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Oxidative Stress-Related Genome-Wide Mendelian Randomization Identifies Causal Genes for Coronary Artery Disease.3 weeks agoAlthough oxidative stress (OS) links to the pathogenesis of coronary artery disease (CAD), its underlying genetic mechanisms remain unclear. Through summary data-based Mendelian randomization (SMR) and colocalization, this research seeks to assess the potential causal links between OS-related genes and CAD. Summary-level data on the methylation, expression, and protein abundance levels of OS-related genes were obtained from the corresponding quantitative trait loci (QTL) studies. We obtained genome-wide association study summary statistics for CAD from a previous study (discovery), the FinnGen and UK Biobank (replication). Two-sample MR analysis was conducted to verify the associations between key genes expressions and meta-analysis cohort of CAD risk. Mediation analysis was conducted to evaluate the mediating role of gene expression variation in the causal pathway linking methylation levels of key loci to the risk or progression of the disease. We identified 35 methylation loci, 7 genes, and 12 proteins in the discovery cohort. By integrating multiomic data, we identified SMARCA4, NAGLU, SREBF1, RPTOR, and HLA-B as potential causal targets associated with CAD. The two-sample MR analysis once again confirmed that the expressions of the SMARCA4, SREBF1, and HLA-B genes in the meta-analysis cohort showed a significant association with the risk of CAD, and this association was consistent with the direction of the SMR. Furthermore, both the expression and methylation of SMARCA4 were positively associated with CAD, and the direct and indirect effects of SMARCA4 methylation were confirmed. In summary, our results identified potential causal associations between SMARCA4, NAGLU, SREBF1, RPTOR, HLA-B, and CAD. The findings highlight the necessity for further exploration into the underlying etiology of CAD.Cardiovascular diseasesAccessCare/ManagementAdvocacyEducation
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Using Interpretable Machine Learning with SHAP to Assess Dynapenic Abdominal Obesity as a Stroke Risk Predictor: A Prospective Cohort Study.3 weeks agoStroke is a major cause of mortality and disability worldwide, with a particularly high burden in China. While dynapenic abdominal obesity (DAO) is associated with adverse cardiometabolic outcomes, its relationship with stroke risk remains unclear. We examined whether DAO predicts stroke using interpretable machine learning in a nationally representative cohort of middle-aged and older Chinese adults.
We analysed prospective data from the China Health and Retirement Longitudinal Study, including 11,207 participants aged ≥ 45 years. Dynapenia was defined as a handgrip strength ≤ 28 kg (men)/≤ 18 kg (women); abdominal obesity was defined as a waist circumference ≥ 90 cm (men)/≥ 80 cm (women). Stroke events were identified via self-reported physician diagnoses. We employed logistic regression, subgroup analyses, multiple machine learning models, and Shapley additive explanations (SHAP) to assess the association and evaluate robustness.
Over the 4-year follow-up period, 210 (1.9%) participants experienced stroke. DAO was significantly associated with increased stroke risk (adjusted OR = 1.58, 95% CI: 1.21-2.06). Subgroup analysis demonstrated consistent associations across all subgroups (all interaction p-values > 0.05). XGBoost demonstrated the highest predictive performance (AUC = 0.92, accuracy = 0.84). SHAP analysis ranked DAO as the fourth most important predictor after age, BMI, and residence.
DAO was independently associated with an increased risk of stroke, with an interpretable machine learning model further supporting its potential as a predictor. Maintaining muscle strength and managing abdominal obesity may reduce the risk of stroke in older adults. These findings suggest that DAO may serve as a potential risk marker for stroke. Future research, including external validation and implementation studies, is needed before any recommendations for screening or intervention can be made.Cardiovascular diseasesAccessAdvocacyEducation -
Short-Term Turkish Coffee Consumption Elevates Cardiovascular Risk Markers, Decreases Leptin Levels, and Impairs Sleep Quality in Healthy Young Women: A Pilot Randomized Controlled Trial.3 weeks agoUnfiltered Turkish coffee (UTC) is a traditional drink with high levels of bioactive compounds, but evidence of the associated specific physiological effects is inconclusive, and few studies have examined coffee in general. This pilot study aimed to investigate the short-term effects of daily UTC consumption on cardiovascular parameters, lipid profile, appetite-regulating hormones (leptin, ghrelin), glucose metabolism, inflammatory markers, and sleep quality in healthy young women.
This is a pilot randomized controlled trial that randomly assigned 40 healthy young women (aged 18-25 years) to intervention and control groups at a 1:1 ratio after 3 weeks of caffeine washout. The intervention group consumed three 40 mL cups of traditional-brewed UTC daily for 4 weeks, whereas the controls maintained abstinence from caffeine. The primary outcomes were cardiovascular (blood pressure, heart rate), lipid parameters, and the secondary ones were appetite hormones (leptin, ghrelin), glucose metabolism (markers), inflammatory biomarkers, and sleep quality, which were evaluated at baseline and at week 4.
UTC consumption produced significant between-group differences (time × group interactions) compared to controls: systolic blood pressure (+3.0 mmHg; p = 0.025), heart rate (+10.6 bpm; p = 0.007), and insomnia severity scores (+4.05 points intervention vs. -1.00 points control; p ≤ 0.001), while significantly decreasing leptin levels (-0.04 ng/mL; p = 0.014). Significant changes in low-density lipoprotein (LDL) cholesterol were found (p = 0.002), although high-density lipoprotein (HDL) changes were no longer found significant on baseline correction (p = 0.385). Body composition parameters (body mass index (BMI), body fat mass, fat-free mass, skeletal muscle mass) remained unchanged throughout the intervention (all p > 0.05). No significant effects were observed for fasting blood glucose, glycated hemoglobin (HbA1c), inflammatory markers (C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α)), or ghrelin (all p > 0.05).
Four weeks of UTC intake in this pilot trial were associated with variations in several cardiometabolic variables: interventions in systolic blood pressure (SBP) (+3.0 mmHg) and heart rate (HR) (+11.9 bpm) resulted in higher LDL levels, reduced leptin levels, and poor sleep quality, independent of body composition alterations. However, since the p-values are nominal and not multiplied by a correction, hypothesis-generating results require verification through properly powered studies. These exploratory findings should be considered by individuals with prior cardiovascular risk factors or sleep disorders when considering the intake of unfiltered coffee.
This trial was registered at ClinicalTrials.gov (NCT07133373, https://clinicaltrials.gov/study/NCT07133373). Retrospectively registered on 13 August 2025.Cardiovascular diseasesAccessAdvocacy -
The Selection of an Interposition Graft for Portal Vein Reconstruction: Maximizing the Availability of Autologous Vessels.3 weeks agoPortal vein (PV) reconstruction is a crucial step in pediatric liver transplantation (LT). Pediatric recipients with a hypoplastic or sclerotic PV often require an interposition vein graft. Allogeneic grafts from donors are generally preferred. However, if they are not available, the use of autologous vessels is necessary.
An 8-month-old girl with biliary atresia (BA) underwent living donor LT with a left lateral segment graft. During the operation, portal vein thrombosis (PVT) developed after direct anastomosis between the recipient PV and graft left PV. We used several techniques to resolve this problem, including ligation of collateral circulation and use of interposition grafts from the left internal jugular vein (IJV) and left renal vein (LRV). On postoperative day 1, PVT reoccurred. Emergency exploratory laparotomy was performed for thrombectomy, using the retrohepatic inferior vena cava (IVC) as an additional vascular graft. The final reconstruction successfully utilized a combination of LRV and IVC grafts between the superior mesenteric vein and graft left PV. Postoperatively, the patient received thrombolytic therapy followed by anticoagulants for thrombus prevention, along with immunosuppressive drugs. The patient's postoperative clinical course was uneventful.
Although the IJV and LRV are established options for PV reconstruction in pediatric LT, we propose retrohepatic IVC as a feasible and effective alternative option. This approach maximizes the availability of autologous vessels; however, selection must be individualized based on graft availability and the patient condition.Cardiovascular diseasesAccessCare/Management -
Comparative evaluation of multimodal large language models for diagnostic accuracy in pediatric electrocardiography: a prospective comparative diagnostic accuracy study.3 weeks agoWe evaluated three multimodal LLMs, ChatGPT (GPT-5.2), Gemini 3, and Microsoft Copilot, in pediatric ECG interpretation, focusing on clinically significant abnormalities and emergency arrhythmias with likelihood ratios as primary outcome measures. This prospective comparative diagnostic accuracy study (STARD/STARD-AI) included 264 pediatric patients with 12-lead ECGs (November 2024-November 2025). De-identified images were submitted via standardized zero-shot prompt. Three blinded pediatric cardiologists established the reference diagnosis by majority-vote consensus. Cases were classified as Tier 1 (normal), Tier 2 (abnormal, non-urgent), or Tier 3 (urgent). Two binary endpoints were assessed: clinically significant abnormality (Tier 2 + 3 vs Tier 1) and emergency abnormality (Tier 3 vs Tier 1 + 2). Clinically significant abnormalities were present in 54.5% of patients. AUC values ranged from 0.550 to 0.623, reflecting modest discrimination. For the clinically significant endpoint, + LR values were 2.05 (ChatGPT), 1.26 (Gemini), and 1.21 (Copilot); - LR values were 0.68, 0.55, and 0.81, indicating limited rule-in and insufficient rule-out utility. For the emergency endpoint, Gemini achieved 100% sensitivity (95% CI = 85.1-100.0) with - LR 0.07 (95% CI = 0.00-1.12) in a small subgroup (n = 22); however, specificity of 30.2% and + LR of 1.40 indicate overcalling rather than diagnostic precision. No model achieved clinically meaningful rule-in utility for either endpoint.
Current multimodal LLMs showed limited diagnostic utility in pediatric ECG interpretation, with + LR values near 1.0 across both endpoints. Standalone deployment is not supported; these tools may at most serve as adjunctive screening aids under clinician oversight.
• Deep learning algorithms trained on large ECG datasets perform well in adult populations, but evidence in pediatric ECG interpretation is limited. • General-purpose LLMs show variable accuracy in medical examinations; reliability in subspecialty domains such as pediatric cardiology remains unproven.
• This is the[FCA1] first head-to-head comparative diagnostic accuracy study of multimodal LLMs in pediatric ECG evaluation, using likelihood ratios as primary outcome measures. • All three LLMs showed limited rule-in utility (+LR near 1.0); Gemini achieved potentially meaningful rule-out performance for emergency arrhythmias (-LR = 0.07), but with wide confidence intervals reflecting the small emergency subgroup (n = 22). • Gemini's 100% sensitivity in the emergency subgroup reflects overcalling (specificity 30.2%) consistent with a triage/screening behavior rather than diagnostic precision.Cardiovascular diseasesAccessAdvocacy -
[Design and application of a heartbeat restorer for critical care medicine].3 weeks agoCardiac arrest is a prevalent clinical emergency characterized by its high incidence, sudden onset, challenges in resuscitation, and low success rates. Timely and effective cardiopulmonary resuscitation (CPR) is the key to improving the success rate of patient rescue. Currently, manual CPR serves as the primary clinical approach. Due to the high intensity of physical exertion, the depth and frequency of external chest compression decrease with the extension of CPR time, resulting in a lower success rate of CPR. Although existing mechanical resuscitation devices address issues such as compression frequency, amplitude, and reduce the physical burden on medical staff, they are associated with complications for patients (e.g., sternum and rib fractures). Additionally, these devices are often expensive, bulky, and reliant on external power sources, limiting their clinical utility. To address these issues, the medical staff of the department of critical care medicine of the Second Affiliated Hospital of Zunyi Medical University designed a cardiac resuscitation device specifically for critical care and obtained a National Utility Model Patent of China (patent number: ZL 2019 2 2003762.8). The device is 25 cm long, 20 cm wide, 25 cm high, and weighs approximately 2.5 kg. On one side of the main body, there are longitudinally arranged adjustment knobs, a power switch, a power jack, and a heat dissipation window. The left side of the device features a touchscreen display, which shows parameters including screen contrast, alarm volume, defibrillation energy, time, battery level, heart rate, and electrocardiogram waveforms. Below the touchscreen, a physical control interface-comprising up/down keys, left/right keys, and function buttons-allows adjustment of all parameters displayed on the screen. To the right of the control interface, there is a shock current device that can be directly removed and placed closely to the patient for defibrillation treatment. There is a 48 V lithium battery inside the device, and a solar panel on the other side wall of the main body, which can automatically charge via sunlight. There is a strap on the other side wall of the main body, which contains a flexible sponge layer for comfortable wearing. The upper wall of the main body is equipped with a handle for easy carrying. The heartbeat restorer for critical care medicine has a simple structure, small size, light weight, low cost, easy operation, and strong mobility. It can meet the needs of cardiac arrest patients in different places, especially those in disaster areas who cannot be sent to the hospital for rescue in a timely manner. It is worthy of clinical promotion and application.Cardiovascular diseasesCare/ManagementEducation
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[Effect of selective cerebral mild hypothermia on p300 and lactylation modification in rats following cerebral ischemic reperfusion injury].3 weeks agoTo evaluate the effect of selective cerebral mild hypothermia on p300 and lactylation modification in rats following cerebral ischemic reperfusion injury (CIRI).
Sixty healthy male SD rats aged 6 to 8 weeks of age at SPF grade were selected and divided into sham operation group (Sham group), CIRI group, selective cerebral mild hypothermic intervention group (CIRI+HT group), and normal temperature intervention group (CIRI+NT group) using randomized numerical tables, 15 in each group. A middle cerebral artery occlusion was established using thrombosis, revocation of thrombus after 2 hours of ischemia to achieve reperfusion. Sham group underwent only cervical vascular exposure surgery. Immediately after reperfusion, 20 centigrade (CIRI+HT group) or 37 centigrade (CIRI+NT group) saline was perfused at a constant flow rate of 0.6 mL/min through the left internal carotid artery for 10 minutes, respectively. Brain temperature and rectal temperature of rats were monitored throughout the process. At 24 hours after reperfusion, Modified Neurological Severity Score (mNSS) was used to evaluate the neurological function of rats. Then the rats were sacrificed and brain tissues were obtained. Cerebral infarction was observed by staining with 2,3,5-triphenyltetrazolium chloride (TTC), and the percentage of cerebral infarction volume was calculated. The ischemic penumbra tissue of cerebral cortex was taken. TdT-mediated dUTP nick-end labeling (TUNEL) assay was used to measure neuronal apoptosis rate. Hematoxylin-eosin (HE) staining was employed to observe the morphological changes of nerve cells. Immunofluorescence analysis was used to assess the expression of p300. Western blotting analysis was conducted to assess the level of lactylation modification and p300. In addition, lactate level in the cerebral cortex of the ischemic penumbra area were detected.
Compared with Sham group, mNSS, cerebral infarction volume, neuronal apoptosis rate, lactic acid content, lactic acid modification level and p300 enzyme expression were increased in the CIRI group, CIRI+HT group and CIRI+NT group (all P<0.05). Compared with CIRI group, the CIRI+HT group had decreased mNSS, cerebral infarction volume, and neuronal apoptosis rate, as well as decreased lactate content, lactate modification level, and p300 expression [mNSS: 4.20±1.30 vs. 9.40±1.34, cerebral infarction volume percentage: (31.21±1.20) vs. (41.18±2.33)%, neuronal apoptosis rate: (27.69±2.87)% vs. (48.90±2.08)%, lactate content (mmol/g): 0.44±0.04 vs. 0.63±0.04, lactate modification (lactate modification/β-actin): 0.29±0.03 vs. 0.36±0.03, p300 (p300/β-actin): 0.60±0.02 vs. 0.82±0.02, proportion of p300 positive cells: (46.70±2.97)% vs. (63.80±3.41)%, all P<0.05]. However, there were no significant differences in the above indicators between the CIRI+NT group and the CIRI group (all P>0.05). HE staining showed neurocytes had integrated morphology and clear contours in Sham group, a large amount of cellular edema and irregular nucleus enrichment were observed in CIRI group and CIRI+NT group, and the degree of cell edema and nucleus shrinkage were reduced in CIRI+HT group.
Selective mild hypothermia can alleviates CIRI in rats, and the mechanism may be related to the reduction of lactic acid production, inhibition of p300 expression, and then suppressing lactylation modification level.Cardiovascular diseasesCare/Management -
Parsimonious echocardiography-based model for predicting long-term all-cause mortality in heart failure with preserved ejection fraction.3 weeks agoThe Heart Failure Association Pre-test Assessment, Echocardiography and Natriuretic Peptide, Functional testing, Final aetiology (HFA-PEFF) score and the Heavy, Hypertensive, Atrial Fibrillation, Pulmonary Hypertension, Elder, Filling Pressure (H2FPEF) score facilitate heart failure with preserved ejection fraction (HFpEF) diagnosis but may not adequately stratify mortality risk. We developed and internally validated a parsimonious echocardiography-based model for long-term all-cause mortality in HFpEF and compared its prognostic discrimination with HFA-PEFF and H2FPEF.
In a real-world HFpEF echocardiography database linked to territory-wide electronic health records, 792 adults with HFpEF (left ventricular ejection fraction ≥50%) diagnosed between 2010 and 2016 were randomly split in a prespecified 70:30 ratio into training (n=554) and validation (n=238) cohorts. The primary endpoint was all-cause mortality. A parsimonious model was derived using least absolute shrinkage and selection operator (LASSO)-penalised Cox regression and refitted as a multivariable Cox model.
The final nomogram included age, left ventricular posterior wall thickness at end-systole, mitral E velocity, E/e' ratio and pulmonary artery systolic pressure. During median follow-up of 5.17 years (IQR 2.26-9.14) in the training cohort and 5.75 years (IQR 2.17-9.25) in the validation cohort, 393/554 (70.9%) and 165/238 (69.3%) deaths occurred, respectively. In the validation cohort, the nomogram showed better discrimination than HFA-PEFF and H2FPEF, with 1/3/5-year area under the curves of 0.658/0.706/0.713 versus 0.507/0.561/0.642 and 0.516/0.533/0.607, respectively. Calibration was acceptable at 1 and 3 years but weaker at 5 years, and risk-score tertiles separated survival in both cohorts (log-rank p<0.001).
A five-variable echocardiography-based nomogram showed better discrimination for long-term mortality prediction than the repurposed diagnostic scores evaluated in this cohort. External validation is needed before clinical implementation.Cardiovascular diseasesCare/Management -
Impact of physical activity patterns on major adverse cardiovascular events in adults with hypertension.3 weeks agoPhysical activity (PA) is generally cardioprotective, but the relationship between PA intensity and bout length and major adverse cardiovascular events (MACEs) in adults with hypertension remains unclear.
Participants of the UK Biobank wearables substudy with a clinical diagnosis of hypertension were included. Short bouts of moderate intensity PA were classified as lasting up to 3 min and for vigorous intensity up to 1 min. Long bouts of moderate intensity PA were classified as lasting >5 min and for vigorous intensity >2 min. MACEs were defined as the composite of cardiovascular disease mortality and incidence of stroke, myocardial infarction and heart failure. We used Cox proportional hazards regression and Fine-Gray subdistribution for MACE and subtype analyses.
During an average follow-up of 7.9 (±1.1) years among 38 960 participants (58.1% female; average age 62.1 (±7.7) years), there were 1416 MACE, including 397 stroke, 508 myocardial infarction and 363 heart failure events. Both short and long bouts of moderate intensity PA were associated with lower MACE risk, with subtype analyses showing longer bouts may enhance protective associations. For vigorous intensity PA, amounts accrued through short bouts exhibited a consistent association with lower MACE risk (HR=0.62 (95% CI 0.51 to 0.76) for 22 min/week), while amounts accrued through long bouts were associated with a higher risk of stroke, with a steep gradient of higher risk with longer durations (HR=2.06 (95% CI 1.38 to 3.07) for 44 min/week up to 2.80 (95% CI 1.72 to 4.56) for 64 min/week).
Short and long bouts of moderate intensity PA were associated with a lower risk of overall MACE, with evidence suggesting that longer bouts may enhance this protective association. For vigorous intensity PA, short bouts showed strong associations with lower overall MACE risk, while long bouts were associated with a 2-3 fold higher stroke risk, with a dose-response pattern evident across higher durations. Our results highlight the benefits and risks of PA bout length and intensity in adults with hypertension.Cardiovascular diseasesMental HealthCare/Management -
Home based, tailored intervention to reduce rate of falls after stroke (FAST): randomised trial.3 weeks agoTo investigate the effectiveness of a multidisciplinary, home based, tailored intervention to reduce falls after stroke.
Two armed, randomised trial.
Three states in Australia.
People within 5 years of stroke, aged >50 years, discharged from formal rehabilitation to the community, and able to walk 10 m across flat ground with or without an aid. Those with moderate-to-severe receptive aphasia or walking speed >1.4 m/s without falls in the previous year were excluded.
Over 6 months, the experimental group received a habit forming functional exercise, home fall hazard reduction, and goal directed community mobility coaching; the control group received usual care. Physiotherapist and occupational therapist dyadic teams worked collaboratively to deliver the intervention.
The primary outcome was rate of falls over 12 months. Secondary outcomes were proportion of participants having a fall, community participation, self-efficacy, balance, mobility, physical activity, activities of daily living, depression, and health related quality of life.
Between August 2019 and December 2023, 370 people with stroke were enrolled. At 12 months, a significant between group difference was seen in the rate of falls in favour of the experimental group, representing a 33% reduction in falls (incidence rate ratio 0.67, 95% confidence interval (CI) 0.48 to 0.94; P=0.02). No significant between group difference was seen in the number of participants having a fall (absolute risk reduction 0.03, 95% CI -0.07 to 0.13; P=0.52). The main between group differences in favour of the experimental group were in community participation (Late Life Function and Disability Instrument disability limitation: mean difference 3% (95% CI 1% to 6%); P=0.02), self-efficacy (mean difference 0.6 (0.2 to 1.0); P=0.004), mobility (fast walking speed: mean difference 0.13 (0.06 to 0.19) m/s (P<0.001); preferred walking speed: 0.06 (0.02 to 0.10) m/s (P=0.02)), and balance (Step Test: mean difference 0.06 (0.01 to 0.12) steps/s; P=0.03).
A tailored intervention prevented falls in community dwelling, ambulatory people with stroke. The decrease in the rate of falls was underpinned by clinically worthwhile improvements in self-efficacy, mobility, community participation, and balance.
Australian New Zealand Clinical Trials Registry ACTRN12619001114134.Cardiovascular diseasesCare/ManagementAdvocacy