Search Results (1,714)

Breast cancer remains a major global health challenge, with treatment access further constrained during the COVID-19 pandemic, particularly in resource-limited settings. This study evaluates the in vitro effects of hypofractionated versus conventionally fractionated radiotherapy on three breast cell lines: MCF-7 (oestrogen receptor-positive, ER⁺/PR⁺), MDA-MB-231 (triple-negative: ER⁻/PR⁻/HER2⁻), and MCF-10A (non-tumorigenic mammary epithelial). Cells were exposed to cobalt-60 γ-rays, and radiobiological endpoints assessed included clonogenic survival, α/β ratios, adaptive responses, migration, invasion, and cytotoxicity through lactate dehydrogenase assays. The α/β ratios ranged from 2.5 to 5.4 Gy across breast cancer subtypes. Hypofractionation reduced survival in hormone receptor-positive cells, whereas triple-negative cells exhibited increased survival. Adaptive radiation responses enhanced viability across all cell lines, while non-cancerous MCF-10A cells demonstrated reduced migration following treatment. These findings suggest that hypofractionated radiotherapy may be beneficial in hormone receptor-positive breast cancer, while triple-negative disease may show a trend toward different responses, although this was not statistically significant (MDA-MB-231, p = 0.290). The results underscore the importance of tailoring fractionation strategies to breast cancer subtype and highlight the translational potential of preclinical radiobiology in guiding personalised radiation oncology approaches. Full article

Background: Kidney transplantation outcomes in resource-limited settings remain underreported. This 10-year retrospective review examined the clinical characteristics, long-term pharmacokinetics, and outcomes of kidney transplant recipients at a South African public hospital. Methods: Data from kidney transplant recipients between January 2012 and December 2022 were analysed. Graft and patient survival were assessed using Kaplan–Meier analysis. Cox proportional hazards models were used to evaluate the associations between clinical and pharmacokinetic variables and outcomes. Results: The one- and five-year graft survival rates were 87.9% and 65.6%, respectively. Acute rejection, as confirmed by biopsy, was associated with graft failure (HR, 2.46; p = 0.010). Increasing recipient age at transplantation increased the graft failure risk by about 5.0% per year (HR: 1.05, p = 0.006). Tacrolimus trough and normalised trough levels were lower in the graft loss group 73% and 93% of the time, respectively, despite similar tacrolimus doses. Whereas achieving optimal tacrolimus concentration did not significantly affect graft survival, maintaining a haemoglobin level >10 g/dL improved the chances of 3-, 4-, and 5-year graft survival (p-value, 0.001, 0.001, and <0.001, respectively). Patient survival rates were more favourable than graft survival rates. The 1-year and 5-year patient survival rates were 90.0% and 77.4%, respectively. Conclusions: This study offers insights into transplant outcomes in low-resource public health settings. The findings emphasise the impact of rejection and age on the risk of graft failure and the significance of maintaining adequate haemoglobin levels after transplantation. The results also indicate the need for more nuanced and personalised approaches to tacrolimus monitoring in the long-term following transplantation. Full article

Additive manufacturing has been adopted in several industries including the medical field to develop new personalised medical implants including tissue engineering scaffolds. Custom patient-specific scaffolds can be additively manufactured to speed up the wound healing process. The aim of this study was to design, fabricate, and evaluate a range of materials and scaffold architectures for 3D-printed wound dressings intended for soft tissue applications, such as skin repair. Multiple biocompatible polymers, including polylactic acid (PLA), polyvinyl alcohol (PVA), butenediol vinyl alcohol copolymer (BVOH), and polycaprolactone (PCL), were fabricated using a material extrusion additive manufacturing technique. Eight scaffolds, five with circular designs (knee meniscus angled (KMA), knee meniscus stacked (KMS), circle dense centre (CDC), circle dense edge (CDE), and circle no gradient (CNG)), and three square scaffolds (square dense centre (SDC), square dense edge (SDE), and square no gradient (SNG), with varying pore widths and gradient distributions) were designed using an open-source custom toolpath generator to enable precise control over scaffold architecture. An in vitro degradation study in phosphate-buffered saline demonstrated that PLA exhibited the greatest material stability, indicating minimal degradation under the tested conditions. In comparison, PVA showed improved performance relative to BVOH, as it was capable of absorbing a greater volume of exudate fluid and remained structurally intact for a longer duration, requiring up to 60 min to fully dissolve. Tensile testing of PLA scaffolds further revealed that designs with increased porosity towards the centre exhibited superior mechanical performance. The strongest scaffold design exhibited a Young’s modulus of 1060.67 ± 16.22 MPa and withstood a maximum tensile stress of 21.89 ± 0.81 MPa before fracture, while maintaining a porosity of approximately 52.37%. This demonstrates a favourable balance between mechanical strength and porosity that mimics key properties of engineered tissues such as the meniscus. Overall, these findings highlight the potential of 3D-printed, patient-specific scaffolds to enhance the effectiveness and customisation of tissue engineering treatments, such as meniscus repair, offering a promising approach for next-generation regenerative applications. Full article

Background. Enhanced Recovery After Surgery (ERAS) is a structured, multidisciplinary programme designed to optimise the entire perioperative pathway through evidence-based, patient-centred, standardised care. The objective of this report is to determine whether it is feasible to implement an ERAS^® program in orthopaedic surgery within our institution for primary THA and TKA. Methods. This single-centre quality-improvement project followed the ERAS^® Society certification framework to create and implement an enhanced-recovery pathway for primary total hip and knee arthroplasty. The three-phase roadmap comprised baseline pathway mapping and audit, pilot implementation and refinement, and full roll-out, punctuated by four multidisciplinary seminars. Key aspects of this programme included preoperative education, minimal fasting and early return to feeding, rational choice of regional anaesthesia techniques, administration of multimodal analgesia, reduction in urinary and surgical catheterization, active management of the risk of blood loss and deep vein thrombosis, optimisation of surgical workflow and techniques, and early mobilisation of patients. Global- and element-level compliance was tracked prospectively; ≥70% compliance was required for certification. External ERAS^® Society review at month 15 confirmed data integrity, sustainability planning, and successful certification. Continuous feedback loops drove micro-teaching and order-set optimisation throughout deployment phases. Results. Our ERAS programme for primary THA and TKA was introduced in April 2022. The definitive programme contained 24 mandatory elements grouped into three perioperative areas. After the fourth seminar, the rate of compliance was 81%. The certification was obtained in June 2023. Conclusions. Implementing an ERAS^® programme for primary total hip and knee arthroplasty is feasible within a high-volume academic institution when supported by multidisciplinary teamwork, robust data collection, and iterative feedback mechanisms. Further high-quality outcome-focused research is required to evaluate the clinical impact of individual ERAS components and to validate a personalised ERAS programme incorporating emerging technologies. Full article

The integration of generative AI tools, such as ChatGPT, Gemini, and DeepSeek, into higher education offers transformative opportunities for personalised learning and academic productivity. However, their unregulated use raises concerns about academic integrity, critical thinking, and educational equity. This systematic review synthesises insights from 96 peer-reviewed articles, identifying six key intervention themes, namely, curriculum integration, policy and governance, faculty development, student-centred strategies, assessment adaptation, and technological infrastructure. Together, these themes form a comprehensive intervention framework designed to guide students’ ethical and effective engagement with AI. This review highlights the need for institutions to move beyond fragmented policies, fostering systemic cultural and pedagogical change to align AI use with authentic learning outcomes. By bridging theoretical gaps and providing actionable strategies, this framework equips educators and policymakers to scaffold responsible AI integration across diverse higher education contexts. Full article

Background/Objectives: Parental mental health challenges are associated with parenting difficulties and child mental health issues. Parenting interventions can support families; however, parents with mental health challenges face barriers to accessing parenting support, which is not consistently offered within adult mental health settings. Embedding technology-assisted parenting programs into these settings could provide accessible, holistic support. Partners in Parenting Kids (PiP Kids) is a digital parenting program designed to prevent child anxiety and depression, yet its suitability for parents with mental health challenges and fit within mental health services remains unclear. This study aimed to co-design and adapt PiP Kids for future implementation in an Australian adult mental health service. Methods: Parents who recently sought mental health support (n = 8) and service providers (n = 7) participated in co-design workshops to explore needs and preferences for a technology-assisted parenting program and iteratively develop a prototype. Parents (n = 3) trialled the online component of the prototype and participated in qualitative interviews to assess acceptability. Results: The adapted clinician-supported program was designed to facilitate (1) parent and clinician readiness for parenting support; (2) emotional and social support for parents and clinicians; (3) practical, personalised parenting knowledge; (4) parent-led empowerment; and (5) accessible, integrated support. Prototype clinician training was developed to strengthen the clinician-support component. Parents indicated initial acceptability of the online prototype while reiterating the value of including face-to-face support. Conclusions: This study co-designed an online, clinician-supported parenting program for future embedding within adult mental health settings. The findings highlight key considerations for developing and implementing technology-assisted interventions that promote family-focused care for parents seeking mental health support. Full article

The complement system is a key component of innate immunity, responsible for mediating the rapid clearance of pathogens and coordinating adaptive immune responses. Although complement activation is essential for effective infection control and prevention, its excessive or dysregulated function contributes to the pathogenesis of various immune-mediated disorders. Therefore, therapeutic inhibition of the overactive complement cascade, in which specific components are selectively blocked to suppress pathological activation, plays an important role in the treatment of various complement (immune)-mediated diseases. This article provides an overview of complement inhibition as a therapeutic strategy, highlighting the infectious risks associated with its use. Disruption of complement-dependent host defence mechanisms increases the risk of invasive infections (caused by encapsulated pathogens, e.g., Neisseria spp., Streptococcus pneumoniae and Haemophilus influenzae type B), which represent a significant clinical challenge. Therefore, the use of complement inhibition should not only be effective but also safe in combination with the application of all possible tools to prevent infections. Strategies, such as vaccination and antibiotic prophylaxis, are crucial to minimise these complications, despite the persistence of the risk of breakthrough infections. Furthermore, this review examines advancements in patient risk stratification, evaluates alternative preventive measures, and identifies key gaps in current clinical practice. Future directions include improving monitoring protocols, creating more selective or locally acting complement inhibitors, and implementing biomarker-driven personalised therapies that maximise benefits while reducing side effects. Full article

A theoretical model of learning is proposed which is grounded in the constitutive role of interpersonal relationships, integrating contributions from early developmental psychology and relational philosophy. Using a Theoretical Educational Inquiry approach, the study critically examines dominant competency-based and cognitivist models, identifying their inability to account for learning as a deep personal transformation. Drawing on authors such as Stern, Trevarthen, Hobson, Winnicott, and Kohut, it presents empirical evidence that the self and cognitive-affective capacities emerge within primary relational bonds. However, interpersonal relationships are not the environment where development occurs, but the end towards which it is oriented: if the relational bond is the point of departure, the interpersonal encounter is the telos shaping the whole process. The child’s engagement with inner and outer worlds is driven by the search for such encounter, irreducible to mere relational pleasantness, although this may indicate its realization. Philosophical perspectives from Polo, Levinas, Buber, Whitehead, Spaemann, and Marcel support the understanding of learning as a relational event of co-constitution. Learning implies cycles of crisis and reintegration. This approach shifts the focus from skill acquisition as an end to using it as a means for fostering meaningful interpersonal relationships, thereby reorienting education towards a dignity-centered paradigm. Full article

Background/Objectives: Within Paediatric Palliative Care (PPC), motherhood in the context of severe cognitive impairment is shaped by unique emotional, relational, and identity-related challenges. Traditional understandings of maternal identity are strained when verbal communication and typical developmental milestones are absent. Although caregiving in PPC has been widely studied, the subjective and symbolic dimensions of motherhood in this setting have received far less attention. This study sought to explore how mothers construct, interpret, and make sense of their maternal identity while caring for a child with severe cognitive impairment in a PPC context, and to underscore the clinical relevance of these identity-related processes. Methods: A qualitative study was conducted involving nine mothers of children receiving paediatric palliative care services at a regional centre in Italy. Participants engaged in three online focus groups, totalling 270 min. Reflexive thematic analysis was employed to interpret the transcribed data, using ATLAS.ti software, version 25.0.1 ATLAS.ti Scientific Software Development GmbH, Berlin, Germany, for support. Member reflections were incorporated to validate the findings. Results: Three interconnected themes emerged from the reflexive thematic analysis. First, mothers described the development of a fusion-like, enmeshed mother–child relationship, characterised by embodied attunement, specialised interpretive expertise, and lifelong care dependency. Second, mothers detailed the construction of their maternal role, shaped by emotional labour, identity negotiation, sacrifice, loneliness, and peer support, alongside the construction of the child’s role, in which children were perceived as unique, symbolically meaningful beings whose social presence and limited reciprocity shaped maternal identity. Third, mothers articulated a search for meaning that sustained them throughout the caregiving journey, reframing their experience within a broader existential and relational perspective. Conclusions: Maternal caregiving in PPC encompasses distinct emotional, relational, and symbolic dimensions that extend beyond conventional understandings of motherhood. Grasping these identity-related dynamics has direct clinical relevance: it enables more attuned communication, strengthens the therapeutic alliance, and supports personalised, meaning-oriented care. These insights highlight the need for tailored interventions and further qualitative research to inform health care professionals and interdisciplinary practice. Full article

Background/Objectives: Mathematical modelling provides a quantitative way to describe the fate and action of drugs in the oral cavity, where transport processes are shaped by salivary flow, pellicle formation, biofilm structure and the wash-out effect of gingival crevicular fluid (GCF). Local pharmacokinetics in the mouth differ substantially from systemic models, and therefore a dedicated framework is required. The aim of this work was to present a structured, physiologically based concept that links in vitro release testing with local pharmacokinetics and pharmacodynamics. Methods: A narrative review with elements of systematic search was conducted in PubMed, Scopus and Web of Science (1980–2025) for publications describing drug release, local PBPK, and PK/PD modelling in the oral cavity. Mathematical formulations were grouped into release kinetics, mini-PBPK transport and local PK/PD relations. Classical models (Higuchi, Korsmeyer–Peppas, Peppas–Sahlin) were integrated with a mini-PBPK structure describing saliva–mucosa–biofilm–pocket interactions. Results: The combined model captures adsorption to pellicle, diffusion within biofilm and wash-out by GCF. It allows simulation of variable clinical conditions, such as inflammation-related changes in Q_GCF, and links local exposure to pharmacodynamic outcomes. Case studies with PerioChip^®, Arestin^®, and Atridox^® demonstrate how mechanistic models explain observed therapeutic duration and low-systemic exposure. Conclusions: The proposed mini-PBPK framework bridges empirical release data and physiological transport in the oral cavity. It supports rational formulation design, optimisation of local dosage, and personalised prediction of drug retention in gingival pockets. This modelling approach can become a practical tool for the development of dental biomaterials and subgingival therapies. Full article

Pulmonary arterial hypertension (PAH) is a severe, progressive vasculopathy characterized by endothelial dysfunction, medial hypertrophy, and maladaptive vascular and cardiac remodelling that ultimately leads to right-heart failure and premature death. Despite advances in vasodilator therapies targeting endothelin, nitric oxide, and prostacyclin pathways, a substantial proportion of patients fail to achieve or maintain a low-risk profile, highlighting the need for disease-modifying strategies. Dysregulation of transforming growth factor-β (TGF-β) superfamily signalling, with excessive activin and growth differentiation factor activity and impaired bone morphogenetic protein signalling, plays a central role in PAH pathobiology. Sotatercept, a first-in-class activin signalling inhibitor, restores this imbalance by selectively trapping pro-proliferative ligands, thereby addressing a key molecular driver of pulmonary vascular remodelling. Evidence from pivotal phase II and III trials—PULSAR, STELLAR, ZENITH, and HYPERION—demonstrates that sotatercept significantly improves exercise capacity, haemodynamics, and risk status when added to background therapy. This review summarises the molecular mechanisms underlying sotatercept’s therapeutic effects, synthesises the current clinical evidence, and discusses its emerging role as a disease-modifying agent capable of promoting reverse pulmonary vascular remodelling within contemporary PAH management. Full article

The clinical management of major depressive disorder is constrained by a trial-and-error approach. The clinical management of major depressive disorder is constrained by a trial-and-error approach. While computational methods have focused on static binary classification (e.g., responder vs. non-responder), they ignore the dynamic nature of recovery. Building upon the recently proposed prognostic theory of treatment response, this article presents a methodological framework for its operationalisation. We define a multi-modal data architecture for the theory’s core constructs—the Patient State Vector (PSV), Therapeutic Impulse Function (TIF), and Predicted Recovery Trajectory (PRT)—transforming them from abstract concepts into specified computational inputs. To model the asynchronous interactions between these components, we specify a Time-Aware Long Short-Term Memory (LSTM) architecture, providing explicit mathematical formulations for time-decay gates to handle irregular clinical sampling. Furthermore, we outline a synthetic validation protocol to benchmark this dynamic approach against static baselines. By integrating these technical specifications with a translational pipeline for Explainable AI (XAI) and ethical governance, this paper provides the necessary blueprint to transition psychiatry from theoretical prognosis to empirical forecasting. Full article

Oesophageal cancer remains a significant global health burden with poor survival outcomes despite multimodal treatment. Recent advances in magnetic resonance imaging (MRI) have opened opportunities to improve radiotherapy delivery. This review examines the role of MRI and MR-guided radiotherapy (MRgRT) in oesophageal cancer, focusing on applications in staging, treatment planning, and response assessment, with particular emphasis on magnetic resonance linear accelerator (MR-Linac)-based delivery. Compared to computed tomography (CT), MRI offers superior soft-tissue contrast, enabling more accurate tumour delineation and the potential for reduced treatment margins. Real-time MR imaging during treatment can facilitate motion management, while daily adaptive planning can accommodate anatomical changes throughout the treatment course. Functional MRI sequences, including diffusion-weighted and dynamic contrast-enhanced imaging, offer quantitative data for treatment response monitoring. Early clinical and dosimetric studies demonstrate that MRgRT can significantly reduce radiation dose to critical organs while maintaining target coverage. However, clinical evidence for MRgRT in oesophageal cancer is limited to small early-phase studies, with no phase II/III trials demonstrating improvements in survival, toxicity, or patient-reported outcomes. Long-term clinical benefits and cost-effectiveness remain unproven, highlighting the need for prospective outcome-focused studies to define the role for MRgRT within multimodality treatment pathways. Full article

Background: Coronary artery bypass grafting (CABG) is a well-established revascularization strategy for patients with multivessel coronary artery disease. The effectiveness of CABG is significantly influenced by antiplatelet therapy aimed at maintaining graft patency and reducing thrombotic complications. However, substantial inter-individual variability exists in platelet function responses to standard therapies such as aspirin and clopidogrel, leading to antiplatelet resistance. This variability has been linked to increased risks of myocardial infarction, stroke, and early graft failure. Platelet function testing (PFT) offers a potential strategy to identify resistance and guide more personalized antiplatelet therapy. This study aims to evaluate the association between perioperative platelet function test results and clinical outcomes following CABG. By assessing platelet responsiveness at multiple timepoints and correlating findings with postoperative events, the study seeks to determine whether PFT can stratify risk and improve patient management. Methods: This is a prospective, single-centre, observational cohort study conducted at a tertiary NHS cardiac surgery centre. Patients having elective or urgent isolated CABG will be enrolled and undergo perioperative PFT using the TEG6s system. Clinical outcomes will be monitored for 12 months postoperatively, with primary endpoints assessing the correlation between platelet function results and major adverse cardiovascular and cerebrovascular events (MACCE). Secondary endpoints will include the prevalence of antiplatelet resistance, demographic predictors, and the feasibility of integrating PFT into clinical workflows. Results: This study will report the prevalence of aspirin and clopidogrel resistance in CABG patients based on TEG6s PFT, as well as the correlation between platelet function results and MACCE, postoperative bleeding, and the need for surgical re-exploration. Additionally, it will examine the associations between demographic and clinical factors—such as diabetes status, renal function, BMI, and surgical technique—and variability in platelet responsiveness. The feasibility of incorporating PFT into perioperative workflows will also be evaluated, assessing whether results could support personalized antiplatelet management in future clinical trials. Conclusions: Findings from this study will provide real-world evidence regarding platelet function variability in CABG patients and suggest that PFT may identify those at increased risk of thrombotic complications. This exploratory analysis supports the need for larger interventional trials aimed at optimizing individualized postoperative antiplatelet therapy to improve surgical outcomes. Full article

Compression garments are widely employed in medical and sports contexts for their ability to promote venous return, manage oedema, support musculoskeletal function, and enhance athletic recovery. Advances in textile-based compression systems have been driven by innovations in fibres, yarn structures, fabric structure engineering, and design methods. This review critically examines the current literature on compression garments, highlighting the influence of raw materials and yarn architectures on performance, durability, and wearer comfort. Attention is given specially to fabric structures and manufacturing methods, where the evolution from traditional cut-and-sew methods to advanced seamless, flatbed, and circular knitting technologies is highlighted, along with their impact on pressure distribution and overall garment efficacy. The integration of 3D body scanning, finite element analysis, and predictive modelling, which enables more personalised and precise garment design, is also speculated upon. Moreover, the review highlights testing and evaluation methodologies, spanning both in vivo and in vitro based assessments, pressure sensor studies for real-time monitoring, and theoretical models mostly based on Laplace’s law. This literature survey provides a foundation for future innovations aimed at optimising compression garment design for both therapeutic and athletic use. Full article