In acute heart failure (AHF), non-invasive ventricular-arterial coupling (VAC) surrogates, including right ventricular-pulmonary arterial (RV-PA) and left ventricular-arterial (LV-Ao) coupling, have emerged as practical bedside indices, but their prognostic significance remains largely unknown systematically. We performed a systematic review and meta-analysis to evaluate the prognostic significance of non-invasive VAC assessment, in patients hospitalized with AHF. Outcomes included all-cause mortality, HF hospitalization, length of hospital stay, use of therapies, the composite of all-cause mortality and HF hospitalization, and in-hospital adverse cardiovascular events. Adjusted hazard ratios (aHRs) and odds ratios (aORs) were pooled using random-effects. Subgroup-analyses were performed according to follow-up duration and left ventricular ejection fraction. Thirty-six studies comprising 36,989 patients were analysed. Twenty-eight studies evaluated RV-PA coupling, predominantly the TAPSE/PASP ratio, and eight evaluated LV-Ao coupling, mainly using non-invasive Ea/Ees estimates. RV-PA uncoupling was independently associated with increased all-cause mortality (aHR 1.90; 95% CI 1.42-2.56; I²=49%), with consistent associations at 12 months (aHR 2.03; 95% CI 1.44-2.85) and long-term follow-up (aHR 1.67; 95% CI 1.06-2.64). Associations with HF hospitalization, hospital stay, and the composite endpoint were directionally consistent but not statistically significant. LV-Ao uncoupling was associated with increased in-hospital adverse cardiovascular events (aOR 1.70; 95% CI 1.29-2.24). Sensitivity analyses confirmed robustness of these findings. RV-PA uncoupling predicts mortality, whereas LV-Ao uncoupling identifies patients at increased risk of in-hospital adverse cardiovascular events, supporting VAC-risk-stratification in AHF and future evaluation of VAC-guided therapeutic strategies.

To evaluate the effectiveness of NamakBan, a smartphone application for monitoring sodium intake, on blood pressure, dietary sodium consumption, urinary sodium-to-potassium ratio and hospitalization in adults with primary hypertension.

We conducted a parallel randomized clinical trial at the specialized hypertension clinic of Shahid Modarres Hospital in Tehran, Iran.

Between April 1, 2024, and September 20, 2025, 88 patients with physician-diagnosed primary hypertension were randomized (1:1) to receive standard clinic care (control, n = 44) or standard care plus the NamakBan app (intervention, n = 44). The app (Android) allowed repeated self-reporting of blood pressure and salt intake, medication logging, and PDF output for monitoring. Outcomes were assessed at baseline, 1 month and 2 months. Primary outcomes were systolic and diastolic blood pressure; secondary outcomes were self-reported dietary sodium intake, urinary Na⁺/K⁺ ratio and readmissions.

Baseline characteristics were balanced. Compared with the control, the experimental group showed greater reductions in systolic blood pressure and diastolic blood pressure. Self-reported daily sodium intake declined more in the experimental arm than in the control. Urinary Na⁺/K⁺ ratio decreased within the experimental group over time, but between-group differences were not significant. No hypertension-related hospital readmissions were recorded in the intervention group, whereas four readmissions occurred in the control group; however, this difference was not statistically significant.

In this RCT, the NamakBan application, used alongside usual care, was associated with modest but statistically significant improvements in systolic blood pressure, diastolic blood pressure and self-reported sodium intake over 2 months. However, the objective urinary sodium-to-potassium ratio did not differ between groups. The findings should therefore be interpreted with caution: dietary sodium was assessed via unblinded self-report, follow-up was limited to 2 months, the trial was single-centre and the application was available only on Android.

Integration of such applications into routine nursing and clinical follow-up may improve outcomes and potentially reduce hypertension-related hospital readmissions.

What problem did the study address?: Inadequate monitoring of dietary sodium intake and limited patient engagement in self-management contribute to poor blood pressure control in adults with primary hypertension. Few randomized trials of sodium-focused applications report an objective biochemical measure alongside self-reported intake or health-service outcomes such as readmission. What were the main findings?: Use of the NamakBan smartphone application, in addition to usual care, led to significant reductions in systolic and diastolic blood pressure and an improvement in self-reported sodium intake. No hypertension-related hospital readmissions were observed in the intervention group; however, the between-group difference was not statistically significant. Where and on Whom Will the Research Have an Impact?: This research will benefit adults with primary hypertension and inform nursing practice and outpatient hypertension care, particularly by integrating mobile health interventions into routine clinical follow-up and patient education.

Consolidated Standards of Reporting Trials (CONSORT). No Patient or Public Contribution.

Iranian Registry of Clinical Trials (IRCT): registration code IRCT20240207060927N1.

Adverse drug reaction (ADR)-related hospital admissions may be fatal and increase substantial healthcare costs, but several ADRs are preventable. However, studies on preventable ADRs in Thailand remain limited, particularly with respect to their management and prevention. Aim To determine the frequency, characteristics, and preventability of ADR-related hospital admission, and to evaluate the management, prevention strategies, and associated factors.

A cross-sectional study was conducted among patients admitted to a tertiary care teaching hospital. Data were extracted from the hospital's medical record database for a 9-month period. ADR-related hospital admissions were identified using the International Statistical Classification of Diseases and Related Health Problems, 10^th Revision (ICD-10).

During the study period, 29,927 patients were admitted to the hospital. Of these, 730 admissions were identified as ADR-related based on ICD-10 codes, and 200 patients were included using purposive sampling. The most frequently reported ADRs involved cardiovascular disorders (50.5%), and nervous system disorders (17.0%). The most common suspected drugs were warfarin (38.0%) and paracetamol (5.0%). Approximately 67.1% of ADRs were classified as probable or definite, and 66.0% were considered preventable. The primary management strategy was discontinuation of the suspected drug (82.5%), while discharge counselling was the most commonly employed preventive measure (56.0%). Inappropriate dosage was independently associated with the preventability of ADR-related hospital admissions (OR 0.007; 95% CI 0.001-0.074; p < 0.001), and age groups of 36-65 years and more than 65 years were independently associated with documented ADR-related hospital admissions (OR 7.688; 95% CI 1.533-38.548; p = 0.013 and OR 9.441; 95% CI 1.668-53.422; p = 0.011, respectively).

Warfarin was the most frequently implicated drug in ADR-related hospital admissions. Inappropriate dosing was significantly associated with preventable ADR-related hospitalisations. Implementing targeted strategies, such as dose optimisation and appropriate clinical monitoring, may enhance medication safety and reduce preventable ADRs.

Glioblastoma (GBM) is an aggressive brain tumor with limited treatment options and poor patient survival. This study aimed to identify key genes and altered pathways in GBM and to explore potential drug-repurposing candidates using a systems biology approach.

We analyzed gene expression data from two public datasets (GSE4290 and GSE50161) using Transcriptome Analysis Console. These datasets included 102 GBM samples and 23 non-tumor brain samples. We identified differentially expressed genes using statistical thresholds. A protein-protein interaction network was built using STRING and analyzed in Cytoscape based on degree, betweenness, and closeness metrics. Pathway analysis was carried out using KEGG. Survival analysis was performed with GEPIA2. Drug-gene interactions were screened using DGIdb, and molecular docking was carried out for selected targets.

A total of 1,704 upregulated and 1,345 downregulated genes were detected. Network analysis highlighted TP53, EGFR, CDC42, and STAT3 as central hub genes. Pathway analysis showed major changes in MAPK signaling, neuroactive ligand-receptor interaction, and extracellular matrix-receptor interaction. Higher expression of CDC42, EGFR, and TP53 was associated with shorter overall survival in GBM patients. Drug screening identified 28 approved compounds targeting six core genes. Docking analysis showed strong binding affinity for several candidates, with scores of -8.5 kcal/mol or lower.

This study identified important molecular targets and pathways in GBM and suggests several existing drugs with potential value for therapeutic repurposing. These findings may support future experimental and clinical studies in GBM treatment.

Despite substantial advances in pharmacological therapy, cardiovascular disease remains the leading cause of mortality worldwide. Botanical drugs represent a rich source of structurally diverse bioactive metabolites, yet their translation into modern cardiovascular therapeutics remains limited by chemical complexity, incomplete mechanistic understanding, and challenges in experimental validation. Meanwhile, the rapid expansion of biomedical data resources and advances in artificial intelligence (AI) have created new opportunities to systematically investigate botanical drugs beyond empirical approaches. In this review, we summarize the major biomedical data resources supporting AI-guided ethnopharmacology, including phytochemical and ethnomedicinal databases, multiomics datasets, single-cell and spatial transcriptomics, perturbation-response resources, biological interaction networks, and clinical evidence. We then discuss the computational approaches used for molecular property prediction, drug-target interaction prediction, perturbation-response modeling, and foundation-model transfer learning, highlighting how these complementary strategies address distinct stages of pharmacological discovery. Building on these advances, we propose two complementary AI-guided discovery frameworks: a compound-first strategy that predicts the pharmacological activities of botanical drugs and a disease-first strategy that identifies natural products capable of reversing disease-associated molecular and cellular states. We further discuss emerging applications in cardiovascular diseases, emphasizing the integration of AI with single-cell atlases, disease-state prediction, mechanistic investigation, and experimental validation to prioritize candidate botanical therapeutics. Finally, we outline current challenges in data standardization, model robustness, interpretability, and prospective validation. We propose that AI-guided ethnopharmacology should be viewed as a hypothesis-generation framework that complements, rather than replaces, pharmacological experimentation. When supported by standardized botanical materials, high-quality multimodal data, rigorous biological validation, and prospective clinical evaluation, AI has the potential to accelerate cardiovascular botanical drug discovery and facilitate the translation of ethnomedicinal knowledge into modern precision therapeutics.

Heat stroke is a life-threatening condition characterized by elevated core body temperature (≥ 40°C) and central nervous system (CNS) dysfunction, resulting from body's inability to adequately dissipate heat. It can lead to multiorgan failure, including the cardiovascular system. Takotsubo cardiomyopathy (TCM), also known as stress-induced cardiomyopathy, is an acute syndrome of transient global or regional ventricular dysfunction, most commonly apical ballooning, mimicking acute coronary syndrome, typically occurring after severe physical or emotional stress. Although individually well-described, the combination of severe heat stroke as a trigger for TCM is rare. This case report describes a female patient with severe heat stroke who developed TCM and, due to persistent hyperthermia unresponsive to conventional cooling methods, was successfully cooled using prolonged intermittent hemodiafiltration. It also highlights the importance of timely recognition of atypical complications such as TCM in patients with cardiovascular instability and demonstrates the potential role of hemodialysis as an effective cooling method in cases of refractory hyperthermia.

Early-onset atherosclerotic cardiovascular disease (ASCVD) must be distinguished from cardiovascular risk factors and subclinical vascular abnormalities that may arise at younger ages. This narrative review critically examines lifestyle, environmental, metabolic, psychosocial, and inherited determinants among adolescents (10-19 years), young adults (20-39 years), and selected adults aged 40-54 years who remain within commonly used thresholds for premature events. The 40-54-year band is included selectively to bridge younger-adult prevention with guideline-based adult risk assessment and is not intended to redefine the upper age limit of premature ASCVD. Epidemiological evidence demonstrates a substantial burden of cardiovascular disease (CVD) among people aged 15-39 years; however, evidence of increasing clinically manifest ASCVD is less consistent than evidence of rising obesity, hypertension, dyslipidemia, diabetes, nicotine exposure, and subclinical vascular injury. Established causal drivers, including cumulative exposure to apolipoprotein B-containing lipoproteins and cigarette smoking, are distinguished from predominantly associative evidence concerning sleep disruption, psychosocial stress, e-cigarette use, and air pollution. Prevention should combine population-level health promotion with age-appropriate clinical risk assessment, including lipid screening and measurement of lipoprotein(a) at least once in adulthood, with additional targeted evaluation for familial hypercholesterolemia, a family history of premature ASCVD, obesity, hypertension, diabetes, chronic kidney disease, and smoking or vaping. Coronary artery calcium scoring and carotid imaging are not recommended as universal screening tests for asymptomatic young people, although they may refine clinical decisions in carefully selected adults. Digital tools may support engagement but should complement, rather than replace, validated clinical care and public-health measures.

Cerebrovascular reactivity (CVR), the ability of cerebral blood vessels to dilate or constrict in response to a vasoactive stimulus, is an important measure of cerebrovascular health. Accurate CVR estimation requires accounting for the time required for the vasoactive stimulus to reach each brain region and the time it takes for local arterioles to modulate cerebral blood flow. The temporal search range used to calculate this spatially varying offset can substantially impact CVR estimates, and the appropriate search range may vary across populations, acquisition protocols, and even brain regions. Here, we present an iterative approach for automatically determining the appropriate maximum shift, using breath-hold fMRI data acquired in a cohort of stroke survivors. This approach selectively expands the delay search range only for voxels with estimated delays at the boundary (i.e., near the minimum or maximum shift) until the estimated delay is no longer at the boundary or a predefined value is reached. In the context of stroke, among voxels initially at the boundary, this approach significantly increased the number of voxels with statistically significant CVR (i.e., having a relationship between end-tidal CO₂ and the BOLD signal that is unlikely to be due to random chance). It also resulted in CVR polarity reversals in voxels originally at the early-response boundary and amplified negative CVR values in voxels originally at the late-response boundary, suggesting that using an iterative maximum shift can critically impact CVR interpretation. This approach is broadly applicable beyond stroke, but careful parameter tuning is required, as illustrated by our demonstration of the parameter tuning process for a participant with Moyamoya disease. Together, these findings suggest that iterative delay correction allows for improved CVR assessments in clinical populations.

Cardiovascular diseases (CVDs) remain a leading threat to human health, imposing substantial morbidity and a considerable clinical burden worldwide. Disrupted mitochondrial calcium ions (Ca²⁺) homeostasis is increasingly recognized as a shared pathophysiological feature of diverse CVDs. Mitochondria and the endoplasmic reticulum (ER) are key organelles involved in intracellular Ca²⁺ homeostasis and energy metabolism, and their physical and functional coupling occurs at mitochondria-associated ER membranes (MAMs). Through protein complexes such as IP3R-GRP75-VDAC1, VAPB-PTPIP51 and MFN1-MFN2, MAMs coordinate a finely tuned Ca²⁺-signalling network that is essential for maintaining mitochondrial Ca²⁺ homeostasis. This review provides a systematic overview of the structural organization of MAMs and the molecular mechanisms governing MAM-mediated Ca²⁺ transfer, with particular emphasis on how dysregulated Ca²⁺ signalling at MAMs contributes to myocardial ischaemia-reperfusion injury, atherosclerosis, heart failure (HF), pulmonary arterial hypertension and diabetic cardiomyopathy. Furthermore, on this basis, this review focuses on the IP3Rs‑GRP75‑VDAC1 complex, mitochondrial calcium uniporter (MCU)‑associated calcium‑transport pathways, the endoplasmic reticulum stress‑MAMs‑mitochondrial calcium overload axis, as well as MAMs‑mediated signaling cascades, and systematically elaborates the latest research advances of therapeutic interventions including small‑molecule inhibitors, targeted peptides, calcium chelators, chemical chaperones and natural products. At present, available therapeutic evidence is mostly obtained from cellular and animal models. The process of clinical translation is still constrained by suboptimal target selectivity, dilemmas in bidirectional calcium‑signal regulation, bottlenecks in tissue‑specific delivery and the lack of long‑term safety evaluation. This review is expected to provide theoretical foundations and cutting‑edge insights for novel cardiovascular drug discovery and translational research targeting MAMs‑related calcium homeostasis.

Atherosclerosis, the principal pathological underpinning of cardiovascular diseases, is a multifaceted process encompassing dysregulated lipid metabolism, chronic inflammation, oxidative stress, aberrant vascular smooth muscle cells (VSMCs) proliferation, and plaque destabilization. Lipocalin-2 (LCN-2), a pivotal member of the lipocalin superfamily, serves as a critical nexus integrating lipid metabolism with inflammatory cascades. This review systematically delineates the gene localization, protein architecture, and expression regulation of LCN-2, with a focus on its multifaceted roles and molecular mechanisms across diverse stages of atherosclerosis, including endothelial dysfunction, lipid deposition, inflammatory amplification, foam cell formation, VSMCs phenotypic switching, and plaque rupture. This work highlights the promise of LCN-2 as a diagnostic biomarker and therapeutic target, offering novel insights and strategic directions for the precise prevention and management of atherosclerosis. Given its pathogenic significance, elevated LCN-2 levels in serum, plasma, urine, and plaque tissue serve as diagnostic and prognostic biomarkers for atherosclerosis. Multiple therapeutic strategies targeting LCN-2, including gene knockout, neutralizing antibodies, small-molecule inhibitors, RNA interference and repurposed clinical drugs, have achieved encouraging anti-atherosclerotic effects in preclinical studies. Collectively, LCN-2 acts as a core molecular linker between inflammation and lipid metabolism in atherosclerosis, and targeting LCN-2 holds great potential for the early diagnosis, risk stratification and novel therapeutic intervention of atherosclerotic cardiovascular diseases.