Search Results (2,445)

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

How do regulatory policies, funding structures, and cross-sector coordination shape knowledge flows and institutional transformation? Focusing on the smart medical device sector in Taiwan, this study explores how governance dynamics accelerate system transformation and foster demand for adaptive and integrative innovation systems. Building on the National Biotechnology Innovation System framework and qualitative system dynamics modeling, the study analyzes institutional interactions through 28 semi-structured interviews and 18 policy documents. Findings identify systemic bottlenecks, including translational gaps, coordination challenges, and barriers for traditional manufacturers. These gaps have enabled tech firms to emerge as system leaders by bridging these institutional gaps. This study extends innovation systems theory by conceptualizing an emergent governance function that addresses institutional gaps. At the policy level, the study highlights the importance of enabling institutional change in governance to address structural fragmentation and support system-wide transformation. Full article

Fungi, from saprophytes to pathogens, face predictable daily fluctuations in light, temperature, humidity, and nutrient availability. To cope, they have evolved an internal circadian clock that confers a major adaptive advantage. This review critically synthesizes current knowledge on the molecular architecture and physiological relevance of fungal circadian systems, moving beyond the canonical Neurospora crassa model to explore the broader phylogenetic diversity of timekeeping mechanisms. We examine the core transcription-translation feedback loop (TTFL) centered on the FREQUENCY/WHITE COLLAR (FRQ/WCC) system and contrast it with divergent and non-canonical oscillators, including the metabolic rhythms of yeasts and the universally conserved peroxiredoxin (PRX) oxidation cycles. A central theme is the clock’s role in gating cellular defenses against oxidative, osmotic, and nutritional stress, enabling fungi to anticipate and withstand environmental insults through proactive regulation. We provide a detailed analysis of chrono-pathogenesis, where the circadian control of virulence factors aligns fungal attacks with windows of host vulnerability, with a focus on experimental evidence from pathogens like Botrytis cinerea, Fusarium oxysporum, and Magnaporthe oryzae. The review explores the downstream pathways—including transcriptional cascades, post-translational modifications, and epigenetic regulation—that translate temporal signals into physiological outputs such as developmental rhythms in conidiation and hyphal branching. Finally, we highlight critical knowledge gaps, particularly in understudied phyla like Basidiomycota, and discuss future research directions. This includes the exploration of novel clock architectures and the emerging, though speculative, hypothesis of “chrono-therapeutics”—interventions designed to disrupt fungal clocks—as a forward-looking concept for managing fungal infections. Full article

Background: High-intensity gait training (HIT) is an evidence-based intervention recommended for stroke rehabilitation; however, its implementation in routine practice is inconsistent. This study examined the real-world implementation of HIT in an inpatient rehabilitation setting in Norway, focusing on fidelity, barriers, and knowledge translation (KT) strategies. Methods: Using the Knowledge-to-Action (KTA) framework, HIT was implemented in three phases: pre-implementation, implementation, and competency. Fidelity metrics and coverage were assessed in 99 participants post-stroke. Barriers and facilitators were documented and categorized using the Consolidated Framework for Implementation Research. Results: HIT was delivered with improved fidelity during the implementation and competency phases, reflected by increased stepping and heart rate metrics. A coverage rate of 52% was achieved. Barriers evolved over time, beginning with logistical and knowledge challenges and shifting toward decision-making complexity. The KT interventions, developed collaboratively by clinicians and external facilitators, supported implementation. Conclusions: Structured pre-implementation planning, clinician engagement, and external facilitation enabled high-fidelity HIT implementation in a real-world setting. Pragmatic, context-sensitive strategies were critical to overcoming evolving barriers. Future research should examine scalable, adaptive KT strategies that balance theoretical guidance with clinical feasibility to sustain evidence-based practice in rehabilitation. Full article

The adoption of technological innovations in the maritime industry is of interest to business, policy, and academic communities. In the last group, this interest has translated into the publication of a large but scattered literature, making it difficult to compare findings and identify the dynamics, structures, and patterns that might inform future research. A comprehensive review of past research on this topic might help achieve this. To date, no such review has been carried out, which is an important gap in the literature that this paper contributes to bridging. Two bibliometric review techniques—co-citation analysis of cited references and bibliographic coupling of documents—are applied to 171 journal articles published between 1999 and February 2025 to answer the following questions: 1. What is the knowledge base of this literature? 2. What are the recent research trends (research fronts) in this literature? The analysis reveals that research on “shore power” dominates both the knowledge base and research fronts. Other key research themes centre on “autonomous shipping”, “blockchain”, and “alternative fuels”. Based on these results, implications for future research are drawn. Full article

We summarize our present knowledge of the regulation of photostasis and photosynthetic performance versus photoprotection in response to vernalization and conclude that the enhanced photosynthetic performance of winter crops is due to an inherent increase in photosynthetic energy conversion efficiency induced by vernalization which translates into high seed yield in the field as well as under controlled environment conditions. This is consistent with the published data for enhanced photosynthetic performance of the only two extant terrestrial angiosperms, Colobanthus quitensis and Deschampsia antarctica, native to the frigid conditions of terrestrial Antarctica. The Cold Binding factor family of transcription factors (CBFs/DREBs) governs the enhanced photosynthetic performance of winter cereals as well as the Antarctic angiosperms. In contrast to winter crops, spring varieties survive cold environments by stimulating photoprotection at the expense of photosynthetic performance like that observed for green algae and cyanobacteria. Consequently, this minimizes the photosynthetic energy conversion efficiency of spring varieties and limits their seed yield upon cold acclimation. This review provides critical insights into the regulation of photostasis and the balance between photosynthetic performance and photoprotection in plants and how vernalization has enhanced photosynthetic energy conversion, which is essential for understanding plant adaptation to cold environments and optimizing agricultural productivity for improving crop resilience and yield in challenging climates. Full article

Ongoing interest in the intersection of spirituality and health has prompted a need for integrated research. This report proposes a distinct approach in a model that allows for successful and harmonious cross-fertilization within these latter two areas of interest. Our work is especially pertinent to inquiries around the role of spirituality in mental health, with special attention to chronic pain conditions. The latter have become an open channel for novel avenues to explore the field of spirituality-based interventions within the arena of psychological inquiry. To address this, the authors developed and implemented the Church and Academia Model, a prototype for an innovative collaborative research project, with the aim of exploring the role of devotional practices, and their potential to be used as therapeutic co-adjuvants or tools to enhance the coping skills of patients with chronic pain. Keeping in mind that the church presents a rich landscape for clinical inquiry with broad relevance for clinicians and society at large, we created a unique hybrid research model. This is a new paradigm that focuses on distinct and well-defined studies where the funding, protocol writing, study design, and implementation are shared by experts from both the pastoral and clinical spaces. A team of theologians, researchers, and healthcare providers, including clinical pain psychologists, built a coalition leveraging their respective skill sets. Each expert is housed in their own environs, creating a functional network that has proven academically productive and pastorally effective. Key outputs include the creation and validation of a new psychometric measure, the Pain-related PRAYER Scale (PPRAYERS), an associated bedside prayer tool and a full-scale dissemination strategy through journal publications and specialty society conferences. This collaborative prototype is also an ideal fit for integrated knowledge translation platforms, and it is a promising paradigm for future collaborative projects focused on spirituality and mental health. Full article

Neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, are characterized by progressive neuronal loss and share key pathological features such as oxidative stress, mitochondrial dysfunction, and chronic neuroinflammation. Recent research has highlighted the potential of ketogenic metabolism, particularly the use of ketone bodies like β-hydroxybutyrate, as a therapeutic approach targeting these shared mechanisms. This review provides a comprehensive synthesis of current knowledge on the neuroprotective effects of ketogenic interventions, including both dietary strategies and exogenous ketone supplementation. We discuss how ketone bodies improve mitochondrial function, reduce reactive oxygen species, modulate inflammatory pathways, and influence neurotransmission and synaptic plasticity. Additionally, we examine experimental and clinical evidence supporting the application of ketogenic therapies in neurodegenerative diseases, highlighting disease-specific findings, benefits, and limitations. While preclinical data are robust and suggest meaningful therapeutic potential, clinical studies remain limited and heterogeneous, with challenges related to adherence, safety, and patient selection. The review also addresses the translational relevance of ketogenic strategies, considering their feasibility, combination with other therapies, and the need for personalized approaches based on genetic and metabolic profiles. By critically evaluating existing data, this article aims to clarify the mechanisms through which ketogenic metabolism may exert neuroprotective effects and to outline future directions for research and clinical application in the context of neurodegenerative disorders. Full article

Male-factor infertility accounts for approxiamately half of all infertility cases globally, yet therapeutic options remain limited for individuals with no retrievable spermatozoa, such as those with non-obstructive azoospermia (NOA). In recent years, artificial gametogenesis has emerged as a promising avenue for fertility restoration, driven by advances in two complementary strategies: organotypic in vitro spermatogenesis (IVS), which aims to complete spermatogenesis ex vivo using native testicular tissue, and in vitro gametogenesis (IVG), which seeks to generate male gametes de novo from pluripotent or reprogrammed somatic stem cells. To evaluate the current landscape and future potential of these approaches, a narrative, semi-systematic literature search was conducted in PubMed and Scopus for the period January 2010 to February 2025. Additionally, landmark studies published prior to 2010 that contributed foundational knowledge in spermatogenesis and testicular tissue modeling were reviewed to provide historical context. This narrative review synthesizes multidisciplinary evidence from cell biology, tissue engineering, and translational medicine to benchmark IVS and IVG technologies against species-specific developmental milestones, ranging from rodent models to non-human primates and emerging human systems. Key challenges—such as the reconstitution of the blood–testis barrier, stage-specific endocrine signaling, and epigenetic reprogramming—are discussed alongside critical performance metrics of various platforms, including air–liquid interface slice cultures, three-dimensional organoids, microfluidic “testis-on-chip” devices, and stem cell-derived gametogenic protocols. Particular attention is given to clinical applicability in contexts such as NOA, oncofertility preservation in prepubertal patients, genetic syndromes, and reprocutive scenarios involving same-sex or unpartnered individuals. Safety, regulatory, and ethical considerations are critically appraised, and a translational framework is outlined that emphasizes biomimetic scaffold design, multi-omics-guided media optimization, and rigorous genomic and epigenomic quality control. While the generation of functionally mature sperm in vitro remains unachieved, converging progress in animal models and early human systems suggests that clinically revelant IVS and IVG applications are approaching feasibility, offering a paradigm shift in reproductive medicine. Full article

Eukaryotic elongation factor 1A (eEF1A), the second most abundant intracellular protein, not only plays a key role in peptide elongation, but is also capable of numerous moonlighting functions. Within malignant cells, eEF1A is by no means a neutral bystander but instead actively participates in oncogenic transformations via a myriad of molecular pathways. Thus far, a broad range of small-molecule inhibitors have been identified, which, despite their structural diversity, suppress tumor growth by targeting eEF1A. Interestingly, just as eEF1A enables its oncogenic potential far beyond boosting protein translation, these targeted agents disrupt this oncoprotein via multiple axes distinct from mere protein synthesis inhibition. Whereas the oncogenic mechanisms of eEF1A has been well documented, there lacks a systemic survey of the eEF1A-targeting agents in terms of their mechanisms. Accordingly, the present work aims to examine their multifaceted modes of action more than just blocking protein synthesis. By unveiling these insights, our deepened knowledge of these eEF1A-binding inhibitors will inform the development of future eEF1A-targeted drugs for cancer treatment. Full article

The seasonal patterns of viral diseases in farm animals present significant challenges to global livestock productivity, with cold stress emerging as a potential modulator of host–pathogen interactions. This review synthesizes current knowledge on the expression dynamics of heat shock protein 70 (HSP70) in farm animals under cold-stress conditions and its potential roles as (1) a viral replication facilitator and (2) an immune response regulator. This review highlights cold-induced HSP70 overexpression in essential organs, as well as its effects on significant virus life cycles, such as porcine epidemic diarrhea virus (PEDV), porcine reproductive and respiratory syndrome virus (PRRSV), and bovine viral diarrhea virus (BVDV), through processes like viral protein chaperoning, replication complex stabilization, and host defense modulation. By integrating insights from thermophysiology, virology, and immunology, we suggest that HSP70 serves as a crucial link between environmental stress and viral disease seasonality. We also discuss translational opportunities targeting HSP70 pathways to break the cycle of seasonal outbreaks, while addressing key knowledge gaps requiring further investigation. This article provides a framework for understanding climate-driven disease patterns and developing seasonally adjusted intervention strategies. Full article

Antimicrobial resistance (AMR) has emerged as one of the most pressing global health challenges of our time. Alarming projections of increasing mortality from resistant infections highlight the urgent need for innovative solutions. While many candidates have shown promise in preliminary studies, they often encounter challenges in terms of efficacy and safety during clinical translation. This review examines cutting-edge approaches to combat AMR, with a focus on engineered antimicrobial peptides, functionalized nanoparticles, and advanced genomic therapies, including Clustered Regularly Interspaced Short Palindromic Repeats-associated proteins (CRISPR-Cas systems) and phage therapy. Recent advancements in these fields are critically analyzed, with a focus on their mechanisms of action, therapeutic potential, and current limitations. Emphasis is given to strategies targeting biofilm disruption and quorum sensing interference, which address key mechanisms of resistance. By synthesizing current knowledge, this work provides researchers with a comprehensive framework for developing next-generation antimicrobials, highlighting the most promising approaches for overcoming AMR through rational drug design and targeted therapies. Ultimately, this review aims to bridge the gap between experimental innovation and clinical application, providing valuable insights for developing effective and resistance-proof antimicrobial agents. Full article

Natural products demonstrate potent immunomodulatory properties through checkpoint modulation, macrophage polarization, and T cell/natural killer (NK) cell activation. While cancer organoid-immune co-culture platforms enable physiologically relevant modeling of tumor–immune interactions, systematic investigation of natural product immunomodulation in these systems remains entirely unexplored. We conducted a comprehensive literature analysis examining natural products tested in cancer organoids, immunomodulatory mechanisms from traditional models, technical advances in organoid-immune co-cultures, and standardization requirements for clinical translation. Our analysis reveals a critical research gap: no published studies have investigated natural product-mediated immunomodulation using organoid-immune co-culture systems. Even though compounds like curcumin, resveratrol, and medicinal mushroom polysaccharides show extensive immunomodulatory effects in two-dimensional (2D) cultures, and organoid technology achieves high clinical correlation for drug response prediction, all existing organoid studies focus exclusively on direct cytotoxicity. Technical challenges include compound stability, limited matrix penetration requiring substantially higher concentrations than 2D cultures, and maintaining functional immune populations in three-dimensional (3D) systems. The convergence of validated organoid-immune co-culture platforms, Food and Drug Administration (FDA) regulatory support through the Modernization Act 2.0, and extensive natural product knowledge creates unprecedented opportunities. Priority research directions include systematic screening of immunomodulatory natural products in organoid-immune co-cultures, development of 3D-optimized delivery systems, and clinical validation trials. Success requires moving beyond cytotoxicity-focused studies to investigate immunomodulatory mechanisms in physiologically relevant 3D systems, potentially unlocking new precision cancer immunotherapy approaches. Full article

Background/Objectives: BRIGHTLIGHT was the national evaluation of adolescent and young adult (AYA) cancer services in England. BRIGHTLIGHT results were not available when the most recent healthcare policy (NHSE service specifications for AYA Cancer) for AYA was drafted and therefore did not consider BRIGHTLIGHT findings and recommendations. We describe the co-development and delivery of a Policy Lab to expedite the implementation of the new service specification in the context of BRIGHTLIGHT results, examining the roles of multi-stakeholders to ensure service delivery is optimised to benefit AYA patients. We address the key question, “What is the roadmap for empowering different stakeholders to shape how the AYA service specifications are implemented?”. Methods: A 1-day face-to-face policy lab was facilitated, utilising a unique, user-centric engagement approach by bringing diverse AYA stakeholders together to co-design strategies to translate BRIGHTLIGHT evidence into policy and impact. This was accompanied by an online workshop and prioritisation survey, individual interviews, and an AYA patient workshop. Workshop outputs were analysed thematically and survey data quantitatively. Results: Eighteen professionals and five AYAs attended the face-to-face Policy Lab, 16 surveys were completed, 13 attended the online workshop, three professionals were interviewed, and three AYAs attended the patient workshop. The Policy Lab generated eight national and six local recommendations, which were prioritised into three national priorities: 1. Launching the service specification supported by compelling communication; 2. Harnessing the ideas of young people; and 3. Evaluation of AYA patient outcomes/experiences and establishing a national dashboard of AYA cancer network performance. An animation was created by AYAs to inform local hospitals what matters to them most in the service specification. Conclusions: Policy and research evidence are not always aligned, so when emerging evidence does not support current guidance, further exploration is required. We have shown through multi-stakeholder involvement including young people that it was possible to gain a different interpretation based on current knowledge and context. This additional insight enabled practical recommendations to be identified to support the implementation of the service specification. Full article

The environmental detriments of the growing global production and overconsumption of beef, including greenhouse gas emissions, deforestation, and biodiversity loss, are well-documented. However, public awareness of how dietary choices affect the environment remains limited. This study examines sustainability views on beef consumption and the potential for behavioral change as a step toward more sustainable intake levels. An observational web-based survey was conducted (n = 1367) to assess respondents’ current beef intake frequency, views on beef consumption related to planetary health, tropical deforestation, greenhouse gas emissions, and climate change, and willingness to modify beef consumption behavior. Chi-square tests were used for group comparisons, and weighted average scores were applied to rank levels of resistance to reducing beef intake. Environmental concern related to beef consumption was associated with greater beef cutback intentions and lower long-term intake reduction resistance amongst beef eaters. Beef eaters who strongly agreed that global beef consumption negatively impacts the environment were considerably more likely to express intentions to reduce their long-term beef intake compared to those who strongly disagreed (94.4% vs. 19.6%). Overall, 76.6% of beef eaters indicated wanting to eat less beef or phase it out entirely (30.7% reduce, 29.4% minimize, 16.6% stop), with only 23.4% of them intending to keep their consumption unchanged. Compelling messages that help translate awareness into action, such as the #NoBeefWeek concept explored in this study, may support individuals in adopting more sustainable food choices. These cross-national findings provide evidence for a ‘knowledge–intent’ gap in sustainable diet research, with relevance for health communicators and policymakers. Future research could examine the factors and motivations influencing decisions to modify beef consumption, including the barriers to achieving sustainable consumption levels and the role of suitable alternatives in facilitating this transition. Full article