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Abstract Positively charged residues are commonly located near the cytoplasm-membrane interface, which is known as the positive-inside rule in membrane topology. The mechanism underlying the function of these charged residues remains poorly understood. Herein, we studied the function of cytoplasmic residues in corin, a type II transmembrane serine protease in cardiovascular biology. We found that the positively charged residue at the cytoplasm-membrane interface of corin was not a primary determinant in membrane topology but probably served as a charge-repulsion mechanism in the endoplasmic reticulum (ER) to prevent interactions with proteins in the ER, including the signal peptidase. Substitution of the positively charged residue with a neutral or acidic residue resulted in corin secretion likely due to signal peptidase cleavage. In signal peptidase-deficient cells, the mutant corin proteins were not secreted but retained in the ER. Similar results were found in the low-density lipoprotein receptor and matriptase-2 that have positively charged residues at and near the cytoplasm-membrane interface. These results provide important insights into the role of the positively charged cytoplasmic residues in mammalian single-pass transmembrane proteins.

Abstract Background Low-density lipoprotein cholesterol (LDL-C) is a well-recognized risk factor for cardiovascular diseases. However, several clinical studies demonstrated an inverse association between LDL-C and mortality risk in patients with acute myocardial infarction (AMI), known as the lipid paradox. This study aims to investigate the potential impact of inflammation on the association between LDL-C levels and mortality risks. Methods A total of 5244 patients with AMI from a large nationwide prospective cohort were included in our analysis. Patients were stratified according to LDL-C quartiles. The primary outcome was all-cause mortality, and the secondary endpoint was cardiac mortality. High-sensitive C-reactive protein (hsCRP) > 3 mg/L was defined as high inflammatory risk. Results During a median follow-up of 2.07 years, 297 mortality events (5.5%) and 227 cardiac mortality events (4.2%) occurred. Patients in the lowest LDL-C quartile had the highest incidence of all-cause mortality (7.3%) and cardiac mortality (5.8%). A U-shaped association between LDL-C levels and mortality risk was observed after multivariable adjustment, which persisted only in patients with high hsCRP levels. In contrast, a linear association between LDL-C and mortality risk was shown in patients with low hsCRP levels. Conclusions AMI patients with lower LDL-C levels had a higher risk of mortality. However, this association was only observed in those with high inflammatory risk. In contrast, the relationship between LDL-C and mortality risk was linear in patients with low inflammatory risk. This suggests the importance of considering inflammation when managing LDL-C levels in AMI patients.

Abstract Background Blocking the RhoA/ROCK II/MLC 2 (Ras homolog gene family member A/Rho kinase II/myosin light chain 2) signaling pathway can initiate neuroprotective mechanisms against neurological diseases such as stroke, cerebral ischemia, and subarachnoid hemorrhage. Nevertheless, it is not clear whether and how disrupting the RhoA/ROCK II/MLC 2 signaling pathway changes the pathogenic processes of the blood–brain barrier (BBB) after intracerebral hemorrhage (ICH). The present investigation included the injection of rat caudal vein blood into the basal ganglia area to replicate the pathophysiological conditions caused by ICH. Methods Scalp acupuncture (SA) therapy was performed on rats with ICH at the acupuncture point “Baihui”‐penetrating “Qubin,” and the ROCK selective inhibitor fasudil was used as a positive control to evaluate the inhibitory effect of acupuncture on the RhoA/ROCK II/MLC 2 signaling pathway. Post‐assessments included neurological deficits, brain edema, Evans blue extravasation, Western blot, quantitative polymerase chain reaction, and transmission electron microscope imaging. Results We found that ROCK II acts as a promoter of the RhoA/ROCK II/MLC 2 signaling pathway, and its expression increased at 6 h after ICH, peaked at 3 days, and then decreased at 7 days after ICH, but was still higher than the pre‐intervention level. According to some experimental results, although 3 days is the peak, 7 days is the best time point for acupuncture treatment. Starting from 6 h after ICH, the neurovascular structure and endothelial cell morphology around the hematoma began to change. Based on the changes in the promoter ROCK II, a 7‐day time point was selected as the breakthrough point for treating ICH model rats in the main experiment. The results of this experiment showed that both SA at “Baihui”‐penetrating “Qubin” and treatment with fasudil could improve the expression of endothelial‐related proteins by inhibiting the RhoA/ROCK II/MLC 2 signaling pathway and reduce neurological dysfunction, brain edema, and BBB permeability in rats. Conclusion This study found that these experimental data indicated that SA at “Baihui”‐penetrating “Qubin” could preserve BBB integrity and neurological function recovery after ICH by inhibiting RhoA/ROCK II/MLC 2 signaling pathway activation and by regulating endothelial cell–related proteins.

BackgroundThe clinical need for assisted reproduction continued to increase, so did the need for predictive markers of assisted reproductive technology (ART) outcomes. Among all the markers, sperm DNA integrity was paid more and more attention in the assessment of male fertility in recent years, but its clinical value remains still in doubt.MethodsWe conducted a retrospective cohort study. Couples coming to our reproductive center were retrospectively enrolled, and semen and assisted reproductive technology parameters were assessed. Sperm DNA integrity was analyzed using a flow cytometric method. Statistics were analyzed to investigate the relationship of this on semen quality and ART outcomes.ResultsDNA fragmentation index (DFI) was affected by abstinence days and age, and was a directly correlated with sperm quality parameters (p

Background: Fat grafting after breast prostheses removal has been performed widely for the breast augmentation. However, the postoperative complications and clinical safety of these two procedures are still widely concerned. Here, the authors presented two clinical cases of the complications of autologous fat grafting after breast prostheses removal.Methods: two patients visited our outpatient department, the one of them consulted for a 10-day history of fever and swelling of the left breast, the another consulted for the immovable mass in the left breast. Both of them received the surgery of bilateral breast prostheses removal there years ago and received the surgery of autologous fat grafting to the breasts in the year interval between surgeries. Based on the patient's history, physical examination and magnetic resonance imaging (MRI) examination, the fibro-oil cysts and fibrocystic mass formation were observed in patient A and patient B, respectively. Results: Incision and drainage were performed immediately with the patients. In one patient, a delineated capsular sac was revealed upon dissecting the pectoralis major during intraoperative exploration. Within this sac, a substantial quantity of grey-yellow fibro-oil cysts containing yellow. In another patient, upon dissecting the capsular sac, a fibrocystic mass containing necrotic adipose tissue was observed. Histopathological analysis of the fibro-oil cysts and the fibrocystic mass revealed that the surrounding envelope consisted of fibrous cystic parietal tissue enclosing pale and mildly lipid necrotic tissue. Conclusion: These results indicated that the main reason for the occurrence of these complications might be grafting fat into the remaining capsular sac. In a word, while performing the procedure of breast prosthesis removal, it is imperative to thoroughly excise the capsular sac to prevent the creation of residual capsular sac; Autologous fat should be inserted in multiple directions and correct layers. Prior to surgery, thorough preoperative positioning examinations should be conducted to avert the inadvertent injection of autologous fat.

IntroductionThis study evaluates the effectiveness of soil reconstruction and restoration in the Jiangcang coal mining area on the Qinghai-Tibet Plateau, where harsh environmental conditions pose significant challenges to ecological restoration.MethodsTwo phases of ecological restoration were implemented, with outcomes assessed based on vegetation coverage, species diversity, biomass, soil properties, and community similarity.ResultsThe results demonstrate that soil reconstruction significantly improved soil fertility, vegetation coverage, and community stability without noticeable degradation over time. The use of sheep manure increased species diversity by introducing native seeds, addressing the shortage of suitable grass species in alpine areas. Comparatively, the second phase of restoration, which included soil reconstruction, has elevated the vegetation coverage to 80%, matching natural background levels, and has also demonstrated superior outcomes in terms of soil stability, nutrient content, and other aspects compared to traditional methods. While aboveground biomass showed rapid recovery, belowground biomass lagged, indicating a need for longer-term restoration. Restored slopes exhibited higher similarity to natural alpine meadows compared to platforms, suggesting the dominance of the artificially seeded species on the platform areas hinders the reproduction of other species, which is unfavorable for the evolution of vegetation diversity.DiscussionThis study emphasizes the effectiveness of soil reconstruction, organic amendment, and other restoration measures, providing important experience and reference for mine ecological restoration in similar high-altitude mining areas.

Aiming at the removal of native oxide film on 2024-T3 Al alloy before plasma electrolytic oxidation, the methods to reduce the fatigue damage caused by grit blasting are explored. Effects of the grit size and pressure on surface roughness, residual compressive stress (RCS), and fatigue life of the Al alloy are studied. Increasing grit size and pressure leads to the increase in the surface roughness and RCS. Based on the theorem of momentum and tool cutting principle, mechanism of the grits on the craters and RCS is revealed. It is found that the angularness of the small-sized grit results in the formation of long scratches. The grit with high kinetic energy induces the large craters and high RCS. The craters are the primary fatigue crack initiation source. Moreover, the craters with long scratch and large height lead to the premature fatigue failure of the grit blasted specimens. However, Fatigue behavior is insignificantly affected by the RCS. The results provide new insights into the fatigue deterioration mechanism and life optimization of the grit blasted samples. Consequently, a parameter optimization scheme for the fatigue life of the grit blasted Al alloy is proposed.

Mg-Gd-Y-Zn-Zr alloy is an essential high strength weight ratio material in the aerospace field. It has been fabricated gradually using wire-arc additive manufacturing (WAAM), a key integrated preparation technology for large-scale parts. In this investigation, a Mg-9.4Gd-3.3Y-1.75Zn-0.38Zr (wt.%) alloy was prepared by WAAM based in the cold metal transfer (CMT) process. Investigations were conducted into the microstructural evolution and mechanical properties during the solution and aging heat treatment. With an average grain size of 18.30 ± 9.89 μm, the as-deposited Mg-Gd-Y-Zn-Zr alloy is mainly composed of α-Mg matrix, (Mg,Zn)3(Gd,Y) eutectic phase, RE-rich particles, and rare-earth (RE) segregation zone. Following a 12-h heat treatment at 500 °C, the average grain size of the α-Mg matrix showed no appreciable changes. The α-Mg matrix also dissolved the (Mg, Zn)3(Gd, Y) phases, which led to the production of long period stacking ordered (LPSO) phases and the disappearance of the RE-segregation zone. The appearance of the nanoscale β′ phase following aging heat treatment. The deposited alloys had the following tensile properties: 196.5 ± 24 MPa for ultimate tensile strength (UTS), 157.2 ± 14 MPa for yield strength (YS), and 2.08 ± 0.8% for elongation (EL). The formation of LSPO phase can improve the ductility while the formation of nanoscale β′ phase can improve the strength of Mg-Gd-Y-Zn-Zr alloy. Thus, after heat treatment at 500 °C for 12 h, the alloy's EL rose to 9.27 ± 0.94%. After further aging heat treatment for 225 °C at 24h, the alloy's YS rose to 234±3 MPa and its EL was 4.56 ± 0.25%.

Repairing defects in titanium alloy components is economically justified due to their high cost. In this work, Ti–6Al–4V samples with large area hole defects are repaired by transient liquid-phase sintering. The microstructure and tensile properties after repair have been investigated. The factors of different base powder morphology and the ratio of braze metal are also studied. The results show that by using spherical Ti64 alloy powder with 40 wt% TiZrCuNi braze alloy powder, an overall repair effect with high-density repair zone and good interface combination can be obtained at 960 °C for 3 h. The tensile strength of the as-repaired exceeds that of the matrix, but the elongation is lower than that of the matrix. Finally, the repair experiment conducted at various angles demonstrates this technique's strong practical feasibility.

Abstract With the development of open source software (OSS), software reliability has become an important issue. Due to the complexity of OSS development and testing environment, the fault detection rate of OSS will show a variety of changes. The existing OSS reliability models cannot fully adapt to the complex changes of OSS fault detection. In this paper, we proposed a multi-release OSS reliability model based on three-parameter lifetime distribution. The proposed model can effectively adapt to the complicated changes of fault detection in the processes of development and testing of OSS. Experimental results indicate that the proposed model has the better fitting and predictive performance compared with other multi-release OSS reliability models. Moreover, the proposed model can better adapt to the variety of OSS fault detection environment, and assist developers to evaluate the reliability of OSS.

The stress analysis of micro-arc oxidation (MAO) coated aero Al alloys is the basis to reveal the mechanism of fatigue deterioration. To clarify effects of the coating defects on fatigue life, a stress calculation model with micropores and residual stress is established based on shear lag model in this study. The effects of porosity, substrate elastic modulus, coating thickness and residual stress on the stress are explored. The results indicate that the coating porosity and thickness are the critical factor affecting coating normal stress and interfacial shear stress, respectively. In addition, the residual stress significantly affects the interfacial normal stress. The increasing stress caused by low porosity and residual tensile stress and stress concentration at the large-sized defects are the key factors for fatigue degradation.

IntroductionInvasive Stratified Mucin-producing Carcinoma (ISMC) of the cervix is a newly named cervical adenocarcinoma associated with Human Papilloma virus (HPV). Due to its relative rarity, clinical data, pathological features, and molecular characteristics of ISMC are still under exploration. This study aims to retrospectively analyze the clinical data and pathological features of ISMC patients, summarizing the clinical and pathological morphological characteristics of ISMC. Immunohistochemistry for SLC7A11, SLC3A2, and PD-L1 will be performed on tumor tissues from ISMC patients to preliminarily explore potential therapeutic targets for ISMC.MethodsWe retrospectively reviewed the electronic medical records and pathological slides of 22 ISMC patients, and performed immunohistochemical staining for solute carrier family 7 member 11 (SLC7A11), solute carrier family 3 member 2 (SLC3A2), and programmed death-ligand 1 (PD-L1).ResultsThe patients were aged between 31 and 70 years old. The most common symptoms were abnormal vaginal bleeding and unusual vaginal discharge. HPV testing indicated that the infection rate of HPV type 18 was the highest. All patients underwent extensive hysterectomy and pelvic lymph node dissection. The progression-free survival (PFS) ranged from 3 to 112 months, with a postoperative recurrence rate of 22.7% (5/22). ISMC exhibited diverse characteristic microstructures. Immunohistochemistry results showed that the positive rates of SLC7A11 and SLC3A2 were both 91.0% (20/22). The staining intensity of SLC7A11 in frequent ISMC recurrence cases was significantly stronger than in non-recurrent ISMC cases. PD-L1 positivity was observed in 86.4% (19/22) of cases, defined as having a Combined Positive Score(CPS)≥1.DiscussionISMC demonstrates a high rate of lymph node metastasis and a high recurrence rate, indicating strong invasiveness. Additionally, ISMC exhibits a wide morphological spectrum. SLC7A11, SLC3A2, and PD-L1 are all highly expressed in ISMC tissues. The high expression of SLC7A11 may indicate a high recurrence rate for ISMC. Immunotherapy with checkpoint inhibitors and iron death-related treatments show potential in the treatment of ISMC, with SLC7A11, SLC3A2, and PD-L1 serving as potential therapeutic targets for ISMC.

ABSTRACTThe launch of large language models (LLMs) like ChatGPT in late 2022 and the anticipated arrival of future GPT-x iterations have marked the beginning of the generative artificial intelligence (GAI) era. We conducted a systematic review of how to integrate LLMs including GPT and other GAI models into geospatial science, based on 293 papers obtained from four databases of academic publications – Web of Science (WoS), Scopus, SSRN and arXiv – 26 papers were eventually included for analysis. We statistically outlined the share of domains where LLMs and other GAI models, the type of data that have been used for these models, and the modelling tasks and roles that they play. We also pointed out the challenges and future directions for the next research agenda – along with which we could better position ourselves in the mainstream of science and the cutting-edge research paradigm as others leverage insights from the growing data deluge.

Memory deficits are a hallmark of many different neurological and psychiatric conditions. The Rey–Osterrieth complex figure (ROCF) is the state-of-the-art assessment tool for neuropsychologists across the globe to assess the degree of non-verbal visual memory deterioration. To obtain a score, a trained clinician inspects a patient’s ROCF drawing and quantifies deviations from the original figure. This manual procedure is time-consuming, slow and scores vary depending on the clinician’s experience, motivation, and tiredness. Here, we leverage novel deep learning architectures to automatize the rating of memory deficits. For this, we collected more than 20k hand-drawn ROCF drawings from patients with various neurological and psychiatric disorders as well as healthy participants. Unbiased ground truth ROCF scores were obtained from crowdsourced human intelligence. This dataset was used to train and evaluate a multihead convolutional neural network. The model performs highly unbiased as it yielded predictions very close to the ground truth and the error was similarly distributed around zero. The neural network outperforms both online raters and clinicians. The scoring system can reliably identify and accurately score individual figure elements in previously unseen ROCF drawings, which facilitates explainability of the AI-scoring system. To ensure generalizability and clinical utility, the model performance was successfully replicated in a large independent prospective validation study that was pre-registered prior to data collection. Our AI-powered scoring system provides healthcare institutions worldwide with a digital tool to assess objectively, reliably, and time-efficiently the performance in the ROCF test from hand-drawn images.

Spatially continuous fine particulate matter (PM2.5) mapping with hourly updated is essential for monitoring environmental pollution and promoting public health. The intensive observation of geostationary satellite enables accurate estimation of PM2.5 at a fine-scale. However, current estimation models are still limited by their weak transferability and hard to provide a robust hourly PM2.5 estimation. In this research, we aim to estimate the daytime PM2.5 concentrations at fine spatial and temporal resolution (1 km and hourly) in mainland China using an improved deep learning algorithm and the AOD products from geostationary satellite Himwari-8. An Adaptive Spatio-Temporal Multiscale Neural Network (ASTMNN) which contains three sub-networks and an adaptive weight was proposed to capture the spatiotemporal heterogeneity of hourly PM2.5. The three subnetworks of ASTMNN are spatial adjacency module (SaM), temporal adjacency module (TaM) and global module (GM), which used to incorporate the information from spatial neighborhood, temporal neighborhood, and global spatiotemporal range, respectively. And the weight function combines the outputs from the three subnetworks, where the weights were adaptively trained from the model optimization. The proposed model outperformed most current hourly PM2.5 estimation models with the sample-based, time-based, and site-based cross-validation (CV) R2 of 0.94, 0.89 and 0.83, respectively. Besides, we used our PM2.5 product to track extreme dust events. Our findings provide valuable implications for tracking continuous variation in particulate pollution using geostationary satellites.

Abstract Experiments as Code (ExaC) is a concept for reproducible, auditable, debuggable, reusable, & scalable experiments. Experiments are a crucial tool to understand Human-Building Interactions (HBI) and build a coherent theory around it. However, a common concern for experiments is their auditability and reproducibility. Experiments are usually designed, provisioned, managed, and analyzed by diverse teams of specialists (e.g., researchers, technicians, engineers) and may require many resources (e.g., cloud infrastructure, specialized equipment). Although researchers strive to document experiments accurately, this process is often lacking. Consequently, it is difficult to reproduce these experiments. Moreover, when it is necessary to create a similar experiment, the “wheel is very often reinvented”. It appears easier to start from scratch than trying to reuse existing work. Thus valuable embedded best practices and previous experiences are lost. In behavioral studies, such as in HBI, this has contributed to the reproducibility crisis. To tackle these challenges, we propose the ExaC paradigm, which not only documents the whole experiment, but additionally provides the automation code to provision, deploy, manage, and analyze the experiment. To this end, we define the ExaC concept, provide a taxonomy for the components of a practical implementation, and provide a proof of concept with an HBI desktop VR experiment that demonstrates the benefits of its “as code” representation, that is, reproducibility, auditability, debuggability, reusability, & scalability.

Summary: Autographiviridae phage HH109 is a lytic Vibrio alginolyticus E110-specific phage, but the molecular mechanism underlying host recognition of this phage remains unknown. In this study, a transposon mutagenesis library of E110 was used to show that several capsular polysaccharide (CPS) synthesis-related genes were linked to the phage HH109 infection. Gene deletion combined with multiple functional assays demonstrated that CPS serves as the receptor for the phage HH109. Deletions of CPS genes caused reduction or loss of capsule and reduced adsorption. Comparative genome analysis revealed that phage-resistant mutants harbored loss-of-function mutations in the previously identified genes responsible for CPS biosynthesis. The tail protein gp02 of phage HH109 was identified as the receptor-binding protein (RBP) on CPS using antibody blocking assay, immunofluorescence staining, and CPS quantification. Additionally, we found that the phage HH109 could degrade approximately 88% of mature biofilms. Our research findings provide a theoretical basis against vibriosis.

Aerosols are crucial constituents of the atmosphere, with significant impacts on air quality. Aerosol optical depth (AOD) is critical in assessing solar resources and modeling sky radiance. However, comprehensive aerosol studies at a continental scale are limited, and existing methodologies need to consider spatial characteristics. This study develops a spatio-temporal unmixing with heterogeneity (STUH) model to evaluate spatial patterns and temporal trends of atmospheric aerosols across the African continent. The spatio-temporal AOD data cube, comprising monthly averaged MODIS-derived AOD data from 2001 to 2015, was decomposed using spatially non-negative matrix variabilization to explore the spatial determinants and the impacts of their interactions to AOD using a geographically optimal zones-based heterogeneity (GOZH) model. Our findings reveal an increasing trend of aerosol levels across Africa in the past 15 years, combined with the spatio-temporal AOD pattern explained by five abundance variables. We find that in different regions across Africa, the impact of natural variables on AOD was 1.56 to 3.01 times the impact of human variables, with significant spatial variations. These results are essential for understanding the climatic implications of atmospheric aerosols in Africa.

Zebrafish is a highly advantageous model animal for drug screening and toxicity evaluation thanks to its amenability to optical imaging (i.e., transparency), possession of organ structures similar to humans, and the ease with which disease models can be established. However, current zebrafish drug screening technologies and devices suffer from limitations such as low level of automation and throughput, and low accuracy caused by the heterogeneity among individual zebrafish specimens. To address these issues, we herein develop a high-throughput zebrafish drug screening system. This system is capable of maintaining optimal culturing conditions and simultaneously monitoring and analyzing the movement of 288 zebrafish larvae under various external conditions, such as drug combinations. Moreover, to eliminate the effect of heterogeneity, locomotion of participating zebrafish is assessed and grouped before experiments. It is demonstrated that in contrast to the experimental results without pre-selection, which shows ∼20 % damaged motor function (i.e., degree of attenuation), the drug-induced variations among zebrafish with equivalent mobility reaches ∼80 %. Overall, our high-throughput zebrafish drug screening system overcomes current limitations by improving automation, throughput, and accuracy, resulting in enhanced detection of drug-induced variations in zebrafish motor function.

Abstract Software-defined radios (SDRs) are radio frequency transceivers designed to facilitate digital signal processing through the use of vast libraries of open-source software. Here, we assemble a simple data acquisition system whose architecture, based on SDR, allows us to develop a comprehensive suite of tools to study the vibrations of a few-layer graphene nanomechanical resonator. Namely, we measure the cross-spectrum of vibrations in the frequency domain, we measure their energy decay rate in the time domain, we perform vector measurements of their in-phase and quadrature components, and we control their phase using a time-dependent strain field –all with a single measurement platform. Our approach allows us to tailor our experiments at will and gives us control over every stage of data processing. Overall, our versatile system enables measuring a wide range of nanomechanical properties of graphene by customizing the signal acquisition and replacing some analog electrical circuits, such as filters, mixers, and demodulators, by blocks of code.

Cross-domain computing power networks wish to integrate computational and data resources from multiple computing centers, but existing methods do not pay enough attention to cross-domain file and data management.In this paper, a lightweight data access scheme for cross-domain computing power networks was proposed: (1) accessing parallel file system storage resources of remote computing centers through file system protocol conversion; (2) local caching as a supplement to cope with high IOPS applications; and (3) mounting remote or local storage to specified directories through container binding technology.The prototype system based on this scheme had been deployed on highperformance computing centers in multiple universities.The measured data and user experience showed that the scheme in this paper could meet the requirements of common high-performance computing applications.

Abstract. Background:. Risk assessment and treatment stratification for three-vessel coronary disease (TVD) remain challenging. This study aimed to investigate the prognostic value of left atrial volume index (LAVI) with the Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score II, and its association with the long-term prognosis after three strategies (percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG], and medical therapy [MT]) in patients with TVD. Methods:. This study was a post hoc analysis of a large, prospective cohort of patients with TVD in China, that aimed to determine the long-term outcomes after PCI, CABG, or optimal MT alone. A total of 8943 patients with TVD were consecutively enrolled between 2004 and 2011 at Fuwai Hospital. A total of 7818 patients with available baseline LAVI data were included in the study. Baseline, procedural, and follow-up data were collected. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which was a composite of all-cause death, myocardial infarction (MI), and stroke. Secondary endpoints included all-cause death, cardiac death, MI, revascularization, and stroke. Long-term outcomes were evaluated among LAVI quartile groups. Results:. During a median follow-up of 6.6 years, a higher LAVI was strongly associated with increased risk of MACCE (Q3: hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.06-1.37, P = 0.005; Q4: HR 1.85, 95%CI 1.64-2.09, P