Artificial intelligence (AI) is revolutionizing cardiovascular imaging, with aortic computed tomography angiography (CTA) emerging as a prominent area of application. CTA imaging is essential for the diagnosis, risk stratification, and treatment planning of aortic diseases. However, conventional CTA techniques face limitations such as radiation exposure, contrast agent risks, and reliance on manual interpretation. The integration of AI into aortic CTA offers innovative solutions across multiple domains. AI can enhance image quality, automate anatomical segmentation, improve diagnostic accuracy for aortic emergencies, and provide quantitative tools for prognostic evaluation following interventions like endovascular aortic repair. Furthermore, this review provides the analysis of emerging techniques, including advanced image synthesis methods, Vision Transformer architectures, multi-task learning, weakly supervised learning, and the paradigm shift introduced by Foundation Models, emphasizing their potential for clinical application. This work comprehensively summarizes the current applications and nascent technological paradigms of AI in aortic CTA, along with existing challenges and future research directions.

Although the World Health Organization has clearly defined silent pituitary adenomas (SPAs) and functional adenomas (non-SPAs), the detailed biological mechanisms remain unclear. This study conducted a comprehensive analysis of clinical, genomic, transcriptomic, and proteomic differences between SPA and non-SPA. The results revealed significant differences in mutational profiles, with a notably higher mutation rate of the TCHH gene in non-SPA samples. Transcriptomic and proteomic analyses identified distinct expression patterns, highlighting the enrichment of the oxidative phosphorylation pathway and other related Gene Ontology terms in SPA samples. To validate these findings, 11 additional pituitary adenoma samples were analyzed, confirming the critical role of oxidative phosphorylation in SPA. Activation of oxidative phosphorylation altered the hormone secretion, and the electron transfer chain inhibitor restored this in both human and rat pituitary adenoma cell lines. Furthermore, a protein-protein interaction network was constructed, revealing key regulatory differences between SPA and non-SPA, and identifying MAPK1, MAPK3, IDH1, and PKM as key hubs in the network. MAPK1 and PKM knockdown significantly reduced the hormone secretion and apoptosis of both cell lines. These findings suggest that the oxidative phosphorylation pathway plays a pivotal role in the secretory functions of pituitary adenomas. This study offers new insights into the biological mechanisms underlying pituitary adenomas and provides valuable directions for future research, emphasizing the importance of oxidative phosphorylation in tumor behavior and potential therapeutic targets.

Microplastics (≤5 mm) are increasingly recognized as pervasive environmental pollutants with potential implications for human health. Human exposure occurs primarily through ingestion and inhalation, with limited evidence also suggesting dermal contact. Microplastics have been detected in human blood, placental tissue, and gastrointestinal samples, indicating systemic exposure. Proposed biological pathways include oxidative stress, inflammation, endocrine disruption, and alterations in the gut microbiota; however, direct evidence linking these mechanisms to adverse health outcomes in humans remains limited. This systematic review synthesizes human-based evidence to evaluate health outcomes associated with microplastic exposure. The review includes primary human studies, specifically observational studies and clinical trials, as well as human-focused systematic reviews. Animal and in vitro studies were excluded from outcome synthesis because they do not directly reflect human clinical effects. Mechanistic insights derived from non-human experimental studies were included only to provide biological context and were clearly separated from human outcome data to avoid over-interpretation. A comprehensive literature search was conducted using PubMed, Scopus, Web of Science, and Google Scholar for articles published between January 2010 and May 2025. Primary human studies constituted the core evidence base for data extraction, qualitative synthesis, and certainty of evidence assessment using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework. Systematic reviews were evaluated at the review level only using AMSTAR-2 to assess methodological quality, examine consistency or discordance in reported associations, and identify evidence gaps. These reviews were not decomposed into their constituent primary studies to prevent duplication. In total, 30 articles were included, comprising 22 observational studies, five clinical trials, and three systematic reviews. Across included studies, inflammatory biomarkers (CRP (C-reactive protein), IL-6, TNF-α), endocrine markers (thyroid hormones, cortisol), and oxidative stress indicators (8-OHdG, MDA (malondialdehyde)) were frequently reported. These findings represent recurrent statistical associations and convergent qualitative trends identified through structured narrative synthesis, rather than evidence of biological causation. Evidence related to neurocognitive outcomes and chronic diseases, including diabetes and cardiovascular disease, was limited and inconsistent. Methodological heterogeneity across studies precluded meta-analysis, necessitating an organized qualitative synthesis. Overall, evidence certainty was moderate for inflammatory and endocrine biomarkers but low for neurocognitive and chronic disease outcomes. Overall, current human evidence suggests associative links between microplastic exposure and biological markers of inflammation, oxidative stress, and endocrine alteration. However, causal relationships with specific clinical diseases remain unestablished, underscoring the need for standardized biomarkers, longitudinal cohort studies, and interdisciplinary research to clarify long-term health implications.

Cardiovascular-kidney-liver-metabolic (CKLM) diseases constitute the presence of MASLD, T2D, CKD, obesity and/or CVD, that often co-exist and synergistically increase cardiovascular risk. However, the prevalence, extent and outcomes of the CKLM burden remain poorly understood.

This population-based study utilised National Health and Nutrition Examination Survey (NHANES) 2007-2018 database, examining individuals' number (0-4) and permutations of CKLM diseases, namely: type 2 diabetes (T2D), obesity, metabolic dysfunction-associated steatotic liver disease (MASLD), chronic kidney disease (CKD). The primary outcome was all-cause mortality. Cox regression models were constructed to evaluate the relationship between CKLM phenotypes and all-cause mortality, adjusting for age, sex, race, socioeconomic status, and physical activity.

The weighted cohort represented 97.8 million US adults (mean age 47.7 ± 16.7 years). 54.16% of the cohort had ≥1 CKLM diseases. From 2007 to 2018, the proportion of individuals with ≥2 CKLM diseases increased from 32.4% to 55.6% of the population, with the largest increase in proportion of individuals with 4 diseases. The most common CKLM phenotype was MASLD-obesity (23.0%), followed by MASLD-obesity-T2D (5.1%). The highest mortality rates were observed in individuals with 4 CKLM diseases (21.4%), followed by 3 diseases (12.2%). Cox regression revealed that 4 diseases predicted the highest mortality risk (aHR 2.24, 95%CI: 1.66-3.02, p < 0.001), followed by 3 diseases (aHR 1.52, 95%CI: 1.25-1.85, p < 0.001). The MASLD-T2D-CKD phenotype (aHR 3.13, 95%CI: 1.80-5.42, p < 0.001) and T2D-CKD phenotype (aHR 3.26, 95%CI: 2.33-4.55, p < 0.001) predicted the highest mortality risk.

The CKLM multimorbidity burden is rising in the US population. Higher CKLM burden (≥3 CKLM diseases) and CKD-centric phenotypes (MASLD-T2D-CKD or T2D-CKD) independently predict the highest mortality risk.

Elevated lipoprotein(a) [Lp(a)] is an independent, causal risk factor for atherosclerotic cardiovascular disease (ASCVD), yet testing remains low. As our health system has expanded its efforts to increase Lp(a) awareness, we evaluated testing rates and their impact on care.

Lp(a) testing rates were collected through electronic health record queries between 1/1/2022 to 12/31/2024. Baseline demographics, ASCVD status, Lp(a) testing rates by specialty, lipid lowering therapy (LLT) prescriptions and number of cardiology referrals were collected.

450,412 outpatients had ≥1 lipid panel order and 3.7 % (N = 16,476) had Lp(a) tested. Of those who had Lp(a) measured, 50.5 % were female and 61.8 % identified as White. Most Lp(a) orders were for patients without established ASCVD (68.9 %). Between 2022-2024, Lp(a) orders increased from 3052 to 8425. Most orders were placed by cardiologists, although their proportion decreased (75.5 % in 2022 vs. 62.9 % in 2024) as orders from other specialties increased. We found 67.0 % of patients with normal Lp(a) (<75 nmol/L) levels, 12.2 % with intermediate risk (75 ≥ Lp(a) < 125 nmol/L), 11.3 % with high risk (125 ≥ Lp(a) < 200 nmol/L) and 9.4 % with very high-risk values (≥200 nmol/L). Across the same Lp(a) categories, LLT initiation/escalation rates were 12.8 %, 17.5 %, 20.2 % and 22.1 %. There was a positive association between LLT initiation/escalation and Lp(a) range (p < 0.0001).

While Lp(a) testing was low, it increased substantially over time. High risk Lp(a) levels were found irrespective of ASCVD status and were associated with more aggressive treatment. Systematic strategies to increase Lp(a) awareness and testing are warranted to mitigate cardiovascular risk.

The major neutrophilic peptide alpha-defensin plays a pivotal role in atherogenesis. Atherosclerosis is more frequent in dialysis patients, increasingly ascribed to chronic low-grade inflammation. We investigated the potential association between dialysis treatment and circulating alpha-defensin levels.

In a cohort of hemodialysis (HD) patients, plasma alpha-defensin concentrations were determined immediately before and after a dialysis session. Blood samples were also tested for CBC, CRP, lipid profile, and troponin levels. Body weight change, Urea Reduction Ratio and Kt/V were used to assess dialysis adequacy. Patients were divided into two groups based on alpha-defensin increase post dialysis. Groups were compared for dialysis adequacy, CBC, CRP, LDL levels, and the incidence of new documented coronary artery narrowing post HD initiation. The study was approved by the local IRB and all patients were consented.

A total of 37 HD patients (55% males, median age 66.5 (60.3-78 years)) were recruited. There was a marked surge in median alpha-defensin levels after HD [11,571 vs. 16,661 ng/ml, p=0.009]. Overall, alpha-defensin levels increased in 65% of cases, whereas CRP levels showed no significant rise following dialysis. Similarly, platelet and neutrophil counts exhibited no significant change. Kt/V values were found favorable in HD patients with alpha-defensin decrease (1.48 vs. 1.37, P = 0.24), corresponding to a higher body weight decrease post dialysis (2.4% vs. 1.75%). Moreover, the HD group with alpha-defensin increase was more prone to sustain new cardiovascular events (12.5% vs. 0% at a median time of 5 (3.75-6.57) years), despite demonstrating a better blood lipid profile (LDL 63 vs. 87 mg/dl).

HD is an alpha-defensin generating procedure. Patients are potentially predisposed to atherosclerosis because of their enhanced alpha defensin secretion. alpha-defensin might evolve as a potential therapeutic target for atherosclerosis mitigation in this high-risk population. However, this remains to be validated in future research.

Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a rare autosomal dominant microvascular disorder caused by C-terminal truncating mutations in TREX1 gene, which impair protein localization and lead to multisystem involvement. We report a patient carrying the pathogenic TREX1 variant NM_033629.6:c.703dup (p.Val235fs), the most frequently described mutation in RVCL-S, whose clinical course was consistent with the classic phenotype but with simultaneous pulmonary granulomatous lesions compatible with sarcoidosis. Transcriptomic analysis in both the patient and his pre-asymptomatic daughter, who carries the same variant, revealed a similarly mild upregulation of inflammatory signaling pathways. Treatment with a Janus kinase inhibitor in the patient was followed by transient clinical stabilization before subsequent progression. This case expands the phenotypic spectrum of RVCL-S and underscores the importance of systematic immunological monitoring and clinical surveillance to support future development of timely strategies in asymptomatic carriers.

Subarachnoid haemorrhage (SAH), a devastating subtype of stroke, is predominantly caused by the rupture of intracranial aneurysms. Emerging evidence indicates that the risk of intracranial aneurysm rupture correlates with elevated serum levels of fatty acids and pro-inflammatory cytokines. Moreover, increased serum concentrations of adipocyte fatty acid-binding protein (A-FABP), an inflammation-related adipokine, have been associated with poorer prognosis in SAH. However, the precise roles of A-FABP in SAH pathogenesis and its biomarker potential in cerebrospinal fluid (CSF) remain unclear.

CSF from 40 SAH patients and 30 controls was analysed by targeted fatty acid metabolomics. Experimental SAH mice were induced by endovascular perforation in both genetic deletion and pharmacological inhibition of A-FABP. Brain injury was quantified by neurobehavioural test, inflammatory cytokine expression and TUNEL staining. In vitro, conditioned medium from fatty acid-stimulated microglia was applied to primary neurons to evaluate apoptosis. Microglial metabolic reprogramming was assayed with Seahorse XF assays.

CSF revealed significant metabolic disruption in SAH, characterized by arachidonic acid (AA), linoleic acid and palmitic acid (PA). Enrichment analysis implicated A-FABP plays a crucial role in SAH pathogenesis. Notably, elevated A-FABP levels independently predicted increased SAH severity and poorer prognosis. In mice model of SAH, A-FABP was significantly upregulated in microglia. Genetic deletion and pharmacological inhibition of A-FABP significantly ameliorated brain injury, including neurological deficits, neuroinflammation and neuronal apoptosis. Mechanistically, PA and AA promoted BV2 microglial inflammation via an A-FABP-dependent manner, subsequently inducing apoptosis in co-cultured primary neurons. Moreover, A-FABP inhibition reprogrammed microglial metabolism, enhancing fatty acid β-oxidation and energy supply. Proteomics further identified the JAK2/STAT3 as a downstream pathway of A-FABP-mediated neuroinflammation.

A-FABP is a promising biomarker and translatable therapeutic target to improve SAH outcome. Targeting A-FABP disrupts fatty acids-driven neuroinflammation and microglial metabolic reprogramming to reduce brain injury after SAH.

Semaglutide (Wegovy), a glucagon-like peptide-1 receptor agonist (GLP-1 RA), has attracted global attention for its appetite-suppressing and weight-loss effects. Approved by the U.S. FDA in 2022 for adolescents aged 12 and older, it has since been authorized in several other countries. Despite this, its use among youth remains limited, with ongoing concerns about its long-term safety, efficacy, and suitability during periods of growth and development. Advocates see Wegovy as an important tool for addressing pediatric obesity and its psychological burdens, while critics caution against widespread use in such a vulnerable population. This paper examines an underexplored ethical dimension of Wegovy's use in children: its impact on mental health. We argue that Wegovy may offer mental health benefits for children-such as reducing weight stigma, improving self-esteem, and avoiding invasive interventions such as bariatric surgery. However, these potential benefits are constrained by barriers to access, supply shortages, risks of misuse, and the possibility of reinforcing stigma and class-based discrimination. In light of these considerations, we argue that while Wegovy offers promising health benefits for children, its long-term effects on growth, development, and mental health remain uncertain, warranting further study before definitive policy decisions are made. If future evidence confirms its value, it is our view that access should be equitable and accompanied by reforms to reduce stigma, regulate prescribing, and prevent misuse. Until then, clinicians should prescribe cautiously, ensuring clear medical need and implementing safeguards against risks such as weight regain, treatment interruption, and bias in care.

Older individuals who suffer from mental disorders may encounter accessibility difficulties related to factors such as remoteness and socioeconomic status. The present analysis provides empirical evidence from the INTegRated InterveNtion of pSychogerIatric Care (INTRINSIC) and shows that this network could aid towards the incorporation of tele-psychiatry and tele-neuropsychology into primary healthcare. We propose that such integration, situated within comprehensive health digitalization initiatives, represents a scalable approach to expanding mental health access.

1,143 individuals from 2022 to 2025, from 11 different sites of INTRINSIC were recruited. Data collection was facilitated via the HEllenic Remote MEntal health Services for old-age (HERMES) Digital Platform, including demographic information, Mini-Cog scores, as well as information based on the Old Age Behavioral Risk Factor Surveillance System (OLA-BRFSS). A machine learning (ML) model was developed, trained, and evaluated using nested cross-validation. The classification analysis outcome was the Mini-Cog scores and eighty-three known risk factors were analyzed. Features were selected using Elastic Net regularization. A Random Forest classifier was then trained on the selected feature, and was employed to classify individuals into two Mini-Cog cognitive performance groups.

The ML algorithm employed in this study revealed eight features to be positively associated with low Mini-Cog scores, including subjective complaints of cognitive problems, retirement, polypharmacy, and history of falls. Five variables demonstrated a positive association with higher Mini-Cog scores, including prior diagnosis of an anxiety disorder, insomnia, and physical exercise. The model achieved a ROC-AUC of 0.76 (Figure 3 and Table 4), with a BAC of 0.65.

The present paper presents the first large-scale study on INTRINSIC, including multiple sites and integrating psychiatric, cognitive, medical, as well as sociodemographic variables in state-of-the-art ML models. Our results add to the existing literature on the complex interrelationships of factors affecting cognitive status in older individuals. We propose that INSTRINSIC may function as a benchmark for integrating psychiatric and neuropsychological services within primary healthcare settings, thereby addressing disparities in access to care and diagnostic equity.