Search Results (3,665)

Cardiovascular diseases remain a leading cause of mortality in the United States, driving the need for advanced cardiovascular devices and pharmaceuticals. Mock Circulatory Loops (MCLs) have emerged as essential tools for in vitro testing, replicating pulsatile pressure and flow to simulate various physiological and pathological conditions. While many studies focus on custom MCL designs tailored to specific applications, few have systematically reviewed their use in device testing, and none have assessed their broader utility across diverse biomedical domains. This comprehensive review categorizes MCL designs into three types: mechanical, computational, and hybrid. Applications are classified into four major areas: Cardiovascular Devices Testing, Clinical Training and Education, Hemodynamics and Blood Flow Studies, and Disease Modeling. Most existing MCLs are complex, highly specialized, and difficult to reproduce, highlighting the need for simplified, standardized, and programmable hybrid systems. Improved validation and waveform fidelity—particularly through incorporation of the dicrotic notch and other waveform parameters—are critical for advancing MCL reliability. Furthermore, integration of machine learning and artificial intelligence holds significant promise for enhancing waveform analysis, diagnostics, predictive modeling, and personalized care. In conclusion, the development of MCLs should prioritize standardization, simplification, and broader accessibility to expand their impact across biomedical research and clinical translation. Full article

The development of bioactive materials in endodontics has advanced tissue regeneration by enhancing the biological responses of periradicular tissues. Recently, calcium silicate-based sealers have gained attention for their superior biological properties, including biocompatibility, osteoconductivity, and cementogenic potential. This study aimed to evaluate the cytotoxicity, biocompatibility, and bioactivity of EndoSequence BC Sealer (ES BC) and AH Plus Bioceramic Sealer (AHP BC) using human periodontal ligament stromal cells (hPDLSCs). Biocompatibility was assessed using MTT, Live/Dead, and wound healing assays. ES BC and AHP BC demonstrated significantly higher cell viability and proliferation compared to AH Plus used as a control. Gene expression analysis via real-time quantitative PCR demonstrated that ES BC, especially in set form, significantly upregulated osteogenic markers—alkaline phosphatase (2.49 ± 0.10, p < 0.01), runt-related transcription factor 2 (2.33 ± 0.13), and collagen type I alpha 1 chain (2.85 ± 0.40, p < 0.001)—more than cementogenic markers (cementum protein 1, cementum attachment protein, and cementum protein 23). This differential response may reflect the fibroblast-dominant nature of hPDLSCs, which contain limited cementoblast-like cells. This study supports the superior biocompatibility and regenerative capacity of ES BC and AHP BC compared to AH Plus. While in vitro models provide foundational insights, advanced ex vivo approaches are crucial for translating findings to clinical practice. Full article

Histone post-translational modifications (PTMs) have emerged as promising epigenetic biomarkers with increasing forensic relevance. Unlike conventional genetic markers such as short tandem repeats (STRs), histone modifications can offer additional layers of biological information, capturing individual-specific regulatory states and remaining detectable even in degraded forensic samples. This review highlights recent advances in understanding histone PTMs in forensic contexts, focusing on three key domains: analysis of degraded biological evidence, differentiation of monozygotic (MZ) twins, and postmortem interval (PMI) estimation. We summarize experimental findings from human cadavers, animal models, and typical forensic samples including bone, blood, and muscle, illustrating the stability and diagnostic potential of marks such as H3K4me3, H3K27me3, and γ-H2AX. Emerging technologies including CUT&Tag, MALDI imaging, and nanopore-based sequencing offer novel opportunities to profile histone modifications at high resolution and low input. Despite technical challenges, these findings support the feasibility of histone-based biomarkers as complementary tools for forensic identification and temporal analysis. Future work should prioritize methodological standardization, inter-laboratory validation, and integration into forensic workflows. However, the forensic applicability of these modifications remains largely unvalidated, and further studies are required to assess their reliability in casework contexts. Full article

Intravascular biosensors have become a crucial and novel class of devices in healthcare, enabling the constant real-time monitoring of essential physiological parameters directly within the circulatory system. Recent developments in micro- and nanotechnology have relevantly improved the sensitivity, miniaturization, and biocompatibility of these devices, thereby enabling their application in precision medicine. This review summarizes the latest advances in intravascular biosensor technologies, with a special focus on glucose and oxygen level monitoring, blood pressure and heart rate assessment, and early disease diagnostics, as well as modern approaches to drug therapy monitoring and delivery systems. Key challenges such as long-term biostability, signal accuracy, and regulatory approval processes are critical considerations. Innovative strategies, including biodegradable implants, nanomaterial-functionalized surfaces, and integration with artificial intelligence, are regarded as promising avenues to overcome current limitations. This review provides a comprehensive roadmap for upcoming research and the clinical translation of advanced intravascular biosensors with a strong emphasis on their transformative impact on personalized healthcare. Full article

Healing large bone defects remains challenging. Gelatin scaffolds are biocompatible and biodegradable, but lack osteoinductive activity. Plant-derived exosomes carry miRNAs, growth factors, and proteins that modulate osteogenesis, but free exosomes suffer from poor stability, limited targeting, and low bioavailability in vivo. We developed a 3D GelMA hydrogel loaded with Epimedium-derived exosomes (“GelMA@Exo”) to improve exosome retention, stability, and sustained release. Its effects on MC3T3-E1 preosteoblasts—including proliferation, osteogenic differentiation, migration, and senescence—were evaluated via in vitro assays. Angiogenic potential was assessed using HUVECs. Underlying mechanisms were examined at transcriptomic and protein levels to elucidate GelMA@Exo’s therapeutic osteogenesis actions. GelMA@Exo exhibited sustained exosome release, enhancing exosome retention and cellular uptake. In vitro, GelMA@Exo markedly boosted MC3T3-E1 proliferation, migration, and mineralized nodule formation, while reducing senescence markers and promoting angiogenesis in HUVECs. Mechanistically, GelMA@Exo upregulated key osteogenic markers (RUNX2, TGF-β1, Osterix, COL1A1, ALPL) and activated the PI3K/Akt pathway. Transcriptomic data confirmed global upregulation of osteogenesis-related genes and bone-regeneration pathways. This study presents a GelMA hydrogel functionalized with plant-derived exosomes, which synergistically provides osteoinductive stimuli and structural support. The GelMA@Exo platform offers a versatile strategy for localized delivery of natural bioactive molecules and a promising approach for bone tissue engineering. Our findings provide strong experimental evidence for the translational potential of plant-derived exosomes in regenerative medicine. Full article

Pseudomonas aeruginosa poses significant health threats due to its multidrug-resistant profile, particularly affecting immunocompromised individuals. The pathogen’s ability to produce virulence factors and antibiotic-resistant biofilms, orchestrated through quorum-sensing (QS) mechanisms, complicates conventional therapeutic interventions. This review aims to critically assess the potential of anti-QS strategies as alternatives to antibiotics against P. aeruginosa infections. Comprehensive literature searches were conducted using databases such as PubMed, Scopus, and Web of Science, focusing on studies addressing QS inhibition strategies published recently. Anti-QS strategies significantly attenuate bacterial virulence by disrupting QS-regulated genes involved in biofilm formation, motility, toxin secretion, and immune evasion. These interventions reduce the selective pressure for resistance and enhance antibiotic efficacy when used in combination therapies. Despite promising outcomes, practical application faces challenges, including specificity of inhibitors, pharmacokinetic limitations, potential cytotoxicity, and bacterial adaptability leading to resistance. Future perspectives should focus on multi-target QS inhibitors, advanced delivery systems, rigorous preclinical validations, and clinical translation frameworks. Addressing current limitations through multidisciplinary research can lead to clinically viable QS-targeted therapies, offering sustainable alternatives to traditional antibiotics and effectively managing antibiotic resistance. Full article

The advancement of artificial intelligence (AI), deep learning, and radiomics has introduced novel methodologies for the detection, classification, prognosis, and treatment evaluation of pancreatic ductal adenocarcinoma (PDAC). As the integration of AI into medical imaging continues to evolve, its potential to enhance early detection, refine diagnostic precision, and optimize treatment strategies becomes increasingly evident. However, despite significant progress, various challenges remain, particularly in terms of clinical applicability, generalizability, interpretability, and integration into routine practice. Understanding the current state of research is crucial for identifying gaps in the literature and exploring opportunities for future advancements. This literature review aims to provide a comprehensive overview of the existing studies on AI applications in PDAC, with a focus on disease detection, classification, survival prediction, treatment response assessment, and radiogenomics. By analyzing the methodologies, findings, and limitations of these studies, we aim to highlight the strengths of AI-driven approaches while addressing critical gaps that hinder their clinical translation. Furthermore, this review aims to discuss future directions in the field, emphasizing the need for multi-institutional collaborations, explainable AI models, and the integration of multi-modal data to advance the role of AI in personalized medicine for PDAC. Full article

This study presents the first systematic evaluation of in-context learning for Tarifit machine translation, a low-resource Amazigh language spoken by 5 million people in Morocco and Europe. We assess three large language models (GPT-4, Claude-3.5, PaLM-2) across Tarifit–Arabic, Tarifit–French, and Tarifit–English translation using 1000 sentence pairs and 5-fold cross-validation. Results show that 8-shot similarity-based demonstration selection achieves optimal performance. GPT-4 achieved 20.2 BLEU for Tarifit–Arabic, 14.8 for Tarifit–French, and 10.9 for Tarifit–English. Linguistic proximity significantly impacts translation quality, with Tarifit–Arabic substantially outperforming other language pairs by 8.4 BLEU points due to shared vocabulary and morphological patterns. Error analysis reveals systematic issues with morphological complexity (42% of errors) and cultural terminology preservation (18% of errors). This work establishes baseline benchmarks for Tarifit translation and demonstrates the viability of in-context learning for morphologically complex low-resource languages, contributing to linguistic equity in AI systems. Full article

Melittin, a cytolytic peptide derived from honeybee venom, has demonstrated potent anticancer activity through mechanisms such as membrane disruption, apoptosis induction, and modulation of key signaling pathways. Melittin exerts its anticancer activity by interacting with key molecular targets, including downregulation of the PI3K/Akt and NF-κB signaling pathways, and by inducing mitochondrial apoptosis through reactive oxygen species generation and cytochrome c release. However, its clinical application is hindered by its systemic and hemolytic toxicity, rapid degradation in plasma, poor pharmacokinetics, and immunogenicity, necessitating the development of targeted delivery strategies to enable safe and effective treatment. Nanoparticle-based delivery systems have emerged as a promising strategy for overcoming these challenges, offering improved tumor targeting, reduced off-target effects, and enhanced stability. This review provides a comprehensive overview of the mechanisms through which melittin exerts its anticancer effects and evaluates the development of various melittin-loaded nanocarriers, including liposomes, polymeric nanoparticles, dendrimers, micelles, and inorganic systems. It also summarizes the preclinical evidence for melittin nanotherapy across a wide range of cancer types, highlighting both its cytotoxic and immunomodulatory effects. The potential of melittin nanoparticles to overcome multidrug resistance and synergize with chemotherapy, immunotherapy, photothermal therapy, and radiotherapy is discussed. Despite promising in vitro and in vivo findings, its clinical translation remains limited. Key barriers include toxicity, manufacturing scalability, regulatory approval, and the need for more extensive in vivo validation. A key future direction is the application of computational tools, such as physiologically based pharmacokinetic modeling and artificial-intelligence-based modeling, to streamline development and guide its clinical translation. Addressing these challenges through focused research and interdisciplinary collaboration will be essential to realizing the full therapeutic potential of melittin-based nanomedicines in oncology. Overall, this review synthesizes the findings from over 100 peer-reviewed studies published between 2008 and 2025, providing an up-to-date assessment of melittin-based nanomedicine strategies across diverse cancer types. Full article

Objective: Hearing rehabilitation using hearing aids keeps increasing in the general population. Patient-related outcome measures are essential to evaluate benefits. Although the IOI-HA is routinely used in France, its translated version from 2002 has never been validated. This study aimed to assess the psychometric properties of the French version of the IOI-HA questionnaire. Design: Controlled, prospective, monocentric study performed between February 2024 and January 2025. The forward–backward technique was used for translation of the questionnaire. Study Sample: 100 patients fitted with hearing aids completed the questionnaire. Thirty-five patients were retested 15 days after first completion. Results: Internal consistency, assessed by Cronbach’s alpha, was 0.863. Mean IOI-HA item scores ranged from 3.3 to 4.57. All seven items had a high degree of consistency with the total score, except for item Q1 which had a moderate score (0.45). Cronbach’s alpha after item deletion confirmed internal consistency. Intra-class correlation coefficients ranged from 0.622 (Q7) to 0.767 (Q5) and were all statistically significant (p < 0.001), revealing high reliability over time. No significant correlation was found between item scores and age, unilateral or bilateral hearing aid use or accompanying symptoms (tinnitus, dizziness). Conclusions: The French translation of the IOI-HA questionnaire, published in 2002, is a valid and reliable questionnaire evaluating hearing aid satisfaction. This validated questionnaire can now be used in daily clinical practice. Full article

Background/Objectives: The diminished efficacy of azoles in treating fungal infections is attributed to the emergence of resistance among pathogenic fungi. Employing a synergistic approach with other compounds to enhance the antifungal activity of azoles has shown promise, yet the availability of clinically valuable adjuvants for azoles and allylamines remains limited. Studies have demonstrated that the human host environment provides multiple carbon sources, which can influence the susceptibility of C. albicans to antifungal agents. Therefore, a comprehensive investigation into the mechanisms by which carbon sources modulate the susceptibility of C. albicans to azoles may uncover a novel pathway for enhancing the antifungal efficacy of azoles. Methods: This study explored the impact of various carbon sources on the antifungal efficacy of azoles through methodologies including minimum inhibitory concentration (MIC) assessments, super-MIC growth (SMG) assays, disk diffusion tests, and spot assays. Additionally, the mechanism by which galactose augments the antifungal activity of azoles was investigated using a range of experimental approaches, such as gene knockout and overexpression techniques, quantitative real-time PCR (qRT-PCR), Western blot analysis, and cycloheximide (CHX) chase experiments. Results: This study observed that galactose enhances the efficacy of azoles against C. albicans by inhibiting the translation of Erg1. This results in the suppression of Erg1 protein levels and subsequent inhibition of ergosterol biosynthesis in C. albicans. Conclusions: In C. albicans, the translation of Erg1 is inhibited when galactose is utilized as a carbon source instead of glucose. This novel discovery of galactose’s inhibitory effect on Erg1 translation is expected to enhance the antifungal efficacy of azoles. Full article

Background: Claustrophobia is defined as the fear of enclosed spaces, and it is a rather common specific phobia. Although the Claustrophobia Questionnaire (CLQ) is a valid questionnaire to measure claustrophobia, there have been no studies validating this tool in Greek. Thus, our aim was to translate and validate the CLQ in Greek. Methods: We applied the forward–backward translation method to translate the English CLQ into Greek. We conducted confirmatory factor analysis (CFA) to examine the two-factor model of the CLQ. We examined the convergent and divergent validity of the Greek CLQ by using the Fear Survey Schedule-III (FSS-III-CL), the NEO Five-Factor Inventory (NEO-FFI-NL-N), and the Spielberger’s State-Trait Anxiety Inventory (STAI). We examined the convergent validity of the Greek CLQ by calculating Pearson’s correlation coefficient between the CLQ scores and scores on FSS-III-CL, NEO-FFI-NL-N, STAI-S (state anxiety), and STAI-T (trait anxiety). We examined the divergent validity of the Greek CLQ using the Fisher r-to-z transformation. To further evaluate the discriminant validity of the CLQ, we calculated the average variance extracted (AVE) score and the Composite Reliability (CR) score. We calculated the intraclass correlation coefficient (ICC) and Cronbach’s alpha to assess the reliability of the Greek CLQ. Results: Our CFA confirmed the two-factor model of the CLQ since all the model fit indices were very good. Standardized regression weights between the 26 items of the CLQ and the two factors ranged from 0.559 to 0.854. The convergent validity of the Greek CLQ was very good since it correlated strongly with the FSS-III-CL and moderately with the NEO-FFI-NL-N and the STAI. Additionally, the Greek CLQ correlated more highly with the FSS-III-CL than with the NEO-FFI-NL-N and the STAI, indicating very good divergent validity. The AVE for the suffocation factor was 0.573, while for the restriction factor, it was 0.543, which are both higher than the acceptable value of 0.50. Moreover, the CR score for the suffocation factor was 0.949, while for the restriction factor, it was 0.954. The reliability of the Greek CLQ was excellent since the ICC in test–retest study was 0.986 and the Cronbach’s alpha was 0.956. Conclusions: The Greek version of the CLQ is a reliable and valid tool to measure levels of claustrophobia among individuals. Full article

Water governance in Europe faces mounting challenges from climate change, demographic pressures, and aging infrastructure—especially in Southern regions increasingly affected by drought and institutional fragmentation. In contrast, Nordic countries such as Denmark and Sweden exhibit coherent, integrated governance systems with strong regulatory oversight. This study introduces the Water Governance Maturity Index (WGMI), a document-based assessment tool designed to evaluate national water governance across five dimensions: institutional capacity, operational effectiveness, environmental ambition, equity, and climate adaptation. Applying the WGMI to eight EU countries—four Nordic and four Southern—reveals a persistent North–South divide in governance maturity. Nordic countries consistently score in the “advanced” or “model” range, while Southern countries face systemic gaps in implementation, climate integration, and territorial inclusion. Based on these findings, the study offers actionable policy recommendations, including the establishment of independent regulators, strengthening of river basin coordination, mainstreaming of climate-water strategies, and expansion of affordability and participation mechanisms. By translating complex governance principles into measurable indicators, the WGMI provides a practical tool for benchmarking reform progress and supporting the EU’s broader agenda for just resilience and climate adaptation. Unlike broader frameworks like SDG 6.5.1, the WGMI’s document-based, dimension-specific approach provides granular, actionable insights for governance reform, enhancing its utility for EU and global policymakers. Full article

Background/Objectives: There is a growing need for autism spectrum disorder (ASD) assessment tools that are diagnostically aligned, clinically usable, and accessible across diverse service contexts. The Diagnostic Autism Spectrum Interview—Version 2 (DASI-2) is a freely available, semi-structured clinical interview mapped directly to DSM-5 and ICD-11 criteria. This pilot study aimed to adapt DASI-2 into Hungarian and explore the (1) acceptability of DASI-2 administration, (2) agreement with prior clinical ASD diagnoses, and (3) relationship between DASI-2 observational ratings and ADOS-2 classifications. Methods: Following a multistep translation procedure, DASI-2 was administered to seven children previously assessed for ASD in a multidisciplinary Hungarian clinical setting. The assessment included a parent interview, direct assessment with the child or young person, and completion of the DASI observational record (OR1–OR4). DASI diagnostic outcomes were compared with prior clinical decisions, and OR scores were analyzed in relation to ADOS-2 classifications. Results: All participants completed the DASI-2 interview in full. Agreement with prior clinical diagnosis was found in six of seven cases (κ = 0.70, indicating substantial agreement). When exploring the one non-aligned case, the divergence in diagnostic outcome was due to broader contextual information considered by the initial clinical team which influenced clinical opinion. The five participants diagnosed with ASD showed substantially higher DASI observational scores (mean = 15.26) than the two who were not diagnosed (mean = 1.57), mirroring ADOS-2 severity classifications. Conclusions: These findings support the acceptability and preliminary validity of DASI-2. Its inclusive structured observational record may provide a practical complement to resource-intensive tools such as the ADOS-2; however, further validation in larger and more diverse samples is needed. Full article

A wide range of strategies have been developed to modulate dysfunctional brain activities. This narrative review provides a comparative analysis of biophysical, genetic, and biological neuromodulation approaches with an emphasis on their known or unknown molecular targets and translational potential. The review incorporates data from both preclinical and clinical studies covering deep brain stimulation, transcranial electrical and magnetic stimulation, focused ultrasound, chemogenetics, optogenetics, magnetogenetics, and toxin-based neuromodulation. Each method was assessed based on specificity, safety, reversibility, and mechanistic clarity. Biophysical methods are widely used in clinical practice but often rely on empirical outcomes due to undefined molecular targets. Genetic tools offer cell-type precision in experimental systems but face translational barriers related to delivery and safety. Biological agents, such as botulinum neurotoxins, provide long-lasting yet reversible inhibition via well-characterized molecular pathways. However, they require stereotaxic injections and remain invasive. To overcome individual limitations and improve targeting, delivery, and efficacy, there is a growing interest in the synthesis of multiple approaches. This review highlights a critical gap in the mechanistic understanding of commonly used methods. Addressing this gap by identifying molecular targets may help to improve therapeutic precision. This concise review could be valuable for researchers looking to enter the evolving field of the neuromodulation of brain function. Full article