Cardiovascular diseases (CVD) are a major global public health burden. Annually in the United States, over one million patients undergo arduous cardiac rehabilitation (CR) after experiencing cardiovascular events such as myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery bypass grafting, cardiac valve surgery, and heart transplantation. Although CR can reduce mortality, it fails to fully address residual risks, including chronic inflammation, autonomic dysfunction, and psychological disorders. Meanwhile, low patient participation and completion rates remain a major clinical challenge. Traditional Chinese medicine (TCM) shows multi-target cardioprotective effects that can effectively complement CR. This review focuses on the theoretical compatibility, multi-target mechanisms, and clinical application of TCM integrated with CR. Clinically, TCM effectively compensates for the limitations of conventional CR. Traditional Chinese exercise (TCE) acts as an optimal bridging therapy to facilitate safe rehabilitation initiation in deconditioned populations prior to standard aerobic training. The application of Chinese herbal medicine (CHM) in complex metabolic and psychological comorbidities refractory to conventional pharmacotherapy yields prominent advantages in CR. During inpatient and early outpatient rehabilitation, acupuncture and acupoint stimulation modulate autonomic function, relieving postoperative angina and myocardial ischemia without increasing cardiac burden. Despite promising prospects, inconsistent syndrome classification standards and inadequate high-grade evidence remain obstacles to its global clinical adoption. This review therefore elaborates on the theoretical rationale and clinical evidence to promote the integration of TCM-CR as a novel holistic regimen for CVD rehabilitation.

Anti-amyloid treatment (AAT) with monoclonal antibodies represents a major therapeutic advance in early Alzheimer disease (AD), but its introduction has important and underappreciated implications for vascular neurology. Because many patients with AD also have cerebral amyloid angiopathy and other cerebrovascular pathology, AAT influences stroke diagnosis, acute reperfusion therapy, and long-term antithrombotic management. Clinical trials of lecanemab and donanemab enrolled highly selected patients with minimal baseline cerebrovascular pathology, limiting generalizability to real-world populations with prevalent vascular comorbidity. Amyloid-related imaging abnormalities, particularly vasogenic edema and microhemorrhages, constitute a central safety concern and may clinically mimic acute ischemic stroke, complicating emergency decision-making and increasing the risk of inappropriate intravenous thrombolysis (IVT). Emerging reports of intracerebral hemorrhage following IVT in treated patients underscore the need for revised acute stroke pathways and support consideration of mechanical thrombectomy when otherwise indicated, although AAT-specific safety data are lacking. Beyond the hyperacute phase of stroke, concomitant use of anticoagulants or dual antiplatelet therapy raises unresolved questions regarding hemorrhagic risk, particularly in patients with atrial fibrillation or those requiring complex antithrombotic regimens. Alternative strategies, including left atrial appendage closure, may be considered in selected patients, although evidence in AAT recipients remains limited. As AAT enters routine practice, multidisciplinary collaboration, dedicated imaging protocols, and prospective safety registries will be essential to integrate disease-modifying AD treatment with safe and effective cerebrovascular care.

BackgroundMyocardial infarction (MI) continues to be one of the leading causes of morbidity and death worldwide. The international normalized ratio (INR) to albumin ratio (PTAR), calculated as INR divided by serum albumin, is a composite biomarker reflecting both nutritional status and coagulation abnormalities. While PTAR has shown prognostic relevance across various severe clinical scenarios, its role in forecasting mortality among critically ill MI patients remains insufficiently defined. The objective of this study was to examine the relationship between PTAR and all-cause mortality, and to evaluate its predictive capability through machine learning models.MethodsData from 1616 critically ill MI patients were retrieved from Version 3.1 of the MIMIC-IV database. The primary and secondary outcomes were 30- and 360-day all-cause hospital mortality. The relationship between PTAR and mortality was evaluated using multivariate Cox regression models, and nonlinear associations were further explored through restricted cubic spline (RCS) analysis. Survival analysis was performed using the Kaplan-Meier method. Feature variables were selected through the Boruta algorithm, and eight machine learning models were constructed to evaluate predictive performance.ResultsElevated PTAR levels were independently associated with increased risks of mortality at both 30 and 360 days. In Cox models with full adjustment, participants in the highest PTAR tertile showed a substantially higher risk of mortality relative to those in the lowest category (HR = 2.09, 95% CI: 1.53-2.86 for 30-day mortality; HR = 2.15, 95% CI: 1.69-2.73 for 360-day mortality). RCS analysis demonstrated that the mortality risk increased in a nonlinear fashion with rising PTAR values. Subgroup analyses revealed consistent predictive value across all subgroups. The Boruta algorithm ranked PTAR among the top predictors of mortality. Comprehensively considering the AUC value, calibration curve, and decision curve, the predictive model using LightGBM demonstrated the best performance (AUC = 0.7861).ConclusionOur study revealed a strong positive association between the PTAR and the mortality risk in critically ill patients with MI. Higher PTAR is associated with greater mortality risk. Predictive models based on machine learning demonstrated good performance. These findings suggest that PTAR may serve as a potential predictor of adverse outcomes in critically ill MI patients.

Contrastive learning is a widely adopted self-supervised pretraining strategy, yet its dependence on cohort composition remains underexplored. We present Contrasting by Augmented Patient Electrocardiograms (CAPE) foundation model and pretrain on four cohorts (n = 5,203,269), from diverse populations across three continents (North America, South America, Asia). We systematically assess how cohort demographics, health status, and population diversity influence the downstream performance for prediction tasks also including two additional cohorts from another continent (Europe). We find that downstream performance depends on the distributional properties of the pretraining cohort, including demographics and health status. Moreover, while pretraining with a multi-centre, demographically diverse cohort improves in-distribution accuracy, it reduces out-of-distribution (OOD) generalisation of our contrastive approach by encoding cohort-specific artifacts. To address this, we propose the In-Distribution Batch (IDB) strategy, which preserves intra-cohort consistency during pretraining, discourages learning of spurious cohort-specific features, and instead promotes clinically meaningful variability within cohorts. This leads to improved out-of-distribution robustness, with gains of 9-40% in downstream label prediction performance. This work provides insights into pretraining strategies for more clinically deployable and generalisable foundation models.

The cardiovascular-kidney-metabolic (CKM) syndrome framework has important implications in the care of people with kidney diseases. Cardiovascular screening is important in people with kidney diseases, but the approach may differ in this high-risk population. Multiple pharmacotherapies for CKM syndrome offer significant cardiovascular and kidney benefits.

Cardiovascular-kidney-metabolic (CKM) syndrome highlights the interconnected nature of cardiovascular disease, CKD, and metabolic dysfunction and underscores the need for integrated approaches to prevention and treatment. Patients with kidney diseases are at markedly elevated risk for atherosclerotic cardiovascular events, heart failure, kidney failure, and premature mortality across the spectrum of kidney disease severity. Recent advances in therapeutics, including sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1)-based therapies, and nonsteroidal mineralocorticoid receptor antagonists, alongside established renin-angiotensin system inhibitors and lipid-lowering therapies, have transformed the management of CKM by demonstrating both cardiovascular and kidney benefits. However, important gaps remain in applying the CKM framework to patients with kidney diseases, particularly among individuals with advanced CKD, kidney failure treated with dialysis, kidney transplant recipients, younger and older individuals, and those with nonmetabolic kidney diseases including glomerular disorders. This American Society of Nephrology Kidney Health Guidance provides practical guidance for nephrology clinicians on screening, risk stratification, and pharmacologic management across the CKM spectrum. The guidance emphasizes the importance of longitudinal assessment of estimated glomerular filtration rate and albuminuria as foundational markers of cardiovascular and kidney risk, including the role of cardiac biomarkers and imaging. Integration of cardiovascular and kidney risk prediction models, including the American Heart Association Predicting Risk of Cardiovascular Disease EVENTs (PREVENT) equations and the Kidney Failure Risk Equation (KFRE), may support early identification of high-risk patients and guide treatment intensification. The guidance also reviews evidence supporting sequential and combination approaches to CKM therapies, strategies for managing adverse effects, and special considerations for CKD subpopulations where data are more limited. Adoption of a CKM framework in nephrology practice promotes coordinated, multidisciplinary care and provides an opportunity to shift from organ-specific management toward a more holistic approach aimed at reducing cardiovascular events, slowing kidney disease progression, and improving patient-centered outcomes across the continuum of kidney disease.

Intracranial aneurysm (IA) is a life-threatening cerebrovascular disease with unclear molecular mechanisms and limited drug treatment. Our previous research has shown that melatonin (MLT) has potential protective effects in IA, but its mechanism remains unclear. The purpose of this study is to explore the pathological mechanism of IA and the therapeutic mechanism of MLT by integrating transcriptomic, proteomic and metabolomic analyses.

In this study, mouse models of IA were successfully established by combining elastase injection with angiotensin II infusion. C57BL/6 mice were divided into control, IA model, IA model+MLT, and IA model+nimodipine groups. The pathological conditions were evaluated by hematoxylin-eosin (HE) staining, TUNEL staining, and scanning electron microscopy. Transcriptomic (n=3 for each group), proteomic (n=3 for each group), and metabolomic (n=6 for each group) analyses were performed based on cerebral vascular tissue samples. The screening thresholds for differentially expressed genes and differentially expressed proteins were P <0.05 and fold change >1.5 and fold change <0.667. The screening criteria for differential metabolites were variable importance for the projection (VIP)> 1.0, fold change >1.2 and fold change <0.833, and P <0.05.

MLT alleviated brain tissue damage, vascular endothelial damage, structural disruption, and apoptosis in IA mice. Transcriptomic, proteomic and metabolomic analyses identified numerous differential molecules. Functional annotation revealed that these molecules may be involved in biological pathways and processes such as immune inflammation, vascular remodeling, extracellular matrix remodeling, neuropeptide activity, oxidative stress and metabolic pathways, thereby regulating the occurrence and development of IA or mediating the therapeutic effects of MLT. Furthermore, transcriptomic and proteomic analyses also suggest that there may be extensive post-transcriptional, translational and post-translational regulatory events in the progression of IA and the therapeutic effects of MLT. Integrated transcriptomic and proteomic analyses suggest that Npy may be a key molecule in regulating IA progression and mediating MLT therapeutic effects, and its potential value is further supported by our immunohistochemical validation results.

Multi-omics integrative analysis preliminarily revealed that the potential mechanisms of MLT may involve the regulation of inflammatory response, vascular remodeling, extracellular matrix remodeling, neuropeptide activity, oxidative stress, metabolic pathways, and post-transcriptional/translational regulation.

Thoracic aortic aneurysms and dissections (TAAD) are life-threatening conditions linked to gain-of-function mutations in cGMP-dependent protein kinase I (PKG I), a central regulator of vascular smooth muscle signaling. Among these, substitutions at Val²³⁴ have been associated with kinase overactivation and early-onset disease, despite this residue being distal from the active site and cGMP binding regions. Using NMR, molecular dynamics simulations, and complementary kinase and binding assays, we show that Val²³⁴ acts as a crucial allosteric hub of PKG autoinhibition. TAAD-associated variants at Val²³⁴ disrupt PKG regulation through two distinct yet complementary allosteric mechanisms: by biasing the kinase toward active conformations that increase sensitivity to cGMP and by decreasing the folding stability of the regulatory domain, thereby weakening inhibitory contacts independently of cGMP control. Despite these differences, both mechanisms result in excessive PKG signaling at basal and intermediate cGMP levels, while maximal activity remains unaltered. Together, these findings explain how distal mutations can unpredictably rewire kinase allostery and drive pathogenic vascular signaling.

We describe how school education for refugee children is often interrupted for long periods due to threats and insecurity prior to fleeing, discontinuity and dangers during the exile journey and the inability to immediately realize the universal right to school education for refugee children upon arrival.

We provide an overview of policy-oriented literature on the organization of school education for refugee children. Between immediate integration into mainstream school education and completely segregated schooling, there is a broad spectrum of transitional, temporary, and parallel schooling options for refugee children. However, around half of refugee children worldwide do not have access to school education and those who finally start school, are confronted with language differences, stalled learning processes, psychological trauma, and vulnerability, either in themselves or in their parents. They also experience repeated school changes and can be victim of discrimination, and racism. We present our qualitative research method on the basis of interviews and drawing techniques for young children, investigating the meaning of school for refugee children, their parents, and teachers.

In the results of this qualitative research, we describe how school education during the initial arrival period can restore a sense of normality and provide hope for the future. Refugee parents, children, and careers link school attendance with hope and agency, as well as with developing a future perspective and revivifying of resilience.

We make it clear that the normalizing, hope-bringing and mental health-promoting aspects of any form of early preparatory schooling for refugee children are all too often being pushed into the background by the political conviction that direct integration in regular school classes is the only acceptable option, and by the educational science discussion about the most effective form of early schooling for these children (immediate entry into regular school classes or transitioning through temporary, preparatory school education in language and welcoming classes), a question that for several reasons has not yet been resolved and probably never can or will be.

Neighbourhood characteristics are critical determinants of mental health; however, few studies have applied a multidimensional approach to examine neighbourhood profiles and their association with leading mental health outcomes. In this cross-sectional study, we leveraged data from the All of Us Research Program to identify neighbourhood profiles and examine associations with depression, anxiety and post-traumatic stress disorder (PTSD) in the USA.

First, profiles were derived using latent profile analysis of self-reported neighbourhood characteristics, including accessibility/resources, safety, social cohesion, physical disorder and social disorder. Next, logistic regression models tested associations between neighbourhood profiles and self-reported diagnoses of PTSD, depression and anxiety, adjusting for age, education, income, housing status, health insurance, geographic region and neighbourhood socioeconomic disadvantage.

Among the 153 712 participants (76% non-Hispanic white; 67% female), a diagnosis of PTSD was self-reported by 12%, depression by 37% and anxiety by 28%. Five neighbourhood profiles were identified: high-access/moderate-risk, high-access/high-risk, high-access/low-safety, low-access/protective and high-access/protective. Significant ethnoracial and socioeconomic inequities emerged: the majority of non-Hispanic white participants lived in low-access/protective neighbourhoods, while ethnoracially minoritised and socioeconomically disadvantaged individuals disproportionately lived in high-access/high-risk neighbourhoods. Compared with the high-access/protective profile, all other profiles were associated with an increased likelihood of mental health diagnoses (ps_adj <0.001). The high-access/high-risk profile was associated with the highest likelihood of reporting PTSD (OR=1.87), depression (OR=1.52) and anxiety (OR=1.46).

Using a profiling approach, results reveal that more accessible neighbourhoods with low physical/social disorder and high safety and cohesion are associated with a lower likelihood of a mental health diagnosis. More accessible neighbourhoods may confer both benefits (eg, resources) and risks (eg, higher crime exposure). Evaluating the mechanisms by which multiple neighbourhood exposures influence PTSD, depression and anxiety may better inform interventions aimed at reducing the prevalence of these conditions and narrowing mental health inequities.

Late-life depression presenting with atypical features, progressive functional decline, behavioral changes, or poor response to treatment should prompt consideration of secondary causes. Olfactory groove meningiomas are slow-growing anterior skull base tumors that may remain clinically silent for prolonged periods and may present primarily with neuropsychiatric symptoms due to frontal lobe involvement. We report the case of a 64-year-old woman with a progressive depressive presentation characterized by marked functional decline, apathy, abulia, behavioral disinhibition, impaired insight, and executive dysfunction. Symptoms were initially interpreted as a primary depressive disorder in the context of bereavement and were poorly responsive to psychopharmacological treatment. Neuroimaging revealed a large extra-axial anterior skull base mass centered on the olfactory groove, measuring approximately 63 mm in maximum diameter, with homogeneous contrast enhancement, marked mass effect on the frontal lobes, and extensive vasogenic edema. The patient underwent surgical resection in January 2024. Histopathological examination confirmed a World Health Organization grade 2 olfactory groove meningioma, with brain invasion and spontaneous necrosis. Postoperative imaging showed a small probable residual lesion, and the patient subsequently underwent adjuvant radiotherapy with 60 Gy in 30 fractions using volumetric modulated arc therapy. Follow-up imaging demonstrated a slight reduction in the residual lesion. Clinically, the patient showed postoperative improvement, with preserved orientation and language functions, no focal neurological deficits, and a return to functional independence in daily life, although residual anosmia and non-specific orthostatic symptoms persisted. This case illustrates a strong clinical association between a large olfactory groove meningioma and a late-life neuropsychiatric presentation initially interpreted as depression. Such tumors should be considered when apparent late-life depression is accompanied by progressive functional deterioration, behavioral disinhibition, impaired insight, executive dysfunction, or poor response to adequate psychiatric treatment. Neuroimaging should be considered in these presentations to identify potentially treatable structural brain lesions.