Search Results (2,497)

Background: In recent decades, doctoral education has undergone a profound transformation. As a result, PhD students have become an increasingly vulnerable population, facing greater risk of mental health problems than the general population. A particularly important subgroup comprises PhD students in medicine and health sciences, who often combine doctoral training with clinical work. Their dual roles expose them to additional pressures, with an increased risk of burnout. Given that their context differs considerably from the typical university environment, in this systematic review, we aim to synthesize the current evidence on burnout, impostor syndrome, and research engagement, along with related indicators of psychological distress, among PhD students in medicine and health sciences, as well as identify key risk and protective factors and highlight gaps for future research. Methods: A systematic literature search was conducted in March 2026 across the Web of Science, Scopus, and Ovid MEDLINE databases. Following a screening process based on PRISMA guidelines, 27 studies were included; due to substantial heterogeneity, findings were synthesized narratively. Results: Psychological difficulties appeared to be more strongly associated with institutional factors rather than personal traits. Burnout was highly prevalent and linked to professional isolation and poor relationships with supervisors. Impostor syndrome emerged as a recurrent theme in qualitative accounts, though it was formally assessed with a validated instrument in only one study. Moreover, research engagement did not appear to protect students from burnout. Conclusion: Burnout and psychological distress are widespread among PhD students in medicine and health sciences, and impostor feelings emerged as a recurrent theme, although formally measured in only one study. These findings highlight the need for structural and institutional changes rather than relying solely on individual psychological support. Full article

The global transition to antibiotic-free livestock production, accelerated by antimicrobial-resistance concerns, has intensified the search for alternatives to antibiotic growth promoters, and phytobiotics have emerged as key candidates. Cangzhu, the dried rhizome of Atractylodes lancea (Thunb.) DC, is a crude drug of traditional Chinese medicine that has attracted substantial attention as a multipurpose phytobiotic. This review synthesizes current knowledge on the phytochemistry, gut-protective mechanisms, and practical application of Cangzhu in sustainable livestock production. Its principal bioactive constituents are sesquiterpenoids (atractylone, β-eudesmol, hinesol, atractylenolides I–III), polyacetylenes (including atractylodin), polysaccharides, and flavonoids. Reported gut-protective mechanisms comprise upregulation of tight junction proteins (ZO-1, occludin, claudin-1); dual suppression of the NF-κB and MAPK-signaling pathways; activation of the Nrf2–Keap1 antioxidant axis; modulation of the gut microbiota; and TLR4-mediated stimulation of mucosal immunity. In swine, poultry, and ruminant studies, Atractylodes-based supplementation has been associated with improved growth performance, a lower incidence of diarrhea, favorable intestinal morphology, downregulated pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), beneficial microbiota shifts, and inhibited pathogens. However, much of the mechanistic evidence derives from rodent and in vitro models, and much of the in vivo livestock evidence from the related species A. macrocephala (Baizhu) or multi-herb formulations; direct livestock trials with pure A. lancea remain limited for several endpoints, and the responses observed in these heterogeneous studies depend on the formulation, dose, and animal species used, as indicated by the explicit evidence-tier and source-species tags applied throughout the text, tables, and figures. The reported effective inclusion levels should be read as experimental study ranges and not as standardized dose recommendations. Framed within the One Health paradigm, Cangzhu is therefore best characterized as a mechanistically substantiated candidate alternative to antibiotic growth promoters whose adoption requires species-specific dose validation, quality standardization, and commercial-scale economic confirmation. Full article

Background/Objectives: Inflammatory bowel diseases (IBDs) are an increasingly important global health problem, yet Central Asia remains underrepresented in international IBD data. To evaluate the clinical and demographic characteristics of patients included in the national multicenter clinical IBD registry of the Republic of Kazakhstan (IBD Registry) according to disease activity at registry enrollment visit and to identify factors associated with active IBD at that time. Methods: We conducted a cross-sectional analysis of the registry enrollment visit data from the national multicenter clinical IBD registry of the Republic of Kazakhstan. The study included patients with ulcerative colitis (UC) and Crohn’s disease (CD) registered between 2021 and 2024. Disease activity at the registry enrollment visit was assessed using the full Mayo score for UC and the Harvey–Bradshaw index for CD. Univariable and multivariable logistic regression analyses were performed to identify factors associated with active disease. Results: The analysis included 1521 patients with IBD, 68.4% with ulcerative colitis and 31.6% with Crohn’s disease. At the registry enrollment visit, 77.5% of patients had clinically active disease. In UC, active disease was independently associated with rural residence (aOR 2.11; 95% CI 1.25–3.56), ≥2 exacerbations per year (aOR 3.47; 95% CI 2.18–5.51), current corticosteroid therapy (aOR 5.96; 95% CI 3.04–11.69), and immunosuppressive therapy (aOR 2.71; 95% CI 1.15–6.38), whereas rare exacerbations were associated with lower odds of activity (aOR 0.41; 95% CI 0.23–0.73). In CD, active disease was independently associated with ≥2 exacerbations per year (aOR 2.41; 95% CI 1.47–3.95), colonic (L2) location (aOR 2.32; 95% CI 1.25–4.30), ileocolonic (L3) location (aOR 2.24; 95% CI 1.25–4.04), extraintestinal manifestations (aOR 2.88; 95% CI 1.68–4.93), and current corticosteroid therapy (aOR 1.77; 95% CI 1.03–3.05), whereas immunosuppressive therapy was associated with lower odds of active disease (aOR 0.46; 95% CI 0.24–0.89). Biologic therapy was not independently associated with disease activity in either UC or CD. Conclusions: A high proportion of patients treated at participating secondary and tertiary centers had clinically active IBD at registry enrollment. The profiles of factors associated with activity differed between UC and CD, while frequent exacerbations were consistently associated with active disease in both conditions. These findings should be interpreted as cross-sectional associations rather than causal or prognostic relationships, particularly for treatment-related factors. Full article

Population aging has intensified the search for natural compounds capable of promoting healthy aging and preventing age-related diseases. Among medicinal plants, species of the genus Crataegus (hawthorn) have attracted increasing attention because of their rich phytochemical composition and broad spectrum of biological activities. This review summarizes and critically evaluates current evidence on the geroprotective potential of Crataegus species, integrating data from phytochemical, pharmacological, and mechanistic studies. Particular attention is given to the major bioactive constituents of Crataegus, including flavonoids, oligomeric proanthocyanidins, phenolic acids, and triterpenoids, which exhibit antioxidant, anti-inflammatory, cardioprotective, neuroprotective, metabolic, and anticancer properties. We discuss the growing evidence that these phytochemicals target multiple hallmarks of aging by modulating oxidative stress, chronic low-grade inflammation (inflammaging), mitochondrial dysfunction, cellular senescence, and the senescence-associated secretory phenotype (SASP). Their biological effects are mediated through key signaling pathways involved in cellular homeostasis and longevity, including Nrf2/ARE, NF-κB, PI3K/Akt/mTOR, AMPK, and SIRT1. The review also critically examines findings from in vitro, in vivo, and available clinical studies, highlighting both the therapeutic potential and current limitations of Crataegus-based interventions for age-related disorders. Although preclinical evidence strongly supports the multi-target geroprotective properties of Crataegus species, clinical validation remains limited. Overall, Crataegus represents a promising source of natural geroprotective agents with the potential to promote healthy aging through the modulation of multiple aging-related molecular pathways. Future well-designed clinical studies are essential to establish their efficacy, safety, optimal dosage, and long-term therapeutic value in humans. Full article

Diabetes mellitus is a major global health challenge, and medicinal plants represent an important source of bioactive compounds with therapeutic potential. Ibervillea sonorae (S. Watson) Greene is traditionally used in Mexican medicine for diabetes management and has attracted increasing scientific interest because of its reported antihyperglycemic activity. This systematic review critically evaluated the available preclinical evidence regarding the antihyperglycemic effects of I. sonorae, its proposed molecular mechanisms, phytochemical context, and methodological limitations. Following the PRISMA 2020 guidelines, PubMed, Scopus, and Google Scholar were searched for studies published between January 2010 and February 2026. Eight studies met the inclusion criteria, including animal, cellular, and enzyme-based models. The available evidence indicates that I. sonorae preparations may improve glycemic control through complementary mechanisms involving enhanced glucose uptake and insulin-related responses, including participation of the PI3K/AKT/GLUT4 signaling network, together with inhibition of α-glucosidase and α-amylase activity. AMPK-related mechanisms remain biologically plausible but have not been directly established across the included studies. Phytochemical evidence identifies cucurbitacin-derived constituents, including kinoins, as potentially relevant bioactive compounds; however, most mechanistic findings were obtained using crude extracts or other plant preparations, and their specific contribution cannot yet be attributed to individual constituents. Overall, this review integrates the fragmented preclinical evidence and identifies the principal mechanistic, phytochemical, and methodological gaps that must be addressed before clinical translation. I. sonorae represents a promising candidate for antihyperglycemic research, although phytochemical standardization, rigorous mechanistic studies, comprehensive safety evaluation, and well-designed clinical investigations are required to establish its therapeutic efficacy and safety. Full article

Medicinal plants of the genus Atractylodes, primarily including Atractylodes lancea (Thunb.) DC., Atractylodes chinensis (DC.) Koidz., and Atractylodes macrocephala Koidz., are important traditional Chinese medicinal herbs that are widely recognized for their functions of “strengthening the spleen and drying dampness” and have traditionally been used to treat digestive and metabolic disorders. In recent years, with the increasing global burden of liver diseases, Atractylodes species have attracted growing attention for their potential pharmacological value in liver disease management due to their abundant bioactive compounds and diverse pharmacological activities. This review summarizes reported biological and hepatoprotective effects and proposed mechanisms of Atractylodes medicinal plants and their bioactive compounds in liver-related experimental models, including models relevant to MASLD, ALD, hepatic fibrosis, and HCC. Preclinical studies have reported changes in lipid metabolism, oxidative-stress-related markers, inflammatory responses, fibrotic indices, and tumor-cell phenotypes, accompanied by modulation of signaling pathways including AMPK/SIRT1, PPAR, Nrf2/HO-1, TLR4/MyD88/NF-κB, NLRP3, and TGF-β1/Smad. However, much of the mechanistic evidence is based on pathway-associated changes rather than direct compound–target validation, and clinical evidence remains limited. Overall, the available findings provide a preclinical pharmacological rationale for further investigation of Atractylodes-derived compounds in liver diseases, while their clinical efficacy and therapeutic roles remain to be established. Full article

Background: Pleural effusion is a common clinical presentation in both benign and malignant conditions. The advent of liquid biopsy allowed new possibilities for non-invasive molecular profiling using body fluids. Pleural fluid, by virtue of its proximity to thoracic malignancies and its rich tumour-derived content, represents a particularly compelling matrix for liquid biopsy analysis. This review synthesises current evidence regarding the diagnostic, predictive, and prognostic utility of pleural liquid biopsy in clinical medicine. Methods: A narrative review was conducted using PubMed, MEDLINE, and EMBASE databases. Search terms included combinations of “pleural effusion”, “liquid biopsy”, “circulating tumour DNA”, “circulating tumour cells”, “exosomes”, “next-generation sequencing”, and “biomarkers”. Priority was given to original research articles, systematic reviews, and meta-analyses published between 2013 and 2026. Results: Pleural fluid contains a diverse repertoire of tumour-derived analytes, including cell-free and circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), exosomes, and soluble proteins. These biomarkers enable molecular characterisation of underlying malignancies with sensitivity that often exceeds that of plasma-based liquid biopsy and complements histological tissue biopsy. Detection of actionable mutations, including EGFR, ALK, KRAS, and BRAF alterations, directly informs targeted therapy selection. Furthermore, serial sampling facilitates real-time monitoring of therapeutic resistance, disease progression, and clonal evolution. Conclusions: Pleural liquid biopsy offers a minimally invasive, reproducible, and clinically informative approach to molecular profiling in patients with pleural disease, particularly those with thoracic malignancies. Despite existing challenges in standardisation and analytical sensitivity, its integration into routine clinical pathways holds significant promise for advancing personalised oncological care. Multi-omics integration and artificial intelligence may further consolidate its role in therapeutic decision-making. Full article

Laurus nobilis L. (Lauraceae), widely recognized as bay laurel, has long held prominence in traditional medicine across diverse cultures and has attracted growing attention within contemporary pharmacological research. This review endeavors to synthesize and critically evaluate evidence from in vitro, in vivo, and clinical studies to elucidate the therapeutic potential of this species, an aromatic evergreen shrub native to the Mediterranean region. Its leaves and essential oil have long been utilized in culinary and traditional medicine, and recent scientific studies have revealed a wide range of pharmacological properties. A comprehensive literature search was conducted using the keyword “Laurus nobilis L.” across Scopus, PubMed, and Google Scholar databases. The search included English-language resources published up to 31 January 2025, focusing on in vitro, in vivo, and human studies. Exclusion criteria encompassed letters, conference proceedings, and articles related to agriculture, genetics, nursing, environmental and veterinary sciences, multidisciplinary studies, and non-medical or pharmaceutical themes. The findings indicate that L. nobilis exhibits diverse pharmacological activities, including wound-healing, dental plaque-reduction, hepatoprotective and gastroprotective effects, antidiabetic activity, antioxidant and anti-inflammatory properties, antimicrobial and antiparasitic effects, neuroprotective potential, antigenotoxic and anti-hypersensitivity actions, and renal protection. This review manuscript seeks to further illuminate the pharmacological potential of Laurus nobilis while articulating the biophysical underpinnings and mechanistic coherence through which its bioactive constituents manifest their therapeutic effects. In conclusion, L. nobilis demonstrates significant promise as a natural, effective, and safe therapeutic candidate for various health conditions. Nonetheless, further clinical research is warranted to substantiate its efficacy and safety, thereby enabling its integration into evidence-based medical practice. Full article

Three-dimensional (3D) bioprinting is an evolving biofabrication approach in regenerative medicine with the potential to overcome many limitations of conventional reconstructive techniques, including donor-site morbidity, limited tissue availability, and suboptimal restoration of form and function. Recent advances in biofabrication have accelerated the development of patient-specific living constructs for reconstructive applications. This narrative review synthesizes contemporary evidence on the use of 3D bioprinting in reconstructive surgery, emphasizing developments most relevant to plastic surgery. The current literature on bioprinting technologies, bioinks, tissue-specific applications, translational studies, and regulatory considerations was critically reviewed. Significant progress has been achieved in the bioprinting of skin, cartilage, bone, osteochondral tissues, vascularized constructs, and composite craniofacial tissues. Advances in extrusion-, inkjet-, laser-, and stereolithography-based printing, together with increasingly sophisticated natural and synthetic bioinks, have improved construct fidelity, cellular viability, and tissue-specific functionality. In situ bioprinting, patient-specific computer-aided design, and hybrid biomaterial strategies have further expanded the clinical potential of bioprinted tissues. Despite these advances, major barriers remain, including inadequate vascularization of large constructs, limited mechanical maturation of load-bearing tissues, manufacturing standardization, regulatory uncertainty, and the absence of robust long-term clinical outcomes. Three-dimensional bioprinting is enabling increasingly personalized tissue fabrication, although most applications remain preclinical. Clinical translation will require further advances in biomaterials, vascular engineering, manufacturing standardization, and regulatory science. Full article

Pancreatic neuroendocrine neoplasms (PanNENs) are a heterogeneous group of tumors characterized by variable biological behavior and frequent overexpression of somatostatin receptors, making them ideal candidates for theranostic approaches. Over the past two decades, advances in molecular imaging and peptide receptor radionuclide therapy (PRRT) have fundamentally transformed the diagnosis and management of advanced PanNENs, establishing nuclear medicine as a central component of precision oncology. This review provides a comprehensive overview of the evolving role of theranostics in PanNENs, with particular emphasis on recent developments in nuclear medicine and radiation-based precision medicine. We discuss the biological foundation of molecular imaging, current clinical evidence supporting PRRT, and emerging strategies for personalized radionuclide therapy based on quantitative imaging, patient selection, and individualized dosimetry. Furthermore, we highlight next-generation radiopharmaceuticals, including somatostatin receptor antagonists and α-emitting radionuclides, as well as novel diagnostic tracers that are expanding the scope of theranostic applications. The review also examines the growing impact of artificial intelligence, radiomics, and computational modeling in image analysis, treatment planning, and adaptive radionuclide therapy. Finally, we discuss future perspectives toward adaptive precision theranostics, in which molecular imaging, multi-omics integration, advanced dosimetry, and artificial intelligence converge to support dynamic, patient-specific treatment strategies. Continued technological innovation and multidisciplinary collaboration are expected to further establish theranostics as a cornerstone of personalized management for patients with PanNENs. Full article

The fact that the population is getting older has greatly increased the occurrence of cognitive decline and neurodegenerative diseases, underlining the importance of having reliable biomarkers that can measure biological aging before irreversible neurological damage takes place. New evidence shows that brain aging is not just the result of changes within neurons themselves but is also greatly affected by the gut microbiota via immune, metabolic, endocrine, and neurovascular signaling. This review brings together the existing knowledge about biomarkers of biological aging-such as telomere shortening, epigenetic clocks, oxidative stress, inflammation, cellular senescence, and metabolic dysfunction-as well as established cognitive biomarkers obtained from neuroimaging, cerebrospinal fluid, blood, genetic evaluations, and neuropsychological tests. We also point out that changes associated with age in the composition of the gut microbiota and the metabolites it produces are becoming more and more involved in the mechanisms connecting intestinal dysbiosis, dysfunction of the blood-brain barrier (BBB), neuroinflammation, and age-related cognitive decline. Through this approach of combined and complementary biomarker systems, we hypothesize that the gut microbiota has emerged as a central regulator of biological and cognitive aging and may provide a useful source for development of biomarkers of cognitive resilience and risk of neurodegenerative diseases. Lastly, we consider microbiome-based interventions, including probiotics, prebiotics, dietary changes, fecal microbial transplant, and new treatment modalities derived from molecular studies, as possible approaches to the prevention and management of age-related cognitive decline. Collectively, this review provides a comprehensive framework linking aging biology, microbiome science, and cognitive biomarkers to advance biomarker-driven precision medicine for healthy brain aging. Full article

Biofilm-associated infections represent a critical challenge in modern medicine, accounting for approximately 80% of all microbial infections and demonstrating up to 1000-fold higher antimicrobial resistance compared to planktonic bacteria. The extraordinary recalcitrance of biofilms stems from a complex interplay of physical barriers (extracellular polymeric substance matrix), chemical gradients (pH and oxygen heterogeneity), and biological defenses (persister cells and horizontal gene transfer), rendering conventional antibiotics largely ineffective. This comprehensive review highlights the transformative potential of antimicrobial nanoformulations in overcoming these formidable barriers through strategic design principles and diverse mechanisms of action. Evidence demonstrates that rationally engineered nanocarriers achieve improvements in bacterial killing, biofilm biomass reduction, and colony-forming unit reductions compared to free antibiotics. Advanced stimuli-responsive systems exploiting biofilm-specific triggers (acidic pH, bacterial enzymes, elevated ATP) and externally applied stimuli (near-infrared photothermal therapy, ultrasound sonodynamic therapy) enable on-demand therapeutic activation with unprecedented precision, achieving >99.999% bacterial elimination and near-complete biofilm eradication. Despite these remarkable advances, clinical translation remains hindered by challenges in scalability, comprehensive safety evaluation, and regulatory pathway navigation. This review establishes a consolidated evidence base for the design of next-generation antimicrobial nanoformulations, highlights their potential to address biofilm-associated infections, and identifies key knowledge gaps and translation barriers that must be addressed to realize their therapeutic promise. Full article

Background: For vitamin D, the US National Academies of Sciences, Engineering, and Medicine (NASEM) suggest serum 25-hydroxyvitamin D (25(OH)D) >125 nmol/L is linked to potential toxicity. The European Food Safety Authority (EFSA) recommends that daily doses up to 2000 IU (50 µg) are safe for children aged 1–10 years, and 4000 IU (100 µg) for those aged 11 years and over. We evaluated the consistency between these two guidelines. Methods: We compiled accessible under 18’s clinical trial data for external validation. We tested published physiologically based pharmacokinetic (PBPK) models. We used simulations to explore the serum 25(OH)D pharmacokinetic profiles in children (6–10) and adolescents (11–17). We fitted a new model to the external validation data. Results: Our PBPK model, previously developed for healthy adults, made good predictions for the mean of the validation data. Model simulations suggested the mean should attain serum 25(OH)D > 115 nmol/L among 6-year-old children who take 2000 IU daily, and >125 nmol/L for 11- to 12-year-olds who take 4000 IU daily. We also presented clinical data to demonstrate that 4000 IU daily dosing increased serum 25(OH)D >125 nmol/L in a large proportion of healthy adults. Model parameters for the Cape Town children and the US and European children are different. Conclusions: This analysis highlights the inconsistency between the NASEM and EFSA guidelines and warrants the need for further pharmacokinetic modelling work to support the development of vitamin D safety parameters and guidelines. Our modelling suggests that the currently adopted 125 nmol/L threshold may warrant re-evaluation, as the supporting evidence appears heterogeneous and limited. Full article

Central Asian populations remain underrepresented in pharmacogenomic research, limiting the availability of population-specific data for genotype-informed prescribing and precision medicine. This study analyzed clinically relevant pharmacogenomic variant frequencies in Kazakh, Russian, and Uzbek population groups residing in Kazakhstan using genome-wide genotype data from 1301 individuals: Kazakh (n = 1111), Russian (n = 156), and Uzbek (n = 34). ClinPGx, a PharmGKB-based clinical annotation framework that prioritizes variant–drug associations according to levels of evidence, was used to select variants with evidence levels 1A, 1B, and 2A. In total, 112 directly genotyped variants were retained for population-specific allele and genotype frequency analysis. All 112 variants were queried against the gnomAD v4.1 genome and exome reference datasets. Of these, matching allele-frequency data for the predefined reported allele were available in at least one of the two gnomAD datasets for 103 variants, whereas for 9 variants the VEP-based query did not return a matching gnomAD frequency for that allele. Frequencies were reported for the same predefined reported allele across all groups, and differences between the study groups were assessed using 95% confidence intervals, Fisher’s exact tests, and false discovery rate correction. Genotype counts and the proportions of individuals carrying at least one copy of the reported allele were also summarized for all selected variants. Several pharmacogenomic variants showed population-specific frequency patterns, including NUDT15 rs116855232, SLCO1B1 rs4149056, VKORC1 rs9934438, and UGT1A1 rs10929302. Comparison with gnomAD showed that the observed frequencies were variant-specific and could not be consistently approximated by a single broad genetic ancestry group. Reference-based population structure analysis provided additional ancestry context and supported separate reporting by population group. The study did not evaluate clinical outcomes or make individual prescribing recommendations, and the small Uzbek sample size limits the precision of frequency estimates for this group, particularly for rare variants. Overall, this study provides a clinically prioritized pharmacogenomic frequency resource for underrepresented population groups in Kazakhstan and supports broader Central Asian representation in pharmacogenomic implementation research. Full article

Background/Objectives: Vertebral artery hypoplasia is a common congenital anatomical variant of the vertebral arteries, traditionally considered a benign finding. However, accumulating evidence suggests that VAH may influence vertebrobasilar hemodynamics and contribute to susceptibility to posterior circulation disorders. This systematic review aimed to synthesize current evidence regarding the epidemiology, hemodynamic significance, neurological manifestations, and cerebrovascular outcomes associated with VAH. Methods: This systematic review was conducted according to the PRISMA 2020 guidelines and registered in PROSPERO (CRD420261442242). A systematic search of PubMed/MEDLINE was performed from database inception to 8 June 2026, supplemented by manual reference screening and targeted searches. Studies evaluating VAH diagnosed using vascular imaging or anatomical assessment, including CTA, MRA, Doppler ultrasonography, and DSA, were eligible. Methodological quality was assessed using Joanna Briggs Institute critical appraisal tools, and the level of evidence was classified according to the Oxford Centre for Evidence-Based Medicine framework. Results: Forty-six studies were included in the qualitative synthesis. VAH prevalence varied substantially according to imaging modality, diagnostic criteria, and study population, ranging from approximately 3% to nearly 50%. Across clinical cohorts, VAH was frequently associated with posterior circulation ischemic stroke, transient ischemic attack, and vertebrobasilar insufficiency. Hemodynamic studies demonstrated reduced vertebral artery flow, increased vascular resistance, impaired cerebrovascular reactivity, and altered collateral flow redistribution. VAH was also associated with vestibular disorders, non-stroke neurological syndromes, vertebral artery dissection, and other cerebrovascular anatomical variations. Unlike previous reviews focusing primarily on prevalence or stroke associations, this review integrates epidemiological, anatomical, hemodynamic, computational, and neurological evidence within a unified clinically oriented framework and proposes an evidence-informed conceptual model of VAH as a context-dependent low-flow vascular susceptibility phenotype. Conclusions: Current evidence indicates that VAH represents a clinically relevant vascular susceptibility phenotype rather than merely an incidental anatomical variant. Its clinical significance appears to depend on the interaction between reduced vertebral artery flows, collateral capacity, vascular remodeling, and acquired cerebrovascular risk factors. Standardized diagnostic criteria and prospective multimodal studies are required to define its role in future cerebrovascular risk assessment. Full article