Sex-Specific Risk Factors and Clinical Dementia Outcomes for White Matter Hyperintensities in a large South Korean Cohort.

Objective: White matter hyperintensities (WMH) on brain MRI images are the most common feature of cerebral small vessel disease (CSVD). Studies have yielded divergent findings on the modifiable risk factors for WMH and WMH's impact on cognitive decline. Mounting evidence suggests sex differences in WMH burden and subsequent effects on cognition. Thus, we aimed to identify sex-specific modifiable risk factors for WMH. We then explored whether there were sex-specific associations of WMH to longitudinal clinical dementia outcomes. Methods: Participants aged 49-89 years were recruited at memory clinics and underwent a T2-weighted fluid-attenuated inversion recovery (FLAIR) 3T MRI scan to measure WMH volume. Participants were then recruited for two additional follow-up visits, 1-2 years apart, where clinical dementia rating sum of boxes (CDR-SB) scores were measured. We first explored which known modifiable risk factors for WMH were significant when tested for a sex-interaction effect. We additionally tested which risk factors were significant when stratified by sex. We then tested to see whether WMH is longitudinally associated with clinical dementia that is sex-specific. Results: The study utilized data from 713 participants (241 males, 472 females) with a mean age of 72.3 years and 72.8 years for males and females, respectively. 57.3% and 59.5% of participants were diagnosed with mild cognitive impairment (MCI) for males and females, respectively. 40.7% and 39.4% were diagnosed with dementia for males and females, respectively. Of the 713 participants, 181 participants had CDR-SB scores available for three longitudinal time points. Compared to males, females showed stronger association of age to WMH volume. Type 2 Diabetes was associated with greater WMH burden in females but not males. Finally, baseline WMH burden was associated with worse clinical dementia outcomes longitudinally in females but not in males. Discussion: Elderly females have an accelerated increase in cerebrovascular burden as they age, and subsequently are more vulnerable to clinical dementia decline due to CSVD. Additionally, females are more susceptible to the cerebrovascular consequences of diabetes. These findings emphasize the importance of considering sex when examining the consequences of CSVD. Future research should explore the underlying mechanisms driving these sex differences and personalized prevention and treatment strategies. Clinical trial registration: The BICWALZS is registered in the Korean National Clinical Trial Registry (Clinical Research Information Service; identifier, KCT0003391). Registration Date 2018/12/14.

Behavior of Extracranial-to-Intracranial Extended Arterial Dissections of the Vertebral Artery.

BACKGROUND: Vertebral artery dissections (VADs) may extend from the extracranial to the intracranial vasculature (e+iVAD). We evaluated how the characteristics of e+iVAD differed from those of intracranial VAD (iVAD). METHODS AND RESULTS: From 2002 to 2019, among consecutive patients with cervicocephalic dissection, those with iVAD and e+iVAD were included, and their clinical characteristics were compared. In patients with unruptured dissections, a composite clinical outcome of subsequent ischemic events, subsequent hemorrhagic stroke, or mortality was evaluated. High-resolution magnetic resonance images were analyzed to evaluate intracranial remodeling index. Among 347 patients, 51 (14.7%) had e+iVAD and 296 (85.3%) had iVAD. The hemorrhagic presentation occurred solely in iVAD (0.0% versus 19.3%), whereas e+iVAD exhibited higher ischemic presentation (84.3% versus 27.4%; P<0.001). e+iVAD predominantly presented steno-occlusive morphology (88.2% versus 27.7%) compared with dilatation patterns (11.8% versus 72.3%; P<0.001) of iVAD. The ischemic presentation was significantly associated with e+iVAD (iVAD as a reference; adjusted odds ratio, 3.97 [95% CI, 1.67-9.45]; P=0.002]). Patients with unruptured VAD showed no differences in the rate of composite clinical outcome between the groups (log-rank, P=0.996). e+iVAD had a lower intracranial remodeling index (1.4±0.3 versus 1.6±0.4; P<0.032) and a shorter distance from dural entry to the maximal dissecting segment (6.9±8.4 versus 15.7±7.4; P<0.001). CONCLUSIONS: e+iVAD is associated with lower rates of hemorrhages and higher rates of ischemia than iVAD at the time of admission. This may be explained by a lower intracranial remodeling index and less deep intrusion of the dissecting segment into the intracranial space.

The safety and efficacy of intra-arterial low-dose tirofiban administration during endovascular therapy in patients with large ischemic core volume.

This study aimed to evaluate the safety and efficacy of intra-arterial (IA) administration of low- dose tirofiban during endovascular therapy in patients with large ischemic core volumes on initial brain CT. Patients were divided into two groups based on the use of IA tirofiban. We identified 87 patients (16 and 71 patients in the tirofiban and no-tirofiban groups, respectively) with acute ischemic stroke due to intracranial artery occlusion who underwent endovascular therapy with a low Alberta Stroke Program Early CT scores (2-5). Multivariate logistic regression analysis revealed no association between IA tirofiban administration and serious postprocedural hemorrhagic complications (adjusted odds ratio (aOR), 0.720; 95% confidence interval (CI) 0.099-5.219; p = 0.960), any radiologic hemorrhage (aOR 0.076; 95% CI 0.003-2.323; p = 0.139), or 3-month mortality (aOR, 0.087; 95% CI 0.005-1.501; p = 0.093). However, IA tirofiban was associated with a lower 90-day mRS score (aOR, 0.197; 95% CI 0.015-1.306; p = 0.017) and change of NIHSS compared with baseline (aOR, 0.698; 95% CI 0.531-0.917; p = 0.010). IA tirofiban administration during endovascular therapy in patients with large ischemic core volumes may be effective and safe.

Prediction of Intracranial Atherosclerotic Disease-Related Large-Vessel Occlusion Stroke on the Basis of Novel Cerebral Blood Volume Parameters.

BACKGROUND: Mechanical thrombectomy is an effective treatment method for large-vessel occlusion stroke (LVOS); however, it has limited efficacy for intracranial atherosclerotic disease (ICAD)-related LVOS. We investigated the use of cerebral blood volume (CBV) maps for identifying ICAD as the underlying cause of LVOS before the initiation of endovascular treatment (EVT). METHODS AND RESULTS: We reviewed clinical and imaging data from patients who presented with LVOS and underwent endovascular treatment between January 2011 and May 2021. The CBV patterns were analyzed to identify an increase in CBV within the hypoperfused area and estimate infarct patterns within the area of decreased CBV. Comparisons were made between the patients with an increase in CBV and those without, and among the estimated infarct patterns: territorial, cortical wedge, basal ganglia-only, subcortical, and normal CBV. Overall, 243 patients were included. CBV increase in the hypoperfused area was observed in 23.5% of patients. A significantly higher proportion of ICAD was observed in those with increased CBV than in those without (56.4% versus 19.8%; P<0.001). Regarding the estimated infarct patterns on the CBV, ICAD was most frequently observed in the normal CBV group (territorial, 14.9%; cortical wedge, 10.0%; basal ganglia-only, 43.8%; subcortical, 35.7%; normal, 61.7%). CBV parameters, including "an increase in CBV," "normal CBV infarct pattern," and "an increase in CBV or normal CBV infarct pattern composite," were independently associated with ICAD. CONCLUSIONS: An increased CBV or normal CBV pattern may be associated with ICAD LVOS on the pretreatment perfusion imaging.

Higher HbA1c Is Associated With Greater 2-Year Progression of White Matter Hyperintensities.

White matter hyperintensity (WMH) lesions on brain MRI images are surrogate markers of cerebral small vessel disease. Longitudinal studies examining the association between diabetes and WMH progression have yielded mixed results. Thus, in this study, we investigated the association between HbA1c, a biomarker for the presence and severity of hyperglycemia, and longitudinal WMH change after adjusting for known risk factors for WMH progression. We recruited 64 participants from South Korean memory clinics to undergo brain MRI at the baseline and a 2-year follow-up. We found the following. First, higher HbA1c was associated with greater global WMH volume (WMHV) changes after adjusting for known risk factors (ß = 7.7 × 10-4; P = 0.025). Second, the association between baseline WMHV and WMHV progression was only significant at diabetic levels of HbA1c (P < 0.05, when HbA1c >6.51%), and non-apolipoprotein E (APOE) ε4 carriers had a stronger association between HbA1c and WMHV progression (ß = -2.59 × 10-3; P = 0.004). Third, associations of WMHV progression with HbA1c were particularly apparent for deep WMHV change (ß = 7.17 × 10-4; P < 0.01) compared with periventricular WMHV change and, for frontal (ß = 5.00 × 10-4; P < 0.001) and parietal (ß = 1.53 × 10-4; P < 0.05) lobes, WMHV change compared with occipital and temporal WMHV change. In conclusion, higher HbA1c levels were associated with greater 2-year WMHV progression, especially in non-APOE ε4 participants or those with diabetic levels of HbA1c. These findings demonstrate that diabetes may potentially exacerbate cerebrovascular and white matter disease.

Significance of headache in intracranial vertebrobasilar artery dissections: an observational study.

Headache may represent acute phase of intracranial vertebrobasilar artery dissection (iVBAD). We aimed to evaluate its clinical significance in iVBAD. Consecutive acute iVBAD patients were grouped into ruptured iVBAD, unruptured iVBAD with no headache, isolated headache, or concurrent headache with neurological symptoms. Composite hemorrhagic/ischemic endpoints, and dynamic arterial changes were graded. Clinical characteristics of the four groups, and association between headache and composite outcomes was evaluated. Headaches were precedent in 79% of the ruptured iVBAD patients (maximal delay, 10D). In unruptured iVBAD, when patients with no headache (N = 69), concurrent headache (N = 111), and isolated headache (N = 126) were compared, concurrent headache was associated with ischemic endpoints (isolated headache as reference, adjusted odds ratio: 6.40, 95% confidence interval [2.03-20.19]). While there were no differences in hemorrhagic endpoints, dynamic arterial changes were higher in the isolated headache group (aOR: 3.98, 95% CI [1.72-9.18]) but not for the concurrent headache group (aOR: 1.59 [0.75-3.38]) compared to no headache group. Headache was more commonly severe (48.4% vs. 17.3%, p < 0.001) and ipsilateral (59.7% vs. 45.5%, p = 0.03) for isolated headache compared to concurrent headache, indicating a higher causal relationship. In iVBAD, isolated headache may be considered an acute-phase biomarker, associated with dynamic arterial changes.

Deep learning based automatic detection algorithm for acute intracranial haemorrhage: a pivotal randomized clinical trial.

Acute intracranial haemorrhage (AIH) is a potentially life-threatening emergency that requires prompt and accurate assessment and management. This study aims to develop and validate an artificial intelligence (AI) algorithm for diagnosing AIH using brain-computed tomography (CT) images. A retrospective, multi-reader, pivotal, crossover, randomised study was performed to validate the performance of an AI algorithm was trained using 104,666 slices from 3010 patients. Brain CT images (12,663 slices from 296 patients) were evaluated by nine reviewers belonging to one of the three subgroups (non-radiologist physicians, n = 3; board-certified radiologists, n = 3; and neuroradiologists, n = 3) with and without the aid of our AI algorithm. Sensitivity, specificity, and accuracy were compared between AI-unassisted and AI-assisted interpretations using the chi-square test. Brain CT interpretation with AI assistance results in significantly higher diagnostic accuracy than that without AI assistance (0.9703 vs. 0.9471, p < 0.0001, patient-wise). Among the three subgroups of reviewers, non-radiologist physicians demonstrate the greatest improvement in diagnostic accuracy for brain CT interpretation with AI assistance compared to that without AI assistance. For board-certified radiologists, the diagnostic accuracy for brain CT interpretation is significantly higher with AI assistance than without AI assistance. For neuroradiologists, although brain CT interpretation with AI assistance results in a trend for higher diagnostic accuracy compared to that without AI assistance, the difference does not reach statistical significance. For the detection of AIH, brain CT interpretation with AI assistance results in better diagnostic performance than that without AI assistance, with the most significant improvement observed for non-radiologist physicians.

Comparative and expression analyses of AP2/ERF genes reveal copy number expansion and potential functions of ERF genes in Solanaceae.

BACKGROUND: The AP2/ERF gene family is a superfamily of transcription factors that are important in the response of plants to abiotic stress and development. However, comprehensive research of the AP2/ERF genes in the Solanaceae family is lacking. RESULTS: Here, we updated the annotation of AP2/ERF genes in the genomes of eight Solanaceae species, as well as Arabidopsis thaliana and Oryza sativa. We identified 2,195 AP2/ERF genes, of which 368 (17%) were newly identified. Based on phylogenetic analyses, we observed expansion of the copy number of these genes, especially those belonging to specific Ethylene-Responsive Factor (ERF) subgroups of the Solanaceae. From the results of chromosomal location and synteny analyses, we identified that the AP2/ERF genes of the pepper (Capsicum annuum), the tomato (Solanum lycopersicum), and the potato (Solanum tuberosum) belonging to ERF subgroups form a tandem array and most of them are species-specific without orthologs in other species, which has led to differentiation of AP2/ERF gene repertory among Solanaceae. We suggest that these genes mainly emerged through recent gene duplication after the divergence of these species. Transcriptome analyses showed that the genes have a putative function in the response of the pepper and tomato to abiotic stress, especially those in ERF subgroups. CONCLUSIONS: Our findings will provide comprehensive information on AP2/ERF genes and insights into the structural, evolutionary, and functional understanding of the role of these genes in the Solanaceae.

Glymphatic system evaluation using diffusion tensor imaging in patients with traumatic brain injury.

PURPOSE: Glymphatic system dysfunction has been reported in animal models of traumatic brain injury (TBI). This study aimed to evaluate the activity of the human glymphatic system using the non-invasive Diffusion Tensor Image-Analysis aLong the Perivascular Space (DTI-ALPS) method in patients with TBI. METHODS: A total of 89 patients with TBI (June 2018 to May 2020) were retrospectively enrolled, and 34 healthy volunteers were included who had no previous medical or neurological disease. Magnetic resonance imaging (MRI) with DTI was performed, and the ALPS index was calculated to evaluate the glymphatic system's activity. Wilcoxon rank-sum test was used to compare the ALPS index between patients with TBI and healthy controls. ANOVA was done to compare the ALPS index among controls and patients with mild/moderate-to-severe TBI. Multivariate logistic regression analyses were used to identify independent clinical and radiological factors associated with the ALPS index. The correlation between Glasgow Coma Scale (GCS) score and the ALPS index was also assessed. RESULTS: The ALPS index was significantly lower in patients with TBI than in healthy controls (median, 1.317 vs. 1.456, P < 0.0001). There were significant differences in the ALPS index between healthy controls and patients with mild/moderate-to-severe TBI (ANOVA, P < 0.001). The presence of subarachnoid hemorrhage (P = 0.004) and diffuse axonal injury (P = 0.001) was correlated with a lower ALPS index in the multivariate analysis. There was a weak positive correlation between the ALPS index and GCS scores (r = 0.242, P = 0.023). CONCLUSIONS: The DTI-ALPS method is useful for evaluating glymphatic system impairment and quantifying its activity in patients with TBI.

Angiographic tapering sign as a surrogate marker for large vessel occlusion due to intracranial atherosclerotic stenosis and its clinical implication: a retrospective matched case-control study.

BACKGROUND: The purpose of this study was to investigate whether the initial DSA appearance of the occlusion during mechanical thrombectomy (MT) can help distinguish the nature of the underlying lesion and predict radiological and clinical outcomes. METHODS: We retrospectively reviewed cases of patients with acute ischemic stroke who underwent MT for anterior circulation occlusion between March 2017 and February 2020. Underlying intracranial atherosclerotic stenosis (ICAS) was determined based on the presence of fixed stenosis after endovascular treatment. Patients were categorized based on the appearance of the occlusion observed in the initial DSA as tapering sign (+) or (-) groups. We performed 1:2 propensity score matching to establish a proper control group among the tapering sign (-) group. We analyzed and compared baseline characteristics and clinical outcomes between the two groups. RESULTS: A total of 293 patients (tapering sign (+), n=47; tapering sign (-), n=246) were included in the analysis. The procedure time of MT was significantly longer for the tapering sign (+) group, and the successful recanalization rate after MT was significantly lower in the tapering sign (+) group than in the tapering sign (-) group. Logistic regression showed that ICAS-related occlusion was strongly associated with a positive angiographic tapering sign, and the angiographic tapering sign was a negative factor for the first-pass effect during MT. However, a 3-month good functional outcome was not significantly associated with the angiographic tapering sign. CONCLUSIONS: The tapering sign on the initial DSA could be a surrogate marker for ICAS-related occlusion and procedural difficulty. However, its clinical significance remains unclear.

Bioelectrical Impedance Analysis Can Be an Effective Tool for Screening Fatty Liver in Patients with Suspected Liver Disease.

Background and study aims: Although abdominal ultrasound (USG) or controlled attenuation parameter (CAP) score of transient elastography (TE) is recommended for the diagnosis of fatty liver, issues regarding cost and accessibility still exist. The aim of this study was to evaluate if bioelectrical impedance analysis (BIA) can be used as a reliable screening tool for fatty liver. Patients and methods: A total of 249 patients who underwent all three tests including TE, BIA, and USG were enrolled. The correlation between fat mass measured by BIA, CAP score of TE, and fatty liver grade measured by USG was analyzed. In addition, the cut-off value of BIA which can predict the fatty liver grade was calculated. Results: Fat mass index (FMI) assessed by BIA increased significantly along with the rise in fatty liver grade measured by USG (normal: 6.2 ± 2.4, Gr I: 8.0 ± 3.7, Gr II: 10.6 ± 3.5, Gr III: 10.7 ± 3.7 kg/m2, p < 0.001). In addition, a positive correlation was found between the CAP score of TE and the FMI of BIA. Additionally, a total body fat mass increase by 24.3% or 29.8% in men and 34.8% or 35.1% in women increased the possibility of developing any grade of fatty liver or significant fatty liver (≥Gr II fatty liver), respectively. Conclusion: The total fat or fat mass index of BIA was related to fatty liver as assessed by ultrasound or CAP score, and area under the receiver operating characteristic (AUROC) was about 0.8. Thus, BIA can be used as a screening tool for fatty liver in patients with suspected liver disease.

Influence of endothelial function and arterial stiffness on the behavior of cervicocephalic arterial dissections: An observational study.

Background: The mechanical and physiological properties of the arterial wall might affect the behavior of spontaneous cervicocephalic arterial dissections (CCAD). We aimed to determine the effects of endothelial function and arterial stiffness on the clinical characteristics and outcomes of CCAD using brachial flow-mediated dilation (FMD) and brachial-ankle pulse wave velocity (PWV). Methods: From a single-center database, we identified patients admitted from April 2011 to December 2021 with a diagnosis of CCAD who underwent both FMD and PWV. FMD was classified as normal and decreased according to institutional thresholds. PWV was categorized into tertiles. Comparative and multivariable analyses were performed to determine the effects of FMD and PWV values on major clinical outcomes. Results: A total of 146 patients (age: 47 ± 11 years; men: 77.4%) were included. The main presentation was ischemic stroke in 76.7% of the patients, while 23.3% presented with headache or other symptoms. Healing of the dissection was observed in 55.8%. In multivariable analysis, Normal FMD levels (vs. decreased; adjusted OR: 4.52, 95% CI [1.95 -10.52]) were associated with spontaneous healing of the dissection. Highest PWV tertile (vs. lowest; adjusted OR: 17.05, 95% CI [3.07-94.82]) was associated with ischemic presentation. There was a higher ischemic stroke recurrence in the 3rd PWV tertile, and more frequent aneurysmal enlargement in the lowest PWV tertile, but their frequency was low, precluding multivariable analysis. Conclusion: In spontaneous CCAD, preserved endothelial function was associated with spontaneous arterial healing. Arterial stiffness is associated with ischemic presentation.

Two different domain architectures generate structural and functional diversity among bZIP genes in the Solanaceae family.

The bZIP gene family is one of the largest transcription factor families and has important roles in plant growth, development, and stress responses. However, bZIP genes in the Solanaceae family have not been extensively investigated. Here, we conducted genome-wide re-annotation in nine Solanaceae species and Arabidopsis thaliana. We annotated 935 bZIP genes, including 107 (11%) that were newly identified. Structural analyses of bZIP genes in the Solanaceae family revealed that the bZIP domain displayed two types of architectures depending on the presence of an additional domain, suggesting that these architectures generate diversified structures and functions. Motif analyses indicated that the two types of bZIP genes had distinct sequences adjacent to the bZIP domain. Phylogenetic analyses suggested that the two types of bZIP genes distinctly evolved and ultimately adapted in different lineages. Transcriptome analyses in pepper (Capsicum annuum) and tomato (Solanum lycopersicum) revealed putative functional diversity between the two types of bZIP genes in response to various abiotic stresses. This study extensively updated bZIP gene family annotations and provided novel evolutionary and functional evidence for the role of bZIP genes in Solanaceae plants. Our findings provide evolutionary and functional characteristics of bZIP genes for a better understanding of their roles in Solanaceae plants.

Independent replication of advanced brain age in mild cognitive impairment and dementia: detection of future cognitive dysfunction.

We previously developed a novel machine-learning-based brain age model that was sensitive to amyloid. We aimed to independently validate it and to demonstrate its utility using independent clinical data. We recruited 650 participants from South Korean memory clinics to undergo magnetic resonance imaging and clinical assessments. We employed a pretrained brain age model that used data from an independent set of largely Caucasian individuals (n = 757) who had no or relatively low levels of amyloid as confirmed by positron emission tomography (PET). We investigated the association between brain age residual and cognitive decline. We found that our pretrained brain age model was able to reliably estimate brain age (mean absolute error = 5.68 years, r(650) = 0.47, age range = 49-89 year) in the sample with 71 participants with subjective cognitive decline (SCD), 375 with mild cognitive impairment (MCI), and 204 with dementia. Greater brain age was associated with greater amyloid and worse cognitive function [Odds Ratio, (95% Confidence Interval {CI}): 1.28 (1.06-1.55), p = 0.030 for amyloid PET positivity; 2.52 (1.76-3.61), p < 0.001 for dementia]. Baseline brain age residual was predictive of future cognitive worsening even after adjusting for apolipoprotein E e4 and amyloid status [Hazard Ratio, (95% CI): 1.94 (1.33-2.81), p = 0.001 for total 336 follow-up sample; 2.31 (1.44-3.71), p = 0.001 for 284 subsample with baseline Clinical Dementia Rating ≤ 0.5; 2.40 (1.43-4.03), p = 0.001 for 240 subsample with baseline SCD or MCI]. In independent data set, these results replicate our previous findings using this model, which was able to delineate significant differences in brain age according to the diagnostic stages of dementia as well as amyloid deposition status. Brain age models may offer benefits in discriminating and tracking cognitive impairment in older adults.

Diagnostic usefulness of cone-beam computed tomography versus multi-detector computed tomography for sinonasal structure evaluation.

Objective: Cone-beam computed tomography (CBCT) is a promising imaging modality for sinonasal evaluation, with advantages of relatively low radiation dose, low cost, and quick outpatient imaging. Our study aimed to compare the diagnostic performance and image quality of CBCT with those of multi-detector computed tomography (MDCT) with different slice thickness. Methods: We retrospectively reviewed 60 consecutive patients who had undergone both CBCT and MDCT. MDCT images was reconstructed with 1 and 3 mm slice thickness. The quantitative image quality parameters (image noise, signal-to-noise ratio [SNR], and contrast-to noise ratio [CNR] were calculated and compared between the two imaging modalities. Two observers (ENT surgeon and neuroradiologist) evaluated the presence of seven sinonasal anatomic variations in each patient and interobserver agreements were analyzed. The diagnostic performance of CBCT (0.3 mm) and MDCT (3 mm) was assessed and compared with that of high resolution MDCT (1 mm), which is considered as the gold standard. Results: The image noise was significantly higher and SNR and CNR values were lower in the CBCT (0.3 mm) group than in the MDCT groups (1 and 3 mm). The diagnostic performance of CBCT (0.3 mm) was similar to that of MDCT (1 mm) and superior to that of MDCT (3 mm). The highest interobserver agreement was for high resolution MDCT (1 mm), followed by CBCT (0.3 mm), and MDCT (3 mm). Conclusion: Considering its low radiation dose, low cost, and ease of clinical access, CBCT may be a useful imaging modality for as first line sinonasal evaluation and repeated follow up.Study design: Retrospective study in a tertiary referral university center.Level of evidence: NA.

Structural covariance changes in major cortico-basal ganglia and thalamic networks in amyloid-positive patients with white matter hyperintensities.

Synergistic effects of amyloid deposition and cerebral small vessel disease (CSVD) on the systematic disruption of large-scale brain anatomical organization are not well known. We investigated the brain structural covariance network (SCN) in 245 cognitively impaired older adults with the information of amyloid deposition and CSVD represented by white matter hyperintensities (WMH). We stratified the participants into 4 groups based on amyloid burden (A+/A -) and WMH severity (W+/W-). Using source-based morphometry analysis, we selected 13 independent components (ICs) in functional brain networks. SCNs between ICs were defined using Pearson correlations between individual weights; SCNs of the A+W+ group were compared with those of other groups using Fisher's r-to-z transformation. Our results revealed that SCN characteristics related to amyloid burden with CSVD could be represented by decreased intra- and increased cortico-subcortical inter-network connectivity in the salience (SN) and default mode networks (DMN), decreased cortico-subcortical internetwork connectivity in the central executive network (CEN), and altered internetwork connectivity among DMN-SN-CEN. Amyloid deposition and CSVD maybe associated with altered connectivity in structural networks in the brain and should be considered when assessing network disruption.

Influence of cerebral microbleeds on mechanical thrombectomy outcomes.

In ischemic stroke patients undergoing endovascular treatment (EVT), we aimed to test the hypothesis that cerebral microbleeds (CMBs) are associated with clinical outcomes, while estimating the mediating effects of hemorrhagic transformation (HT), small-vessel disease burden (white matter hyperintensities, WMH), and procedural success. From a multicenter EVT registry, patients who underwent pretreatment MR imaging were analyzed. They were trichotomized according to presence of CMBs (none vs. 1-4 vs. ≥ 5). The association between CMB burden and 3-month mRS was evaluated using multivariable ordinal logistic regression, and mediation analyses were conducted to estimate percent mediation. Of 577 patients, CMBs were present in 91 (15.8%); 67 (11.6%) had 1-4 CMBs, and 24 (4.2%) had ≥ 5. Increases in CMBs were associated with hemorrhagic complications (ß = 0.27 [0.06-0.047], p = 0.010) in multivariable analysis. The CMB effect on outcome was partially mediated by post-procedural HT degree (percent mediation, 14% [0-42]), WMH (23% [7-57]) and lower rates of successful reperfusion (6% [0-25]). In conclusion, the influence of CMBs on clinical outcomes is mediated by small-vessel disease burden, post-procedural HT, and lower reperfusion rates, listed in order of percent mediation size.

De novo phasing resolves haplotype sequences in complex plant genomes.

Genome phasing is a recently developed assembly method that separates heterozygous eukaryotic genomic regions and builds haplotype-resolved assemblies. Because differences between haplotypes are ignored in most published de novo genomes, assemblies are available as consensus genomes consisting of haplotype mixtures, thus increasing the need for genome phasing. Here, we review the operating principles and characteristics of several freely available and widely used phasing tools (TrioCanu, FALCON-Phase, and ALLHiC). An examination of downstream analyses using haplotype-resolved genome assemblies in plants indicated significant differences among haplotypes regarding chromosomal rearrangements, sequence insertions, and expression of specific alleles that contribute to the acquisition of the biological characteristics of plant species. Finally, we suggest directions to solve addressing limitations of current genome-phasing methods. This review provides insights into the current progress, limitations, and future directions of de novo genome phasing, which will enable researchers to easily access and utilize genome-phasing in studies involving highly heterozygous complex plant genomes.

Baseline Clinical and Biomarker Characteristics of Biobank Innovations for Chronic Cerebrovascular Disease With Alzheimer's Disease Study: BICWALZS.

OBJECTIVE: We aimed to present the study design and baseline cross-sectional participant characteristics of biobank innovations for chronic cerebrovascular disease with Alzheimer's disease study (BICWALZS) participants. METHODS: A total of 1,013 participants were enrolled in BICWALZS from October 2016 to December 2020. All participants underwent clinical assessments, basic blood tests, and standardized neuropsychological tests (n=1,013). We performed brain magnetic resonance imaging (MRI, n=817), brain amyloid positron emission tomography (PET, n=713), single nucleotide polymorphism microarray chip (K-Chip, n=949), locomotor activity assessment (actigraphy, n=200), and patient-derived dermal fibroblast sampling (n=175) on a subset of participants. RESULTS: The mean age was 72.8 years, and 658 (65.0%) were females. Based on clinical assessments, total of 168, 534, 211, 80, and 20 had subjective cognitive decline, mild cognitive impairment (MCI), Alzheimer's dementia, vascular dementia, and other types of dementia or not otherwise specified, respectively. Based on neuroimaging biomarkers and cognition, 199, 159, 78, and 204 were cognitively normal (CN), Alzheimer's disease (AD)-related cognitive impairment, vascular cognitive impairment, and not otherwise specified due to mixed pathology (NOS). Each group exhibited many differences in various clinical, neuropsychological, and neuroimaging results at baseline. Baseline characteristics of BICWALZS participants in the MCI, AD, and vascular dementia groups were generally acceptable and consistent with 26 worldwide dementia cohorts and another independent AD cohort in Korea. CONCLUSION: The BICWALZS is a prospective and longitudinal study assessing various clinical and biomarker characteristics in older adults with cognitive complaints. Details of the recruitment process, methodology, and baseline assessment results are described in this paper.

Development and Validation of the Radiology Common Data Model (R-CDM) for the International Standardization of Medical Imaging Data.

PURPOSE: Digital Imaging and Communications in Medicine (DICOM), a standard file format for medical imaging data, contains metadata describing each file. However, metadata are often incomplete, and there is no standardized format for recording metadata, leading to inefficiency during the metadata-based data retrieval process. Here, we propose a novel standardization method for DICOM metadata termed the Radiology Common Data Model (R-CDM). MATERIALS AND METHODS: R-CDM was designed to be compatible with Health Level Seven International (HL7)/Fast Healthcare Interoperability Resources (FHIR) and linked with the Observational Medical Outcomes Partnership (OMOP)-CDM to achieve a seamless link between clinical data and medical imaging data. The terminology system was standardized using the RadLex playbook, a comprehensive lexicon of radiology. As a proof of concept, the R-CDM conversion process was conducted with 41.7 TB of data from the Ajou University Hospital. The R-CDM database visualizer was developed to visualize the main characteristics of the R-CDM database. RESULTS: Information from 2801360 cases and 87203226 DICOM files was organized into two tables constituting the R-CDM. Information on imaging device and image resolution was recorded with more than 99.9% accuracy. Furthermore, OMOP-CDM and R-CDM were linked to efficiently extract specific types of images from specific patient cohorts. CONCLUSION: R-CDM standardizes the structure and terminology for recording medical imaging data to eliminate incomplete and unstandardized information. Successful standardization was achieved by the extract, transform, and load process and image classifier. We hope that the R-CDM will contribute to deep learning research in the medical imaging field by enabling the securement of large-scale medical imaging data from multinational institutions.