Citations

Importance Elevated low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for cardiovascular disease, the leading cause of premature death worldwide. Assessing the LDL-C–related burden is critical for guiding prevention and treatment strategies. Objectives To estimate the global, regional, and national burden of ischemic heart disease and ischemic stroke attributable to elevated LDL-C (relative to 35-54 mg/dL) from 1990 to 2023 and to quantify the contributions of population growth, aging, risk-deleted burden, and exposure changes to burden trends. Design, Setting, and Population This comparative risk assessment, part of the Global Burden of Disease Study 2023, estimated population-level LDL-C exposure and associated health loss in 204 countries and territories. Mean LDL-C levels were estimated using spatiotemporal gaussian process regression based on 806 studies across 161 countries. Relative risks were derived from meta-analyses of 38 randomized clinical trials. Population-attributable fractions for deaths and disability-adjusted life-years (DALYs) were estimated by age and sex for adults aged 25 years or older from 1990 to 2023, with 95% uncertainty intervals. Exposure Population-level LDL-C concentrations. Main Outcomes and Measures Population-attributable fractions, counts, and rates (all ages and age standardized per 100 000) of LDL-C–attributable deaths and DALYs from ischemic heart disease and ischemic stroke, with uncertainty intervals. Results In 2023, elevated LDL-C accounted for 3.6 million deaths (95% uncertainty interval, 2.2-5.4 million; 6.0% of global mortality) and 90.7 million DALYs (95% uncertainty interval, 58.9-123.3 million; 3.2% of DALYs). Although global all-ages rates remained stable, age-standardized death and DALY rates decreased by 45.6% and 39.5%, respectively, since 1990. In 2023, age-standardized LDL-C–attributable DALY rates were highest in Eastern Europe and lowest in high-income Asia-Pacific. One-third of the global LDL-C burden occurred in India and China. Population growth and aging drove the increasing burden, with notable regional disparities in LDL-C exposure and risk-deleted DALY rates shifting toward middle-sociodemographic settings. Conclusions and Relevance Despite declining age-standardized rates, the absolute LDL-C burden has increased since 1990 due to demographic changes and has shifted toward middle-sociodemographic countries. Measurement and surveillance gaps persist. Strengthened prevention, diagnosis, and treatment access strategies are essential to mitigate the health burden of LDL-C.

ABSTRACT Introduction Cardiogenic shock (CS) carries high morbidity and mortality. However, evidence for mechanical circulatory support (MCS) in non‐ischemic CS remains limited, as prior trials have focused on infarct‐related shock. Methods We performed a retrospective cross‐sectional study using the Nationwide Inpatient Sample (2017–2019), identifying hospitalizations with a principal diagnosis of CS and excluding acute myocardial infarction. Patients were categorized into mutually exclusive groups: no MCS, intra‐aortic balloon pump (IABP) only, Impella only, or extracorporeal membrane oxygenation (ECMO) only. Primary outcomes were in‐hospital mortality, length of stay (LOS), and total hospital cost. Survey‐weighted multivariable models adjusted for demographics, hospital characteristics, and comorbidity burden using Elixhauser and Charlson indices. Results Among 104 045 hospitalizations, 6040 received MCS. IABP was most common, followed by Impella and ECMO. Among patients receiving a single MCS strategy, overall in‐hospital mortality was 29.5%., with lower mortality in the IABP group (19.9%) compared with Impella (37.4%) and ECMO (44.3%). After adjustment, IABP was associated with lower observed in‐hospital mortality versus no MCS (aOR 0.58, 95% CI 0.53–0.64; p < 0.01), whereas Impella and ECMO showed increased aOR. IABP and ECMO were associated with longer LOS, while Impella was not. All MCS strategies were associated with higher costs, with ECMO showing the greatest increase (cost ratio 3.30, 95% CI 3.12–3.50). Conclusion In non‐ischemic CS, MCS strategies demonstrate distinct profiles of mortality and resource utilization. IABP was associated with lower observed in‐hospital mortality, whereas all MCS were linked to higher costs, highlighting heterogeneity in outcomes and the need for further research.

Abstract Objectives Medical nutrition therapy significantly impacts cardiovascular risk and overall health, but effects on muscle diseases remain unclear. This systematic review evaluates the safety and efficacy of dietary interventions and supplements on muscle disease outcomes. Methods A multidisciplinary team conducted a PRISMA-guided systematic review registered on PROSPERO. Searches were conducted across multiple databases and screened against pre-specified inclusion criteria. Results Of 107 full-text articles screened, 51 met inclusion criteria. Most identified interventions used dietary supplements rather than whole dietary approaches. In inflammatory myopathies, creatine (loading dose 20 g/day, maintenance 3 g/day) combined with exercise improved high-intensity functional performance in PM and DM over 6 months. In Duchenne muscular dystrophy, creatine (2–10 g/day for 8–16 weeks) improved maximal voluntary contraction and fatigue resistance. Carbohydrate-rich diets (65% CHO) reduced exercise-related symptoms in McArdle disease, while high-dose creatine (150 mg/kg/day) paradoxically worsened symptoms. Four trials of aceneuramic acid (6 g/day for 48 weeks) in GNE myopathy demonstrated dose-dependent strength improvements, leading to regulatory approval in Japan. High-protein supplementation showed positive trends for muscle preservation in critical illness myopathy. Quality assessment revealed 31% at low risk of bias, 49% with some concerns and 20% at high risk. Conclusion Evidence for nutritional interventions in muscle diseases remains limited, especially for inflammatory myopathies. The strongest support emerged for mechanistically targeted approaches: creatine with exercise, carbohydrate-rich and ketogenic diets in McArdle disease and sialic acid in GNE myopathy. Future research requires adequately powered multicentre trials with standardized outcomes, with focus on inflammatory myopathies.

Most genetic variants associated with complex traits are hypothesized to regulate gene expression. To understand the genetics underlying gene expression variability, we characterized 14,324 RNA-sequencing samples from the Trans-Omics for Precision Medicine program and performed expression and splicing quantitative trait locus (e/sQTL) analyses in six tissues and cell types, including whole blood ( n = 6454) and lung ( n = 1291). We detected tens of thousands of secondary cis-e/sQTLs, showing that secondary cis-e/sQTL discovery remains unsaturated. We fine-mapped UK Biobank–derived genome-wide association study (GWAS) signals from 164 traits and identified e/sQTL colocalizations for 10,611 GWAS signals, including 7096 that colocalize with secondary e/sQTLs. Our results suggest that even larger e/sQTL analyses will uncover additional secondary e/sQTLs, further benefiting GWAS interpretation.

Abstract Background Cardiac magnetic resonance elastography (MRE) allows the non-invasive quantification of myocardial stiffness, but long-interval reproducibility data at 3.0 T single-frequency 140-Hz remain limited. Purpose To evaluate the short- and long-interval reproducibility of 3.0 T cardiac MRE for left ventricular (LV) myocardial stiffness across healthy volunteers and patients with conditions associated with elevated myocardial stiffness. Materials and Methods This prospective single-center study included 69 participants: 60 healthy volunteers and 9 with cardiovascular disease (6 with aortic stenosis and 3 with long-standing hypertension). All participants underwent baseline cardiac MRE (scanner: Signa Premier 3.0 T, GE Healthcare, driver: Resoundant), an immediate short-interval rescan (SIR) within 5 minutes, and a long-interval rescan (LIR) after approximately 1 month. Left ventricular myocardial stiffness and octahedral shear strain signal-to-noise ratio were measured independently by 2 readers. Reproducibility was assessed using Bland-Altman analysis, intraclass correlation coefficients (ICCs), within-subject coefficient of variation, standard error of measurement, and smallest detectable change at the 95% confidence (SDC95) level. Results Baseline LV myocardial stiffness was higher in the disease group than in healthy volunteers, 11.73 ± 1.01 kPa and 7.80 ± 0.70 kPa (mean ± SD; P &lt; .001), respectively. Inter-reader agreement was excellent across all timepoints, with ICCs of 0.970 at baseline (95% CI, 0.953-0.982), 0.966 for SIR (95% CI, 0.945-0.979), and 0.962 for LIR (95% CI, 0.939-0.976). Within-reader scan-rescan reproducibility was also excellent. For Reader 1, stiffness ICC was 0.979 for the SIR (95% CI, 0.966-0.987) and 0.957 for the LIR (95% CI, 0.932-0.973), with SDC95 values of 0.616 kPa (95% CI, 0.528-0.741) and 0.869 kPa (95% CI, 0.744-1.044), respectively. Reader 2 showed excellent reproducibility, with ICCs ≤0.943. Conclusions 3D single-frequency 140-Hz cardiac MRE at 3.0 T provides excellent short- and long-interval reproducibility for LV myocardial stiffness quantification. The SDC95 values may help distinguish true longitudinal stiffness changes from measurement variability.

Objective Lennox–Gastaut syndrome (LGS) is a severe treatment‐resistant epilepsy. Although vagus nerve stimulation (VNS) and deep brain stimulation (DBS) are established therapies, comparative data and the impact of dual neuromodulation remain limited. We compared seizure outcomes across VNS, DBS, and combined DBS + VNS therapy in LGS. Methods This retrospective cohort study at Mayo Clinic (2005–2024) included LGS patients treated with VNS and/or DBS . Seizure frequency was assessed at 6, 12, and 24 months post‐stimulation. Responder was defined as 50% or more seizure reduction. Results Forty patients were included (42% female, median, 150 seizures/month). Eleven patients underwent sequential VNS followed by DBS and contributed data to 2 treatment epochs, yielding 3 treatment groups: VNS alone (n = 29), DBS alone (n = 12), and DBS + VNS (n = 10). At 24 months, median seizure reduction rate was comparable between VNS (50%; 95% confidence interval [ CI], 44–75%) and the overall DBS cohort (59%, 95% CI, 33–86%) ( p = 0.54). However, a significant difference emerged when comparing the 3 treatment arms ( p = 0.027). Specifically, DBS + VNS therapy yielded significantly greater median reduction rate (81%, 95% CI, 60–99%) than DBS alone (43%, 95% CI, 0–58%) ( p adj = 0.027) or VNS alone (50%, 95% CI, 44.4–75.0%) ( p adj = 0.048). Four patients attained sustained seizure freedom above 1 year at last follow‐up. Interpretation VNS and DBS provide comparable seizure reduction in LGS over a 2‐year follow‐up period. DBS + VNS was associated with further improvements in seizure reduction in this small, retrospective dataset. This possibility warrants further investigation. ANN NEUROL 2026

TAF7, a core subunit of the general transcription factor TFIID, regulates transcription and additionally functions as an RNA chaperone that directs nascent nuclear RNAs to cytoplasmic polysomes, thereby influencing protein synthesis. Here, we identify a set of novel cytoplasmic interactors and a previously unappreciated cytoplasmic role for TAF7 in oncogenesis. BioID-mediated proximity labeling identified STAT3 and the CCT and WASH complexes as prominent cytoplasmic interactors of TAF7. These interactions were validated by co-immunoprecipitation and proximity ligation assays. We further showed that cytoplasmic TAF7 levels increased during oncogenesis in proportion to cancer cell pathogenicity. Notably, TAF7 engagement with STAT3, CCT and WASH complexes is markedly enhanced during cellular transformation, consistent with their functions in cancer progression. Together, these findings reveal a cytoplasmic TAF7 interactome and implicate elevated cytoplasmic TAF7 as associated with oncogenesis.

Background/Objectives: To develop and evaluate a deep learning-based quality control system for Lumbar Spinal Digital Radiographs (LSDR), designed to automate and improve their evaluation and reduce reliance on manual reviews. Methods: This retrospective study utilized a deep learning workflow comprising image segmentation, feature extraction, and a classification model. The dataset, including anteroposterior (AP) and lateral (LAT) X-ray images, was expanded through data augmentation techniques. Four U-Net-based models were assessed: standard U-Net, Swin-UNet, Attention U-Net, and Attention U-Net with the weight map, with the latter selected for its superior performance. Extracted features, such as brightness, contrast, and anatomical positioning, were used in an XGBoost classifier, which was evaluated using mean intersection over union (mIoU), accuracy, sensitivity, specificity, and AUC. Results: The Attention U-Net with weighted attention outperformed the other models, achieving high mIoU scores in both AP and LAT views. The XGBoost classifier achieved the best performance in classifying images as “qualified” or “unqualified,” with an AUC of approximately 0.9, high accuracy, and balanced sensitivity and specificity. This approach effectively addressed class imbalances and improved model accuracy compared to traditional machine learning models such as MLP and SVM. Conclusions: The developed automated quality control system demonstrated potential for enhancing image quality, enhancing diagnostic reliability, and optimizing clinical workflow efficiency.

Autonomous robotic-assisted surgery (RAS) has emerged as a promising objective in biomedical technology, further enhanced by miniaturization toward microrobotic-assisted surgery (μ-RAS). This reduction in scale promises minimally invasive, partially or fully automated surgical procedures, with the potential to reduce patient recovery times, lower medical costs, and enable previously unavailable procedural options. This perspective highlights the specific advances in RAS that potentially map to the microscale (μ-RAS), organized across five surgical domains: endovascular, endoluminal, laparoscopic, ophthalmic, and orthopedic. We examine both clinical demands and technological advances in surgical robotics and identify the key innovations required for progress across these surgical fields. Our contribution is distinct in combining the perspectives of both surgical experts and bioengineering innovators, outlining a roadmap for the advancement and eventual integration of autonomous RAS and μ-RAS into mainstream surgical practice.