Search Results (244)

Diabetes mellitus (DM) is a complex metabolic disorder characterized by chronic hyperglycemia and represents a major global public health concern due to its rapidly increasing prevalence. Although current pharmacological therapies effectively achieve glycemic control, their long-term use is limited by adverse effects, high costs, patient compliance issues, and increasing interest in safer, multi-targeted therapeutic strategies. In this context, plant-derived bioactive compounds have gained attention as complementary or alternative approaches to metabolic disease management. Gymnema sylvestre (Retz.) R.Br. ex Sm (GS), traditionally known as “gurmar” (“sugar destroyer”), is one of the most extensively studied medicinal plants with significant antidiabetic potential. This review evaluates the antidiabetic effects of G. sylvestre, focusing on its phytochemical composition, molecular mechanisms, and impact on diabetes-related complications. Major bioactive constituents, including triterpenoid saponins (gymnemic acids), gurmarin-like peptides, flavonoids, and sterols, regulate glucose homeostasis, inhibit intestinal glucose absorption, preserve pancreatic β-cell function, stimulate insulin secretion, modulate lipid metabolism, and suppress inflammatory signaling pathways. Experimental and clinical evidence indicates that G. sylvestre modulates oxidative stress and inflammation associated with complications such as nephropathy, neuropathy, retinopathy, vascular dysfunction, and dyslipidemia. This review adopts a mechanism-oriented framework integrating phytochemical structure–molecular target–metabolic outcome relationships and discusses emerging strategies, including nanotechnology-based delivery systems, molecular docking, and multi-component phytotherapy. Overall, G. sylvestre represents a promising multi-target phytotherapeutic agent, highlighting directions for future mechanistic and clinical research. Full article

Diabetes mellitus represents a major global health challenge with rapidly increasing prevalence and substantial morbidity driven by metabolic and vascular complications. Extracellular vesicles (EVs) have emerged as critical mediators of intercellular communication and are increasingly implicated in the pathogenesis and progression of diabetes. This review summarizes current knowledge on EV biology, including their classification, cellular sources, biogenesis, uptake mechanisms, and molecular cargo. We discuss the contribution of EV-associated microRNAs to immune dysregulation and β-cell damage in type 1 diabetes mellitus (T1DM), as well as the role of EVs in insulin resistance, metabolic signaling, and vascular dysfunction in type 2 diabetes mellitus (T2DM). Particular emphasis is placed on EV-mediated modulation of endothelial function, angiogenesis, and tissue repair, alongside their involvement in the impairment of insulin receptor integrity. We further explore how lifestyle factors may influence EV composition and function, highlighting their potential integration into preventive strategies. Finally, we evaluate the emerging therapeutic potential of EVs as biomarkers and delivery systems, while addressing current limitations and future directions. Collectively, EVs represent a promising frontier in understanding diabetes pathophysiology and developing innovative diagnostic and therapeutic approaches. Unlike previous reviews that examine EVs separately as biomarkers or therapeutic vehicles, this review integrates emerging evidence supporting EVs as mediators of systemic communication linking pancreatic islets, adipose tissue, immune cells, vascular endothelium, kidney, heart, and retina throughout diabetes progression. We further critically evaluate translational barriers that currently limit clinical implementation of EV-based diagnostics and therapeutics. Full article

Wireless Body Area Networks (WBANs) have become an essential component of modern Internet of Medical Things (IoMT) healthcare systems, enabling continuous monitoring of patient physiological signals through wearable sensors. Despite their advantages, WBAN environments remain highly prone to cyber threats, privacy breaches, and single points of failure. To address these risks, this work proposes a Hybrid Multi-Metric Anomaly Detection (HM-MAD) framework deployed on the NodeMCU-32S platform with BLE 5.0 connectivity for secure continuous glucose monitoring (CGM) data transmission. The detection model simultaneously analyses physiological signals, system-level parameters, and network-level communication metrics, enabling the reliable identification of multiple cyberattacks. The proposed system focuses on securing data transmission against relay attacks, where attackers induce communication delay without modifying payloads, potentially leading to false glucose readings, improper insulin dosage delivery, unauthorized control or denial-of-service. The Convolutional Neural Network (CNN) and Bi-Directional Long Short Term Memory (BiLSTM) model classifies attack types including timing manipulation, replay attacks, power glitches, firmware tampering, and sensor spoofing. Experimental evaluation demonstrates that the proposed CNN + BiLSTM framework achieves 94.6% detection accuracy with an average inference latency of 15 ms, representing a 50% latency reduction compared to Transformer-based intrusion detection models (30 ms), while simultaneously reducing computational overhead by 28% in terms of floating-point operations and memory utilization. These results indicate that the HM-MAD framework provides an effective and scalable solution for protecting resource-constrained IoMT healthcare systems against emerging cyber threats. Full article

Background/Objectives: Advanced technologies in type 1 diabetes mellitus (T1DM) management have reshaped the strategies used to achieve optimal glucose control. Continuous subcutaneous insulin infusion (CSII) and automated insulin delivery (AID) systems are effective alternatives to multiple daily injections (MDI). This study aims to evaluate glycemic regulation in children and adolescents transitioning from MDI to insulin pumps and to raise awareness among patients and their families regarding the benefits of these systems. Methods: 50 pediatric patients with T1DM (24 males, 26 females; mean age 10.76 ± 3.2 years) were evaluated. Cycle 1 established MDI metrics 3 months pre-transition. In cycle 2, patients transitioned either to an AID system (Medtronic MiniMed 780G, (Northridge, CA, USA), 78%), or a non-automated system (Omnipod DASH, 22%). Data were assessed at 3 and 6 months post-initiation. Parameters assessed were glycosylated hemoglobin (HbA1c), time in range (TIR), time above range (TAR), time below range (TBR), glucose management indicator (GMI) and coefficient of variation (CV). Results: The cohort exhibited a statistically significant increase in TIR (p = 0.0038) with mean values of 70.9% at 3 months and 73.2% at 6 months. TAR significantly reduced (p = 0.033) to 26.5% and 24.3% at 3 and 6 months, respectively. Sub-analysis in the AID group revealed a marked increase in TIR (p = 0.0001) alongside significant reductions in TAR (p = 0.0009) and GMI (p = 0.03). Conclusions: Transitioning from MDI to insulin pump therapy, particularly AID systems, leads to modest but significant improvements in specific sensor metrics (TIR, TAR) in real-world clinical practice. The consistency of these results across age groups indicates that AID systems can successfully overcome pediatric and adolescent diabetes management challenges. Full article

Food-derived bioactive peptides have become a research hotspot in diabetes nutritional intervention due to their high safety, wide availability, and multi-target activities. This review addresses this by proposing a systems biology integration framework that defines these peptides as pleiotropic regulators of the gut microbiota-immune inflammation-metabolic signaling network, offering a novel systems-level perspective beyond previous reviews focused on single enzymes or pathways. The framework consists of three synergistic tiers. Tier 1 inhibits α-amylase, α-glucosidase or dipeptidyl peptidase-IV (DPP-IV) to control postprandial blood glucose. Tier 2 corrects insulin resistance by modulating phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), activating nuclear factor erythroid 2-related factor 2 (Nrf2), and suppressing nuclear factor kappa-B (NF-κB). Tier 3 uses the gut as a hub to remotely coordinate metabolism via the gut–liver and gut–pancreas axes. The review also systematically summarizes the major sources and preparation methods of food-derived antidiabetic peptides, analyzes their advantages including multi-target network regulation, safety, and sustainability, as well as challenges such as oral bioavailability, insufficient clinical evidence, processing stability, and regulatory hurdles. Finally, it outlines future directions focusing on three actionable priorities: AI-assisted design, oral delivery systems, and high-quality clinical studies. This framework offers a new perspective for applying food-derived peptides in precision nutrition intervention for diabetes. Full article

Monopolar radiofrequency (MRF) is a well-established modality for non-invasive facial rejuvenation; however, its clinical utility is frequently constrained by patient discomfort and inconsistent thermal delivery. This study evaluated the efficacy, safety, and mechanistic profile of a novel MRF system incorporating continuous water cooling (RF-CWC) designed to optimize thermal distribution and enhance patient tolerance. In a prospective, single-arm clinical trial involving 22 female participants, a single RF-CWC treatment utilizing region-specific static and sliding delivery modes yielded statistically significant improvements in jawline lifting, alongside a volumetric increase in the midface and a concomitant volumetric reduction in the lower face (p < 0.001) over an 8-week follow-up period, with no adverse events reported. To elucidate the underlying cellular mechanisms, the system was further evaluated using an ultraviolet B (UVB)-induced ex vivo human skin model and an in vivo porcine model. Histological, immunohistochemical, and ELISA analyses revealed that RF-CWC effectively mitigated UVB-induced dermal degradation ex vivo by significantly up-regulating elastin, insulin-like growth factor, and hyaluronic acid, while down-regulating matrix metalloproteinase-1, interleukin-1α, and heat shock protein 72 (p < 0.05). Furthermore, the in vivo model demonstrated time-dependent increases in collagen types I and III and elastin without thermal tissue damage, with the sliding mode and higher shot counts correlating with enhanced extracellular matrix (ECM) remodeling. Comparative analyses demonstrated that RF-CWC achieved superior ECM restoration and reduced inflammatory cell infiltration relative to traditional cryogen spray-cooled RF systems. Taken together, these findings suggest that the RF-CWC system may promote robust ECM remodeling and significant facial neocollagenesis while minimizing inflammatory responses, potentially presenting an optimized, highly effective, and patient-friendly advancement in MRF technology. Full article

Background/Objectives: Regular physical exercise is strongly recommended for individuals with type 1 diabetes mellitus (T1DM) because of its beneficial effects on cardiovascular fitness, insulin sensitivity, metabolic control, and overall health. Nevertheless, participation in physical activity remains limited, largely due to the fear of exercise-induced hypoglycemia and glycemic instability. Glycemic responses to exercise in T1DM are influenced by the interaction between exercise modality, circulating insulin levels, nutritional status, and diabetes technologies. Continuous aerobic exercise, resistance training, high-intensity interval exercise, and mixed intermittent activities elicit distinct metabolic and hormonal responses, resulting in heterogeneous glycemic trajectories. This narrative review aimed to provide a clinically oriented synthesis of the physiological mechanisms underlying exercise-related glycemic fluctuations in T1DM and to discuss integrated insulin- and carbohydrate-based strategies to support safer participation in physical activity in the context of modern diabetes technologies. Methods: A structured narrative review was conducted using PubMed/MEDLINE, Scopus, and complementary searches in Google Scholar to identify experimental studies, observational studies, systematic reviews, consensus statements, and clinical guidelines focused on exercise-related glycemic responses in individuals with T1DM. Only articles published in English were considered. Evidence was selected and synthesized according to relevance to exercise modality, insulin therapy strategies, carbohydrate management, and diabetes technologies, including continuous glucose monitoring, continuous subcutaneous insulin infusion, and automated insulin delivery systems. The final narrative synthesis was based on 44 selected studies, reviews, consensus statements, and guidance documents considered most relevant to the objectives of this narrative review. Results: Available evidence indicates that continuous moderate-intensity aerobic exercise is most consistently associated with progressive glucose declines and increased risk of hypoglycemia, particularly when performed in the presence of elevated insulin on board. In contrast, resistance exercise and short-duration high-intensity or anaerobic exercise more frequently induce stable glycemia or transient hyperglycemia through adrenergic stimulation and increased hepatic glucose output. Mixed and intermittent exercise modalities often produce more variable responses depending on exercise sequencing, nutritional status, and insulin exposure. Across studies, integrated adjustment of basal and prandial insulin doses together with individualized carbohydrate supplementation emerged as the most effective strategy to reduce exercise-related glycemic instability. Continuous glucose monitoring and insulin pump technologies improved glucose trend awareness and management flexibility; however, physical exercise remains a challenging condition for current automated insulin delivery algorithms and still requires active user-driven decision-making. Conclusions: Exercise management in T1DM should be based on an individualized interpretation of exercise modality, glucose trends, insulin exposure, and nutritional context rather than on fixed glucose thresholds alone. Combining anticipatory insulin adjustments, tailored carbohydrate strategies, and appropriate use of diabetes technologies may substantially reduce glycemic variability and improve confidence toward physical activity participation. Structured education and individualized clinical guidance remain essential to translate physiological knowledge into effective real-world exercise management. Full article

Background and Aims: Automated insulin delivery (AID) systems are standard of care for type 1 diabetes mellitus (T1DM). Tubeless AID systems may improve treatment acceptance, but real-world European data in patients transitioning from multiple daily injections (MDI) or open-loop patch pump therapy are limited. This study evaluated real-world glycemic, safety, and quality-of-life (QoL) outcomes after transition to a tubeless automated closed-loop system (Omnipod 5^®, OP5^®). Research Design and Methods: In this prospective, multicenter observational study, adults with T1DM transitioned from MDI or open-loop continuous subcutaneous insulin infusion to OP5^® and were followed for 180 days. Continuous glucose monitoring-derived metrics and validated patient-reported outcome measures were assessed. Subgroup analyses were performed by prior therapy. Results: Of the 94 enrolled participants, 88 completed the study. At 180 days, HbA1c decreased from 7.5% to 7.1% (p < 0.001), and time in range increased from 59.0% to 68.0% (p < 0.001) without increased hypoglycemia. The proportion achieving TIR_70–180 ≥ 70% rose from 12.5% to 43.2%. Improvements were greater among prior MDI users. Treatment satisfaction and diabetes-related QoL improved significantly. The mean time in automated mode was 90.9%. Conclusions. Transition to tubeless AID significantly improved glycemic and psychosocial outcomes, supporting its effectiveness in routine clinical practice. Full article

Glucose-responsive smart insulin delivery systems that mimic the pancreatic insulin release system can improve the health and quality of life of patients with diabetes. In this study, a spherical drug delivery carrier encapsulating insulin was developed to achieve improved glucose accessibility and a rapid pH response using polyhedral oligomeric silsesquioxane (POSS) as a sterically stabilizing structure. Highly sensitive poly(acrylic acid) (PAA)-POSS-aminophenylboronic acid (APBA)@insulin (386 ± 69 nm), a spherical drug delivery carrier encapsulating insulin, was synthesized using POSS, a hydrophobic material, and PAA and APBA, which respond to pH and glucose, respectively. The drug carrier has dual reactivity with pH and glucose, and the synthesis of the carrier was confirmed through Fourier transform infrared (FT-IR) spectroscopy, which verified that the particles were stable at each pH through the zeta-potential data. In particular, PAA-POSS-APBA@insulin exhibited highly sensitive drug delivery characteristics, in which the backbone of PAA was expanded under acidic conditions (around pH 5.0) and insulin bound to the boronic acid inside could rapidly and selectively react with trace amounts of glucose. PAA-POSS-APBA@insulin nanoparticles exhibited no HeLa cell cytotoxicity up to a high concentration of 640 μg/mL, and the cell growth rate increased with the concentration, indicating biocompatibility. The average blood glucose level of diabetic mice treated with POSS-APBA@insulin (4.0 IU/kg) decreased for >6 h and remained stable. Thus, PAA-POSS-APBA@insulin can function as a stimulatory-responsive drug carrier targeting hyperglycemic environments. Full article

Background: Evidence supports the effectiveness and safety of open-source automated insulin delivery (AID) in patients with type 1 diabetes. However, evidence regarding the clinical application of open-source AID in perioperative patients with type 2 diabetes remains limited. Methods: This was an open-label, single-center, exploratory pilot randomized controlled trial (RCT) with parallel groups. Patients with diabetes (excluding type 1 diabetes mellitus) scheduled for elective surgery were randomly assigned to the closed-loop group (open-source hybrid closed-loop AID system) or the control group (conventional insulin pump). The primary outcome was the percentage of time in the target glucose range (TIR, 3.9–10.0 mmol/L). Other efficacy and safety outcomes were also compared between the groups. Results: A total of 49 participants were included and randomized to the closed-loop group (n = 25) or the control group (n = 24). Participants underwent abdominal, orthopedic, thoracic surgery, or neurosurgery during hospitalization. Patients in the closed-loop group had significantly higher TIR than patients in the control group (76.4 ± 14.1% vs. 61.2 ± 20.0%, p = 0.005). Compared with the control group, the closed-loop group also exhibited a 15.6 percentage point reduction in time above range (TAR, >10 mmol/L) without increasing time below range (TBR, <3.9 mmol/L). There were no episodes of severe hypoglycemia (<2.2 mmol/L) or diabetic ketoacidosis in either group. Conclusions: This study demonstrates that in patients with diabetes undergoing elective surgery, the open-source hybrid closed-loop AID system provides better glycemic control than conventional insulin pump therapy. Full article

The obesity–metabolic syndrome–diabetes continuum is driven by interconnected mechanisms including insulin resistance, dysfunctional adiposity, chronic inflammation and progressive cardio–renal–metabolic injury. This triggered a need for therapies that extend beyond glucose lowering alone. The benefits of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as disease-modifying drugs include weight loss, cardiovascular risk reduction, glycemic control and renal protection. However, treatment burden, adherence issues and access restrictions may limit the long-term effects of injectable formulations. One significant translational development that aims to close this gap is oral GLP-1-based treatments. In this review, we examine the mechanistic rationale, formulation science and clinical development of oral GLP-1 RAs. Oral semaglutide is presented as the first validated proof of concept for systemic peptide delivery by the gastrointestinal route. The biological barriers to oral peptide absorption, including enzymatic degradation, low epithelial permeability, pharmacokinetic variability and epithelial safety constraints, are critically discussed. Enabling technologies such as SNAC-based gastric absorption, nanocarriers, mucoadhesive systems and stability-optimization platforms are evaluated. Evidence from the PIONEER program and related studies demonstrating meaningful glycemic and weight-loss efficacy, acceptable safety and clinical utility in patients with type 2 diabetes and chronic kidney disease is further synthesized. Beyond first-generation oral peptide platforms, we discuss the emerging landscape of non-peptide oral GLP-1 RAs, dual and triple incretin agonists, precision dosing strategies and model-informed drug development. Oral GLP-1-based therapeutics are shifting from a formulation breakthrough to a broader translational strategy for disease modification across the obesity–metabolic syndrome–diabetes continuum. Long-term renal outcomes, access and implementation barriers remain important priorities for future research. Full article

Purpose: Natural polysaccharides have shown considerable potential in the management of type 2 diabetes mellitus (T2DM) due to their multi-target metabolic regulatory effects. However, their clinical translation is limited by poor oral stability and low intestinal permeability. Snow lotus polysaccharide (SIP), a representative plant-derived polysaccharide, exhibits promising metabolic benefits but suffers from these delivery barriers. This study aimed to develop an oral nanodelivery system to enhance the gastrointestinal stability and intestinal transport of SIP, thereby improving its in vivo efficacy. Methods: SIP-loaded chitosan–tripolyphosphate nanoparticles (SIP@CS-TPP) were prepared via ionic crosslinking and characterized in terms of particle size, surface charge, morphology, and structural features. In vitro release behavior under simulated gastrointestinal conditions was evaluated. Ex vivo intestinal permeation was assessed using an isolated intestinal sac model. The metabolic regulatory effects were further investigated in a high-fat diet/streptozotocin-induced T2DM rat model. Results: SIP@CS-TPP nanoparticles exhibited a uniform particle size of 188.9 ± 12.8 nm, a surface charge of 28.3 ± 5.1 mV, and good stability after freeze-drying. A pH-responsive and diffusion-controlled release profile was observed. Ex vivo studies demonstrated significantly enhanced intestinal transport, with an approximately 3.7-fold increase in apparent permeability compared with free SIP. In vivo, SIP@CS-TPP improved glycemic control, glucose tolerance, insulin resistance, lipid metabolism, oxidative stress, and inflammatory responses more effectively than free SIP at the same dose. Conclusions: The CS-TPP nanodelivery system effectively enhances the oral delivery and metabolic regulatory effects of SIP. This study highlights the potential of a delivery-oriented strategy to improve the in vivo performance of natural polysaccharides and provides a promising approach for their application in metabolic disease management. Full article

Polycystic ovarian syndrome (PCOS) is a complex endocrine and metabolic disorder that affects reproductive health, metabolic function, and long-term cardiovascular health in women of reproductive age. The syndrome is characterized by hyperandrogenism, chronic anovulation, insulin resistance, oxidative stress, and ovarian microenvironment remodeling. While current treatments focus on symptom relief through hormone regulation, insulin sensitizers, or ovulation induction, there is a need to target the underlying molecular and cellular processes that drive disease progression and infertility. Breakthroughs in reproductive and metabolic medicine have led to the development of next-generation therapeutics for PCOS that aim to restore ovarian function at the molecular level. Nanoparticle- and nanofiber-based drug delivery systems offer targeted delivery to the ovaries, improved bioavailability, and controlled release of insulin sensitizers, antioxidants, and anti-androgens. Metabolic reprogramming strategies that target insulin resistance, mitochondrial dysfunction, and autophagy have emerged as potential disease-modifying interventions. In addition, AI-enabled precision medicine approaches are reshaping PCOS management through phenotype-based classification, predictive modeling, and personalized fertility optimization. In this review, we highlight recent advancements in understanding the molecular pathophysiology of PCOS and introduce novel therapeutics that harness intelligent drug delivery, ovarian microenvironment restoration, and AI-based interventions. We discuss the potential of these innovative strategies to update PCOS management options for long-term ovarian restoration and fertility. Full article

Background/Objectives: Impairment in pulsatile insulin release contributes to insulin resistance and is one of the earliest markers of developing type 2 diabetes. Insulin delivered to the liver in pulses has a stronger glucose-lowering effect than continuous insulin delivery. Whether pulsatility benefits the islet itself is an open question. We previously showed that reducing glucokinase activity with the glucokinase inhibitor D-mannoheptulose (MH) improves function in islets exposed to prolonged hyperglycemic conditions. In this study, we test whether pulsatile vs. continuous delivery impacts the effectiveness of MH in islets. Methods: Islets were exposed to high-glucose conditions (20 mM glucose) for 24 or 48 h to induce early adaptations to hyperglycemia. We then used a specially designed perifusion system to impose pulsatile activity by exposing mouse islets to 3 min of MH in 20 mM glucose and 3 min of only high levels of glucose. Islets given intermittent MH for 18 h were compared with continuous delivery of MH at a full (2.5 mM) or half (1.25 mM) dose. Results: MH delivered by the forced oscillatory system reversed the effects of hyperglycemia and restored glucose sensing more effectively than continuous delivery. Specifically, fura-2AM imaging of intracellular calcium showed that islets given pulsatile MH had greater reductions in the elevated basal calcium caused by hyperglycemic conditions, improved the glucose stimulation index, and improved phase 0 response (indicating glucose-stimulated calcium uptake by the endoplasmic reticulum). Conclusions: These findings suggest that the loss of oscillatory glucose metabolism in islets contributes directly to beta-cell dysfunction. Full article

Background/Objectives: Continuous glucose monitoring (CGM) has transformed diabetes management by enabling high-resolution assessment of glucose dynamics, with well-established use in type 1 diabetes (T1D) and insulin-treated type 2 diabetes (T2D), and expanding applications across broader populations, including non-insulin-treated T2D and gestational diabetes. However, real-world implementation remains constrained by economic barriers, fragmented reimbursement, workflow challenges, and limited capacity for continuous data interpretation. This review examines key barriers to CGM implementation and synthesizes current evidence on pharmacist-integrated CGM care as an emerging model to support CGM adoption across clinical and community-based settings. Methods: A narrative literature review was conducted to synthesize evidence on pharmacist-integrated CGM services in diabetes care. Literature was identified through structured searches of PubMed, Embase, and the Cochrane Library, supplemented by Google Scholar and citation tracking, covering publications from January 2010 to December 2025. Studies were selected based on predefined criteria, including those reporting clinical outcomes, pharmacist involvement, or health system and implementation factors related to CGM use. Relevant survey-based and real-world studies were also considered to capture healthcare professionals’ perspectives and implementation experiences. Evidence was synthesized thematically across clinical, behavioral, and health system domains. Results: Available evidence suggests that pharmacist-integrated CGM care is associated with improvements in glycemic management, including increased time in range, reduced glycemic variability, and more timely pharmacotherapy optimization. Pharmacist involvement may also support patient education, self-management, and engagement with digital health technologies, and facilitate ongoing data interpretation and treatment adjustment between clinical encounters. However, evidence remains heterogeneous and geographically limited, with predominantly retrospective and pilot studies and few randomized trials, constraining the robustness and external validity of the findings. Further studies are needed to confirm its clinical effectiveness, comparative effectiveness, and economic value. Conclusions: Pharmacist-integrated CGM represents a promising and operationally feasible approach to supporting CGM use in routine diabetes care. While current evidence indicates potential benefits in glycemic management and care delivery processes, further research and implementation efforts are required to support its effective and sustainable adoption across diverse healthcare settings. Full article