Search Results (8,046)

The COVID-19 pandemic placed unprecedented pressure on diagnostic services worldwide. The first cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the UK were confirmed on 31 January 2020, prompting National Health Service (NHS) laboratories to scale diagnostic procedures. The demand for testing rapidly exceeded historical norms for respiratory virus diagnostics, necessitating substantial government investment in consumables, assay development, and workforce expansion. This review presents a retrospective evaluation of SARS-CoV-2 diagnostic platforms deployed within the Norfolk and Norwich University Hospital (NNUH) trust and compares them with those implemented by other regional laboratories during the pandemic. It examines the molecular mechanisms, performance, scalability, and specificity of the multiple molecular testing approaches to optimise workflow based on the evolving technology. The integration of complementary platforms through a stratified testing strategy enabled high-throughput population screening while preserving diagnostic resolution for complex respiratory cases, substantially improving laboratory efficiency and resilience. The emerging diagnostic methodologies, RT-LAMP and CRISPR-based assays, are described, and we discuss their potential roles in future outbreaks. We critically evaluate the overall preparedness of UK health services for the COVID-19 pandemic and highlight key priorities for future pandemic preparedness at both local and national levels. Full article

Endocrine-disrupting chemicals (EDCs) are a diverse group of environmental pollutants capable of interfering with hormonal and immune system regulation. In recent years, increasing concern has been raised about the effects of chemicals, including bisphenols, phthalates, per- and polyfluoroalkyl substances (PFAS), insecticides, and parabens, on maternal and fetal health, primarily due to their widespread exposure in human populations. Pregnancy represents a critical window characterized by tightly regulated hormonal and immunological adaptations. Emerging evidence suggests that EDC exposure during this period may alter maternal microbiota, disrupt immune responses, and interfere with endocrine signaling. These changes may increase susceptibility to bacterial and viral infections, including bacterial vaginosis, urinary tract infections, and intrauterine infections, all of which are associated with adverse pregnancy outcomes. This review summarizes the current evidence on the sources and mechanisms of exposure to endocrine disruptors during pregnancy and examines the potential biological pathways linking endocrine disruption to the development of infections. Particular emphasis is placed on the interactions between immune regulation, hormonal signaling, and changes in the microbiome, which may contribute to increased susceptibility to infections. A deeper understanding of these complex mechanisms is critical to improve risk assessment, develop effective public health strategies, and ultimately protect maternal and fetal health in an environment of increasing chemical exposure. A literature search was conducted using PubMed/MEDLINE, Scopus, and Web of Science, including studies published up to January 2026. Full article

Background/Objectives: The rapid expansion of New Approach Methodologies (NAMs) is transforming oral biopharmaceutics by offering mechanistically rich, human-relevant tools that can reduce reliance on animal testing while improving translational confidence. Regulatory agencies, including the Food and Drug Administration (FDA) and the European Medicines Agency (EMA), are increasingly open to NAM-generated evidence, provided that methods are fit-for-purpose and scientifically justified. This review synthesizes current advances and evaluates how NAMs can be integrated across drug-development stages to enhance the prediction of oral absorption, formulation performance, and regulatory decision-making. Methods: A comprehensive literature review was conducted across classical and emerging methodologies, including in vitro permeability and solubility models, organoids, organ-on-a-chip (OoC) systems, machine learning frameworks, and mechanistic approaches such as the physiologically based pharmacokinetic (PBPK) and biopharmaceutics (PBBM) models. Emphasis was placed on physiological relevance, predictive performance, validation status, and regulatory applicability. Results: Classical tools remain essential for the Biopharmaceutics Classification System (BCS)-based biowaivers and risk-based assessments, yet they often lack physiological fidelity. NAMs provide enhanced representation of intestinal architecture, hydrodynamics, transporter activity, and metabolism. Organoids and microphysiological systems generate high-quality permeability and metabolic data, while computational NAMs enable scalable prediction of ADME properties and formulation behavior. When integrated into PBPK/PBBM models, these methods have great potential in predicting in vivo performance in humans. Evidence demonstrates that NAMs can refine, reduce, and, in specific contexts, replace animal studies without compromising scientific rigor. Conclusions: NAMs complement, rather than displace, classical biopharmaceutic tools, enabling a more mechanistic, human-centered, and ethically responsible framework for drug development. Their effective implementation will depend on continued validation, standardization, and regulatory harmonization as the field transitions toward fully NAM-supported biopharmaceutical assessment. Full article

Objectives: Endodontic complications are among the most frequently reported biological complications in tooth-supported fixed dental prostheses (FDPs). The aim of this study was to evaluate the prevalence of periapical complications in FDPs placed on vital and non-vital abutments and to identify risk factors for these lesions. Methods: This retrospective clinical trial was conducted on participants who had attended routine follow-up visits at the dental hospital at Qassim University, Saudi Arabia. Participants were examined clinically and radiographically for the presence of periapical lesions. Information was recorded on the design, material, location of the prostheses, and oral hygiene. The survival and lesion-free survival rates were determined using the Kaplan–Meier method. Life-table analysis was performed to assess the mean time to event. Univariate Cox proportional hazards regression analysis was used to assess potential risk factors for the development of periapical lesions (α = 0.05). Results: A total of 495 FDPs were placed in 302 participants, with a mean age of 45.7 ± 13.4 years and a mean follow-up period of 7.5 ± 6.5 years. Lesions were detected in 32.3% of FDPs during follow-up. There were no significant differences in the prevalence of lesions in vital compared with non-vital abutments or between males and females (p > 0.05). Poor oral hygiene was the most significant risk factor for the development of periapical lesions (p < 0.05). Univariate Cox regression analysis showed that anterior–posterior FDPs had a higher risk of lesions (p = 0.035). No significant associations were found between lesions and the material used or the design of the abutment (p > 0.05). Conclusions: Periapical complications in FDPs are mainly influenced by oral hygiene and the location of the FDPs, whereas abutment vitality and material type appear to have limited impact. Full article

To address the issue of traditional bistable vibration energy harvesters (BVEHs) being prone to becoming trapped in a single potential well—which results in a narrowed energy harvesting bandwidth and reduced efficiency—this paper proposes a method that utilizes the nonlinear electromagnetic force generated during the induction process to modulate the kinematic behavior of the oscillator. The characteristics and influencing factors of the nonlinear force produced during electromagnetic induction are analyzed. A dual-cantilever beam structure is designed, with an iron-core coil and a magnet placed at the respective free ends. A mathematical model of a piezoelectric–electromagnetic coupled bimodal broadband vibration energy harvester is established and numerically simulated. Furthermore, a vertical vibration experimental platform is constructed to conduct frequency sweep tests. The experimental results demonstrate that the proposed piezoelectric–electromagnetic coupled bimodal broadband vibration energy harvester effectively improves energy harvesting efficiency. Within the frequency range of 5–20 Hz, the system exhibits two vibration modes, with resonant frequencies of approximately 7.7 Hz and 15.7 Hz. For a single-layer PVDF piezoelectric film, the maximum output power at the first and second resonance points is 8.9 μW and 9.7 μW, respectively. The electromagnetic module achieves maximum output powers of 0.39 W and 0.71 W. Moreover, within the frequency ranges of 6.3–9.8 Hz and 14–17.7 Hz (a total bandwidth of 7.2 Hz), the device maintains a stable power output. The effective bandwidth is broadened by approximately 80%, demonstrating excellent broadband performance. Full article

This paper explores the ways in which AI-based urban mapping tools may influence informal sustainability learning, with a particular emphasis on their use in participatory “Green Walk” activities in Manchester. As cities continue to integrate algorithmic systems to respond to environmental concerns, it becomes increasingly relevant to ask how such technologies affect not only governance structures but also public modes of understanding and engagement. Grounded in theories of place-based learning, embodied cognition, and constructionism, the study captured participants’ interaction with AI-generated maps that visualised carbon data, land use, and ecological sites. Drawing on semi-structured interviews and field observations, the findings suggest that combining algorithmic representations with real-world walking experiences helped participants develop a stronger awareness of local environmental issues. The study points out both the pedagogical potential and limitations of AI-based tools in sustainability education. While they can support conceptual learning and foster new perspectives, they are not neutral or universally accessible. The effectiveness of these tools depends on how they are embedded within inclusive, dialogic, and situated pedagogical practices. Overall, this paper contributes to a more nuanced understanding of digital tools in place-based learning and informal education. Full article

Gla-rich protein (GRP), also known as UCMA, is a vitamin K-dependent protein that has emerged as an important regulator of pathological calcification and inflammation. Vascular calcification is a major complication of chronic kidney disease and cardiovascular disorders and is now recognized as an active and tightly regulated process rather than a passive accumulation of minerals. Increasing evidence indicates that GRP plays a protective role in mineral homeostasis through its strong calcium-binding capacity and its dependence on vitamin K-mediated gamma carboxylation. This work represents a comprehensive narrative review aimed at summarizing and critically discussing the current scientific knowledge on GRP. Available experimental and clinical data are analyzed with respect to gene expression, molecular regulation, vitamin K dependency, and underlying mechanisms of action. Particular emphasis is placed on the dual function of GRP in inhibiting ectopic calcification and modulating inflammatory responses. The evidence linking altered GRP levels or changes in its carboxylation status with chronic kidney disease, vascular calcification, calcific aortic valve disease, osteoarthritis, and tumor-associated microcalcifications is systematically examined. Current findings collectively support the concept that GRP is a multifunctional protein operating at the interface of mineral metabolism, inflammation, and tissue remodeling. Despite promising experimental data, important knowledge gaps remain, including the absence of standardized assays capable of distinguishing different GRP forms and the lack of longitudinal clinical studies evaluating its predictive value. This manuscript highlights the potential of GRP as a biomarker of disturbed mineral homeostasis and cardiovascular risk, while emphasizing the need for further research to clarify its precise biological functions and clinical relevance. Full article

The management of deep subgingival carious lesions presents significant challenges for achieving durable adhesive restorations due to limited access, moisture control, and proximity to periodontal tissues. Two main approaches are currently adopted to manage these cases: Deep Margin Elevation (DME) and Surgical Crown Lengthening (SCL). This systematic review (PROSPERO registration CRD420250654262) aimed to compare the performance and survival of restorations placed following DME versus SCL in teeth with deep subgingival margins. A comprehensive literature search was conducted in PubMed, B-ON, and the Cochrane Library for studies published between 2014 and 2025. Following PRISMA guidelines, six studies were included. Methodological quality and risk of bias were assessed using ROBINS-I, RoB 2, and the CARE guidelines. The available evidence indicates that both DME and SCL provide satisfactory periodontal stability, high restoration survival rates, and a low incidence of recurrent caries. DME emerged as a minimally invasive strategy that facilitates adhesive procedures by relocating deep margins to more accessible positions, potentially improving marginal integrity while preserving tooth structure and gingival architecture, particularly in patients with a thick gingival biotype. The choice between DME and SCL should be individualized. Further long-term clinical studies are required to clarify their impact on adhesive interface durability in subgingival environments. Full article

This work presents a loop-shaped (hairpin) resonator incorporating a defective ground structure (DGS) to enhance sensitivity for monitoring water–glucose solutions. The proposed sensor exhibits two resonant frequencies at 2.61 GHz and 4.07 GHz, with reflection coefficients of −46.60 dB and −23.00 dB, respectively. A set of measurements was conducted to compare the performance of the resonator with and without the DGS under two sample-placement configurations: one with water and water–glucose solutions positioned over the feed lines and metallic resonant elements, and another with the water–glucose solutions placed directly over the ground plane. Among the evaluated cases, the ground-plane configuration proved to be the most advantageous, as it produced no frequency shift while yielding distinct magnitude responses of −41.91 dB, −45.62 dB, −47.74 dB, and −49.69 dB for glucose concentrations of 100, 150, 200, and 250 mg/dL, respectively. Overall, the resonator with the defective ground structure consistently demonstrated higher sensitivity and a more stable response pattern, indicating its strong potential for glucose-level monitoring applications. Full article

This paper examines DisAbitanti, a participatory cultural initiative developed in Corigliano d’Otranto (Grecìa Salentina, Southern Italy) to explore how performative and community-based practices may contribute to sustainable and proximity tourism in small heritage towns. The study adopts an exploratory qualitative case study design, combining participatory action research and artistic research, drawing on participant observation, reflective field diaries, semi-structured interviews with local actors and participants, and analysis of project materials and relevant local planning documents. The analysis identifies a set of emerging patterns suggesting that the reactivation of abandoned or underused spaces through site-specific performances and collective storytelling is associated with forms of resident participation, reconfiguration of resident–visitor roles, and off-season cultural activation. These dynamics contribute to strengthening local identity and social cohesion, while highlighting the role of cultural practice in place-based governance processes. The analysis indicates that performative interventions can act as catalysts for the emergence of informal governance dynamics within the case study, connecting local associations, artists, residents, and cultural organizers. This claim is supported by empirically observed indications, including the number and diversity of actors involved and the emergence of new collaborative interactions. While the findings are not intended to be generalizable, they provide analytical insight into how performative practices may enable forms of place-based coordination around heritage use and spatial activation, linking heritage experience to habitability and spatial equity. The paper concludes that DisAbitanti offers a context-sensitive approach for translating sustainability principles—consistent with the UN 2030 Agenda—into situated tourism governance practices, with potential relevance for other small inner peripheral towns facing seasonality and spatial marginalization. Full article

How can we best leverage higher education to address the pressing issues we face? While the SDGs reflect a global landscape dominated by complex, interconnected ‘wicked’ problems, Higher Education Institutions (HEIs) remain largely tethered to siloed, decontextualized instructional models. The inability of HEIs to shift practices to foster transversal, 21st-century skills necessary to navigate uncertain futures is a critical competency gap. This paper highlights the transformative potential of challenge-based learning (CBL) and place-based learning (PBL), high-impact experiential pedagogies, as critical tools for sustainability transformations. The Consortium for Adaptive Futures, an interdisciplinary and transnational community of practice, was launched in early 2025 to promote co-learning among faculty from North America and Europe for these practices. Drawing on insights from an inaugural symposium in Dublin, we identify three critical elements to HEI transformations that support sustainability and 21st-century skills to address grand challenges. These are: the importance of real-world relevance in education; the need for pedagogical shifts and faculty development to support these new roles; and the essential role of supportive institutional structures and resources to enable sustained engagement. In doing so, we issue a call to arms to HEIs and forward a reimagining of undergraduate education. Full article

Molecular spin-crossover (SCO) compounds constitute prototypical systems exhibiting first-order phase transitions. These transitions involve an abrupt switch between two well-defined states with distinctly different magnetic, optical, and vibrational properties. One state is diamagnetic (low-spin), while the other is paramagnetic (high-spin). Upon heating, the transition occurs at a characteristic temperature, T_up. Upon cooling, it takes place at a lower temperature, T_down < T_up, thereby giving rise to thermal hysteresis. Accordingly, each SCO compound is defined by a distinct pair of transition temperatures, T_up and T_down. The investigation of these molecular solids is of great importance, both for elucidating first-order phase transitions—including the potential emergence of re-entrant phases—and for their broad range of prospective applications. The critical temperatures T_up and T_down are pivotal in defining their practical utility. We present a strategy to modify and tune the transition temperatures of spin-crossover (SCO) compounds to suit different applications. The approach combines a given SCO material with layers of a second SCO system, enabling precise control of the characteristic temperatures of the resulting heterostructure. We illustrate this method with three case studies that span the 100 K–400 K temperature range. All simulations were performed using Monte Carlo methods within the Metropolis algorithm framework. Full article

Twenty strains of Schizophyllum commune from the BIOTEC culture collection were selected for this study. S. commune is characterized by white to gray fan-shaped caps with lobed margins and distinctive split gills. Phylogenetic analysis of combined LSU rDNA and ITS rDNA sequences data using maximum parsimony placed the fungi in a strongly supported clade with S. commune. All strains were primarily screened for exopolysaccharide (EPS) and biomass production using potato dextrose broth (PDB) and peptone yeast glucose medium (PYGM) in 250 mL flasks shaken at 200 rpm for 7 days. The results revealed three strains with high EPS production, each exceeding 2.3 g/L, namely MMCR00487, MMCR00474 and MMCR00256. These strains were selected for media optimization using a Plackett–Burman design. Among them, MMCR00256 exhibited the highest EPS yield of 8.34 ± 1.47 g/L, followed by MMCR00487 and MMCR00474. Therefore, the strain MMCR00256 was further optimized by central composite design. The results revealed that the optimized medium for MMCR00256 increased the production of EPS to 10.39 ± 1.69 g/L, with a biomass yield of 26.28 ± 1.63 g/L (395 mg/g). The 5 L bioreactor optimization tested two inoculum types (mycelial and pellet) and two media (CCD and estimated) using strain MMCR00256. The mycelial inoculum grown in the estimated medium produced the highest EPS yield of 8.37 ± 0.26 g/L after 3 days, with 13.56 ± 2.94 g/L biomass. In conclusion, this study demonstrates that S. commune MMCR00256, when cultivated using the estimated medium and mycelial inoculum, can achieve enhanced exopolysaccharide production with improved efficiency, highlighting its significant potential for the development of efficient and scalable schizophyllan production processes at the industrial scale. Furthermore, this study provides essential insights into the cultivation and optimization of schizophyllan in S. commune. Full article

Qualitative analysis of biochemical reaction systems reveals fundamental system-level properties that are independent of precise kinetic parameters, often context-dependent, or experimentally inaccessible. By focusing on structural and topological features—such as conservation relations, feedback loops, and pathway interconnections—qualitative analysis identifies invariant behaviors, robustness mechanisms, and potential failure modes inherent to the signaling network. In this study, we use Petri nets as a formal modeling framework to conduct qualitative analysis of the integrated MAPK and PI3K/Akt signaling network. By exploiting structural properties including place invariants, transition invariants, and siphons, the analysis establishes a direct correspondence between the Petri net structure and biologically meaningful conservation laws, signaling modules, and characteristic dynamic behaviors. The results demonstrate that the proposed model is structurally consistent, biologically plausible, and modular. Minimal semi-positive place invariants confirm mass conservation, indicating that proteins and enzymes circulate within closed molecular pools. Minimal semi-positive transition invariants identify canonical kinase–phosphatase cycles underlying sustained and reversible signaling. Hierarchical decomposition reveals a modular organization reducible to reusable enzymatic motifs, reflecting biological reuse across cascades and supporting scalability. Additionally, the identification of sixteen siphons that are also traps highlights persistent subsystems that ensure continuous regulator availability, confirming the robustness and dynamic sustainability of the integrated network. Full article

Memory is generally thought to be stored within centralized neural circuits. However, whether learned behaviors can persist in the absence of a brain remains unresolved. Planaria (Girardia spp.) possess a primitive cephalic ganglion and a remarkable capacity for regeneration, providing a unique system to examine non-cephalic memory retention. The primary aim of this study was to determine whether sucrose-induced conditioned place preference (CPP) is retained in posterior, brainless planarian fragments. Planaria were trained using a Pavlovian conditioning paradigm in which an initially unpreferred surface was paired with a 10% sucrose solution, resulting in a robust shift in surface preference. Following amputation, anterior fragments containing the cephalic ganglion as well as posterior fragments lacking the brain preserved the conditioned preference, demonstrating that reward-associated memory is stored even outside the cephalic nervous system. As a secondary objective, we examined the role of dopaminergic reinforcement using a D1 dopamine receptor antagonist during training. While antagonist-treated planaria failed to develop a CPP, posterior fragments from these amputated planaria likewise showed no conditioned preference, indicating that dopamine-dependent signaling is essential for sucrose-associated memory formation across the body. These results provide support for the hypothesis that reward-associated memory in planaria is distributed beyond the brain and can be modulated by dopaminergic pathways, highlighting the utility of this model for exploring fundamental mechanisms of reward, memory, and potential pharmacological interventions. Full article