhinosinusitis and exhibiting significant sinus opacification on baseline CBCT scans. Upper airway volumetric measurements were performed using CBCT scans acquired pre- (T1) and post-treatment (T2), with data analyzed using Invivo 5 software. Results: RAMPA therapy significantly increased upper airway volume in both cohorts. The clear sinus group showed an approximate 18% mean increase (4886.9 mm³ absolute), while the opacified sinus group demonstrated a remarkably greater 61% mean increase (11,192.8 mm³ absolute). This difference was statistically significant. In the clear sinus group, airway volume gain positively correlated with treatment duration (p = 0.0303). Conversely, no significant correlation was found in the opacified sinus group (p = 0.288), suggesting rapid obstruction relief as a dominant mechanism. Sex did not significantly influence outcomes, and age was not a strong independent predictor of volume change magnitude. Conclusions: RAMPA therapy effectively increases upper airway volume in pediatric patients, with a substantially greater effect in those with baseline sinus opacification due to rapid obstruction resolution complementing skeletal changes. The mechanism of action differs by sinus status, with clear sinus patients showing gradual, duration-dependent skeletal adaptation and opacified sinus patients exhibiting immediate, duration-independent gains primarily from sinus clearance. These findings provide crucial insights for tailored clinical decision-making. Full article

Background: The use of pesticides among smallholder farmers, agrochemical sellers, and agricultural officers involves a complex interplay of knowledge, economic factors, and regulatory frameworks. Therefore, this study explores the patterns, practices, and socio-environmental dynamics of pesticide use among smallholder farmers and agro-input sellers in Iringa and Njombe. Method: This study employed a qualitative, phenomenological design, guided by the socio-ecological model (SEM), to explore the lived experience of farmers, agro-dealers, and extension officers. It involved a total of 23 interviews performed in the Njombe and Iringa regions. Data were collected between October 2024 and March 2025, using a combination of in-depth phenomenological interviews, key informant interviews, and field observations, and were categorized into themes and subthemes analyzed using InVivo. Results: The study involved a total of 23 participants drawn from the Iringa and Njombe regions. The gender distribution was nearly balanced, with 52.1% male and 47.8% female respondents. The mean age of participants was 33 years (95% CI: 29.3–37.3). In terms of education, over half (52.17%) had completed primary school. The findings show that smallholders in Iringa and Njombe widely use mixed pesticides and fertilizers, rely on trusted brands, and adapt to climate impacts, but face challenges with regard to unsafe mixing, poor storage, fake products, and weak regulation, highlighting the need for better education, market oversight, and safer practices. Conclusion: Using the socio-ecological model, the findings indicate that pesticide use among smallholder horticultural farmers in Iringa and Njombe is influenced by a complex interaction of socio-economic constraints, market forces, climate variability, and institutional shortcomings. Although farmers have some awareness of safe practices, systemic barriers continue to limit the adoption of sustainable pesticide management. Full article

Although metabolic pathways profoundly influence disease behavior, osteosarcoma (OS) still lacks a glutamine metabolism–based framework for patient stratification. By integrating single-cell RNA sequencing with bulk cohorts, we delineated a glutamine-associated transcriptional program and translated it into an externally validated, clinically oriented risk model. After rigorous quality control and doublet removal, 19 clusters were annotated into 10 cell types. Glutamine metabolism–related gene (GRG) scores, quantified by five orthogonal algorithms (AUCell, UCell, singscore, ssGSEA, and AddModuleScore), revealed pronounced intratumoral heterogeneity, particularly within osteoblastic cells. A composite GRG score correlated with 641 genes, defining 188 differentially expressed genes; intersecting positively correlated and up-regulated genes yielded 91 candidates. Through a 10-fold cross-validated benchmark of 10 machine-learning algorithms and 101 combinations, Step-Cox [forward] + Ridge emerged as the optimal pipeline, producing a five-gene prognostic model (GPX7, COL11A2, CPE, MSMO1, SGMS2) with moderate yet reproducible performance in independent cohorts. Functionally, stable MSMO1 knockdown in U2OS cells suppressed proliferation, migration, and invasion; increased apoptosis; altered GS, GLS, and α-ketoglutarate; and dampened Wnt/β-catenin signaling. Clinically, the model stratifies OS patients into molecular risk subgroups with distinct outcomes, supporting identification of high-risk individuals and informing personalized glutamine-targeted or combination therapies. Mechanistically, glutamine metabolism shapes the OS tumor microenvironment by modulating immune-evasion and angiogenic cues, underscoring its dual role in metabolic adaptation and immune–metabolic crosstalk. Collectively, this study establishes a single-cell–anchored, glutamine-coupled state in OS, introduces an externally validated prognostic tool with translational promise but modest discriminative power, and positions MSMO1 as a metabolic–signaling node warranting further mechanistic and in-vivo investigation. Full article

This paper will present in vivo release profiles of Doxorubicin.HCl from halo-spun drug-loaded rubbery porous mats. For the very first time, Fluorescent Organism Bioimaging (FOBI) was used to follow drug release in a live animal model with induced tumors. A new predictive model based on apparent diffusion coefficients to simulate release profiles will also be presented and could have general applications for release profile predictions. Surprisingly, histological evaluation found that the tissue layer forming next to the drug-eluting mats had unordered morphology and only necrotic cells. This is a stunning contrast to the highly regular collagen structure next to mats without the drug, typical of an adverse foreign body type reaction. The findings suggest that this drug-eluting fiber mat can be used as a local chemotherapy approach coupled with mitigation of capsular contracture, the major complication associated with breast reconstruction following mastectomy. Full article

We provide an automated characterization of human retinal cells, i.e., RPE’s based on the non-invasive AO-TFI retinal imaging and PR’s based on the non-invasive AO-FI retinal imaging on a large-scale study involving 171 confirmed healthy eyes from 104 participants of 23 to 80 years old. Comprehensive standard checkups based on SD-OCT and Fondus imaging modalities were carried out by Ophthalmologists from the Luzerner Kantonsspital (LUKS) to confirm the absence of retinal pathologies. AO imaging imaging was performed using the Cellularis^® device and each eye was imaged at various retinal eccentricities. The images were automatically segmented using a dedicated software and RPE and PR cells were identified and morphometric characterizations, such as cell density and area were computed. The results were stratified based on various criteria, such as age, retinal eccentricity, visual acuity, etc. The automatic segmentation was validated independently on a held-out set by five trained medical students not involved in this study. We plotted cell density variations as a function of eccentricity from the fovea along both nasal and temporal directions. For RPE cells, no consistent trend in density was observed between 0° to 9° eccentricity, contrasting with established histological literature demonstrating foveal density peaks. In contrast, PR cell density showed a clear decrease from 2.5° to 9°. RPE cell density declined linearly with age, whereas no age-related pattern was detected for PR cell density. On average, RPE cell density was found to be ≈6313 cells/mm² ($\pm \sigma =757$), while the average PR cell density was calculated as ≈10,207 cells/mm² ($\pm \sigma =1273$). Full article

Nanotheranostics combines therapeutic and diagnostic functions within multifunctional nanoparticle platforms to enable precision medicine. This review outlines a comprehensive framework for engineering nanotheranostic systems, focusing on core material composition, surface functionalization, and stimuli-responsive drug delivery. Targeting strategies—from ligand-based recognition to biomimetic interfaces—are examined alongside therapeutic modalities such as chemotherapy, photothermal and photodynamic therapies, gene silencing via RNA interference, and radio sensitization. We discuss advanced imaging techniques (fluorescence imaging FI), magnetic resonance imaging (MRI), positron emission tomography (PET), and photoacoustic imaging for real-time tracking and treatment guidance. Key considerations include physicochemical characterization (e.g., article size, surface charge, and morphology), biocompatibility, in-vitro efficacy, and in-vivo biodistribution. We also address challenges such as rapid biological clearance, tumor heterogeneity, and clinical translation, and propose future directions for developing safe, adaptable, and effective nanotheranostic platforms. This review serves as a roadmap for advancing next-generation nano systems in biomedical applications. Full article

The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), catalyzed unprecedented innovation in molecular diagnostics to address critical gaps in rapid pathogen detection. Over the past five years, CRISPR-based systems, isothermal amplification techniques, and portable biosensors have emerged as transformative tools for nucleic acid detection, offering improvements in speed, sensitivity, and point-of-care applicability compared to conventional PCR. While numerous reviews have cataloged the technical specifications of these platforms, a critical gap remains in understanding the strategic and economic hurdles to their real-world implementation. This review provides a forward-looking analysis of the feasibility, scalability, and economic benefits of integrating these next-generation technologies into future pandemic-response pipelines. We synthesize advances in coronavirus-specific diagnostic platforms and attempt to highlight the need for their implementation as a cost-saving measure during surges in clinical demand. We evaluate the feasibility of translating these technologies—particularly CRISPR-Cas integration with recombinase polymerase amplification (RPA)—into robust first-line diagnostic pipelines for novel viral threats. By analyzing the evolution of diagnostic strategies during the COVID-19 era, we aim to provide strategic insights and new directions for developing and deploying effective detection platforms to better confront future viral pandemics. Full article