Search Results (5,507)

Breast cancer is the leading cause of cancer-related mortality among women world-wide, and early screening is critical for improving patient survival. Medical imaging plays a central role in breast cancer screening, diagnosis, and treatment monitoring. However, conventional imaging modalities—including mammography, ultrasound, and magnetic resonance imaging—face limitations such as low diagnostic specificity, relatively slow imaging speed, ionizing radiation exposure, and dependence on exogenous contrast agents. Photoacoustic imaging (PAI), a novel hybrid imaging technique that combines optical contrast with ultrasonic spatial resolution, has shown great promise in addressing these challenges. By revealing anatomical, functional, and molecular features of the breast tumor microenvironment, PAI offers high spatial resolution, rapid imaging, and minimal operator dependence. This review outlines the fundamental principles of PAI and systematically examines recent advances in its application to breast cancer screening, diagnosis, and therapeutic evaluation. Furthermore, we discuss the translational potential of PAI as an emerging breast imaging modality, complementing existing clinical techniques. Full article

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with early-life origins. Maternal obesity has been associated with increased ASD risk, yet the mechanisms and timing of susceptibility remain unclear. Using a mouse model combining in vitro fertilization (IVF) and embryo transfer, we separated the effects of pre-conception and gestational obesity. We found that maternal high fat diet (HFD) exposure prior to conception alone was sufficient to induce ASD-like behaviors in male offspring—including altered vocalizations, reduced sociability, and increased repetitive grooming—without anxiety-related changes. These phenotypes were absent in female offspring and those exposed only during gestation. Cortical transcriptome analysis revealed dysregulation and isoform shifts in genes implicated in ASD, including Homer1 and Zswim6. Whole-genome bisulfite sequencing of hippocampal tissue showed hypomethylation of an alternative Homer1 promoter, correlating with increased expression of the short isoform Homer1a, which is known to disrupt synaptic scaffolding. This pattern was specific to mice with ASD-like behaviors. Our findings show that pre-conceptional maternal obesity can lead to lasting, isoform-specific transcriptomic and epigenetic changes in the offspring’s brain. These results underscore the importance of maternal health before pregnancy as a critical and modifiable factor in ASD risk. Full article

The emergence and spread of antimicrobial resistance among pathogens are significantly reducing available therapeutic options, highlighting the urgent need for novel and complementary treatment strategies. Antimicrobial photodynamic therapy (aPDT) is a promising alternative approach that can overcome antimicrobial resistance through a multitarget mechanism of action, exerting direct bactericidal and fungicidal effects with minimal risk of resistance development. Although aPDT has shown efficacy against a variety of pathogens, data on its activity against large collections of clinical multidrug-resistant strains are still limited. In this study, we assessed the antimicrobial activity of the photosensitizer RLP068/Cl combined with a red light-emitting LED source at 630 nm (Molteni Farmaceutici, Italy) against a large panel of Gram-negative and Gram-positive bacterial strains harboring relevant resistance traits and Candida species. Our results demonstrated the significant microbicidal activity of RLP068/Cl against all of the tested strains regardless of their resistance phenotype, with particularly prominent activity against Gram-positive bacteria (range of bactericidal concentrations 0.05–0.1 µM), which required significantly lower exposure to photosensitizer compared to Candida and Gram-negative species (range 5–20 µM). Overall, these findings support the potential use of RLP068/Cl-mediated aPDT as an effective therapeutic strategy for the management of localized infections caused by MDR organisms, particularly when conventional therapeutic options are limited. Full article

Cardiorenal syndrome (CRS) is a term used to describe the combined dysfunction of the heart and kidneys. This complex disorder is widely acknowledged to be challenging in both its diagnosis and management, and this is the case particularly in the elderly population, due to multi-morbidity, polypharmacy, and age-related physiological changes. Given advancements in medicine and more prolonged cumulative exposure to risk factors in the elderly population, it is likely that the prevalence of chronic kidney disease (CKD) and heart failure (HF) will continue to rise going forward. Hence, understanding the mechanisms involved in the development of CRS is paramount. There are five different CRS types—they are categorised depending on the primary organ involved the acuity of disease. The pathophysiological process behind CRS is complex, involving the interplay of many processes including hemodynamic changes, neurohormonal activation, inflammation, oxidative stress, and endothelial dysfunction and vascular stiffness. The numerous diagnostic and management challenges associated with CRS are significantly further exacerbated in an elderly population. Biomarkers used to aid the diagnosis of CRS, such as serum creatinine and brain natriuretic peptide (BNP), can be challenging to interpret in the elderly population due to age-related renal senescence and multiple comorbidities. Polypharmacy can contribute to the development of CRS and therefore, before initiating treatment, coordinating a patient-centred, multi-speciality, holistic review to assess potential risks versus benefits of prescribed treatments is crucial. The overall prognosis of CRS in the elderly remains poor. Treatments are primarily directed at addressing the sequelae of the underlying aetiology, which often involves the removal of fluid through diuretics or ultrafiltration. Careful considerations when managing elderly patients with CRS is essential due to the high prevalence of frailty and functional decline. As such, in these patients, early discussions around advance care planning should be prioritised. Full article

This study presents an integrated geospatial framework for assessing the risk to high-speed railway (HSR) infrastructure, combining a persistent scatterer interferometric synthetic aperture radar (PS-InSAR) analysis with multi-criteria decision-making in a geographic information system (GIS) environment. Focusing on the Honam HSR corridor in South Korea, the model incorporates both maximum ground deformation and subsidence velocity to construct a dynamic hazard index. Social vulnerability is quantified using five demographic and infrastructural indicators, and a two-stage analytic hierarchy process (AHP) is applied with dependency correction to mitigate inter-variable redundancy. The resulting high-resolution risk maps highlight spatial mismatches between geotechnical hazards and social exposure, revealing vulnerable segments in Gongju and Iksan that require prioritized maintenance and mitigation. The framework also addresses data limitations by interpolating groundwater levels and estimating train speed using spatial techniques. Designed to be scalable and transferable, this methodology offers a practical decision-support tool for infrastructure managers and policymakers aiming to enhance the resilience of linear transport systems. Full article

Breast cancer (BC) progression appears to be significantly influenced by the diabetic microenvironment, characterised by hyperglycaemia and hyperinsulinemia, though the exact cellular mechanisms remain partly unclear. This study investigated the effects of exposure to supra-physiological levels of glucose and insulin on two distinct BC cell models: hormone-responsive MCF-7 cells and triple-negative MDA-MB-231 cells. To evaluate the effects triggered by high insulin level in different BC cell subtypes, we analysed the activation status of PI3K/AKT and MAPK pathways, cell proliferation, cell distribution in cell cycle phases and cell migration. High insulin level significantly activates the insulin metabolic pathway via AKT phosphorylation in both cell lines while inducing pro-proliferative stimulus and modulation of cell distribution in cell cycle phases only in the hormone-responsive MCF-7 cell line. On the contrary, high-glucose containing medium alone did not modulate proliferation nor further increased it when combined with high insulin level in both the investigated cell lines. However, following insulin treatment, the MAPK pathway remained unaffected, suggesting that the proliferation effects in the MCF-7 cell line are mediated by AKT activation. This linkage was also demonstrated by AKT phosphorylation blockade, driven by the AKT inhibitor MK-2206, which negated the proliferative stimulus. Interestingly, while MDA-MB-231 cells, following chronic hyperinsulinemia exposure, did not exhibit enhanced proliferation, they displayed a marked increase in migratory behaviour. These findings suggest that chronic hyperinsulinemia, but not hyperglycaemia, exerts subtype-specific effects in BC, highlighting the potential of targeting insulin pathways for therapeutic intervention. Full article

Environmental risk assessment (ERA) for pesticide approval in the context of predatory insects remains inadequate as it often overlooks the influence of agricultural practices. An increasing number of studies have shown that prolonged and synergistic pesticide exposure can elevate insect mortality. However, such effects remain largely unstudied in non-target predatory carabid beetles. The carabid beetle Platynus assimilis was subjected to repeated oral and continuous contact exposure to low doses of prothioconazole (20 g ha⁻¹), lambda-cyhalothrin (0.4 g ha⁻¹), or their combination over a 64-day period. The food consumption rate, body mass, locomotor activity, and mortality were monitored throughout the experiment. All pesticide-treated groups showed significantly increased final mortality, with median lethal times (LT₅₀) of 51.6 days for prothioconazole, 60.3 days for lambda-cyhalothrin, and 12.2 days for their combination. A significant synergistic effect on mortality was observed in the combined treatment group, with the highest synergistic ratio detected 20 days after the first exposure. Pesticide-treated beetles exhibited significant abnormalities in locomotor activity and body mass compared to the untreated group. These findings demonstrate that both time-cumulative mortality and potential synergistic interactions, reflecting field-realistic conditions, must be considered in ERA. Failure to do so may lead to an underestimation of pesticide toxicity to predatory carabids. Full article

Background/Objectives: Traumatic brain injury (TBI), especially mild TBI (mTBI), is frequently caused by traffic accidents, falls, or sports injuries. Although computed tomography (CT) is the gold standard for diagnosis, overuse can lead to unnecessary radiation exposure, increased healthcare costs, and emergency department saturation. Blood-based biomarkers have emerged as potential tools to optimize CT scan use. This systematic review aims to evaluate recent evidence on the role of specific blood biomarkers in guiding CT decisions in patients with mTBI. Methods: A systematic search was conducted in the PubMed, Cochrane, and CINAHL databases for studies published between 2020 and 2024. Inclusion criteria focused on adult patients with mTBI evaluated using both CT imaging and at least one of the following biomarkers: glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and S100 calcium-binding protein B (S100B). After screening, six studies were included in the final review. Results: All included studies reported high sensitivity and negative predictive value for the selected biomarkers in detecting clinically relevant intracranial lesions. GFAP and UCH-L1, particularly in combination, consistently identified low-risk patients who could potentially forgo CT scans. While S100B also showed high sensitivity, discrepancies in cutoff values across studies highlighted the need for harmonization. Conclusions: Blood biomarkers such as GFAP, UCH-L1, and S100B demonstrate strong potential to reduce unnecessary CT imaging in mTBI by identifying patients at low risk of significant brain injury. Future research should focus on standardizing biomarker thresholds and validating protocols to support their integration into clinical practice guidelines. Full article

Background/Objectives: Growth prediction may be used by the clinical orthodontist in growing individuals for diagnostic purposes and for treatment planning. This process appraises chronological age and determines the degree of skeletal maturity to calculate residual growth. In developmental deviations, overlooking such diagnostic details might culminate in erroneous conclusions, unstable outcomes, recurrence, and treatment failure. The present review aims to systematically present and explain the available means for predicting growth in humans. Traditional, long-known, popular methods are discussed, and modern digital applications are described. Materials and methods: A search on PubMed and the gray literature up to May 2025 produced 69 eligible studies on future maxillofacial growth prediction without any orthodontic intervention. Results: Substantial variability exists in the studies on growth prediction. In young orthodontic patients, the study of the lateral cephalometric radiography and the subsequent calculation of planes and angles remain questionable for diagnosis and treatment planning. Skeletal age assessment is readily accomplished with X-rays of the cervical vertebrae and the hand–wrist region. Computer software is being implemented to improve the reliability of classic methodologies. Metal implants have been used in seminal growth studies. Biochemical methods and electromyography have been suggested for clinical prediction and for research purposes. Conclusions: In young patients, it would be of importance to reach conclusions on future growth with minimal distress to the individual and, also, reduced exposure to ionizing radiation. Nevertheless, the potential for comprehensive prediction is still largely lacking. It could be accomplished in the future by combining established methods with digital technology. Full article

Background and Objectives: Lower limb defects often present significant reconstructive challenges due to limited soft tissue availability and exposure of critical structures. Perforator-based flaps offer reliable solutions, with minimal donor site morbidity. This study aimed to evaluate the efficacy of infrared thermography (IRT) in preoperative planning and postoperative monitoring of perforator-based flaps, assessing its accuracy in identifying perforators, predicting complications, and optimizing outcomes. Materials and Methods: A prospective observational study was conducted on 76 patients undergoing lower limb reconstruction with fascio-cutaneous perforator flaps between 2022 and 2024. Perforator mapping was performed concurrently with IRT and Doppler ultrasonography (D-US), with intraoperative confirmation. Flap design variables and systemic parameters were recorded. Postoperative monitoring employed thermal imaging on days 1 and 7. Outcomes were correlated with thermal, anatomical, and systemic factors using statistical analyses, including t-tests and Pearson correlation. Results: IRT showed high sensitivity (97.4%) and positive predictive value (96.8%) for perforator detection. A total of nine minor complications occurred, predominantly in patients with diabetes mellitus and/or elevated glycemia (p = 0.05). Larger flap-to-defect ratios (A/C and B/C) correlated with increased complications in propeller flaps, while smaller ratios posed risks for V-Y and Keystone flaps. Thermal analysis indicated significantly lower flap temperatures and greater temperature gradients in flaps with complications by postoperative day 7 (p < 0.05). CRP levels correlated with glycemia and white blood cell counts, highlighting systemic inflammation’s impact on outcomes. Conclusions: IRT proves to be a reliable, non-invasive method for perforator localization and flap monitoring, enhancing surgical planning and early complication detection. Combined with D-US, it improves perforator selection and perfusion assessment. Thermographic parameters, systemic factors, and flap design metrics collectively predict flap viability. Integration of IRT into surgical workflows offers a cost-effective tool for optimizing reconstructive outcomes in lower limb surgery. Full article

Carassius auratus exhibits significant physiological and behavioral alterations under the combined stress of temperature and dissolved oxygen (DO) fluctuations, which are common challenges in aquaculture. In this investigation, we employed controlled thermal and DO gradients to characterize the multidimensional response profile of this species. The key findings revealed that thermal elevation profoundly influenced blood glucose and cortisol concentrations. Notably, exposure to hyperoxic conditions markedly attenuated stress responses relative to hypoxia at equivalent temperatures: cortisol levels were significantly suppressed (reductions of 60.11%, 118.06%, and 34.72%), while blood glucose levels exhibited concurrent increases (16.42%, 26.43%, and 26.34%). Distinctive behavioral patterns, including floating head behavior, surface swimming behavior, and rollover behavior, were identified as indicative behaviors of thermal–oxygen stress. Molecular analysis demonstrated the upregulated expression of stress-associated genes (HSP70, HSP90, HIF-1α, and Prdx3), which correlated temporally with elevated cortisol and glucose concentrations and the manifestation of stress behaviors. Furthermore, a muscle texture assessment indicated that increased DO availability mitigated the textural deterioration induced by heat stress. Collectively, this work establishes an authentic biomarker framework, providing crucial threshold parameters essential for the development of intelligent, real-time environmental monitoring and dynamic regulation systems to enhance climate-resilient aquaculture management. Full article

While boreal forests constitute 30% of the Earth’s forested area and are responsible for 20% of the global carbon sink, there is considerable concern about their sustainability. This paper focuses on the role of elevated CO₂, examining whether wood volume in these forests has responded to increased CO₂ over the last 60 years. To accomplish this, we use a rich set of wood volume measurement data from the Province of Alberta, Canada, and deploy quasi-experimental techniques to determine the effect of elevated CO₂. While the few experimental studies that have examined boreal forests have found almost no effect of elevated CO₂, our results indicate that a 1.0% increase in lifetime exposure to CO₂ leads to a 1.1% increase in aboveground wood volume in these boreal forests. This study showcases the value of research designs that use natural settings to better account for the effects of prolonged exposure to elevated CO₂. Our results should enable improved delineation of the drivers of historical changes in wood volume and carbon storage in boreal forests. In addition, when combined with other studies, these results will likely aid policymakers in designing management or policy approaches that will enhance the sustainability of forests in boreal regions. Full article

Artificial intelligence (AI) has become the mainstream of analysis tools in remote sensing. Various semantic segmentation models have been introduced to segment land cover from aerial or satellite images, and remarkable results have been achieved. However, they often lack universal performance on unseen images, making them challenging to provide as a service. One of the primary reasons for the lack of robustness is overfitting, resulting from errors and inconsistencies in the ground truth (GT). In this study, we propose a method to mitigate these inconsistencies by utilizing redundant models and verify the improvement using a public dataset based on Google Earth images. Redundant models share the same network architecture and hyperparameters but are trained with different combinations of training and validation data on the same dataset. Because of the variations in sample exposure during training, these models yield slightly different inference results. This variability allows for the estimation of pixel-level confidence levels for the GT. The confidence level is incorporated into the GT to influence the loss calculation during the training of the enhanced model. Furthermore, we implemented a consensus model that employs modified masks, where classes with low confidence are substituted by the dominant classes identified through a majority vote from the redundant models. To further improve robustness, we extended the same approach to fuse the dataset with different class compositions based on imagery from the Korea Multipurpose Satellite 3A (KOMPSAT-3A). Performance evaluations were conducted on three network architectures: a simple network, U-Net, and DeepLabV3. In the single-dataset case, the performance of the enhanced and consensus models improved by an average of 2.49% and 2.59% across the network architectures. In the multi-dataset scenario, the enhanced models and consensus models showed an average performance improvement of 3.37% and 3.02% across the network architectures, respectively, compared to an average increase of 1.55% without the proposed method. Full article

Background: Pain is a complex phenomenon characterized by unpleasant experiences with profound heterogeneity influenced by biological, psychological, and social factors. According to the National Health Interview Survey, 50.2 million U.S. adults (20.5%) experience pain on most days, with the annual cost of prescription medication for pain reaching approximately USD 17.8 billion. Theranostic pain nanomedicine therefore emerges as an attractive analgesic strategy with the potential for increased efficacy, reduced side-effects, and treatment personalization. Theranostic nanomedicine combines drug delivery and diagnostic features, allowing for real-time monitoring of analgesic efficacy in vivo using molecular imaging. However, clinical translation of these nanomedicines are challenging due to complex manufacturing methodologies, lack of standardized quality control, and potentially high costs. Quality by Design (QbD) can navigate these challenges and lead to the development of an optimal pain nanomedicine. Our lab previously reported a macrophage-targeted perfluorocarbon nanoemulsion (PFC NE) that demonstrated analgesic efficacy across multiple rodent pain models in both sexes. Here, we report PFC-free, biphasic nanoemulsions formulated with a biocompatible and non-immunogenic plant-based coconut oil loaded with a COX-2 inhibitor and a clinical-grade, indocyanine green (ICG) near-infrared fluorescent (NIRF) dye for parenteral theranostic analgesic nanomedicine. Methods: Critical process parameters and material attributes were identified through the FMECA (Failure, Modes, Effects, and Criticality Analysis) method and optimized using a 3 × 2 full-factorial design of experiments. We investigated the impact of the oil-to-surfactant ratio (w/w) with three different surfactant systems on the colloidal properties of NE. Small-scale (100 mL) batches were manufactured using sonication and microfluidization, and the final formulation was scaled up to 500 mL with microfluidization. The colloidal stability of NE was assessed using dynamic light scattering (DLS) and drug quantification was conducted through reverse-phase HPLC. An in vitro drug release study was conducted using the dialysis bag method, accompanied by HPLC quantification. The formulation was further evaluated for cell viability, cellular uptake, and COX-2 inhibition in the RAW 264.7 macrophage cell line. Results: Nanoemulsion droplet size increased with a higher oil-to-surfactant ratio (w/w) but was no significant impact by the type of surfactant system used. Thermal cycling and serum stability studies confirmed NE colloidal stability upon exposure to high and low temperatures and biological fluids. We also demonstrated the necessity of a solubilizer for long-term fluorescence stability of ICG. The nanoemulsion showed no cellular toxicity and effectively inhibited PGE2 in activated macrophages. Conclusions: To our knowledge, this is the first instance of a celecoxib-loaded theranostic platform developed using a plant-derived hydrocarbon oil, applying the QbD approach that demonstrated COX-2 inhibition. Full article

Background and Clinical Significance: Traumatic dental injuries, particularly complicated crown fractures of permanent incisors, are common in adolescents, with maxillary central incisors most frequently affected due to their prominent position. These injuries, often resulting from sports or accidents, require prompt management to prevent complications such as pulp necrosis or infection, which can compromise long-term prognosis. Fragment reattachment offers a conservative, esthetically favorable approach when the fractured segment is intact, with outcomes comparable to composite restorations. This case report underscores the importance of timely intervention and advanced restorative techniques in pediatric dentistry. Case Presentation: A 16-year-old male presented with a complicated crown fracture of the upper left central incisor sustained during a soccer game. The fracture extended subgingivally with pulp exposure. The patient preserved the fragment in saline. Treatment involved fragment reattachment using a dentin bonding agent and flowable composite resin, followed by single-visit root canal therapy due to delayed presentation (48 h). A glass fiber post was placed to reinforce the restoration due to significant coronal loss. Three years of follow-up visits (1, 3, 6, 12, 24, and 36 months) revealed no clinical or radiographic complications, with the tooth remaining asymptomatic and functional. Conclusions: This case underscores the effectiveness of fragment reattachment when combined with meticulous technique and long-term monitoring. Full article