Search Results (2,339)

Nonsense mutations, responsible for ~11% of gene lesions causing human monogenic diseases, introduce premature termination codons (PTCs) that lead to truncated proteins and nonsense-mediated mRNA decay (NMD). In the central nervous system (CNS), these mutations drive severe, progressive neurological conditions such as spinal muscular atrophy, Rett syndrome, and Duchenne muscular dystrophy. Readthrough therapies—strategies to override PTCs and restore full-length protein expression—have evolved from early aminoglycosides to modern precision tools including suppressor tRNAs, RNA editing, and CRISPR-based platforms. Yet clinical translation remains hampered by inefficient CNS delivery, variable efficacy, and the absence of personalized stratification. In this review, we propose a translational framework—the 4 Ds of Readthrough Therapy—to systematically address these barriers. The framework dissects the pipeline into Detection (precision patient identification and biomarker profiling), Delivery (engineered vectors for CNS targeting), Decoding (context-aware molecular correction), and Durability (long-term safety and efficacy). By integrating advances in machine learning, nanocarriers, base editing, and adaptive trial designs, this roadmap provides a structured strategy to bridge the translational gap. We advocate that a synergistic, modality-tailored approach will transform nonsense suppression from palliative care to durable, precision-based cures for once-untreatable neurological disorders. Full article

Artificial intelligence (AI) is rapidly reshaping adult cardiac surgery, enabling more accurate diagnostics, personalized risk assessment, advanced surgical planning, and proactive postoperative care. Preoperatively, deep-learning interpretation of ECGs, automated CT/MRI segmentation, and video-based echocardiography improve early disease detection and refine risk stratification beyond conventional tools such as EuroSCORE II and the STS calculator. AI-driven 3D reconstruction, virtual simulation, and augmented-reality platforms enhance planning for structural heart and aortic procedures by optimizing device selection and anticipating complications. Intraoperatively, AI augments robotic precision, stabilizes instrument motion, identifies anatomy through computer vision, and predicts hemodynamic instability via real-time waveform analytics. Integration of the Hypotension Prediction Index into perioperative pathways has already demonstrated reductions in ventilation duration and improved hemodynamic control. Postoperatively, machine-learning early-warning systems and physiologic waveform models predict acute kidney injury, low-cardiac-output syndrome, respiratory failure, and sepsis hours before clinical deterioration, while emerging closed-loop control and remote monitoring tools extend individualized management into the recovery phase. Despite these advances, current evidence is limited by retrospective study designs, heterogeneous datasets, variable transparency, and regulatory and workflow barriers. Nonetheless, rapid progress in multimodal foundation models, digital twins, hybrid OR ecosystems, and semi-autonomous robotics signals a transition toward increasingly precise, predictive, and personalized cardiac surgical care. With rigorous validation and thoughtful implementation, AI has the potential to substantially improve safety, decision-making, and outcomes across the entire cardiac surgical continuum. Full article

Background/Objectives: Peritoneal metastases (PMs) remain difficult to treat because the peritoneum–plasma barrier limits drug penetration from the systemic circulation. Intraperitoneal chemotherapy (IPC), particularly repeated intraperitoneal (IP) administration via implantable ports, can achieve high local drug exposure with prolonged retention. This review summarizes the pharmacological rationale, clinical evidence, and future directions of catheter-based IPC, with emphasis on combined IP and systemic chemotherapy for ovarian, gastric, and pancreatic cancers. Methods: We narratively reviewed prospective clinical trials and key retrospective studies evaluating IPC and compared repeated catheter-based IPC with hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC). Efficacy, safety, practice considerations, and opportunities for ascites-based monitoring were examined. Results: In ovarian cancer, several randomized trials demonstrated improved progression-free survival (PFS), and in selected trials, improved overall survival (OS) was demonstrated using IP plus intravenous (IV) therapy, although in the latter trials, toxicity and catheter-related complications limited treatment completion. A phase III Intraperitoneal Therapy for Ovarian Cancer with Carboplatin (iPocc) trial further showed significantly prolonged PFS with IP carboplatin and weekly paclitaxel, with non-catheter-related toxicity comparable to that of IV therapy. In gastric and pancreatic cancer, phase II studies reported symptomatic control, cytologic conversion, and higher rates of conversion surgery in selected patients, although confirmatory phase III data are limited. Device complications, including infection, obstruction, and leakage, occurred, but were manageable. Conclusions: Repeated catheter-based IPC is a feasible approach that enhances intraperitoneal drug delivery and complements IV chemotherapy. Future priorities include randomized trials, pharmacokinetic optimization, and biomarker-guided patient selection, supported by serial ascites assessment to refine indications and improve outcomes. Full article

Background: Antibiotics are essential for treating infections; however, they disrupt the microbiome and key microbiome-dependent functions. Clinical evidence is mixed for probiotic supplementation following antibiotics due to product heterogeneity and inconsistencies in evaluating biological mechanisms that drive clinical consequences. Accordingly, this study investigates the effects of a multi-species synbiotic on gut microbiome composition and function, and gut barrier integrity, during and following antibiotics. Methods: In a randomized, placebo-controlled trial designed to assess proof-of-mechanism, healthy adult participants received a daily synbiotic (53.6 billion AFU multi-species probiotic and 400 mg Indian pomegranate extract; DS-01) or matching placebo for 91 days. All participants also received ciprofloxacin (500 mg orally twice daily) and metronidazole (500 mg orally three times daily) for the first 7 days. Samples were collected at baseline and Days 7, 14, 49, and 91. Endpoints included fecal microbiome composition, fecal acetate and butyrate levels, urinary Urolithin A (UroA), serum p-cresol sulfate (pCS), gut barrier integrity, and safety. Results: The multi-species synbiotic significantly increased the alpha-diversity of Bifidobacterium and Lactobacillus at all timepoints compared to placebo, including short-term (Day 7, p < 0.0001) and end-of-study (Day 91, p < 0.001). The multi-species synbiotic enhanced recovery of native beneficial microbes, including butyrate-producing species and a novel Oscillospiraceae species (UMGS1312 sp900550625, p < 0.001). Beneficial microbiome-dependent metabolites increased, including fecal butyrate (119%, p < 0.05), fecal acetate (62%, p < 0.01), and UroA (13,008%, p < 0.05), whereas detrimental metabolite pCS decreased (68%, p < 0.05) compared to placebo. Functionally, the multi-species synbiotic improved gut barrier integrity rapidly (Day 7; 305%, p < 0.05) and over the long-term (Day 91; 161%, p < 0.05) compared to placebo. Conclusions: During and after antibiotics, this multi-species synbiotic promotes recovery of gut microbiome diversity and native beneficial microbes, microbiome metabolite recovery, and gut barrier function, all of which underpin antibiotic-associated gastrointestinal symptoms. Full article

Background: Therapeutic drug monitoring (TDM) is essential for ensuring safe, effective, and individualized anti-infective therapy, particularly in patients with complex clinical needs. Variability in pharmacokinetics, challenges in drug administration, and high-dose regimens can compromise adherence and increase the risk of therapeutic failure or resistance. Swallowing difficulties, a common barrier to oral therapy, often necessitate alternative administration routes or customized formulations. However, interventions such as pharmaceutical compounding or manipulation of solid dosage forms may significantly alter drug bioavailability and pharmacokinetic profiles, making TDM indispensable for guiding dose adjustments and maintaining therapeutic targets. Objectives: This review not only emphasizes the clinical relevance of TDM but also addresses practical strategies that enable therapy when standard formulations are unsuitable or unavailable, while minimizing risks that could compromise treatment efficacy and safety. Special focus is given to anti-infective agents, such as antibiotics, antivirals, and antifungals, illustrating how TDM, combined with tailored pharmaceutical approaches, supports precision dosing and informed decision-making. Conclusions: Through clinical examples and pharmacokinetic considerations, we demonstrated that TDM is a cornerstone of personalized medicine, improving outcomes, and reducing adverse effects in anti-infective treatment. Full article

Cardiovascular diseases (CVDs) and Alzheimer’s disease (AD) are among the most prevalent chronic conditions, contributing significantly to global morbidity and healthcare burdens. These diseases are increasingly recognized as interconnected through shared mechanisms such as vascular dysfunction, oxidative stress, hypertension, and systemic inflammation, collectively referred to as the CVD-AD axis. Although therapeutic strategies exist for each condition, integrated approaches targeting these common pathways remain limited. This review highlights marine-derived bioactive peptides (BAPs) as multifunctional, sustainable agents for the simultaneous prevention of CVD and AD. It summarizes recent advances in their production, purification, and characterization, with emphasis on enzymatic hydrolysis and separation techniques. Marine BAPs exhibit diverse bioactivities, antioxidant, anti-inflammatory, lipid-lowering, antihypertensive, and neuroprotective, addressing key pathological mechanisms of the CVD-AD axis. Their small size, stability, and favorable safety profile support absorption and initial bioavailability, while sustainable sourcing from underutilized marine biomass enables eco-friendly production. Despite their potential, barriers to scalable production, product standardization, and regulatory approval remain; however, incremental advances are being made toward overcoming these issues. Together with these advances, marine BAPs remain promising candidates for functional foods and nutraceuticals, providing integrated preventive strategies for age-related diseases and supporting long-term cardiovascular and cognitive health. Full article

As social robots increasingly enter public environments, their acceptance depends not only on technical robustness but also on ethical integrity, accessibility, transparency, and consistent system behaviour across diverse users. This paper reports an in situ pilot deployment of an ARI social robot functioning as a university receptionist, designed and implemented in alignment with the SecuRoPS framework for secure, ethical, and reliable social robot deployment. Thirty-five students and staff interacted with the robot in a real public setting and provided structured feedback on safety, privacy, usability, accessibility, ethical transparency, and perceived reliability. The results indicate strong user confidence in physical safety, data protection, and regulatory compliance while revealing persistent challenges related to accessibility and interaction dynamics. These findings show that reliability in public-facing robotic systems extends beyond fault-free operation to include equitable and consistent user experience across contexts. Beyond reporting empirical outcomes, the study contributes in three key ways. First, it demonstrates a reproducible method for operationalising lifecycle governance frameworks in real-world deployments. Second, it provides new empirical insights into how trust, accessibility, and transparency are experienced by end users in public spaces. Third, it delivers a publicly available, open-source GitHubrepository containing reusable templates for ARI robot applications developed using the PAL Robotics ARI SDK (v23.12), lowering technical entry barriers and supporting reproducibility. By integrating empirical evaluation with practical system artefacts, this work advances research on reliable intelligent environments and provides actionable guidance for the responsible deployment of social robots in public spaces. Full article

Tryptophan (Trp) metabolism is involved in regulating various physiological and pathological processes, including neurological function, immune response, and gut homeostasis. This article focuses on autism spectrum disorder (ASD) and explores its relationship with abnormalities in the gut microbiota–Trp–brain axis. Studies have shown that ASD patients exhibit Trp metabolism disorders, with gut microbiota dysbiosis inducing systemic inflammation, activating indoleamine 2,3-dioxygenase 1 (IDO1), and promoting increased Trp entry into the kynurenine pathway (KP). This leads to a series of pathological changes, including the production of neurotoxic substances, serotonin system disorders, and impaired intestinal barrier function, which in turn exacerbate ASD symptoms through the gut–brain axis. Furthermore, based on preclinical and clinical studies, we have summarized that specific probiotic strains (such as Lactobacillus and Bifidobacterium) can alleviate the clinical manifestations of ASD by regulating the gut microbiota–Trp metabolic axis, improving immune responses, and enhancing intestinal barrier function. We emphasize that current probiotic interventions still face challenges such as insufficient long-term safety assessments and unclear molecular mechanisms. Future research should combine multi-omics technologies and multi-modal approaches to promote the development of personalized and precise intervention strategies. In summary, this review highlights the crucial role of tryptophan metabolism in ASD and the potential of probiotics as a novel adjunctive therapy targeting this metabolic pathway. Full article

Polyamide 6 is an important engineering thermoplastic; however, its practical use is often constrained by its high flammability. Although aluminum diethylphosphinate is widely employed as a flame retardant for polyamide 6, its relatively slow char-forming kinetics hinders the attainment of the stringent 750 °C glow-wire ignition temperature required for electrical applications at moderate loadings. To address this limitation, a synergist was fabricated via the self-assembly of phytic acid, benzoguanamine, and ZnSO₄·7H₂O and subsequently incorporated to enhance the char-forming capability and flame retardancy of polyamide 6/aluminum diethylphosphinate composites. The results revealed that the synergist acted as an efficient charring promoter, improving flame retardancy. At a total loading of 15 wt%, the composite reached a UL-94 V-0 rating and high limiting oxygen index of 30.7%. Cone calorimetry data indicate that the peak heat release rate decreased by 34.0%, and the smoke production rate decreased by 33.3% compared with the polyamide 6/aluminum diethylphosphinate composites. Mechanistic analysis indicated that the synergist catalyzed the carbonization of the polyamide 6, enabling the formation of a dense thermally insulating char barrier in the condensed phase. Notably, the optimized formulation achieved a glow-wire ignition temperature of 750 °C, demonstrating its strong potential for high-safety electrical applications. Full article

FABP4 (fatty acid-binding protein 4) is a lipid chaperone and secreted adipokine linking dysregulated fatty acid handling with inflammation, cellular stress, and insulin resistance in obesity. By modulating nuclear receptor signaling (notably PPARγ) and enhancing NF-κB/MAPK activation in adipocytes and macrophages, FABP4 contributes to maladaptive adipose remodeling and systemic metabolic decline. This review critically summarizes recent preclinical evidence on natural bioactive compounds that regulate FABP4 expression and associated adipogenic programs in models of adipogenesis and diet-induced obesity. Data from 3T3-L1/OP9 adipocytes, rodent studies, and selected alternative models indicate that many plant-derived extracts and phytochemicals (e.g., polyphenols, saponins, coumarins, terpenoids, and fermented products) down-regulate FABP4 at mRNA and/or protein levels. These effects are frequently accompanied by suppression of PPARγ/C/EBPα/SREBP1c signaling, activation of AMPK-related pathways, reduced lipid accumulation, and improved metabolic outcomes including lower weight gain, reduced adipocyte hypertrophy, improved steatosis, and favorable serum lipid profiles. Natural compounds from non-plant sources (animal- and microbe-derived metabolites) further broaden FABP4-targeting strategies, supporting FABP4 as a cross-class therapeutic node. Key translational barriers include poor extract standardization, incomplete identification of active constituents, limited oral bioavailability, microbiome-dependent variability, and scarce clinical validation. Future work should prioritize well-characterized lead scaffolds, targeted delivery, rational combinations, and standardized, adequately powered clinical trials assessing dose, durability of FABP4 suppression, and cardiometabolic safety. Full article

The growing demand for sustainable materials and the valorization of waste streams have intensified research on wastewater biorefineries and bioplastics. Within this framework, this study aims to develop and characterize poly (lactic acid) (PLA)-based films partially substituted with microalgae biomass derived from wastewater treatment at different concentrations (PLA-MA: 0, 10, 20, 30, 40, and 50%). The films were produced and systematically characterized in terms of their morphological (SEM), structural (FTIR), physical (thickness, weight, swelling, and solubility), thermal (TGA), mechanical (tensile strength, elongation at break, and Young’s modulus), optical (colorimetry and UV–Vis), barrier (water vapor permeability), and biodegradability properties. FTIR analysis confirmed the successful incorporation of microalgae biomass into the polymeric matrix and indicated good compatibility at low biomass loadings, whereas higher concentrations (>20%) introduced hydrophilic functional groups associated with increasing structural incompatibility. Partial substitution of PLA with microalgae biomass significantly modulated the physical, mechanical, and optical properties of the resulting composites. Notably, biodegradability assays revealed that the PLA-MA 50% composite achieved 89% degradation within 120 days, demonstrating that microalgal biomass markedly accelerates material decomposition. Furthermore, antimicrobial tests conducted for PLA-MA 0%, 20%, and 50% confirmed the safety of wastewater-derived microalgae for incorporation into the polymer matrix. Overall, these results highlight the potential of wastewater-derived microalgae biomass as a promising and sustainable component for short-life-cycle bioplastic applications, particularly in the agricultural sector. Full article

Sepsis is a life-threatening condition characterized by a dysregulated host response to infection, often resulting in multiorgan dysfunction. Among affected systems, the gastrointestinal tract plays a central role in sepsis progression by promoting systemic inflammation through impaired barrier function, immune imbalance, and microbiome alterations. Recent research has identified selected medical gases and gasotransmitters as promising therapeutic candidates for preserving gut integrity in sepsis. In particular, hydrogen, carbon monoxide, and hydrogen sulfide exhibit antioxidative, anti-inflammatory, and cytoprotective properties. These gases act through defined molecular pathways, including activation of Nrf2, inhibition of NF-κB, and preservation of tight junction integrity, thereby supporting intestinal barrier function. In addition, they influence immune cell phenotypes and autophagy, with indirect effects on the gut microbiome. Although most supporting evidence derives from preclinical models, translational findings and emerging safety data highlight the potential of gut-targeted gas-based strategies. This review summarizes current mechanistic and translational evidence for gut-protective medical gases in sepsis and discusses their integration into future organ-specific and mechanism-based therapeutic approaches. Full article

Chimeric antigen receptor (CAR)-engineered immune cell therapies have revolutionized cancer treatment, with CAR-T cells demonstrating remarkable efficacy against hematological malignancies. However, the effectiveness of CAR-T and other lymphocyte-based therapies against solid tumors remains limited, primarily due to the immunosuppressive tumor microenvironment and poor infiltration of effector cells. Recently, CAR-macrophage (CAR-M) immunotherapy has emerged as a promising strategy to overcome these barriers. Leveraging the innate tumor-homing ability, phagocytic function, and antigen-presenting capacity of macrophages, CAR-M therapies offer unique advantages for targeting solid tumors. This review provides a comprehensive overview of the development and current state of CAR-Macrophage immunotherapy, including advances in CAR design and macrophage engineering, preclinical and clinical progress, and mechanistic insights into their anti-tumor activity. The review critically examined both the benefits and limitations of CAR-M approaches, addressing persistent challenges such as cell sourcing, durability, and safety, while also exploring innovative strategies to enhance therapeutic efficacy. Finally, future perspectives and the potential clinical impact of CAR-macrophage therapies were outlined, underscoring their emerging role in the evolving landscape of cancer immunotherapy. Full article

Introduction: Nursing informatics aims to improve patient care through rapid access to patient data, systematic assessment, a reduction in clinical errors, evidence-based practice, cost-effectiveness, and improved patient outcomes and safety. Background: Despite being the largest workforce in healthcare, nurses are not being adequately prepared to use nursing informatics, and this has been attributed to poor digital literacy, limited professional development, and a lack of undergraduate informatics education. Objectives: This scoping review aims to review contemporary published literature on the benefits, barriers, and enablers for embedding nursing informatics into undergraduate nursing education with a focus on the Australian healthcare context. Methods: A scoping review was conducted using the PRISMA-ScR checklist and the JBI Manual for evidence synthesis in adherence with an a priori scoping review protocol. A comprehensive search of JBI, Cochrane, CINAHL, Ovid, ProQuest, PubMed, and Scopus databases was performed. Two reviewers independently screened the results via Covidence, with discrepancies resolved via a third reviewer. Results: Two searches were conducted for this scoping review. In the first search, a total of 3227 articles were identified through database searches, with an additional 76 articles identified through bibliographic and grey literature searches. Following duplicate removal and screening, 46 articles met the inclusion criteria. In the second search, a total of 1555 articles were identified, and after duplicate removal and screening, 16 articles met the inclusion criteria. Duplicate removal during the second search round included those articles identified in the first search. The combined searches resulted in a total of 62 sources for this review. Conclusions: Despite the early adoption of nursing informatics in Australia in the 1980s, barriers remain to effective nursing informatics engagement and proficiency, including a lack of understanding of nursing informatics, limited infrastructure and resources, inadequate digital literacy of students and faculty, and the evolving nature of nursing informatics. Definitions of nursing informatics and associated fields, development of university faculty competency, access to digital health technologies, competency standards, digital literacy of the student cohort, faculty digital proficiency, and leadership from professional nursing bodies are all viewed as integral foundations for the development of student competency in nursing informatics. Full article

The escalating global incidence of ulcerative colitis (UC) underscores the demand for novel therapeutic strategies. This study investigated the fermentation of Periplaneta americana (PA) powder using two conventional dairy starter strains, Lactobacillus delbrueckii subsp. bulgaricus SN22 and Streptococcus thermophilus SN05, to enhance its functional properties, particularly anti-inflammatory activity, via microbial processing. Both strains demonstrated favourable safety and antimicrobial activity. Untargeted metabolomics revealed that fermentation significantly altered the metabolite profile of the PA supernatant, enriching compounds with potential bioactivities, notably anti-inflammatory (e.g., 3-anisic acid) and antioxidant (e.g., vitamin U) properties. In the DSS-induced mouse colitis model, treatment with the fermented supernatant alleviated intestinal inflammation compared to the unfermented group. This was demonstrated by significantly reduced levels of the pro-inflammatory cytokines IL-1β and TNF-α, along with improved maintenance of intestinal barrier integrity. Further in vitro assays showed that the fermented supernatant significantly suppressed proliferation and clonogenicity in human HT-29 colon cancer cells, while also inducing reactive oxygen species accumulation and apoptosis. Results demonstrate these strains are multifunctional starters possessing superior antimicrobial and anti-inflammatory efficacy. This study employed LAB fermentation of insect-derived matrices to derive bioactive components. The fermentation products exhibited anti-inflammatory potential, offering a potential microbial transformation strategy for developing functional products for adjunctive UC intervention. Full article