Search Results (11,267)

Background: Adverse drug reactions (ADR) pose substantial risks to patient safety and challenge clinical decision-making. However, traditional predictive approaches frequently fail to deliver interpretable insights into the complex interplay between pharmaceuticals and biological systems. Methods: We propose the KRDQN (Knowledge Graph Reinforced Deep Q-Network) predictive framework. First, a knowledge graph (KG) that encompasses five entity types—drug, target, pathway, gene, and adverse drug reaction (ADR)—is constructed, and each node is enriched with intrinsic attribute features. A Deep Q-Network (DQN) is subsequently deployed within a reinforcement learning paradigm to generate interpretable ADR predictions. Model performance is evaluated by five-fold cross-validation, with accuracy and AUC reported. Finally, the Spearman correlation coefficients between drug–drug similarity and path–path similarity are computed, and case studies are conducted to further assess the predictive capability of KRDQN. Results: We evaluated KRDQN on a comprehensive data set encompassing both drug–drug interactions and ADR records. Experimental results demonstrate that KRDQN surpasses state-of-the-art baselines, attaining a recall of 0.8171 and an AUC of 0.8327. Furthermore, to demonstrate the practical value of the KRDQN prediction framework, we applied it to predict potential ADRs and their mechanism pathways for the drugs sunitinib and indomethacin. The results indicated that the KRDQN framework could identify biological mechanism pathways consistent with clinical evidence. Conclusions: In this study, we developed the reinforcement learning-based KRDQN predictive framework, which outperforms existing baselines in predictive performance and yields interpretable adverse drug reaction (ADR) predictions, thereby serving as a powerful tool for pharmacovigilance and clinical decision-making. Full article

Objective: Adolescence is a high-risk period for problematic eating behaviours, including overeating. However, few studies have explored adolescent perceptions of these eating behaviours and whether there is a shared understanding between adolescents and parents. This study aimed to investigate perceptions of eating behaviours, focusing on overeating, in Australian adolescents and parents. Method: Adolescents aged 13–19 years, and parents of adolescents, participated in two interviews for exploration and thematic deepening of participant perceptions, underpinned by Integrated Knowledge Translation Framework principles. Interviews explored perceptions of overeating and other eating behaviours, including help-seeking and stigma. Data were analysed thematically. Results: Twelve adolescents (59% female) and seven parents (100% female) participated in the interviews, with three major themes emerging. In theme 1, “perceptions of overeating”, interpretations of overeating varied; however, both adolescents and parents associated problematic overeating with increased frequency and impacts on functioning. Discrepancies between adolescent and parent perceptions of overeating terms such as binge eating were present. In theme 2, “beliefs about overeating”, adolescents felt that broaching the topic of overeating and help-seeking for overeating to be more challenging than restrictive eating disorders due to stigma. In theme 3, “perceptions of other eating behaviours”, there were differences between how adolescents perceived healthy eating and dieting compared to parents. Discussion: Differences in adolescent and parent understanding of eating behaviour terminology highlights a need for a shared language to support appropriate detection of problematic eating behaviours. There is a need for prevention and early intervention approaches that promote awareness and accessible support pathways for overeating to prevent progression to an eating disorder. Full article

Polymeric micro- and nanoplastic particles (MPs/NPs) have recently been recognized as potential biomedical pollutants that can enter the human bloodstream. Advances in analytical techniques have detected various polymers in human blood, raising concerns about their possible interactions with circulating cells, especially red blood cells (RBCs). RBCs are abundant, highly flexible, and lack internal repair mechanisms. This review summarizes current knowledge of how MPs and NPs interact with RBCs, emphasizing how physicochemical factors, including particle size, surface chemistry, environmental aging, and protein corona formation, influence hemocompatibility. Studies indicate that MPs can bind to RBC membranes, change the ζ-potential, reduce deformability, induce vesiculation and eryptosis, and, in some cases, cause hemolysis. These sublethal and lethal effects could have clinical significance, as even minor impairments in RBC mechanics may affect microvascular blood flow, oxygen delivery, and splenic clearance. Vulnerable populations—such as neonates and transfusion recipients—may be particularly susceptible to microparticle-induced RBC stress. While experimental data suggest MPs can harm RBCs, significant uncertainties remain regarding actual exposure levels, in vivo toxicity, and long-term health consequences. Addressing these gaps will require a multidisciplinary approach that combines environmental science, membrane biophysics, analytical chemistry, and clinical hematology to evaluate the health risks associated with increased microplastic exposure. Full article

Background: Undernutrition among infants and young children in South Asia remains a major public health concern, contributing to high rates of morbidity and mortality. While quantitative systematic reviews have identified various risk factors for undernutrition, no review has focused on qualitative studies. This study aims to review published literature on family member and healthcare provider perceptions about influences on undernutrition among infants and young children in South Asia. Methods: We searched for qualitative research articles published from 2000 to 2026 in the PubMed, Scopus and CINAHL databases, and used the Critical Appraisal Skills Program (CASP) tool to assess the quality of selected articles. Selected articles were analyzed thematically. The PROSPERO registration number is CRD42022385382. Results: After screening 201 research articles, 19 articles were selected for inclusion in this review. Perceived influences of undernutrition among children were categorized into individual, socio-cultural, economic, environmental and system factors. Interconnected influences included maternal illness, single motherhood, mothers’ knowledge and awareness, convenience of providing low-quality ready-made and junk food, spiritual beliefs and superstition, violence against women, financial constraints in a context of rising food prices and seasonal impacts on food production, and physical accessibility of healthcare services. Conclusions: This review emphasizes the complex interplay of influences on undernutrition among young children in South Asia. Potential interventions must be culturally tailored and gender-sensitive, with key strategies including nutrition education, community-based support, maternal health improvements, and policies addressing food insecurity and healthcare accessibility. Full article

Aging is accompanied by profound alterations in immune function that collectively drive increased susceptibility to infection, reduced vaccine efficacy, impaired tissue repair, and heightened risk of age-related diseases (ARDs). These alterations are characterized by the coexistence of immunosenescence and inflammaging. Rather than reflecting isolated cellular defects, immune aging emerges as a systems-level reprogramming of immune networks that disrupts the initiation, resolution, and regenerative phases of inflammatory responses. In particular, aging is associated with impaired resolution of inflammation, defective efferocytosis, reduced responsiveness to pro-resolving signals, and diminished regenerative capacity, leading to persistent inflammatory milieus and tissue damage. This review summarizes recent advances in the mechanisms underlying immune dysfunction in aging, with a focus on how chronic inflammation, failed resolution, and defective repair reinforce one another. We discuss how alterations in innate and adaptive immunity, immunometabolism, cellular senescence, and immune–tissue interactions drive inflammaging and contribute to major ARDs, including cancer, neurodegenerative, and cardiometabolic diseases. Finally, we highlight emerging therapeutic strategies aimed at restoring immune balance and resolution. By adopting a systems-level and network-based perspective, this review underscores immune aging as a modifiable driver of ARDs and identifies key knowledge gaps and future directions toward interventions that promote healthy aging and extended healthspan. Full article

The majority of approved drug products comprise formulations of either chemically synthesized small molecules or large molecular entities derived from living cells, commonly referred to as biologics. Over the past two decades, there has been remarkable growth in the approval of biologics for a variety of disorders, including respiratory diseases. The preference for biologics stems from their high target specificity, strong binding affinity, and favorable safety profiles. Most approved biologics are peptides or proteins, which are unsuitable for oral administration due to negligible bioavailability, resulting from their large molecular size, polarity, and susceptibility to enzymatic degradation in the gastrointestinal tract. Consequently, the majority of biologics are administered parenterally, delivering the drug systemically to reach target sites. However, achieving therapeutic concentrations of locally acting respiratory drugs in the lungs via systemic delivery often requires high doses, which increases the risk of adverse effects. For respiratory disorders, nasal and pulmonary drug deliveries are the preferred noninvasive routes. These routes bypass gastrointestinal and first-pass metabolism and deliver therapeutic agents directly to their local site of action. This approach enables a faster onset of action, reduces the required dose by orders of magnitude, and significantly lowers the risk of systemic adverse effects. These advantages have driven the successful development of inhaled formulations for certain rescue and maintenance medications that were originally administered orally or parenterally. Despite this, treatment options for respiratory diseases remain largely limited to small molecules, with only a single inhaled biologic approved in 1993, even though several parenterally administered biologics have since been approved for pulmonary disorders. The scarcity of inhaled biologics is primarily due to the inherent complexity of these drug substances, which impacts all stages of product development, including manufacturing, characterization, purification, stability, formulation design, delivery, and preclinical and clinical evaluations of safety and efficacy. Additionally, sponsors’ interest in developing inhaled biologics may be tempered by the lack of regulatory guidance addressing the multidisciplinary and intricate nature of their development. This article, together with the accompanying review, addresses both regulatory considerations and scientific challenges in the development of inhaled biologics. To the authors’ knowledge, these works represent seminal efforts to examine available regulatory guidance and the applicable literature across various phases of product development beyond safety and efficacy evaluations. We examined the formal regulatory expectations and summarized the requirements as they apply to inhaled products and inhaled biologic protein therapeutics. In parallel, we explored scientifically relevant considerations in the development of inhalation-specific protein therapeutics for which regulatory guidance remains limited, evolving, or absent. While they should not be considered definitive, it is hoped that these contributions will stimulate scientific and regulatory interest, ultimately promoting the identification and resolution of gaps to advance the development of locally acting biologics and address unmet patient needs. Full article

Type 2 diabetes (T2D) is a major global healthcare challenge and burden on the quality of life in affected individuals. While lifestyle management is the mainstay treatment for T2D, the advent of gut-incretin-based therapies with powerful effects on metabolic health, appetite and weight regulation has focussed attention on the role of the gut in the risk, progression and management of T2D. Beyond the tongue, intestinal sweet taste receptors (STRs) are increasingly being identified and functionally characterised. Growing evidence now supports a role for nutrient-activated (e.g., sugars) intestinal STRs in the release of gut hormones from enteroendocrine cells (EECs) and the control of blood glucose and body weight. However, the specific STR pathway and mechanisms linking STRs to these homeostatic controls are poorly understood, with a notable gap existing between evidence from preclinical studies and clinical validation. This review explores intestinal STR-EEC functions and the evidence on how these functions regulate glucose metabolism and energy homeostasis. We further discuss the impact of environmental and dietary factors on these signalling pathways. Full knowledge of the signalling and regulation of intestinal STR-EEC and integrated neural pathways will bridge the current knowledge gap, with a high potential to develop new novel strategies targeting STRs or EECs that preserve hedonic taste rewards and reduce cravings, as well as improve the management of individuals with metabolic diseases. Full article

Percutaneous left atrial appendage occlusion (LAAO), patent foramen ovale (PFO) closure, and atrial septal defect (ASD) closure rely on temporary antithrombotic therapy to prevent device-related thrombus during endothelialization, yet optimal regimens remain uncertain and vary widely across clinical practice. This review synthesizes contemporary evidence on postprocedural antithrombotic strategies, comparing efficacy and safety data and identifying key gaps in knowledge. After LAAO, therapeutic approaches range from short-term anticoagulation with vitamin K antagonists or direct oral anticoagulants to dual or single antiplatelet therapy in patients with high bleeding risk; observational data increasingly support DOAC-based regimens, although device-related thrombus remains a significant concern, and follow-up imaging protocols are inconsistent. Following PFO and ASD closure, antiplatelet-only regimens—typically brief dual antiplatelet therapy followed by aspirin—are widely used, with evidence suggesting that simplified or abbreviated strategies may be sufficient in selected patients. Despite extensive clinical experience, high-quality comparative trials are limited, and optimal therapy, duration, and surveillance remain debated. Standardized imaging definitions, randomized studies, and individualized risk-based frameworks are needed to optimize antithrombotic care after atrial structural interventions. Full article

Background/Objectives: There is a lack of cohesion in integrating current knowledge on the genetic and environmental etiology of dental impaction. The primary aim of this article is to review the current literature to identify candidate genes involved in the pathogenesis of dental impaction. Methods: A scoping review was conducted following PRISMA-ScR guidelines to identify and organize the available body of evidence. Relevant literature was searched in MEDLINE (via PubMed), Scopus, and Web of Science, with the final search conducted on 03 January 2026. Eligibility criteria included case–control, cohort, cross-sectional observational, and case report studies in humans. Selected studies focused on syndromic and non-syndromic variants, inheritance patterns, and genetic analyses. Risk of bias was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklists and AMSTAR 2. Results: Only 18 studies met the eligibility criteria. Most articles were case reports and retrospective observational studies, revealing a multifaceted genetic landscape underlying dental impaction, with mutations affecting transcription factors and signaling pathways critical for odontogenesis, particularly RUNX2, FGFR1, MSX1, PAX9, and AXIN2. Overall, the included studies showed moderate methodological quality. Conclusions: Current evidence does not clearly support specific genes as causal factors in dental impaction, but instead suggests a complex, likely polygenic susceptibility that modulates the anatomical threshold for tooth eruption. This review highlights RUNX2, FGFR1, MSX1, PAX9, and AXIN2, as well as emerging candidates involved in eruption and bone remodeling pathways. Future progress depends on standardized phenotyping, large replicated cohorts, and functional studies linking genetic variation to dental follicle-mediated eruptive remodeling. Full article

Greenhouse gas emissions associated with plastic production and disposal span the entire plastic life cycle, establishing a direct link between plastic pollution and climate change. This review demonstrates that micro- and nanoplastics (MNPs) also function as active components of climate feedback systems by disrupting marine trophic structures, altering microbial assemblages, and diminishing the ocean’s capacity for carbon storage. Synthesized evidence further indicates that environmental degradation of polymers enhances surface reactivity, facilitating the sorption and transport of persistent contaminants, including per- and polyfluoroalkyl substances (PFAS) and antibiotic-resistant bacteria (ARB). These interactions amplify combined risks to ecosystems and public health under climate change scenarios. This review also reveals that many existing remediation strategies prioritize waste reduction or physical removal while failing to account for contaminant–plastic–climate interactions, thereby limiting their long-term effectiveness. By integrating climate-related processes, polymer transformation, and contaminant dynamics, this review identifies critical knowledge gaps and underscores the need for mitigation strategies that jointly address plastic pollution, climate feedbacks, and emerging public health threats. Full article

Background/Objectives: Childhood cancer survivors face long-term cancer-related health risks, and daily behaviours, such as physical activity and recreational screen use, may influence their long-term overall wellbeing. Yet, little is known about survivors’ knowledge and understanding of recommended guidelines or their patterns of structured and unstructured activity. This study aimed to (i) assess survivors’ knowledge of physical activity and screen time guidelines, (ii) describe their self-reported (un)structured activity and screen use across weekdays and weekends, and (iii) examine associations with health-related quality of life. Methods: This secondary analysis used data from a feasibility pilot study of an intervention for survivors aged 8–13 years who had completed cancer treatment at least 12 months earlier. Participants self-reported physical activity, recreational screen use, knowledge of guidelines, and health-related quality of life (HRQoL). We used descriptive statistics and non-parametric tests to analyse behavioural patterns and associations. Results: Over one-third of survivors underestimated or overestimated the recommended physical activity and screen time (35%), whilst 23–50% reported ‘don’t know’. Participation in ‘Physical Education’ classes at school did not differ between summer and winter school terms, yet there was greater participation in structured physical activities in winter compared to summer school terms (median 270 vs. 170 min/week). For unstructured physical activities, 69% reported engaging in a median of 60 min/week at school on most days of the week in summer, whilst most survivors (96%) did not report any unstructured activity in winter. Only 19% met the recommended daily minimum of 60 min of physical activity year-round. Excessive screen use increased from school days (19%) to weekends (46%), notably handheld device screen time. We did not find any significant associations between meeting physical activity and screen time recommendations and HRQoL. Conclusions: Survivors frequently engage in irregular structured and unstructured physical activity levels and increased screen time. These findings emphasise the need for targeted, year-round interventions to improve physical activity, reduce recreational screen use, and support long-term survivorship health. Full article

Cognitive impairment is a serious comorbidity in chronic obstructive pulmonary disease (COPD), consistently associated with adverse clinical outcomes, including impaired self-management, poor treatment adherence, reduced participation in pulmonary rehabilitation, and increased risk of mortality. Despite this, it remains inconsistently recognised and insufficiently addressed during routine COPD assessment. This narrative review synthesises current evidence on the recognition and management of cognitive impairment in COPD, with a particular focus on understanding why it continues to be under-recognised and inadequately managed in clinical practice. Across care settings, cognitive concerns are commonly identified informally, assessed selectively, or deferred altogether, even when clinicians acknowledge their relevance to respiratory assessment, treatment implementation, and patient engagement. This persistent evidence–practice gap suggests the influence of factors extending beyond disease- or patient-related explanations alone. Emerging evidence indicates that clinician-level determinants, particularly clinical confidence, play a central role in shaping cognitive care practices. Limited clinical confidence appears to mediate the translation of existing knowledge and competence into clinical action, influencing decisions to initiate assessment, communicate cognitive concerns, assume clinical ownership, and pursue follow-up or referral. These confidence-related barriers are further reinforced by educational limitations, time constraints, diagnostic ambiguity, particularly in the early cognitive impairment stage, and the absence of clear operational guidance within COPD-specific frameworks. Conceptualising cognitive care through the lens of clinical confidence provides a coherent explanation for the underrecognition of cognitive impairment in COPD. It also helps account for observed variability in clinical decision-making, highlighting clinical confidence as a modifiable intermediary between knowledge, competence, and practice and a potential target for strengthening integrated, patient-centred COPD care. Full article

Background: In recent years, aesthetic medicine and cosmetic surgery have seen significant growth, reflecting changing sociocultural views on beauty and self-care; however, public knowledge and awareness of associated risks remain inconsistent. This study aimed to assess knowledge, attitudes, and behaviours toward aesthetic medicine and cosmetic surgery in a large metropolitan population in Southern Italy using the Knowledge–Attitude–Practice (KAP) framework. Methods: A cross-sectional survey was conducted between June 2021 and January 2022 among 1079 adults aged 18–72 years residing in the metropolitan area of Naples. A structured questionnaire collected socio-demographic data and assessed knowledge, attitudes, and behaviours related to surgical and non-surgical aesthetic procedures. Descriptive statistics and multiple linear regression analyses were performed to identify predictors of knowledge, attitudes, and behaviours. Results: Overall, 66.8% of participants reported having undergone general beauty treatments, while 9.8% declared the use of cosmetic medicine procedures. A total of 5.1% had undergone botulinum toxin treatments, 11% reported filler injections, and 9.8% had experienced plastic surgery. A majority had strong knowledge, especially on non-surgical procedures, but there were gaps in their knowledge on side effects, regulations, age limits, and qualifications. Most viewed appearance as important, though with critical views of excessive aesthetic treatments and claimed limited social media influence. Female sex and parental status were positively associated with aesthetic behaviours, while attitudes emerged as the strongest predictor of engagement. Conclusions: Aesthetic practices are widely accepted within this urban population, yet important informational deficiencies persist. Targeted educational interventions based on the KAP framework are warranted to enhance health literacy, promote safe decision-making, and foster realistic expectations regarding aesthetic medicine and cosmetic surgery. Full article

Background: Type 2 diabetes mellitus (T2DM) is commonly managed with complex pharmacotherapy combined with dietary modification, which increases the risk of clinically relevant drug–food interactions (DFIs). Despite their potential impact on treatment efficacy and safety, patient knowledge of DFIs—particularly in the context of modern therapies such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs)—remains insufficiently explored. Methods: This cross-sectional study assessed knowledge of DFIs among 103 adults with T2DM using a self-administered, expert-validated questionnaire. Data on sociodemographic characteristics, clinical variables, anti-diabetic therapy (including GLP-1 RAs), sources of education, and attendance at dietary consultations were collected. Knowledge scores were calculated based on correct responses and categorized into tertiles (low, moderate, high). Associations were analyzed using non-parametric tests. Multivariable logistic regression was performed to identify independent predictors of moderate-to-high DFI knowledge. Results: Substantial gaps in DFI knowledge were identified, particularly regarding interactions involving dietary fiber, dairy products, grapefruit juice, and nutrient deficiencies associated with long-term pharmacotherapy. Knowledge level was not significantly associated with age, educational attainment, diabetes duration, or GLP-1 RA use. Female sex was associated with higher knowledge in univariate analysis (p = 0.026); however, this association did not remain significant in the multivariable regression model. Attendance at at least one dietary consultation in the previous year was significantly associated with higher knowledge levels (p = 0.041) and remained an independent predictor in multivariable analysis (OR = 2.31; 95% CI: 1.04–5.15; p = 0.039). Most participants reported not receiving prior education on DFIs, while expressing a strong need for more frequent counseling. Conclusions: Patients with T2DM demonstrate insufficient knowledge of clinically relevant DFIs, including selected issues related to GLP-1 RA therapy. Attendance at structured dietary consultations was independently associated with higher levels of DFI knowledge; however, the directionality and causality of this relationship cannot be established. Given the cross-sectional design and the assessment of knowledge rather than behavioral or clinical outcomes, these findings should be interpreted as hypothesis-generating. Further longitudinal and interventional studies are required to determine whether improved DFI knowledge translates into meaningful changes in dietary behavior, treatment adherence, or metabolic outcomes. Full article

Rabies remains a zoonotic public health problem in Ghana despite the availability of effective preventive measures, including mass dog vaccination and timely post-exposure prophylaxis (PEP). We conducted a community-based cross-sectional mixed-methods study between June and December 2025 to assess rabies-related knowledge, risk perception, health-seeking behaviour following dog bites, and dog vaccination practices within a One Health framework. Structured face-to-face interviews were conducted with 450 adults from selected urban and rural communities in the Greater Accra, Ashanti, and Bono East regions, supplemented by focus group discussions. Quantitative data were analysed using descriptive statistics, chi-square tests, and multivariable logistic regression. Overall, 68% of respondents had heard of rabies; however, detailed knowledge of transmission and prevention was limited, with 189 (42.0%) correctly identifying dogs as the main source of transmission. Following suspected exposure, 162 (36.0%) reported using home remedies or traditional treatments. Dog vaccination coverage was 31.1%, below the level required to interrupt transmission. Educational level, place of residence, and prior dog-bite exposure were significantly associated with rabies knowledge, health-seeking behaviour, and vaccination practices (p < 0.05). This study provides updated evidence on community rabies knowledge, risk perception, and preventive practices, highlighting behavioural and structural gaps that may hinder effective control in Ghana. Full article