Search Results (489)

The rapid digitalisation of healthcare has accelerated the adoption of telemedicine, Electronic Health Records (EHRs), and the Internet of Medical Things (IoMT), transforming healthcare delivery into a highly interconnected and patient-centric ecosystem. In response to growing concerns about data security, privacy, and interoperability, blockchain technology has emerged as a promising solution for its decentralization, immutability, auditability, and secure access control. However, many existing blockchain infrastructures rely on classical cryptographic primitives, including RSA- or elliptic-curve-based public-key mechanisms and cryptographic hash functions such as SHA-256, whose relevant security properties may be affected by sufficiently powerful quantum attacks. This review investigates the convergence of blockchain and quantum technologies to address emerging security threats in e-health systems. A structured literature review was conducted in accordance with the PRISMA 2020 guidelines using the IEEE Xplore, PubMed, ACM Digital Library, Google Scholar, and Crossref databases, covering studies published between January 2018 and June 2025. Following a systematic screening and eligibility-verification process, 57 relevant studies were selected and analyzed. The review evaluates quantum-resilient security mechanisms, including Quantum Key Distribution (QKD), Quantum Random Number Generation (QRNG), and NIST-standardized Post-Quantum Cryptography (PQC) algorithms specified in FIPS 203, FIPS 204, and FIPS 205. Based on the identified research gaps in the state of the art, this study also proposes a novel four-layer Quantum-Blockchain Security Architecture (QBSA) designed for secure healthcare environments. The analysis further reveals significant challenges associated with lightweight PQC deployment for IoMT devices, interoperability standardization, quantum hardware limitations, and regulatory compliance in cross-institutional healthcare systems. The findings highlight the necessity of integrating quantum-resilient cryptographic frameworks with blockchain infrastructures to support the development of secure, scalable, and patient-centric next-generation e-health ecosystems. Full article

Background/Objectives: Gabapentin is a first-line treatment for neuropathic pain, classically understood to reduce neuronal excitability through binding to the alpha-2-delta-1 (α2δ-1) subunit of voltage-gated calcium channels. However, this neuron-centric model does not fully explain its variable clinical efficacy across pain syndromes. In parallel, chronic pain is increasingly conceptualized as involving neuron–glia–immune interactions, in which microglial activation, astrocytic signaling, and inflammatory mediators may contribute to central sensitization. Methods: A structured narrative review was conducted using PubMed, Web of Science, and Google Scholar for articles available through December 2025. The search focused on gabapentin/gabapentinoids, chronic and neuropathic pain, α2δ-1 mechanisms, neuron–glia interactions, neuroinflammation, central and peripheral sensitization, nociplastic pain, cytokine/chemokine signaling, and neuroimmune modulation. Basic science studies, animal models, translational studies, clinical trials, reviews, meta-analyses, and guidelines were narratively synthesized. Results: Preclinical evidence indicates that gabapentin reduces neuronal hyperexcitability and may secondarily attenuate neuron-to-glia signaling, glial activation, and cytokine- and chemokine-related pathways. However, these neuroimmune effects remain predominantly preclinical, model-dependent, and incompletely validated in humans. Clinical evidence supports gabapentin for selected neuropathic pain conditions, but human studies rarely evaluate glial activation, cytokine signaling, or neuroimmune biomarkers. Conclusions: Gabapentin remains best understood as a neuronal α2δ-1 modulator. Although preclinical and translational evidence suggests biologically plausible secondary effects on neuroimmune signaling, these mechanisms have not been validated as biomarkers or prescribing targets in humans. The conceptual framework presented in this review supports mechanism-informed clinical reasoning and individualized pain management but should not be interpreted as a biomarker-guided prescribing algorithm. Clinically, gabapentin should be prescribed selectively for patients with neuropathic or sensitized pain features, using predefined functional goals, appropriate renal dose adjustment, careful safety monitoring, and discontinuation when meaningful benefit is not achieved. Full article

Background: Cellular senescence exerts a complex influence on BRCA progression and TME remodeling. However, the specific roles of ASIGs in regulating the TME and determining patient outcomes remain unclear. Methods: Using TCGA (training), METABRIC (validation), and single-cell RNA-seq datasets, we systematically characterized ASIGs in BRCA. Prognostic ASIGs were identified to define molecular subtypes and construct a 17-gene LASSO-Cox risk model, which was integrated with clinical factors to develop a prognostic nomogram. Microenvironmental features and cell–cell communication networks were deconstructed using computational deconvolution and single-cell algorithms (SCISSOR and CellChat). Results: We established a robust 17-gene ASIG-based prognostic signature that effectively stratified BRCA patients into high- and low-risk groups and served as an independent prognostic predictor (HR = 3.94, p < 0.001). The nomogram accurately predicted 1-, 3-, and 5-year overall survival. Notably, the two risk groups exhibited strikingly distinct TME landscapes. The low-risk group was characterized by a coordinated, B cell-centric immune network, whereas the high-risk group displayed T cell exhaustion and immunosuppressive myeloid infiltration. Conclusions: The ASIG-based prognostic risk model is independent of traditional clinicopathological factors, providing a robust tool for patient risk stratification and offering biological insights into senescence-driven microenvironmental remodeling. Full article

Raynaud’s Phenomenon (RP) serves as the clinical sentinel for systemic autoimmunity, frequently predating connective tissue disease diagnosis by years. While RP is a largely benign functional vasospasm in the general population, its prevalence in Systemic Sclerosis (SSc) approaches 99%. A fundamental mystery in Rheumatology is the divergent fate of the microvasculature across connective tissue diseases. RP can occur in other autoimmune diseases; it is usually not associated with the relentless transition to obliterative vasculopathy. In SSc, the vessel lumen is physically occluded by intimal proliferation and perivascular fibrosis, yet the mechanism triggering this ischemia remains poorly understood. Beyond the classic tri-phasic color change, SSc patients frequently report other early distressing sensory symptoms, specifically intense pruritus, neuropathic burning, and profound edema. Historically dismissed as secondary to ischemia, we propose that these sensations are primary markers of the underlying pathological driver. We challenge the traditional B-cell/T-cell-centric view of SSc by introducing the concept of autoallergy. We hypothesize that these sensory symptoms represent chronic, IgE-mediated activation of resident mast cells. This mast cell-driven circuit, triggered by SSc-specific autoantigens, acts as a persistent secretory pump for pro-fibrotic cytokines, fundamentally distinguishing SSc vasculopathy from the purely inflammatory vascular patterns seen in other connective tissue diseases. Targeting the IgE–mast cell axis early in the course of the disease may offer a novel therapeutic window to halt the transition from functional vasospasm to permanent structural obliteration. Full article

Anesthesia reimbursement remains anchored to time-based benchmarks, despite evidence that they poorly capture clinical complexity and variability. Recent reforms, including Utah’s 2026 ban on time limits, underscore growing policy concern. This commentary proposes replacing time-centric metrics with risk-adjusted, outcome-focused models that reflect perioperative value and patient-centered care. Full article

Despite major advances in lipid-lowering therapy and the widespread implementation of statins, ezetimibe, and PCSK9-targeted interventions, cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide. Intensive lowering of low-density lipoprotein cholesterol (LDL-C) has substantially reduced cardiovascular events; however, a considerable degree of residual cardiovascular risk persists even among patients achieving very low LDL-C levels. This observation has shifted contemporary cardiovascular research toward a broader understanding of atherosclerosis as a multifactorial disorder involving triglyceride-rich lipoproteins (TRLs), apolipoprotein B (APOB)-containing particles, dysfunctional high-density lipoproteins (HDLs), lipoprotein(a) [Lp(a)], endothelial dysfunction, and chronic vascular inflammation. Emerging evidence further suggests that psychological and behavioral factors, including specific personality traits and chronic psychosocial stress, may contribute independently to cardiovascular disease susceptibility and outcomes. The present review summarizes emerging risk factors associated with residual cardiovascular risk and highlights novel therapeutic strategies beyond LDL-C lowering. Collectively, current evidence supports a transition from a simplistic LDL-C-centric paradigm toward a multiple risk factor approach for atherosclerosis prevention and treatment. Full article

Lipoprotein(a) [Lp(a)] has emerged as a major genetically determined cardiovascular risk factor that extends beyond the traditional low-density lipoprotein cholesterol (LDL-C)-centred model of atherosclerotic disease. Despite optimal LDL-C lowering, a substantial proportion of patients continue to experience cardiovascular events, highlighting the clinical relevance of residual cardiovascular risk. This review summarizes current evidence regarding the epidemiology, genetics, pathophysiology and therapeutic implications of Lp(a) in cardiovascular disease. Epidemiological, genetic, and Mendelian randomization studies consistently demonstrate an independent and likely causal association between elevated Lp(a) and atherosclerotic cardiovascular disease, ischemic stroke, calcific aortic valve stenosis, heart failure, and recurrent cardiovascular events, even in patients with well-controlled LDL-C levels. Lp(a) promotes atherosclerosis through proatherogenic, proinflammatory, and prothrombotic mechanisms, largely mediated by oxidized phospholipids and the structural homology of apolipoprotein(a) with plasminogen. Current guidelines increasingly recognize Lp(a) as a risk-enhancing factor capable of refining cardiovascular risk stratification beyond traditional algorithms, thus recommending measuring Lp(a) at least once in a lifetime in all adults. Accurate measurement and standardization of Lp(a) remain essential in clinical practice due to apo(a) isoform size variability; reporting in molar concentrations (nmol/L) is preferred as it better reflects particle number being less affected by isoform size variations and improves the reliability of cardiovascular risk stratification. Collectively, these findings support the integration of Lp(a) into precision-based cardiovascular prevention strategies and suggest a paradigm shift from an exclusively LDL-centric approach toward genetically informed risk assessment and treatment. Full article

Background/Objectives: The aim of this study was to show a standardized four-step technique that can offer individually personalized full-mouth therapy for each complex dental patient with erosive tooth wear resulting from bulimia nervosa, focusing on the individualized vertical dimension of occlusion (VDO), functional and aesthetic stability, and patient-reported outcomes, including dental symptoms, nutrition, self-perception, and quality of life. Methods: The following steps are proposed for structured full-mouth rehabilitation. Step 1: Intraoral diagnosis via a single computer-aided impression. Step 2: Determination of a new adequate vertical dimension of occlusion and soft tissue prediction. Step 3: Removable sample dentures—prototypes. Step 4: Non-prep/minimal-prep crowns as the long-term provisional/definitive treatment. Results: Nine adults (11% male) with dental erosion caused by bulimia nervosa (78%), gastro-esophageal reflux (11%), and soft drinks (11%) were part of this cohort. The novel digital workflow enabled restoration of an individualized vertical dimension of occlusion, stable occlusion, appropriate centric and eccentric contacts, biomimetic dental anatomy, harmonious tooth proportions, and optimized red–white aesthetics. Dental problems (hypersensitivity, dental pain), nutritional behavior, body perception, and quality of life improved after the full-mouth rehabilitation. Conclusions: The presented digital workflow offers a promising approach for full-mouth rehabilitation in patients with severe dental erosion, particularly associated with bulimia nervosa, enabling structured restoration planning and stepwise evaluation of the vertical dimension of occlusion and functional adaptation. Prospective studies with larger cohorts are needed to confirm long-term clinical outcomes and patient-reported benefits. Full article

Background and Objectives: Kidney dysfunction and hyponatremia are prevalent in decompensated liver cirrhosis and are associated with suboptimal prognoses. Most prognostic tools used in cirrhosis are hepatic-centric and necessitate the utilization of multiple laboratory and clinical variables. This study endeavored to delineate and assess kidney function- and serum sodium-based prognostic models for the prediction of in-hospital mortality in patients with liver cirrhosis. Materials and Methods: This retrospective single-center cohort study comprised 547 hospitalized patients with liver cirrhosis and comprehensive data pertaining to serum urea, creatinine, sodium, age, sex, and in-hospital outcome. In-hospital mortality was the primary endpoint. Kidney function was evaluated via the assessment of serum urea, serum creatinine, and estimated glomerular filtration rate (eGFR), using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 equation. Simple categorical and point-based scores were constructed. Model discrimination, calibration, and operating characteristics were compared with MELD, Child–Pugh, and ALBI scores, as well as with selected combined models. Results: Of the 547 patients, 147 individuals (26.9%) succumbed during the hospitalization period. In the full model, lower eGFR, elevated urea levels, and diminished serum sodium concentrations were independently associated with in-hospital mortality, whereas age and sex did not demonstrate statistical significance. The full model appeared to exhibit moderate discrimination (AUC 0.701, 95% CI 0.652–0.750). A biochemical model based on urea, creatinine and sodium appeared to yield a similar AUC (0.696), and a renal–electrolyte model encompassing eGFR, urea, and sodium seemed to demonstrate an AUC of 0.694. A simple creatinine–sodium score may have attained an AUC of 0.681 and appeared to effectuate the stratification of mortality from 16.4% in the low-risk group to 53.1% in the high-risk group. Adding renal–electrolyte variables or the simple score to MELD did not appear to confer substantial enhancement to performance. Conclusions: Kidney dysfunction and hyponatremia at admission have been identified as independent predictors of in-hospital mortality in liver cirrhosis. A simple creatinine–sodium score may afford practical bedside risk stratification and may complement MELD-based assessment in routine clinical care. Full article

Background/Objectives: As a key health information and communication technology, mobile health information services (MHISs) play a critical role in delivering health information, enabling remote monitoring, and supporting patient well-being. However, widespread resistance among older adults hinders their access to these information services and undermines these benefits. Employing the technology–personal–environment (TPE) framework, this study constructed and verified a comprehensive model to explain older adults’ resistance to MHIS use. Methods: Quantitative data from 430 elderly individuals aged 65 and above from China who participated in the free health check-up basic public health program were analyzed using structural equation modeling. Results: Technology access barriers, technology usage barriers, declining physiological conditions, and resistance to change were positively related to technology anxiety. Declining physiological conditions, resistance to change, social legitimacy power, and perceived institutional effort were negatively related to perceived autonomy. Additionally, technology anxiety was positively related to resistance to MHIS use, while perceived autonomy was negatively related to resistance to MHIS use. Conclusions: The findings clarify the mechanisms linking technological barriers, individual characteristics, and environmental factors to older adults’ resistance to MHIS use. Therefore, relevant health information service providers should adopt systematic actions that simultaneously alleviate technology anxiety through user-centric design and supportive training while fostering perceived autonomy by respecting older adults’ choices and enabling meaningful participation. These findings offer actionable insights for healthcare information system designers and providers to reduce older adults’ exclusion from digital health information ecosystems, thereby enhancing patient well-being among aging populations. Full article

Acanthamoeba keratitis (AK) and mycotic keratitis (MK) are severe infectious diseases of the cornea. A major challenge to treatment is the poor bioavailability of conventional eye drop formulations, resulting in significant loss of the therapeutic compound. The present study describes the preparation of self-nanoemulsifying drug delivery systems (SNEDDSs) utilizing 3D-molded inserts as a vehicle for the co-delivery of voriconazole (VOR) and diclofenac sodium (DIC). Characterization of the SNEDDS and the 3D-molded inserts involved analysis of droplet size, polydispersity index (PDI), and zeta potential (ZP), followed by an ex vivo transcorneal permeation. Careful optimization of the SNEDDS composition was fundamental for obtaining a nanoemulsion with a droplet size under 100 nm, a PDI below 0.35, and a variable ZP (ranging from −14.6 ± 0.1 to 16.3 ± 2.4 mV). These properties facilitated a marked improvement in voriconazole’s solubility and subsequent transcorneal permeability. The investigation of the inserts revealed that the in vitro drug release could be tailored for immediate release or extended release. Moreover, ex vivo permeation studies demonstrated that the inserts delivered voriconazole to the cornea at concentrations more than the minimum inhibitory concentration. This work successfully demonstrates the formulation of a patient-centric, personalized drug delivery platform for the treatment of AK and MK. Full article

This paper reviews hybrid quantum–classical (HQC) architectures for COVID-19-related respiratory medical-image analysis. To address the heterogeneity of existing studies, we propose an architecture-centric taxonomy based on the functional role and placement of the quantum module. Reviewed models are grouped into three archetypes: Archetype A, where quantum circuits act as patch-level quanvolutional preprocessors; Archetype B, where classical feature extractors are coupled with quantum classifier heads; and Archetype C, where quantum circuits generate intermediate features for downstream classical classifiers. Ten peer-reviewed journal studies were selected through a PRISMA-inspired search and analyzed across architecture, diagnostic performance, quantum resource reporting, validation rigor, computational scalability, and deployment feasibility. The review shows that HQC models often report promising binary COVID-19 screening results on CT or chest X-ray images, but multiclass respiratory classification remains less stable. Key limitations include simulator-dominated evaluation, limited external validation, unclear patient-wise splitting, incomplete reporting of qubit counts, circuit depth, and shots, and insufficient comparison with strong classical baselines. Overall, current HQC models should be viewed as exploratory quantum-augmented classical pipelines rather than clinically validated diagnostic systems. No conclusive task-level quantum advantage has yet been demonstrated for COVID-19 medical imaging. Future progress requires standardized benchmarking, transparent quantum-resource reporting, patient-wise and multi-center validation, hardware-aware evaluation, and interpretable hybrid designs compatible with NISQ-era constraints. Full article

Health tourism represents a dynamic sector operating at the intersection of medical services, international patient mobility, and tourism development. Despite its growing prominence, the academic literature frequently conflates health tourism with medical and wellness tourism—a conceptual ambiguity that complicates the establishment of robust, sustainable legal frameworks. Addressing this gap, the present paper conceptualizes health tourism as an overarching framework that encompasses recovery, wellness, and medical sub-sectors. Within this comprehensive paradigm, we explore the contemporary landscape of health tourism in Northern Cyprus through a stakeholder-driven qualitative lens. Utilizing a qualitative case study design, data were gathered via semi-structured interviews with 40 key respondents representing healthcare, travel, public administration, academia, and related professional domains, and subsequently subjected to thematic analysis using NVivo 15 software. The findings reveal that the sector in Northern Cyprus is heavily skewed toward medical tourism, with a concentrated focus on in vitro fertilization (IVF), cosmetic surgery, dental care, and bariatric procedures. Conversely, wellness and rehabilitation tourism remain largely untapped strategic niches. The analysis further indicates that sectoral growth is constrained by structural bottlenecks, including fragmented governance, limited international recognition, transport and accessibility barriers, inadequate accreditation systems, lack of stakeholder synergy, and ethical concerns regarding advertising and patient safety. Moving beyond standard environmental sustainability, this research underscores that long-term destination resilience requires ethical governance, clinical quality controls, patient-rights advocacy, transparent legal frameworks, and community-level economic integration. Ultimately, this study proposes an integrated, stakeholder-centric paradigm tailored to the unique socio-political and structural realities of Northern Cyprus, offering actionable policy recommendations that enrich the discourse on sustainable medical tourism from a small-island perspective. Full article

Background: Regional dietary variations in China are well-documented, but their mortality associations in local populations, particularly among individuals with type 2 diabetes (T2D) or hypertension, remain unclear. This study aimed to identify dietary clusters in Suzhou and investigate their associations with mortality. Methods: This prospective analysis included 53,269 participants aged 30–79 years from the China Kadoorie Biobank (CKB) Suzhou Wuzhong subcohort. The baseline diet was assessed via a food frequency questionnaire, and three dietary clusters were identified by K-means clustering of 10 food groups. Multivariable Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause, cardiovascular disease (CVD), diabetes-related, and cancer mortality, stratified by baseline health status, T2D, and hypertension. Results: During follow-up, 1263 deaths occurred among healthy adults, 351 in T2D, and 2410 in hypertension. The Traditional/Preserved-Heavy cluster was characterized by lower intake frequencies across most food groups and more frequent preserved vegetable intake; the Meat-Centric cluster by relatively moderate intake frequencies and higher meat and poultry intake; and the Plant-and-Dairy-Abundant cluster by relatively abundant overall dietary intake, more frequent intake of fresh fruit, dairy products, and soybean products, and less frequent preserved vegetable intake. With the Meat-Centric cluster (cluster 2) as the reference, the Plant-and-Dairy-Abundant cluster (cluster 3) in T2D was associated with lower all-cause (HR = 0.61, 95% CI: 0.44–0.85), CVD (0.47, 0.24–0.91), and diabetes-related mortality (0.25, 0.09–0.71). BMI modified the association with all-cause mortality in T2D (p interaction = 0.033). In hypertension, cluster 1 was linked to higher all-cause (1.13, 1.03–1.23) and CVD mortality (1.17, 1.00–1.37), whereas cluster 3 was associated with a lower risk of diabetes-related mortality (0.40, 0.16–0.98). Conclusions: A dietary habit rich in fruit, dairy products, soybean products, and less frequent preserved vegetable intake was associated with lower mortality risk, particularly in T2D patients, whereas a habit with lower overall intake and more frequent preserved vegetable intake was linked to higher mortality in hypertension participants. These findings should be interpreted in light of the accompanying socioeconomic and lifestyle differences across dietary clusters. Full article

Background: Sepsis-associated cardiac dysfunction has historically been characterized as predominantly systolic, yet the burden of heart failure with the preserved ejection fraction (HFpEF) phenotype among patients with heart failure (HF) first documented during sepsis remains poorly defined. Methods: In a single-center retrospective cohort of adults (≥18 years) admitted to a tertiary-care hospital between 1 January 2022 and 31 December 2024, we identified patients whose first sepsis diagnosis (ICD-10) coincided with their first HF diagnosis (ICD-10 I50.x) during the same encounter, with no prior HF in the EHR. Patients were classified by ICD-10 subtype as HFpEF, HFrEF, combined, or unspecified; the unspecified group underwent echocardiographic reclassification when LVEF was documented. Demographics, selected comorbidities, peak inflammatory markers, and unadjusted in-hospital and subsequent-encounter outcomes were compared between HFpEF and HFrEF. Results: Of 924 patients with HF first documented during sepsis, 438 (47.4%) were ICD-10–coded HFpEF and 405 (43.8%) HFrEF. HFpEF patients were older (74.0 vs. 69.2 years; p < 0.001) and more often female (53.0% vs. 37.0%; p < 0.001), with higher prevalence of COPD exacerbation (21.5% vs. 13.1%; p = 0.004) and hypothyroidism (26.3% vs. 17.5%; p = 0.034). HFrEF patients exhibited higher peak lactate (2.88 vs. 2.48 mmol/L; p = 0.009) and procalcitonin (8.52 vs. 7.24 ng/mL; p = 0.011). Unadjusted in-hospital mortality (28.1% vs. 27.7%; p = 0.95), ICU admission (75.8% vs. 74.8%; p = 0.80), and length of stay did not differ. Subsequent encounters were descriptively more frequent after HFpEF (11.0% vs. 6.2%). Conclusions: ICD-10–coded HFpEF and HFrEF occurred at nearly equal frequency among adults with HF first documented during sepsis, challenging the systolic-centric paradigm. Despite distinct demographic and biochemical profiles, unadjusted in-hospital outcomes did not differ. These descriptive findings, limited by administrative-coding-based phenotype classification, the absence of multivariable adjustment, and unmeasured sepsis-severity and comorbidity variables, are hypothesis-generating and support phenotype-aware prospective study of HF arising during sepsis. Full article