Search Results (1,861)

Students are frequently assigned factual readings to learn disciplinary knowledge, yet such readings are often experienced as effortful, externally imposed, and assessment-driven. By contrast, fiction read for pleasure can absorb readers so deeply that they voluntarily learn characters, histories, places, rules, and lore from imaginary worlds. This contrast is not simply a matter of facts versus fiction. It reflects several overlapping dimensions, including narrative versus expository structure, assigned versus self-chosen reading, assessment pressure versus voluntary engagement, and isolated information versus richly connected worlds. In this Perspective paper, I provide: (1) an examination of why fictional worlds and fiction more generally can be so engaging, (2) an overview of mechanisms that support engagement, comprehension, and memory, and (3) design principles for making assigned factual readings more engaging. This is a conceptual synthesis rather than a systematic review or report of new empirical data. I distinguish less-mutable differences between pleasure reading and assigned reading from mutable design levers that educators and authors can use. My goal is not to suggest that educational readings should become fiction, nor that pleasure is a substitute for rigour, but rather to identify how factual readings can be made more engaging by leveraging narrative schema, mental imagery, prior knowledge, self-relevance, topic interest, and social reading, alongside assessments that reward meaningful understanding. Full article

Sarcopenia is an age-related progressive decline in skeletal muscle mass, strength, and physical performance that increases the risk of falls, disability, and reduced quality of life among older adults. Its pathogenesis is multifactorial and involves chronic low-grade inflammation, hormonal disturbances, insulin resistance, and mitochondrial dysfunction, leading to an imbalance between muscle protein synthesis and degradation. The aim of this study was to summarise current knowledge regarding the mechanisms underlying sarcopenia, contemporary diagnostic methods, and the effectiveness of modern nutritional and exercise-based strategies, with particular emphasis on technologies supporting patient monitoring. This study is a structured narrative review conducted across PubMed, Scopus, and Web of Science databases, with the literature search completed on 1 March 2026. Separate searches were performed for thematic sections, including pathophysiology, diagnosis, physical activity, nutritional interventions, plant-derived compounds, and digital health technologies. While the core search focused on publications from 2023–2025, specific time-bound deviations were applied: the search for plant-derived compounds was extended back to 2020, and combined interventions were searched up to March 2026 to ensure the inclusion of the most recent evidence. The review included 53 peer-reviewed primary studies (RCTs and observational) and secondary literature (reviews and meta-analyses) involving individuals aged ≥60 years. The most robust evidence supports multicomponent interventions, particularly the synergy between resistance training and adequate protein intake (1.2–1.5 g/kg/day), often supplemented with leucine, vitamin D, omega-3 fatty acids, and creatine. Such strategies effectively counteract anabolic resistance by combining mechanical loading with the stimulation of the mTORC1 signalling pathway, leading to significant improvements in muscle mass, strength, and physical function. While isolated protein or micronutrient supplementation shows limited effectiveness in the absence of exercise, their role as supportive elements in multimodal strategies is well-documented. Furthermore, emerging digital health technologies—including wearable sensors and telerehabilitation—are proving essential for clinical practice, enabling precise, continuous monitoring of physical activity and gait parameters under free-living conditions, which enhances both patient adherence and long-term therapeutic outcomes. Full article

Alcohol-related liver disease (ALD) and metabolic dysfunction and alcohol-related liver disease (MetALD) are increasingly recognised as biologically heterogeneous conditions, but circulating novel adipokines have not been systematically synthesised in this setting. We searched PubMed/MEDLINE, Embase, Web of Science, Scopus and Cochrane CENTRAL from inception to 31 December 2025 for studies measuring chemerin, visfatin/nicotinamide phosphoribosyltransferase (NAMPT), vaspin, omentin-1 or retinol-binding protein 4 (RBP-4) in adults with ALD or MetALD; data were synthesised narratively using Synthesis Without Meta-Analysis (SWiM). Grey literature and non-English databases were not searched, which may have led to incomplete retrieval of small single-centre studies. Five studies were included. Direct ALD evidence came mainly from three cross-sectional alcoholic cirrhosis cohorts, while one population cohort linked baseline RBP-4 to incident MetALD/ALD. RBP-4 showed a phase-dependent pattern, increasing before incident MetALD/ALD but decreasing in established cirrhosis with impaired synthetic function. Chemerin was reduced, omentin-1 was markedly elevated, vaspin was nonspecific and historical visfatin/NAMPT assays were difficult to interpret. Current evidence supports a hypothesis-generating three-axis framework: hepatic source failure, impaired hepatic clearance/portal-systemic shunting and alcohol-driven adipose-liver inflammation. The available evidence chiefly reflects chronic alcohol-related cirrhosis together with limited incident MetALD/ALD risk data, rather than the full ALD/MetALD spectrum. Prospective MetALD-stratified cohorts with isoform-specific assays and objective alcohol biomarkers are required. Full article

Background and Objectives: Diabetes mellitus is a major systemic modifier of oral infection, periodontal inflammation, and tissue healing. Persistent hyperglycemia may intensify oxidative stress, immune dysfunction, dysbiotic biofilm activity, and advanced glycation end-product/receptor signaling, thereby reducing the predictability of periapical and periodontal healing. In patients with endo-periodontal lesions, these mechanisms may interact with pulpal infection and periodontal breakdown, complicating diagnosis, prognosis, and therapeutic sequencing. This review summarizes current evidence on diabetes, glycated hemoglobin (HbA1c), and endo-periodontal outcomes and proposes an HbA1c-guided clinical framework for risk stratification and treatment planning. Materials and Methods: A structured narrative review with an expert-informed clinical framework was conducted using the literature published between January 2016 and December 2025. Eligible sources included consensus reports, clinical practice guidelines, systematic reviews, meta-analyses, umbrella reviews, randomized and non-randomized clinical studies, observational studies, and selected mechanistic studies or contemporary narrative reviews with direct relevance to the framework. Case reports, animal studies, and in vitro investigations without direct relevance to the clinical framework were excluded from the main synthesis. Results: Diabetes is associated with increased periodontal severity, impaired periodontal treatment response, a higher prevalence of radiolucent periapical lesions in root-filled teeth, delayed periapical healing, and increased non-retention of endodontically treated teeth. Periodontal therapy is safe in diabetic patients and may be associated with modest reductions in HbA1c, especially when baseline metabolic control is poor. Conclusions: HbA1c should complement, not replace, pulpal testing, periodontal charting, and radiographic assessment. The proposed framework prioritizes endodontic infection control when pulpal necrosis or active intracanal infection is present, adapts periodontal intervention to metabolic risk, and postpones elective surgical or regenerative procedures in poorly controlled diabetes until medical stabilization is achieved. Full article

Background: Artificial intelligence (AI) is increasingly entering hospital practice through diagnostic, predictive, workflow, operational, and generative applications. Hospitals often govern these systems as procurement or information-technology projects rather than as clinical–organizational interventions requiring indication, evaluation, monitoring, accountability, and withdrawal. Objective: To refine the concept of an “AI Hospital Formulary” as an operational, proportional, and accountable framework for the safe, equitable, and sustainable adoption of hospital AI. Design and Methods: This is a perspective article using a structured, non-systematic narrative synthesis and conceptual framework development. Targeted literature and policy sources were identified through purposive searches and citation chaining through 20 July 2026. The synthesis compares the formulary with existing oversight approaches, maps its lifecycle gates to regulatory and risk management duties, and applies the framework to a worked example based on published evaluations of the Epic Sepsis Model. The EQUATOR reporting-guideline selection tool was consulted, and SANRA was used to strengthen the narrative synthesis component. Framework: The revised framework combines a hospital-wide AI register, a standardized formulary monograph, six lifecycle gates, proportional review pathways, governance-of-governance safeguards, cloud and data-sovereignty controls, continuous monitoring of technical and behavioral feedback loops, and explicit renewal or deprescribing criteria. The worked example shows how version-specific evidence can lead to local validation, controlled implementation, restriction, suspension, or renewal rather than automatic adoption. Conclusions: Hospitals should not merely purchase, install, and update AI systems. They should prescribe, monitor, audit, renew, restrict, and, when necessary, deprescribe them. The AI Hospital Formulary is proposed as a complementary institutional layer that converts external standards and existing governance approaches into documented portfolio decisions at the hospital level. Full article

Background: Invasive coronary angiography has historically been the reference standard for coronary, valvular, and structural heart disease. Over the past decade, coronary computed tomography angiography (CCTA), CT-derived fractional flow reserve (CT-FFR), photon-counting detector computed tomography (PCCT), and cardiac magnetic resonance (CMR) have expanded the range of clinical questions answerable without an intra-arterial catheter, but this shift has been uneven across clinical domains. Methods: We performed a narrative review and synthesis of randomized trials, registries, society guidelines, and consensus documents (2009–2026) identified through PubMed and major cardiovascular guideline databases, written from a joint cardiology and cardiac-surgical standpoint. Results: The boundary has shifted asymmetrically, by which we mean a domain-dependent rather than uniform displacement of invasive angiography. Non-invasive imaging is now established as the first-line approach for stable chest pain at low-to-moderate pretest probability, for pre-transcatheter aortic valve replacement (TAVR) and structural procedural planning, and for aortic disease. It remains contested for stable multivessel disease and pre-coronary artery bypass grafting (CABG) planning, where CCTA- or CT-FFR-only planning is still investigational. Invasive angiography stays first-line for ST-elevation myocardial infarction (STEMI), cardiogenic shock, and complex percutaneous coronary intervention (PCI), where diagnosis and therapy are inseparable. Conclusions: Invasive and non-invasive modalities are complementary rather than competing. The appropriate first-line investigation depends on the disease domain, pretest probability, anatomical complexity, imaging quality, and whether diagnosis and treatment can be separated. We propose a complexity-stratified, heart-team framework and identify the surgical research gaps that remain. Full article

Background: Critically ill children with cancer are vulnerable to sepsis and septic shock, secondary hemophagocytic lymphohistiocytosis (HLH), cytokine release syndrome, delayed chemotherapy clearance, and multiorgan dysfunction. Although hemoadsorption can remove inflammatory mediators and selected toxins, evidence in pediatric oncology remains limited and heterogeneous. Objective: To systematically review the indications, technical application, biomarker and physiologic findings, safety reporting, and clinical outcomes of hemoadsorption in critically ill pediatric oncology and hemato-oncology patients. Methods: We conducted a PRISMA-guided systematic review of PubMed, Scopus, and Web of Science from January 2017 to 1 June 2026, supplemented by reference screening. The search strategy was expanded to capture cartridge-based hemoadsorption and related extracorporeal blood purification modalities, including albumin dialysis systems, but direct synthesis was restricted to cartridge-based hemoadsorption. Evidence was stratified as direct pediatric oncology evidence, supportive hemato-oncology/transplant evidence, or contextual mixed pediatric critical-care evidence. Because included reports were small, uncontrolled, and clinically heterogeneous, synthesis followed a structured narrative approach without meta-analysis. Results: Twelve reports met the inclusion criteria; most were case reports, case series or retrospective observational studies. Hemoadsorption was most often described for septic shock, sepsis-like hyperinflammation, or secondary HLH, with smaller experience in delayed methotrexate clearance, CAR-T-cell-associated cytokine release syndrome, and post-transplant hyperbilirubinemia. Reported devices included CytoSorb, Jafron HA330, and HA230. Direct pediatric oncology reports described before–after reductions in IL-6, IL-10, C-reactive protein, procalcitonin, or ferritin, together with changes in oxygenation, vasoactive support, or organ dysfunction scores. However, all findings were vulnerable to confounding by concurrent antimicrobials, immunomodulation, kidney replacement therapy, source control, and natural recovery. Mortality outcomes were reported using non-equivalent horizons and were summarized narratively. Conclusions: Hemoadsorption has been attempted as adjunctive rescue support in selected critically ill pediatric oncology and hemato-oncology patients. Current evidence is insufficient to determine treatment effect, survival benefit, optimal timing, device selection, anticoagulation strategy, or pharmacokinetic safety. Full article

With increasing rail traffic intensity, reliable detection of shallow subsurface rail damage is essential for operational safety. This critical narrative review evaluates non-destructive testing technologies relevant to defects whose active crack front or principal scattering zone lies within the upper approximately 0.5–10 mm of the rail, while treating the 10–15 mm range as a transition to deeper-defect verification. Magnetic flux leakage, magnetic particle inspection, visual inspection, eddy current testing, and conventional ultrasonic testing are first examined as screening or confirmatory comparators. The review then focuses on four ultrasonic surface-wave excitation routes—contact piezoelectric, active air-coupled, electromagnetic acoustic, and laser ultrasonic—and distinguishes source-specific laboratory capability from demonstrated field evidence. Because the cited studies use different defect geometries, rail conditions, sensor configurations, speeds, and decision criteria, their numerical values are reported as source-conditioned evidence rather than as a normalized ranking. An engineering decision matrix links defect depth and size, inspection speed, surface condition, and noise environment to a recommended screening–confirmation workflow. The synthesis identifies contact piezoelectric UT/PAUT as the most mature quantitative confirmation route, while EMAT, air-coupled UT, and laser UT retain method-specific advantages but require stronger natural-defect and in-service validation. Full article

Background/Objectives: Colitis involves both local intestinal damage and systemic dysfunction, driven by oxidative stress and immune imbalance. Histamine, acting through its receptors, influences these processes, yet its therapeutic relevance in colitis remains unclear. This review systematically examines histamine-mediated signaling in colitic inflammation and evaluates preclinical and clinical data on antihistamines to assess their potential as a mechanism-based treatment. Methods: A structured literature search was conducted using PubMed and Google Scholar to identify studies addressing histamine signaling and the use of antihistamines in colitis, using keywords such as “colitis,” “histamine,” “histamine receptors,” and “antihistamines.” Relevant experimental and clinical studies were screened and critically analyzed to provide an integrated overview of mechanistic and therapeutic insights. This review was designed as a mechanistic narrative synthesis based on a structured search and qualitative appraisal rather than a formal systematic review with quantitative risk-of-bias grading. Results: Findings from preclinical investigations consistently indicate that pharmacological manipulation of histamine signaling—especially through H3 and H4 receptor subtypes—reduces inflammatory activity and modulates oxidative balance in animal models of colitis. Conversely, clinical evidence concerning H1 and H2 receptor antagonists remains scarce and discordant, lacking sufficient support for a definitive causal relationship or unambiguous therapeutic efficacy. Importantly, no clinical studies to date have assessed the effects of selective H3 or H4 receptor blockers in individuals with colitis, revealing a substantial disconnect between bench research and bedside application. Existing human trials have mainly concentrated on mucosal endpoints, with little attention paid to systemic manifestations or oxidative stress-related parameters. Conclusions: Histamine-dependent signaling constitutes a mechanistically credible target in colitis, connecting immune activation, impairment of the epithelial barrier, and oxidative injury. Although experimental data are encouraging, clinical corroboration remains absent. Antihistamines may hold greater promise for alleviating systemic oxidative stress than for directly ameliorating intestinal inflammation. Rigorously designed clinical trials that incorporate both gastrointestinal and systemic outcome measures are necessary to elucidate their therapeutic position. Full article

Background: Gestational diabetes mellitus (GDM) and polycystic ovary syndrome (PCOS) are clinically distinct disorders that share important metabolic features. This Perspective proposes a non-causal intergenerational framework linking maternal PCOS-related metabolic vulnerability, susceptibility to GDM, intrauterine metabolic exposure, and later reproductive-metabolic risk in female offspring. Methods: A narrative synthesis of evidence from reproductive endocrinology, obstetrics, diabetology, developmental biology, and public health was undertaken. The strength of evidence supporting individual components of the proposed continuum was qualitatively appraised. Separately, aggregated surveillance data from Belgrade for 2015–2024 were used as a registry-based illustration of ICD-10 O24.4-coded GDM diagnoses. No formal time-series analysis, causal modeling, or forecasting was performed. Results: Evidence was strongest for the increased risk of GDM among women with PCOS and for the association between intrauterine exposure to maternal diabetes and later offspring metabolic susceptibility. Evidence linking maternal PCOS with offspring metabolic vulnerability was less definitive, while direct evidence that GDM exposure leads to clinically diagnosed PCOS in female offspring remained weak and indirect. Registry-recorded GDM rates varied across years, but this variability may reflect differences in screening, diagnostic criteria, coding, reporting completeness, and healthcare access rather than true changes in prevalence. Conclusions: The proposed GDM–PCOS continuum is a hypothesis-generating and probabilistic framework, not an established causal pathway. Its clinical value lies in connecting prevention opportunities before conception, during pregnancy, after delivery, and across the life course. Longitudinal maternal–offspring studies are required to test the proposed relationships. Full article

This narrative review critically summarizes the literature on the associations of Type A and Type D personality, together with related personality traits, with cardiovascular disease (CVD) onset, prognosis, cardiac surgery, and rehabilitation outcomes. For the past half a century, there has been a consistent interest in the question of whether or not there is a connection between personality qualities and CVD. At the same time as individuals with a Type A personality who were angry, competitive, and excessively motivated were overrepresented among patients seeking treatment for CVD, it was also noted that these individuals were more likely to acquire coronary artery disease or syndrome. Anger and animosity were among the unfavorable impacts that were found to be connected with worse cardiovascular outcomes, according to the findings of research. After that, a new personality entity was brought into existence, which was referred to as the type D “distressed” personality. This personality type coupled negative affectivity and social inhibition. Type D personality subsequently became a major focus of research, and several studies reported associations with poorer patient-reported health and adverse cardiac outcomes. However, these findings have not been consistently replicated, and the stability, incremental predictive value, and independence of Type D personality from depression, disease severity, and other psychosocial factors remain debated. As a result, there are a number of criticisms that pertain to the current knowledge of the connection between personality construct and the risk of developing cardiovascular diseases as well as the outcome of these diseases. This review provides a critical narrative synthesis of supportive and conflicting evidence and highlights the methodological limitations that currently prevent definitive causal or prognostic conclusions. Full article

Background/Objectives: Periodontitis is a chronic oral infection in which Porphyromonas gingivalis (Pg) acts as a keystone pathogen capable of systemic dissemination and immune evasion. A possible association between Pg and acute myocardial infarction (AMI) has been proposed; this systematic review is, to our knowledge, among the first to evaluate this association through a pathogen-specific synthesis integrating both microbial and serological evidence. Methods: Five electronic databases (PubMed, Scopus, Embase, Web of Science, Cochrane Library) were searched from inception to February 2025, with a supplementary top-up search performed in July 2026 that identified no additional eligible studies. Observational studies assessing Pg presence or anti-Pg antibody levels in participants with and without AMI were eligible. Methodological quality was assessed using the Newcastle–Ottawa Scale (NOS). Findings were synthesised narratively due to substantial clinical and methodological heterogeneity. The protocol was registered in PROSPERO (CRD42025644043). Results: Twelve case-control studies (5147 participants; 2518 AMI cases, 2629 controls) were included. Six evaluated serum anti-Pg antibodies and six used direct microbial or molecular detection. Three studies in each category reported a significant Pg–AMI association; three in each category did not. NOS scores ranged from 6 to 9 (eight studies rated good quality; four fair quality). Heterogeneity in antigen selection, sampling site, immunoglobulin isotype, and confounder adjustment precluded meta-analysis. Conclusions: The available evidence suggests a possible but inconsistent association between Pg and AMI, insufficient to establish a causal relationship. Standardised detection protocols and prospective longitudinal studies with comprehensive confounder adjustment are needed. The detection of Pg in isolation is not currently validated for AMI risk stratification, and the available evidence does not establish a causal relationship between Pg and AMI. Full article

Background: Modern intensive care paradigms prioritize optimal analgesia over heavy sedation. While morphine, fentanyl, and remifentanil are widely used, sufentanil is relatively unknown in several countries. Aimed primarily at intensive care physicians, this narrative review evaluates the utilization of sufentanil in critically ill adult patients across four fundamental dimensions: (1) translational pharmacology (chemical structure, pharmacokinetics, pharmacodynamics, and pharmacogenomics); (2) indications and safety precautions; (3) clinical evidence in ICU patients; and (4) therapeutic positioning in contemporary ICU analgosedation and future research directions. Methods: A comprehensive literature search was conducted in PubMed/MEDLINE focusing on the translational pharmacology, safety parameters, and clinical studies of sufentanil critically ill adults. The synthesis was structured according to SANRA principles for high-quality narrative reviews and includes articles published up to February 2026. Results: Sufentanil exhibits an exceptionally high affinity for the µ-opioid receptor, providing a potency 10-fold greater than fentanyl and 1000-fold greater than morphine. It has an experimental therapeutic index (LD50/ED50) nearly two orders of magnitude wider than that of fentanyl, enabling safe, highly granular bedside titration. Unlike morphine, hepatic CYP3A4 biotransformation yields completely inactive metabolites, preventing toxic accumulation during acute kidney injury. Furthermore, receptor-binding dynamics suggest a lower propensity for recruiting β-arrestins and activating NMDA pathways, potentially reducing opioid-induced hyperalgesia (OIH). Clinically, pilot trials in neurocritical cohorts demonstrate that sufentanil maintains reliable cerebral hemodynamic stability. In postoperative cardiac surgery and large ICU registries, sufentanil may reduce the mechanical ventilation duration, accelerate extubation, and shorten ICU length of stay. Conclusions: For critically ill adults, sufentanil is an excellent alternative to traditional opioids because it offers high-precision titratability, potent analgesia, and a safer metabolic profile. Full article

Exercise-induced myokines, such as IL-6, irisin, and myostatin, play crucial roles in mediating systemic adaptations and modulating tumor progression. This narrative review synthesizes evidence on how regular moderate-intensity exercise affects the myokine network within the tumor microenvironment (TME) of solid tumors. Results from the 86 included studies indicate that structured training (aerobic: 45–65% VO₂ max; resistance: 45–70% 1RM) enhances the expression of beneficial myokines that support immune surveillance, reduce inflammation, and improve muscle–tumor cross-talk. IL-6 demonstrates a dual modulatory effect on inflammation and immunity; irisin contributes to tumor apoptosis, while myostatin downregulation supports muscle integrity and metabolic balance. Evidence suggests that exercise-induced alterations in these factors may influence tumor angiogenesis and immune infiltration, offering potential therapeutic implications. Overall, tailored exercise regimens represent a promising non-pharmacological strategy to optimize myokine signaling in cancer management. Further human studies are needed to confirm these mechanistic effects and define optimal exercise protocols. While existing data suggest that structured exercise may beneficially modulate myokine profiles and thereby influence tumor biology, these conclusions are based on limited qualitative evidence rather than quantitative synthesis. Further well-controlled clinical studies are required to confirm causality and define optimal exercise prescriptions for oncology settings. Full article

Background: Progesterone is an endogenous pregnancy hormone widely used in reproductive medicine and obstetrics. Its developmental relevance should be interpreted by distinguishing direct molecular plausibility from indirect obstetric effects, including stabilization of the maternal–decidual–placental maternal–decidual–placental environment, cervical stability, and prolongation of gestation. Methods: A focused qualitative narrative review was performed using targeted literature searches and thematic synthesis. This approach was chosen because the available evidence is heterogeneous with respect to indication, formulation, route, dose, timing, comparator group, and offspring follow-up, making quantitative synthesis inappropriate for the present objective. Results: Direct progesterone-related pathways include receptor-mediated signaling, neuroactive metabolites, and biologically plausible epigenetic regulation; however, human evidence for persistent therapy-induced molecular programming remains limited. Indirect pathways are better supported and include decidualization, immune tolerance, placental stabilization, cervical integrity, uterine quiescence, and prevention of prematurity in selected pregnancies. Clinical evidence should be interpreted separately for placebo-controlled trials, untreated pathological cohorts, and observational follow-up studies because underlying maternal conditions may themselves influence offspring outcomes. Potential risk signals also require formulation-specific interpretation, particularly for synthetic progestogens and 17-alpha hydroxyprogesterone caproate, for which long-term observational data and regulatory reassessments have raised concerns regarding efficacy and possible offspring safety signals. Inadvertent exposure to contraceptive progestins during unrecognized pregnancy, including progestin-only preparations and levonorgestrel-releasing intrauterine systems, should be considered separately from therapeutic obstetric progesterone use. Available evidence has not shown a consistent early adverse signal for natural progesterone when used for recognized indications, although long-term offspring data remain limited and cannot be generalized to synthetic progestogens or 17-alpha hydroxyprogesterone caproate. Conclusions: Progesterone-related therapies should be considered indication-specific and formulation-specific rather than interchangeable. Current evidence supports a cautious and comparator-aware interpretation: natural progesterone appears acceptable for recognized clinical indications based on available short-term and early childhood data, but evidence beyond early childhood remains insufficient for broad safety generalizations. Full article