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Performance Evaluation of Algorithms to Estimate Daily Sedentary Time Using Wrist-Worn Sensors in Free-Living Adults
Purpose: Given the limited real-world testing of algorithms for wrist-worn sensors to estimate sedentary time, we examined the performance of 21 algorithms in free-living adults. Methods: Seventy-one adults (35–65 years) wore a GENEActiv (wrist) and an activPAL (thigh) sensor for up to 10 days. activPAL was our reference measure. We estimated sedentary time (hours/day) using 21 classification algorithms, including cut-point and machine-learning methods. Valid days from each monitor were matched by date and mean values were calculated. Equivalence testing (±10%) and linear regression were used to compare each algorithm’s estimate to the reference, over all participants and by sex and age. Results: activPAL recorded a mean of 9.4 hr/day sedentary. Five of 21 algorithms (24%) estimated sedentary time within 10% (±0.94 hr) of the reference. Two of these methods employed machine-learning algorithms (Trost Extended, OxWearables) and three employed cut-points (GGIR Euclidean norm minus one [ENMO] 40 mg; Bakrania ENMO 32.6 mg; Fraysse ENMOa 62.5 mg). Variance explained in linear regression was relatively high for the machine-learning (R2 = .44–.63) and cut-point algorithms developed for younger (R2 = .30–.64) and older (R2 = .45–.66) adults. More accurate performance was noted for algorithms developed in studies using posture-based ground truth measures and conducted in free-living settings. Conclusion: Fifteen of 21 (71%) algorithms produced estimates of sedentary time that were moderate-strongly correlated with the reference measure, but only five (24%) were within 10% of the reference. Free-living benchmarking studies like this can identify more accurate and precise algorithms to estimate sedentary time and identify characteristics of algorithm development studies that yield better results.
Developing Trustworthy Artificial Intelligence Models to Predict Vascular Disease Progression: the VASCUL-AID-RETRO Study Protocol.
INTRODUCTION: Abdominal aortic aneurysms (AAAs) and peripheral artery disease (PAD) are two vascular diseases with a significant risk of major adverse cardiovascular events and mortality. A challenge in current disease management is the unpredictable disease progression in individual patients. The VASCUL-AID-RETRO study aims to develop trustworthy multimodal predictive artificial intelligence (AI) models for multiple tasks including risk stratification of disease progression and cardiovascular events in patients with AAA and PAD. METHODS: The VASCUL-AID-RETRO study will collect data from 5000 AAA and 6000 PAD patients across multiple European centers of the VASCUL-AID consortium using electronic health records from 2015 to 2024. This retrospectively-collected data will be enriched with additional data from existing biobanks and registries. Multimodal data, including clinical records, radiological imaging, proteomics, and genomics, will be collected to develop AI models predicting disease progression and cardiovascular risks. This will be done while integrating the international ethics guidelines and legal standards for trustworthy AI, to ensure a socially-responsible data integration and analysis. PROPOSED ANALYSES: A consensus-based variable list of clinical parameters and core outcome set for both diseases will be developed through meetings with key opinion leaders. Blood, plasma, and tissue samples from existing biobanks will be analyzed for proteomic and genomic variations. AI models will be trained on segmented AAA and PAD artery geometries for estimation of hemodynamic parameters to quantify disease progression. Initially, risk prediction models will be developed for each modality separately, and subsequently, all data will be combined to be used as input to multimodal prediction models. During all processes, data security, data quality, and ethical guidelines and legal standards will be carefully considered. As a next step, the developed models will be further adjusted with prospective data and internally validated in a prospective cohort (VASCUL-AID-PRO study). CONCLUSION: The VASCUL-AID-RETRO study will utilize advanced AI techniques and integrate clinical, imaging, and multi-omics data to predict AAA and PAD progression and cardiovascular events. CLINICAL TRIAL REGISTRATION: The VASCUL-AID-RETRO study is registered at www.clinicaltrials.gov under the identification number NCT06206369. CLINICAL IMPACT: The VASCUL-AID-RETRO study aims to improve clinical practice of vascular surgery by developing artificial intelligence-driven multimodal predictive models for patients with abdominal aortic aneurysms or peripheral artery disease, enhancing personalized medicine. By integrating comprehensive data sets including clinical, imaging, and multi-omics data, these models have the potential to provide accurate risk stratification for disease progression and cardiovascular events. An innovation lies in the extensive European data set in combination with multimodal analyses approaches, which enables the development of advanced models to facilitate better understanding of disease mechanisms and progression. For clinicians, this means that more precise, individualized treatment plans can be established, ultimately aiming to improve patient outcomes.
Early Atrial Remodeling Drives Arrhythmia in Fabry Disease.
BACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by α-Gal A (α-galactosidase A) deficiency, resulting in multiorgan accumulation of sphingolipid, namely globotriaosylceramide. This triggers ventricular myocardial hypertrophy, fibrosis, and inflammation, driving arrhythmia and sudden death. Atrial fibrillation is common, yet the cellular mechanisms accounting for this are unknown. METHODS: To address this, we conducted ECG analysis from a large cohort of 115 adults with FD at varying cardiomyopathy stages. ECG P-wave characteristics were compared with non-FD controls. Cellular contractile and electrophysiological function were examined in a novel atrial cellular FD model developed and imputed into in silico atrial models to provide insight into mechanisms of arrhythmia. Induced pluripotent stem cells were genome-edited using Clustered Regularly Interspaced Short Palindromic Repeats-Cas9 to introduce the GLA p.N215S variant and differentiated into induced pluripotent stem cell-derived atrial cardiomyocytes (iPSC-CMs). Contraction, calcium handling, and electrophysiology experiments were conducted. Bi-atrial in silico models were developed with cellular changes as in GLA p.N215S iPSC-CMs. RESULTS: ECG analysis demonstrated P-wave duration and PQ interval shortening in FD adults before the onset of cardiomyopathy. Patients with FD exhibited a higher incidence of premature atrial contractions and increased risk of atrial fibrillation compared with healthy controls. GLA p.N215S iPSC-CMs were deficient in α-Gal A and exhibited globotriaosylceramide accumulation. Atrial GLA p.N215S iPSC-CMs demonstrated a more positive diastolic membrane potential, faster action potential upstroke velocity, greater incidence of delayed afterdepolarizations, greater contraction force, and alterations in calcium handling compared with wild-type iPSC-CMs. Simulations with these changes in the in silico models resulted in similar P-wave morphology changes to those seen in early FD cardiomyopathy and increased atrial fibrillation vulnerability. CONCLUSIONS: These findings provide novel insights into underpinning mechanisms for atrial arrhythmia and a rationale for early P-wave changes in FD. These may be targeted to develop therapeutic strategies to reduce the arrhythmic burden in FD.
Effect of supplementation with vitamin D on biochemical markers of iron status and erythropoiesis in older people: BEST-D trial.
Previous observational studies suggested that vitamin D may control absorption of iron by inhibition of hepcidin, but the causal relevance of these associations is uncertain. Using placebo-controlled randomization, we assessed the effects of supplementation with vitamin D on biochemical markers of iron status and erythropoiesis in community-dwelling older people living in the United Kingdom (UK). The BEST-D trial, designed to establish the optimum dose of vitamin D3 for future trials, had 305 participants, aged 65 years or older, randomly allocated to 4000 IU vitamin D3 (n=102), 2000 IU vitamin D3 (n=102), or matching placebo (n=101). We estimated the effect of vitamin D allocation on plasma levels of hepcidin, soluble transferrin receptor (sTfR), ferritin, iron, transferrin, saturated transferrin (TSAT%), and the sTfR-ferritin index. Despite increases in 25-hydroxy-vitamin D, neither dose had significant effects on biochemical markers of iron status or erythropoiesis. Geometric mean concentrations were similar in vitamin D3 arms vs placebo for hepcidin (20.7 [SE 0.90] vs 20.5 [1.21] ng/mL), sTfR (0.69 [0.010] vs 0.70 [0.015] µg/mL), ferritin (97.1 [2.81] vs 97.8 [4.10] µg/L) and sTfR-ferritin ratio (0.36 [0.006] vs 0.36 [0.009]), respectively, while arithmetic mean levels were similar for iron (16.7 [0.38] vs 17.3 [0.54] µmol/L), transferrin (2.56 [0.014] vs 2.60 [0.021] g/dL), and TSAT% (26.5 [0.60] vs 27.5 [0.85]). The proportions of participants with ferritin <15 µg/L and TSAT<16% were unaltered by vitamin D3 suggesting that 12 months of daily supplementation with moderately high doses of vitamin D3 are unlikely to alter the iron status of older adults.
Alcohol consumption and cancer risk in South Korea and the UK: prospective cohort studies.
BACKGROUND: This study aimed to compare cancer incidence rates between South Korea and the UK, and assess the associated cancer risks due to alcohol consumption. METHODS: Data were pooled from the Korean Cancer Prevention Study-II and the Korean Genome Epidemiology Study Biobank for South Korea, and from UK Biobank (UKB) for the UK, with follow-up until 2020. Age-standardized incidence rates were calculated by using the World Health Organization standard population. Hazard ratios (HRs) for cancer incidence were analysed in relation to alcohol consumption levels. RESULTS: The overall cancer incidence rates were similar between South Korea and the UK. However, the incidence of liver, stomach, and thyroid cancers was more than five times higher in the Korean cohort. Compared with never drinkers, consuming ≥50 g of alcohol daily increased the overall cancer risk by 24% in the Korean data and by 11% in the UKB data. In Korea, heavy drinking (≥50 g/day) was associated with higher risks of esophageal cancer (HR = 12.59), liver cancer (HR = 1.65), head and neck cancer (HR = 2.06), alcohol-related cancers (HR = 1.60), and stomach cancer (HR = 1.43). In the UKB cohort, it was linked to increased risks of head and neck cancer (HR = 1.95), breast cancer (HR = 1.12), and alcohol-related cancers (HR = 1.18). Both cohorts showed a lower risk of thyroid cancer with increased alcohol consumption. CONCLUSION: Alcohol consumption is associated with an increased risk of alcohol-related cancers in both South Korean and UK populations.
Stent-Retriever Thrombectomy in STEMI With Large Thrombus Burden: The RETRIEVE AMI Randomized Trial.
BACKGROUND: Percutaneous coronary intervention (PCI) restores epicardial flow in ST-segment elevation myocardial infarction (STEMI), but large thrombus burden (LTB) can impair myocardial perfusion due to embolization. While manual aspiration (MA) devices have limited efficacy in STEMI, the success of stent-retriever thrombectomy (SRT) in stroke suggests it as a promising option for STEMI. OBJECTIVES: The RETRIEVE AMI (stent-retriever thrombectomy for thrombus burden reduction in patients with acute myocardial infarction) trial assessed the safety and efficacy of Solitaire X SRT vs Export MA in STEMI patients with LTB. METHODS: This single-center study enrolled 81 STEMI patients with LTB (TIMI thrombus grade ≥4) and randomized them to PCI, MA-assisted, or SRT-assisted PCI. The primary endpoint was difference in prestent thrombus volume by optical coherence tomography between SRT and either comparator; coprimary endpoints included device-related target vessel complications and major adverse cardiac and cerebrovascular events through 6 months. RESULTS: SRT was performed in 26 cases (one crossover), and MA in 27. No device-related arterial complications or cerebrovascular events occurred in the SRT arm. Baseline thrombus volume was significantly higher in the SRT group (18.3 mm3) compared to MA (7.7 mm3) and no modification (9.8 mm3; P = 0.04). Prestent thrombus volume was not significantly different between SRT (7.7; IQR: 2.3-18.6) and either MA (4.8; IQR: 1.8-8.4; P = 0.17) or no thrombus modification (9.8; IQR: 4.5-18.1; P = 1.00). Both techniques significantly reduced prestent thrombus burden (SRT: 12.8%; IQR: 4.4%-21.5%; P = 0.016 and MA: 13.0%; IQR: 3.8%-19.4%; P = 0.003) compared to no modification (22.8%; IQR: 10.4%-27.7%). No device-related clinically relevant arterial injury was detected and in-hospital and 6-month major adverse cardiac and cerebrovascular events did not differ between arms. CONCLUSIONS: RETRIEVE AMI demonstrates the feasibility of Solitaire X SRT in STEMI with LTB. Prestent thrombus volume was not different between SRT, MA, or no thrombus modification, although SRT extracted larger thrombus volume than MA. Larger multicenter studies using optical coherence tomography-based criteria are needed to minimize variability and enhance comparative assessments.
[Prevalence and influencing factors of preserved ratio impaired spirometry in adults aged 40 years and above in 10 areas in China].
Objective: To describe the prevalence of preserved ratio impaired spirometry (PRISm) in participants from the China Kadoorie Biobank (CKB) and explore the influencing factors. Methods: The CKB project conducted the baseline survey, the first and the second resurvey in 2004-2008, 2008, and 2013-2014, respectively. Based on the lung function tests, the participants were categorized into three groups: regular, PRISm, and airflow obstruction. The prevalence of PRISm was reported by gender, age, and region at the baseline survey. The secular trend in the prevalence of PRISm was described during the three surveys. Finally, we used the multiple logistic regression model to examine the factors related to PRISm in the baseline survey. Results: After standardization for gender, age, and region according to the sixth national census data in 2010, the overall prevalence of PRISm and airflow obstruction among the 434 760 participants at baseline was 24.8% and 6.1%, respectively. The prevalence of PRISm was higher in rural (25.4%) than that in urban areas (24.3%). Of the 10 study regions, Gansu had the highest prevalence of PRISm (56.0%), while Henan had the lowest (15.4%). After standardization for gender, age, and region according to the baseline population, the prevalence of PRISm decreased from 24.9% at baseline to 15.7% in the second resurvey, and the prevalence of airflow obstruction increased from 5.9% to 21.4%. Unmarried status, current smoking, using solid fuels for cooking, low body weight, being overweight, obesity, and central obesity were associated with an increased risk of PRISm. In contrast, higher education attainments, increased household income, and maintaining a specific degree of physical activity were associated with a reduced risk of PRISm. Conclusions: The prevalence of PRISm was high in adults aged 40 years and above in China, and it varied by sociodemographic and lifestyle factors.
All-cause and cause-specific mortality in individuals with COPD in China: a 16-year follow-up cohort study.
The prevalence of chronic obstructive pulmonary disease (COPD) is rising in China, yet population-based evidence on COPD-related mortality risk remains limited. This study examined the association between prevalent COPD and all-cause and cause-specific mortality in a large Chinese cohort. 484,301 adults aged 30 to 79 years who received spirometry at the baseline of the China Kadoorie Biobank Study (2004-2008) were included. COPD was defined as FEV1/ FVC
Multi-ancestry genome-wide association analyses incorporating SNP-by-psychosocial interactions identify novel loci for serum lipids.
Serum lipid levels, which are influenced by both genetic and environmental factors, are key determinants of cardiometabolic health and are influenced by both genetic and environmental factors. Improving our understanding of their underlying biological mechanisms can have important public health and therapeutic implications. Although psychosocial factors, including depression, anxiety, and perceived social support, are associated with serum lipid levels, it is unknown if they modify the effect of genetic loci that influence lipids. We conducted a genome-wide gene-by-psychosocial factor interaction (G×Psy) study in up to 133,157 individuals to evaluate if G×Psy influences serum lipid levels. We conducted a two-stage meta-analysis of G×Psy using both a one-degree of freedom (1df) interaction test and a joint 2df test of the main and interaction effects. In Stage 1, we performed G×Psy analyses on up to 77,413 individuals and promising associations (P
Neuroticism, omega-3 fatty acids, and risk of incident dementia.
BACKGROUND: High levels of neuroticism are associated with an increased risk of dementia, yet the underlying biological mechanisms remain poorly understood. Investigating the role of metabolites, the downstream products of metabolic processes, may offer valuable insights into this association. METHODS: In 215,624 dementia-free UK Biobank participants aged 40-69 years, we assessed neuroticism's associations with 249 nuclear magnetic resonance-measured metabolites using linear regression. Metabolites reaching Bonferroni-corrected significance were further tested for associations with incident all-cause dementia, Alzheimer's disease (AD) and vascular dementia (VaD) using Cox proportional-hazards regression, and with white matter hyperintensities volume using linear regression. Causality in significant observational relationships was evaluated through two-sample Mendelian randomization. RESULTS: Neuroticism was significantly associated with 119 out of 249 metabolites (Bonferroni-adjusted p
GWAS meta-analysis of CSF Alzheimer's disease biomarkers 18,948 individuals reveal novel loci and genes regulating lipid metabolism, brain volume and autophagy.
Cerebrospinal fluid (CSF) amyloid beta (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau181) are well accepted markers of Alzheimer's disease. We performed a GWAS meta-analysis including 18,948 individuals of European and 416 non-European ancestry. We identified 12 genome-wide significant loci across all three biomarkers, eight of them novel. We replicated the association of CSF biomarkers with APOE , CR1 , GMNC/CCDC50 and C16orf95/MAP1LC3B . Novel loci included BIN1 for Aβ42 and GNA12, MS4A6A, SLCO1A2 with both t-tau and p-tau181, as well as additional loci on chr. 8, near ANGPT1 and chr. 9 near SMARCA2 . We also demonstrated that these variants were not only associated with CSF level of the three biomarkers but also showed significant association with AD risk, disease progression and/or brain amyloidosis. The associated genes are implicated in lipid metabolism independent APOE , as well as autophagy and brain volume regulation driven by t-tau and p-tau181 dysregulation.