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Postmenopausal osteoporosis is a prevalent metabolic bone disorder characterized by a decrease in bone mineral density and deterioration of bone microstructure. Despite the high prevalence of this disease, no effective treatment for osteoporosis has been developed. Exercise has long been considered a potent anabolic factor that promotes bone mass via upregulation of myokines secreted by skeletal muscle, exerting long‐term osteoprotective effects and few side effects. Irisin was recently identified as a novel myokine that is significantly upregulated by exercise and could increase bone mass. However, the mechanisms underlying exercise‐induced muscle‐bone crosstalk remain unclear. Here, we identified that polyunsaturated fatty acids (arachidonic acid and docosahexaenoic acid) are increased in skeletal muscles following a 10‐week treadmill exercise programme, which then promotes the expression and release of FNDC5/irisin. In osteoblasts, irisin binds directly to Cav1, which recruits and interacts with AMP‐activated protein kinase α (AMPKα) to activate the AMPK pathway. Nrf2 is the downstream target of the AMPK pathway and increases the transcription of HMOX1 and Fpn. HMOX1 is involved in regulating the cell cycle and promotes the proliferation of osteoblasts. Moreover, upregulation of Fpn in osteoblasts enhanced iron removal, thereby suppressing ferroptosis in osteoblasts. Additionally, we confirmed that myotube‐derived exosomes are involved in the transportation of irisin and enter osteoblasts through caveolae‐mediated endocytosis. In conclusion, our findings highlight the crucial role of irisin, present in myotube‐derived exosomes, as a crucial regulator of exercise‐induced protective effects on bone, which provides novel insights into the mechanisms underlying exercise‐dependent treatment of osteoporosis. [ABSTRACT FROM AUTHOR]

SUMMARY: The mechanistic basis by which boron (B) deprivation inhibits root growth via the mediation of root apical auxin transport and distribution remains elusive. This study showed that B deprivation repressed root growth of wild‐type Arabidopsis seedlings, which was related to higher auxin accumulation (observed with DII‐VENUS and DR5‐GFP lines) in B‐deprived roots. Boron deprivation elevated the auxin content in the root apex, coinciding with upregulation of the expression levels of auxin biosynthesis‐related genes (TAA1, YUC3, YUC9, and NIT1) in shoots, but not in root apices. Phenotyping experiments using auxin transport‐related mutants revealed that the PIN2/3/4 carriers are involved in root growth inhibition caused by B deprivation. B deprivation not only upregulated the transcriptional levels of PIN2/3/4, but also restrained the endocytosis of PIN2/3/4 carriers (observed with PIN‐Dendra2 lines), resulting in elevated protein levels of PIN2/3/4 in the plasma membrane. Overall, these results suggest that B deprivation not only enhances auxin biosynthesis in shoots by elevating the expression levels of auxin biosynthesis‐related genes but also promotes the polar auxin transport from shoots to roots by upregulating the gene expression levels of PIN2/3/4, as well as restraining the endocytosis of PIN2/3/4 carriers, ultimately resulting in auxin accumulation in root apices and root growth inhibition. Significance Statement: While boron (B) deprivation‐induced root growth inhibition is causally associated with auxin accumulation and transport, the underlying mechanisms remain unknown. This work showed that enhanced auxin biosynthesis resulting from upregulation of the expression levels of auxin biosynthesis‐related genes in shoots and increased protein levels of PIN2/3/4 carriers in the plasma membrane mediated by increased transcript levels of PIN2/3/4 genes in roots combined with restrained endocytosis of PIN2/3/4 carriers result in auxin overaccumulation in root apices and consequently root growth inhibition. [ABSTRACT FROM AUTHOR]

Objective: To explore the value of mixed reality (MR) in sentinel lymph node biopsy (SLNB) in patients with breast cancer. Methods: A total of 300 patients with breast cancer who underwent SLNB enrolled and were randomly divided into two groups. In group A, only dye (an injection of methylene blue) was used to detect sentinel lymph nodes, while in group B MR was used for positioning in addition to dye. (MR localization method: Before the surgery, we built a 1:1 3D reconstruction model based on the patient's CT or MRI original data, and after the patient was injected with dye, we completed MR localization by overlapping the pre-marked image with the model.) Results: During surgery, the detection time in group B was significantly shorter than in group A (3.62 ± 1.20 vs.7.87 ± 1.86; p < 0.001). At 1-month post-surgery follow-up, the incidence of pain in group B was lower than that in group A (2.70 vs. 8.28%, p = 0.036). The incidence of upper limb dysfunction was lower in group B than in group A (2.03 vs. 8.97%, p = 0.009). In terms of the incidence of pain, group B was better than group A (0.68 vs. 3.45%, p = 0.094). The satisfaction of the two groups was scored, and the results showed that group B was better than group A (4.04 ± 0.91 vs.3.32 ± 0.94, p < 0.001). Conclusion: The application of MR to SLNB in breast cancer can significantly reduce the detection time and the occurrence of complications and improve patient satisfaction. [ABSTRACT FROM AUTHOR]

Background: Triple‐negative breast cancer (TNBC) is the subtype of breast cancer with the worst prognosis, and it is highly heterogeneous. There is growing evidence that the tumor immune microenvironment (TIME) plays a crucial role in tumor development, maintenance, and treatment responses. Notably however, the full effects of the TIME on prognosis, TIME characteristics, and immunotherapy responses in TNBC patients have not been fully elucidated. Methods: Gene Expression Omnibus and The Cancer Genome Atlas data were used to data analysis. Single‐cell sequencing and tissue microarray analysis were used to investigate gene expression. The concentrations and distributions of immune cell types were determined and analyzed using the CIBERSORT strategy. Tumor immune dysfunction and exclusion score and the IMvigor210 cohort were used to estimate the sensitivity of TNBC patients with different prognostic statuses to immune checkpoint treatment. Results: Five immune‐related genes associated with TNBC prognosis (IL6ST, NR2F1, CKLF, TCF7L2, and HSPA2) was identified and a prognostic evaluation model was constructed based on those genes. The respective areas under the curve of the prognostic nomogram model at 3 and 5 years were 0.791 and 0.859. The group with a lower nomogram score, with a better prognosis survival status and clinical treatment benefit rate. Conclusion: A prognostic model for TNBC that was closely related to the immune landscape and therapeutic responses was constructed. This model may help clinicians to make more precise and personalized treatment decisions pertaining to TNBC patients. [ABSTRACT FROM AUTHOR]

SUMMARY: The supply of boron (B) alleviates the toxic effects of aluminum (Al) on root growth; however, the mechanistic basis of this process remains elusive. This study filled this knowledge gap, demonstrating that boron modifies auxin distribution and transport in Al‐exposed Arabidopsis roots. In B‐deprived roots, treatment with Al induced an increase in auxin content in the root apical meristem zone (MZ) and transition zone (TZ), whereas in the elongation zone (EZ) the auxin content was decreased beyond the level required for adequate growth. These distribution patterns are explained by the fact that basipetal auxin transport from the TZ to the EZ was disrupted by Al‐inhibited PIN‐FORMED 2 (PIN2) endocytosis. Experiments involving the modulation of protein biosynthesis by cycloheximide (CHX) and transcriptional regulation by cordycepin (COR) demonstrated that the Al‐induced increase of PIN2 membrane proteins was dependent upon the inhibition of PIN2 endocytosis, rather than on the transcriptional regulation of the PIN2 gene. Experiments reporting on the profiling of Al3+ and PIN2 proteins revealed that the inhibition of endocytosis of PIN2 proteins was the result of Al‐induced limitation of the fluidity of the plasma membrane. The supply of B mediated the turnover of PIN2 endosomes conjugated with indole‐3‐acetic acid (IAA), and thus restored the Al‐induced inhibition of IAA transport through the TZ to the EZ. Overall, the reported results demonstrate that boron supply mediates PIN2 endosome‐based auxin transport to alleviate Al toxicity in plant roots. Significance Statement: Aluminum toxicity and boron deficiency are limiting factors for agricultural production in acid soils, which make up almost half of the world's arable land. Boron fertilization alleviates aluminum toxicity but the mechanism remains unclear. The study shows that boron supply releases aluminum‐induced root growth arrest by facilitating endosome‐based polar auxin transport via PIN2 polar localization in the upper half of the plasma membrane (shootward). We provide solid support for boron fertilizer in remediating aluminum toxicity in acid soils. [ABSTRACT FROM AUTHOR]

Background and purpose: The association between nonstenotic plaque at the petrous internal carotid artery (ICA) and embolic stroke of undetermined source (ESUS) remains unknown. We aimed to test the hypothesis that the presence of a larger build‐up of petrous plaque is more prevalent in the ipsilateral versus the contralateral side among ESUS patients without plaque in the intracranial and proximal ICA. Methods: From a total of 243 patients with ESUS and 160 patients with small‐vessel disease (SVD) without proximal ICA plaque, we enrolled 88 ESUS and 103 SVD patients without ipsilateral nonstenotic intracranial and proximal ICA plaque in the present study. Targeting the petrous segment of the ICA on two sides, plaque burden including plaque thickness, lumen area, vessel area, wall area, and percentage of luminal stenosis, and composition features (presence/absence of the ruptured fibrous cap, ulcer plaque, thrombus, discontinuity of plaque surface [DPS], intraplaque hemorrhage and complicated plaque) were assessed by high‐resolution magnetic resonance imaging. Results: We found a higher prevalence of petrous plaque thickness ≥3.5 mm ipsilateral versus contralateral to the stroke (25/88 [28.4%] vs. 12/88 [13.6%], odds ratio [OR] 3.60, 95% confidence interval [CI] 1.34–9.70), but this imbalance was not seen in SVD. In patients with plaque thickness ≥3.5 mm, the presence of DPS (OR 4.05, 95% CI 1.11–14.78) and complicated plaque (OR 5.00, 95% CI 1.10–22.82) was more closely related to an index ESUS, a finding that was not evident in the subgroup with petrous plaque <3.5 mm (p for interaction = 0.027). Conclusions: The present study provided the first evidence supporting a potential etiological role of vulnerable petrous plaque in ESUS. [ABSTRACT FROM AUTHOR]

Objective: To investigate an association between percentage lipid‐rich necrotic core (LRNC) and an index ischemic stroke in an embolic stroke of undetermined source (ESUS) cohort. Methods: A total of 167 ESUS patients with 259 non‐stenotic intracranial plaques including 155 ipsilateral and 104 contralateral to stroke were finally enrolled in the current analysis. The multi‐dimensional parameters involving remodeling index (RI), plaque burden (PB), LRNC, discontinuity of plaque surface (DPS), intraplaque hemorrhage (IPH), and vulnerable plaque defined as presence of complicated plaque were evaluated by high‐resolution magnetic resonance imaging. Results: We found that %LRNC was an independent predictor for ESUS in model 1 (OR: 2.574, 95% CI: 1.854–3.573, P < 0.001), and model 2 (OR: 2.550, 95% CI: 1.835–3.545, P < 0.001), but the association was not seen in PB. In receiver operating characteristic curve analysis, the discrimination of LRNC for ESUS was significantly superior to that of PB (absolute difference: 0.121, 95% CI: 0.056–0.205, P < 0.001). Importantly, a significantly positive synergy between the remodeling pattern and LRNC in response to plaque vulnerability was found by Sankey diagram (P for interaction = 0.001). Conclusion: This is the first report that LRNC, beyond PB, may be correlated with an index ESUS, and a synergistic effect between positive remodeling and larger LRNC could promote plaque vulnerability. The findings suggest that a potential target subgroup may benefit from stroke prevention with intensive statin, although this must be confirmed in future. [ABSTRACT FROM AUTHOR]

Background: Cone-beam computed tomography (CBCT) is widely used for daily image guidance in radiation therapy, enhancing the reproducibility of patient setup. However, its application in adaptive radiotherapy (ART) is limited by many imaging artifacts and inaccurate Hounsfield units (HUs). The correction of CBCT image is necessary and of great value for CBCT-based ART. Purpose: To explore the synthetic CT (sCT) generation from CBCT images of thorax and abdomen patients, which usually surfer from serious artifacts duo to organ state changes. In this study, a streaking artifact reduction network (SARN) is proposed to reduce artifacts and combine with cycleGAN to generate highquality sCT images from CBCT and achieve an accurate dose calculation. Methods: The proposed SARN was trained in a self -supervised manner. Artifact-CT images were generated from planning CT by random deformation and projection replacement, and SARN was trained based on paired artifact--CT and CT images. The planning CT and CBCT images of 260 patients with cancer, including 120 thoracic and 140 abdominal CT scans, were used to train and evaluate neural networks. The CBCT images of another 12 patients in late treatment fractions, which contained large anatomy changes, were also tested by trained models. The trained models include commonly used U-Net, cycle-GAN, attention-gated cycleGAN (cycAT), and cascade models combined SARN with cycleGAN or cycAT. The generated sCT images were compared in terms of image quality and dose calculation accuracy. Results: The sCT images generated by SARN combined with cycleGAN and cycAT showed the best image quality, removed the most artifacts, and retained the normal anatomical structure. The SARN+cycleGAN performed best in streaking artifacts removal with the maximum percent integrity uniformity (PIUm) of 91.0% and minimum standard deviation (SD) of 35.4 HU for delineated artifact regions among all models. The mean absolute error (MAE) of CBCT images in the thorax and abdomen were 71.6 and 55.2 HU, respectively, using planning CT images after deformable registration as ground truth. Compared with CBCT, the thoracic and abdominal sCT images generated by each model had significantly improved image quality with smaller MAE (p < 0.05). The SARN+cycAT obtained the minimum MAEs of 42.5 HU in the thorax while SARN+cycleGAN got the minimum MAEs of 32.0 HU in the abdomen. The sCT generated by U-Net had a remarkably lower anatomical structure accuracy compared with the other models. The thoracic and abdominal sCT images generated by SARN+cycleGAN showed optimal dose calculation accuracy with gamma passing rates (2 mm/2%) of 98.2% and 96.9%, respectively. Conclusions: The proposed SARN can reduce serious streaking artifacts in CBCT images. The SARN combined with cycleGAN can generate highquality sCT images with fewer artifacts, high-accuracy HU values, and accurate anatomical structures, thus providing reliable dose calculation in ART. [ABSTRACT FROM AUTHOR]

Background and purpose: The aim was to investigate the characteristics of non‐stenotic intracranial plaque (NSIP) in embolic stroke of undetermined source (ESUS) subtypes by high‐resolution magnetic resonance imaging. Methods: Consecutive patients with ESUS who were mandatory for high‐resolution magnetic resonance imaging were retrospectively enrolled. Based on the location and arterial supply of the infarct, the ESUS were categorized into three types: cortical ESUS, subcortical ESUS and mixed ESUS. The NSIP parameters including plaque location, morphology (plaque distribution, remodeling index and plaque burden) and composition (thick fibrous cap, discontinuity of plaque surface, intraplaque hemorrhage and complicated plaque) were evaluated amongst the subtypes. Results: Of 243 patients, there were 87 (35.8%) cortical ESUS, 127 (52.3%) subcortical ESUS and 29 (11.9%) mixed ESUS. Significant differences were found in plaque location (p < 0.001), plaque quadrant (p < 0.001), remodeling index (p < 0.001), plaque burden (p < 0.001), discontinuity of plaque surface (p < 0.001), intraplaque hemorrhage (p = 0.001) and complicated plaque (p < 0.001) of ipsilateral NISP amongst the different ESUS subtypes, except for fibrous cap (p = 0.135). However, no differences were found amongst contralateral NISP. In addition, the clinical characteristics of the differences between ESUS subtypes were striking, including age (p = 0.004), initial National Institutes of Health Stroke Scale (p < 0.001), coronary artery disease (p = 0.039), serum urea (p = 0.011) and creatinine (p = 0.002). Conclusion: This is the first report of significantly heterogeneous characteristics of ipsilateral NSIP and clinical findings amongst ESUS subtypes, which may suggest their different underlying mechanisms. [ABSTRACT FROM AUTHOR]

Introduction: GDF15 may be a potential biomarker for neurodegenerative diseases. In this analysis, we aimed to quantitative analysis the levels of GDF15 in patients with neurological diseases and in health control, and then to determine its potential diagnostic utility. Methods: Two researchers separately conducted a systematic search of the relevant studies up to January 2021 in Embase, PubMed, and Web of Science. Effect sizes were estimated to use the standardized mean difference (SMD) with 95% confidence interval (CI). Sensitivity and specificity were calculated by the summary receiver operating characteristics curve (SROC) method. The sensitivity analysis was performed by the "one‐in/one‐out" approach. Considering the considerable heterogeneity among studies, random‐effects model was used for the meta‐analysis investigation. Results: A total of eight articles were included in this meta‐analysis and systematic review. The pooled results of the random effect model indicated GDF15 levels were significantly higher in patients with neurodegenerative disease than healthy people (SMD = 0.92, 95% CI: 0.44–1.40, Z = 3.75, p < 0.001). Sensitivity and specificity of biomarker of GDF15 were 0.90 (95% CI: 0.75–0.97), 0.77 (95% CI: 0.67–0.65), and AUC = 0.87 (95% CI: 0.84–0.90), respectively. Conclusions: GDF15 levels were higher in patients with neurodegenerative disease than healthy people. And serum levels of GDF15 were a better marker for diagnostic utility of neurodegenerative disease. [ABSTRACT FROM AUTHOR]

Summary: Improvement of ewe reproduction is considerable by appropriately increasing litter size and sustaining non‐seasonal breeding. However, their genetic makeups have not been entirely elucidated. Genome‐wide analyses of 821 individuals were performed by combining three genomic approaches (genome‐wide association study, XP‐nSL, and runs of homozygosity). Consequently, 35 candidate genes including three domestication genes (TSHR, GTF2A1, and KITLG) were identified. Other than the FecB mutation at BMPR1B, we described a significant association of a missense mutation rs406686139 at seasonal lambing‐associated TSHR gene with litter size. Some promising novel genes may be relevant for sheep reproduction by multitude biological processes, such as FETUB functioning in fertilization, HNRNPA1 in oogenesis, DCUN1D1 in spermatogenesis, and HRG in fertility outcome. The present study suggests that improvement of ewe reproduction is attributed to selective breeding, and casts light on the genetic basis and improvement of sheep reproduction. [ABSTRACT FROM AUTHOR]

The present study aimed to explore the potential hub genes and pathways of ischaemic cardiomyopathy (ICM) and to investigate the possible associated mechanisms. Two microarray data sets (GSE5406 and GSE57338) were downloaded from the Gene Expression Omnibus (GEO) database. The limma package was used to analyse the differentially expressed genes (DEGs). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, Disease Ontology (DO) and Gene Ontology (GO) annotation analyses were performed. A protein‐protein interaction (PPI) network was set up using Cytoscape software. Significant modules and hub genes were identified by the Molecular Complex Detection (MCODE) app. Then, further functional validation of hub genes in other microarrays and survival analysis were performed to judge the prognosis. A total of 1065 genes were matched, with an adjusted p < 0.05, and 17 were upregulated and 25 were downregulated with|log2 (fold change)|≥1.2. After removing the lengthy entries, GO identified 12 items, and 8 pathways were enriched at adjusted p < 0.05 (false discovery rate, FDR set at <0.05). Three modules with a score >8 after MCODE analysis and MYH6 were ultimately identified. When validated in GSE23561, MYH6 expression was lower in patients with CAD than in healthy controls (p < 0.05). GSE60993 data suggested that MYH6 expression was also lower in AMI patients (p < 0.05). In the GSE59867 data set, MYH6 expression was lower in CAD patients than in AMI patients and lower in heart failure (HF) patients than in non‐HF patients. However, there was no difference at different periods within half a year, and HF was increased when MYH6 expression was low (p < 0.05–0.01). We performed an integrated analysis and validation and found that MYH6 expression was closely related to ICM and HF. However, whether this marker can be used as a predictor in blood samples needs further experimental verification. [ABSTRACT FROM AUTHOR]

The intrinsic conflicts between mechanical performances and processability are main challenges to develop cost‐effective impact‐resistant materials from polymers and their composites. Herein, polyhedral oligomeric silsesquioxanes (POSSs) are integrated as side chains to the polymer backbones. The one‐dimension (1D) rigid topology imposes strong space confinements to realize synergistic interactions among POSS units, reinforcing the correlations among polymer chains. The afforded composites demonstrate unprecedented mechanical properties with ultra‐stretchability, high rate‐dependent strength, superior impact‐resistant capacity as well as feasible processability/recoverability. The hierarchical structures of the hybrid polymers enable the co‐existence of multiple dynamic relaxations that are responsible for fast energy dissipation and high mechanical strengths. The effective synergistic correlation strategy paves a new pathway for the design of advanced cluster‐based materials. [ABSTRACT FROM AUTHOR]

Objective: To explore the correlations between the habit of betel quid and areca nut (BQ‐AN) chewing and the prognosis of oral cancer (OC). Methods: We performed a systematic review and meta‐analysis to clarify this issue. Data searches were performed using PubMed, Web of Science, Epistemonikos, and Embase databases through November 2019. The primary outcome was the difference in the prognosis of OC between BQ‐AN chewers and non‐chewers, measured in terms of 5‐year overall survival (OS) and 5‐year disease‐specific survival (DSS) log (HR) reported in articles. The pooled HR with 95% CI of 5‐year OS and 5‐year DSS was calculated using a fixed‐effects model. Results: Ten articles with eleven OS or DSS survival studies (one of the articles contained two studies), which were published between 2003 and 2017, were eligible for inclusion in the present study. All the 11 studies were observational studies, among which 10 were retrospective and 1 was prospective. One study measured both OS and DSS. Eight studies, with a total of 2,761 patients, used 5‐year OS as the primary endpoint and four studies, with a total of 2,551 patients, used 5‐year DSS. Overall, the pooled HR evaluating BQ‐AN chewers was 1.26 (95% CI: 1.09–1.46) for 5‐year OS and 1.40 (95% CI: 1.15–1.70) for 5‐year DSS, compared with non‐chewers. There was a significant association between BQ‐AN chewing and OC survival. Conclusions: Betel quid and areca nut chewing is significantly associated with poor prognosis in patients with OC. [ABSTRACT FROM AUTHOR]

Background: Few studies have compared the etiology and clinical features between pure lateral medullary infarction (LMI) and pure medial medullary infarction (MMI). Methods: All patients included were hospitalized at The First Affiliated Hospital and The Second Affiliated Hospital of Wenzhou Medical University from January 2015 to July 2020. Their risk factors, clinical manifestation, stroke mechanisms and short‐term prognosis were analyzed retrospectively. Results: Among the 387 patients enrolled, 266 (68.7%) had LMI, 109 (28.2%) had MMI, and 12 (3.1%) (nine men and three women) had LMI plus MMI. We analyzed the 375 patients of LMI and MMI. The average ages of LMI and MMI were 59.4 years and 62.69 years, respectively. Univariate analysis and multivariable logistic regression was used to investigate the existing risk factors of MMI relative to LMI. Prior infarction, poor glycemic control, and atherosclerosis were more frequently associated with MMI than with LMI. The clinical manifestation was significantly different between LMI and MMI. We used modified Rankin Scale (mRS) score as the short‐term prognostic evaluation criteria, and MMI appeared worse than LMI. Conclusions: This study reveals that: (1) patients with MMI are older than those with LMI; (2) prior infarction, poor glycemic control, and atherosclerosis are independent risk factors of MMI than that of LMI; (3) the clinical manifestations of LMI and MMI are heterogeneous; (4) short‐term prognosis of MMI is worse than LMI. [ABSTRACT FROM AUTHOR]

Background The potential causes or sources of embolic stroke of undetermined source (ESUS) vary. This study aimed to investigate the main cause of deep ESUS by evaluating nonstenotic intracranial atherosclerotic plaque. Methods and Results We retrospectively screened consecutive patients with unilateral anterior circulation ESUS. After excluding the patients with possible embolism from an extracranial artery such as aortic arch plaque, carotid plaque, and so on, the enrolled patients with ESUS were categorized into 2 groups: deep ESUS and cortical with/without deep ESUS. All patients underwent intracranial high-resolution magnetic resonance imaging to assess the characteristics of nonstenotic intracranial atherosclerotic plaque. Biomarkers of atrial cardiopathy (ie, P-wave terminal force in lead V1 on ECG, NT-proBNP [N-terminal pro-brain natriuretic peptide] and left atrial diameter) were collected. A total of 155 patients with ipsilateral nonstenotic intracranial atherosclerotic plaque were found, with 76 (49.0%) in deep ESUS and 79 (51.0%) in cortical with/without deep ESUS. We found more prevalent plaque in the M1 segment of the middle cerebral artery and the ostia of the perforator, with a smaller remodeling index plaque burden, and less frequent occurrence of complicated plaque in deep ESUS versus cortical with/without deep ESUS. Higher BNP (brain natriuretic peptide) levels and a higher prevalence of atrial cardiopathy in cortical with/without deep ESUS versus deep ESUS. Moreover, the discrimination of vulnerable plaque for predicting ESUS was significantly enhanced after adjusting for or further excluding patients with deep ESUS. Conclusions The current study provides the first high-resolution magnetic resonance imaging evidence that cortical with/without deep ESUS and deep ESUS should be 2 distinct entities and that atherosclerosis, not embolism, might be the main cause of deep ESUS.