Search Results (1,250)

The interplay between the environmental exposome and the cancer genome remains a critical gap in precision oncology. While somatic mutational signatures—genomic fossils imprinted by exposures such as ultraviolet radiation; tobacco smoke; and industrial pollutants—are well characterised for their etiological significance; their functional impact on therapeutic efficacy remains largely unexplored. We hypothesised that these environmental genomic scars induce distinct pharmacogenomic vulnerabilities and resistance mechanisms that vary by geographical exposure patterns. This study employs two complementary analytical frameworks. First, a linear regression-based pharmacogenomic screen across four datasets (GDSC1, GDSC2, CTRP, CCLE; 1001 cell lines, 31 cancer types) identified 608 statistically significant (p < 0.01) mutational signature–drug interactions, revealing that UV-associated signature SBS7a is associated with broad-spectrum therapeutic resistance, including to BRAF inhibitors (PLX-4720, p < 10⁻⁴), while pollution-driven oxidative stress (SBS18) is associated with sensitivity to p38 MAPK inhibition (VX-702, r = −0.45, p < 10⁻⁹). Second, an XGBoost predictive model trained exclusively on 33,679 GDSC2 records using a 1265-feature matrix integrating 40 SBS signatures, drug chemistry descriptors, proteomic features, and two satellite-derived environmental variables (NASA PM_2.5 and UV)—achieved R² = 0.7973 on a 20% holdout set (grouped cross-validation R² = 0.7296). SHAP analysis revealed that satellite-derived PM_2.5 (Zone_PM25) ranked 7th of 1265 features, exceeding all 40 individual SBS mutational signatures. Synthesising these findings with satellite-derived atmospheric data, we constructed an exploratory spatially interpolated risk surface spanning 122 nations, generating the hypothesis that uniform drug efficacy assumptions may not apply globally. These findings suggest that a patient’s environmental exposure history may constitute a measurable pharmacogenomic variable. This exploratory framework warrants validation in independent datasets and with individual-level geographic data before clinical application. Full article

Medical device manufacturing requires strict quality control, reliable traceability, and compliance with regulatory requirements. In many cases, inspection activities are still carried out manually and production information is recorded separately, which can result in inconsistent defect detection and limited visibility of manufacturing performance. This paper presents the development and industrial implementation of an integrated closed-loop quality control architecture for a sterile single-use medical device assembly line, addressing the lack of integration between inspection, traceability, and control systems in existing manufacturing approaches. In the proposed approach, we combine radio-frequency identification, machine vision inspection, programmable logic control, and centralized production monitoring. RFID tags store the status of each unit at individual stations so that defective products cannot proceed to downstream operations. Machine vision systems verify component presence, detect missing parts, and confirm color-specific assembly requirements during production. The architecture was tested through implementation on an assembly line and evaluated with comparative pilot studies against a traditional manual inspection process. The upgraded line achieved scrap cost reductions of 52.77% and 53.23% while also improving inspection consistency and production traceability. The results demonstrate that integrating machine vision inspection with RFID traceability can significantly improve quality control and manufacturing efficiency in regulated medical device production. Full article

Background: Enhanced Recovery After Surgery (ERAS) pathways depend on nursing-led safety behaviours such as early mobilisation, opioid-sparing analgesia, device minimisation, and reliable discharge teaching to prevent immobility-related, opioid-related, and device-related harms. However, pre-licensure medical–surgical preparation inconsistently embeds these competencies, leaving ERAS delivery and patient-safety vulnerable to variation. Objective: To develop an evidence-informed, practice-development framework that translates ERAS principles into measurable nursing competencies and management priorities explicitly linked to patient-safety, quality improvement, and harm reduction in acute surgical care. Methods: This practice-development framework paper used a narrative literature review of ERAS guidelines, AACN Essentials, and published simulation reports (MEDLINE, CINAHL, Embase, Scopus, ERIC) to identify recurring competencies and scenario features. These were inductively organised and mapped to patient-safety priorities to derive a four-domain framework. Findings: Identified simulations emphasised early mobilisation and multimodal analgesia; nutrition, fluid stewardship, device minimisation, and ERAS-focused patient education were less represented. High-fidelity and virtual formats improved knowledge and confidence but rarely reported patient-level outcomes. These gaps informed a four-domain framework: (1) ERAS clinical pillars and priority nursing competencies; (2) scenario and modality design (including a worked POD-1 colorectal case); (3) assessment and feedback strategies anchored by the Lasater Clinical Judgement Rubric; and (4) implementation tools for nurse managers and ERAS leads to integrate simulation into orientation and quality dashboards. The framework conceptually links competencies to safety-relevant endpoints including opioid-related adverse events, immobility-related complications, device-related harms, and discharge-education reliability. Conclusions: ERAS-aligned simulation may offer a feasible, scalable patient-safety and practice-development strategy for aligning pre-licensure preparation with nursing-management priorities for harm reduction. The framework provides a conceptual model that warrants empirical evaluation. It maps ERAS pillars to nursing competencies, operationalises these through a reusable colorectal scenario, and links simulation-derived competencies to unit-level recovery and safety agendas. Full article

A quantification technique for costal cartilage calcification using ¹⁸F-sodium fluoride–positron emission tomography/computed tomography (¹⁸F-NaF-PET/CT) has yet to be established, and the effects of aging and other demographic variables on costal cartilage calcification remain understudied. This study aims to introduce a quantification methodology for assessing costal cartilage calcification using ¹⁸F-NaF-PET/CT, assess age-related changes in its ¹⁸F-NaF uptake in females and males, and examine the relationship between its ¹⁸F-NaF uptake and CT attenuation as well as ¹⁸F-NaF uptake and coronary artery calcification. In this retrospective study, we analyzed subjects from the Cardiovascular Molecular Calcification Assessed by ¹⁸F-NaF PET/CT (CAMONA) clinical trial. This study evaluated 130 subjects (mean age 48.7 ± 14.5 years; n = 67 females). We manually generated regions of interest overlying the costal cartilages from ribs 8 to 10 on the left side, carefully avoiding osseous uptake from adjacent ribs and sternum, to measure cartilaginous ¹⁸F-NaF uptake. Non-parametric statistical analyses (Spearman correlations, Mann–Whitney U tests, Kruskal–Wallis tests) and receiver operating characteristic analysis were performed to evaluate sex-specific age-related changes in uptake, correlations between imaging parameters, and associations with coronary artery calcium (CAC) score. In females, the mean ¹⁸F-NaF uptake (as assessed by average SUV_mean) was 0.69 ± 0.38 while the corresponding mean Hounsfield Unit (HU) was 108.0 ± 40.0. In males, the mean ¹⁸F-NaF uptake (as assessed by average SUV_mean) was 0.63 ± 0.22, and the mean HU was 104.0 ± 24.0. There was a significant correlation between ¹⁸F-NaF uptake and age in both females (p = 0.003, r = 0.36) and males (p < 0.0001, r = 0.63). The correlation was significantly stronger in males than females (Fisher’s z-test, p = 0.040). There was a significant correlation between CAC score and costal cartilage SUV_mean in both females (r = 0.26, p = 0.036) and males (r = 0.51, p < 0.0001). This study introduces a quantification technique to assess costal cartilage calcification using ¹⁸F-NaF-PET/CT and demonstrates that the calcification increases with age, more strongly in males than in females, and ¹⁸F-NaF uptake is correlated with CAC score. This technique can be applied to other cartilages of interest, in both physiological and pathological conditions, to assess the effects of aging and various demographic variables on cartilage calcification. Full article

Pulmonary diseases such as Chronic obstructive pulmonary disease (COPD), asthma, pulmonary fibrosis, and acute respiratory infections remain a major global health challenge due to their complex pathophysiology and limited therapeutic options. Conventional 2D cultures and animal models have provided foundational insights; however, they often fail to accurately replicate the human lung’s intricate architecture, immune interactions, and patient-specific variability. Recent advances in vitro technologies have transformed pulmonary research, enabling the generation of physiologically relevant and translational disease models. The review highlights the progression of lung research platforms from traditional monolayer cultures to advanced systems such as air–liquid interface models and 3D lung organoids. These cutting-edge models more effectively mimic the biochemical, mechanical, and spatial microenvironment of the respiratory system, enhancing the fidelity of disease modelling and drug screening. In parallel, the integration of computational modelling and artificial intelligence (AI) has emerged as a powerful synergistic approach. AI-driven analytics facilitate high-throughput imaging, biomarker discovery, and patient-stratified therapeutic prediction, while computational tools simulate disease networks, mechanobiological interactions, and pharmacological responses. The convergence of these technologies supports a deeper understanding of pulmonary disease progression and accelerates the development of precision therapeutics. Collectively, this review underscores the transformative potential of combining in vitro lung models with advanced computational and AI methodologies. This synergy not only improves translational relevance and reduces reliance on animal testing but also paves the way for personalised interventions that better address the complexity of human pulmonary disease. Full article

Mohandas K. Gandhi (popularly known as Mahatma Gandhi) has primarily been recognized for his work in developing the theory and practice of nonviolence (ahimsa) for the purpose of building a culture of sustainable peace. Although Gandhi’s writings do not explicitly engage such categories as negative and positive peace, peace and international relations, or pacifism and nonviolence, scholars in peace studies have nonetheless assessed his contributions to the evolution of the field. This article advances the study of peace by emphasizing the dynamic nature of nonviolence (ahimsa), which is inextricably connected to Gandhi’s vision of sarvodaya (uplift of all). It further argues that his approach to peacebuilding, grounded in the upholding of pluralism across civic life, offers a conceptual framework for disrupting hegemonic monolithic systems. Gandhi lived in a time when the concept of pluralism had not gained currency; however, his vision, rooted in the values of diversity and tolerance, can appropriately be understood under the now widely accepted concept of pluralism. Gandhi thus uniquely connected nonviolence, peace, pluralism, and sarvodaya. For him, peaceful co-existence mandates attention to diversity—an approach that can enrich contemporary conversations in a divided political, social, and religious landscape. As a political leader and social reformer, he promoted indigenous languages, diverse village industries, local economies, and multi-faith religious education. In his later life, he also advocated for inter-caste and interreligious marriages in order to mitigate communal tensions. Such attention to diversity offers a promising path toward realizing the goal of sustainable peace and sarvodaya in a contemporary landscape increasingly prone to monolithic systems. Sarvodaya inherently requires a commitment to pluralistic, dialogical, dialectical, and nonviolent engagement in all spheres of life. By emphasizing shared humanity and committing to diversity, Gandhi offers a social philosophy of respect for all life as well as uplift of all trades, languages, and belief systems grounded in the vision of welfare of all. His practical methods of engaging diverse actors, along with his radical efforts to disrupt autocratic, authoritative, and centralized systems, affirm that the objectives of sarvodaya and sustainable peace can be realized only through a radical pluralism. Full article

Background/Objectives: Overexpression of transferrin receptor (TFR1) is common in cancer and may be associated with inferior treatment outcomes. Due to these patterns and TFR1’s essential role in iron metabolism, the protein has been targeted for cytotoxic drug delivery. More recently, increased TFR1 expression has been linked to tumor microenvironment (TME) infiltration by immune effectors in selected tumors, but a comprehensive assessment of the genomic landscape associated TFRC (the gene encoding TFR1) expression has not been conducted. Methods: By utilizing a pan-cancer database of 93,248 patients with whole-exome and whole-transcriptome sequencing, we assessed TFRC-associated multiomic patterns. Results: We found that high TFRC expression correlates with significantly worse overall survival in multiple common solid tumor types, a higher tumor mutational burden (TMB), an increase in infiltrating effector cells with upregulated immune checkpoint markers within the TME, and increased frequency of specific high-risk genomic alterations. Further assessment in cell line models revealed increased susceptibility to cytotoxic T cells when iron metabolism is elevated, despite upregulation of the checkpoint ligand PD-L1. Conclusions: High TFRC expression, therefore, indicates worse clinical risk across multiple common tumor types but potentially increased susceptibility to cytotoxic immune effectors, informing the development of TFR1 biomarker-driven therapeutic strategies. Full article

Changes in the maternal serum cytokine landscape occur throughout pregnancy, representing immune adaptations and modifications to support a healthy pregnancy. A better understanding of normal cytokine patterns can help improve the management of pregnancy and potentially predict complications. Using maternal serum samples collected at four different timepoints from 29 subjects, we characterized the longitudinal serum cytokine patterns throughout normal pregnancy with a multiplex ELISA of 96 cytokines. Based on unsupervised principal component analyses of the 96-cytokine data, we developed an integrated panel that incorporated the data of 21 key cytokines. This integrated immune signature allowed us to distinguish serum samples collected at different stages of healthy pregnancy and evaluate their chemotactic properties in vitro. We also evaluated the potential of using integrated cytokine scores for identifying pathological condition like preeclampsia before clinical signs are presented. This study explored new approaches of developing serum biomarker panels for immune profiling and early detection of pathological conditions during pregnancy. Full article

Nipah virus (NiV) is a highly pathogenic zoonotic paramyxovirus responsible for sporadic outbreaks of severe disease with high case fatality rates in South and Southeast Asia. Human infection occurs through spillover from natural reservoirs, primarily fruit bats, or via human-to-human transmission, and is characterized by a broad clinical spectrum ranging from asymptomatic infection to acute respiratory disease and fatal encephalitis. Following entry via ephrin-B2 and ephrin-B3 receptors, NiV exhibits marked endothelial and neuronal tropism, leading to systemic vasculitis, disruption of the blood–brain barrier, and direct infection of the central nervous system. Disease progression is driven by a complex interplay between viral replication strategies and host immune responses. NiV effectively counteracts innate immunity through multiple viral proteins that inhibit interferon signaling, while simultaneously inducing dysregulated inflammatory responses that contribute to tissue damage and multi-organ failure. Neurological involvement represents the most severe manifestation, often resulting in acute or relapsing encephalitis with long-term sequelae among survivors. Despite the severity of the disease, no licensed antiviral therapies or human vaccines are currently available. Therapeutic development has focused on neutralizing monoclonal antibodies targeting viral glycoproteins and small-molecule antivirals that inhibit viral RNA synthesis, both of which show promising results in preclinical models, but remain limited by timing and translational challenges. In parallel, several vaccine platforms—including viral vectors, mRNA-based constructs, and recombinant protein subunits—have advanced to early-phase clinical trials, demonstrating encouraging immunogenicity. Beyond biomedical interventions, effective outbreak containment relies on integrated public health strategies. The “Kerala model” highlights the importance of rapid case identification, isolation, contact tracing, and community engagement within a One Health framework to mitigate transmission and reduce mortality. This review synthesizes the current knowledge on NiV pathogenesis, immune evasion, clinical manifestations, and emerging therapeutic and vaccine strategies, while highlighting critical gaps and future directions for improving the preparedness and response to this high-consequence emerging pathogen. Full article

This systematic literature review (SLR) evaluates the existing literature on the benefits, implementation challenges, and ethical concerns associated with Artificial Intelligence (AI)-driven Knowledge Management Systems (KMS) across industries. The SLR followed PRISMA guidelines to identify studies from Scopus, Web of Science, JSTOR, and Google Scholar, using inclusion and exclusion criteria. Critical Appraisal Skills Programme (CASP) checklists were used to assess methodological quality and risk of bias in the included studies, and a structured narrative synthesis was employed to synthesize the findings. The review of 21 articles reveals benefits like improved knowledge capture and creation, storage, retrieval, personalization, and efficient dissemination, which lead to effective decision-making and performance improvements. The implementation barriers are categorized as organizational, technological, ethical, and financial, which generate a lack of trust, inability to manage, lack of interoperability, and monetary constraints. These barriers can be overcome by adopting Kotters’ Eight Stage Change Model, developing interoperability frameworks, evolving ethics benchmarks and standard guidelines for governance, and using viability analyses that incorporate both financial and non-financial considerations. In addition to bridging the gap between AI and KMS theories, the paper also provides practical and actionable insights about managing implementation and governance challenges. Full article

Given livestock’s crucial role in global food security and economic stability, the alarming threat of climate change calls for the implementation of effective mitigation strategies for climate-resilient livestock production. Management and nutritional strategies offer temporary relief, whereas genetic approaches represent a permanent solution. The role of genetic tools in enabling the development of climate-resilient livestock breeds is widely recognized. Genetic tools like microarrays, RNA-seq, omics, and GWAS can improve the understanding of livestock’s climate adaptability at a molecular level. These tools facilitate the identification of biomarkers for thermo-tolerance, bordering on climate-resilient livestock breeding. Among them, studies employing genome-wide association studies (GWAS) have increased in recent years. GWAS have the potential to improve the genetic basis of thermo-tolerance in heat-stressed livestock populations. GWAS have been used to identify candidate genes for complex and economically important traits in livestock. These include growth, reproduction, disease resistance, milk, meat, and wool production traits under heat stress conditions. This makes GWAS a useful tool for identifying biomarkers that can be incorporated in breeding programs through marker-assisted selection (MAS). The integration of these potential biomarkers into selection and breeding programs would allow GWAS to substantially refine breeding strategies, thereby advancing the climate-resilient potential and sustainability of the livestock sector. Furthermore, GWAS, when utilized along with emerging technologies like Artificial Intelligence (AI), machine learning (ML), and deep learning (DL) for genomic prediction, can predict genetic aspects of livestock adaptation more efficiently and precisely. Thus, future studies should focus on integrated modeling approaches for improving the climate resilience of livestock without jeopardizing their production potential. Such an effort will contribute to sustainable livestock production as well as ensure food security for the growing human population amid changing climate conditions. Full article

Glioblastoma (GBM) is the most lethal and aggressive primary brain tumor in adults. Despite a standard-of-care regimen involving surgical resection, radiotherapy and temozolomide (TMZ), median overall survival typically hovers between 12 and 15 months. This poor prognosis is driven by profound intratumoral heterogeneity, glioma stem cell populations, and an immunosuppressive microenvironment that collectively fuel resistance to traditional apoptosis-centric therapies. Ferroptosis—a form of regulated cell death driven by iron-dependent phospholipid peroxidation and the collapse of antioxidant defenses—has emerged as a compelling alternative for eliminating therapy-refractory GBM cells. This review examines the molecular machinery of ferroptosis in glioma and explores how an additional regulatory layer, noncoding RNAs (ncRNAs), modulates this process. We highlight key experimentally validated axes where microRNAs, long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) orchestrate iron handling and antioxidant thresholds. These include sensitizers like miR-147a and circLRFN5, which promote iron overload, and resistors like circCDK14 and TMEM161B-AS1, which act as “ferroptosis brakes”. Furthermore, we discuss how integrative analyses of TCGA and CGGA cohorts have yielded ferroptosis-related lncRNA signatures that robustly predict patient survival. Finally, we outline the clinical potential of these ncRNAs as biomarkers and therapeutic targets while addressing the delivery challenges, such as the blood–brain barrier, that must be overcome to achieve precision, ferroptosis-oriented GBM therapy. Full article

The parks and open spaces of planned neighbourhood are generally underutilized in cities due to the lack of a Child-Friendly Environment (CFE). The quality of parks and open spaces can be elevated by addressing and improving the deficiencies identified in their conditions. There is a need to identify the parameters for rating neighbourhood parks and open spaces. This research aims to understand the level of CFEin the planned neighbourhood parks of a metropolitan city. The research considers three parks as case study areas, Gandhi Park, Maharanapratap Park, and Balmiki Park in the city of Lucknow, the state capital of Uttar Pradesh, India’s most populous state. The research employed the Analytical Hierarchy Process (AHP) method to rate the parks with the use of a nine-point weighting scale. The research identified various dimensions under five major parameters of CFE, namely: perception, physical, social, cognitive, and emotional. The cognitive and perception parameters are observed to play the most significant role in generating CFE. The research result could be used in planning and developing CFE parks and open spaces in neighbourhoods by incorporating the critical dimensions and key elements of the identified parameters in policy guidelines, norms and standards. Full article