Association of Mismatch Profiles and Clinical Outcome from Endovascular Therapy in Large Infarct: A Post-Hoc Analysis of the ANGEL-ASPECT Trial.

OBJECTIVES: We investigated whether patients with large infarct and the presence or absence of perfusion mismatch are associated with endovascular treatment benefit. METHODS: This is a post-hoc analysis of the Endovascular Therapy in Anterior Circulation Large Vessel Occlusion with a Large Infarct (ANGEL-ASPECT) randomized trial, which enrolled patients within 24 hours of onset with ASPECTS 3 to 5 or ASPECTS 0 to 2 with an infarct core 70 to 100 ml. Mismatch ratio was defined as time-to-maximum (Tmax) >6 s cerebral volume/ischemic core volume, and mismatch volume was defined as Tmax >6 s volume minus ischemic core volume. We divided patients into mismatch ratio ≥1.2 and mismatch volume ≥10 ml, and mismatch ratio ≥1.8 and mismatch volume ≥15 ml groups. The primary outcome was the 90-day modified Rankin Scale score ordinal distribution. Safety outcomes were symptomatic intracranial hemorrhage and 90-day mortality. RESULTS: There were 425 patients included. In both the mismatch ratio ≥1.2 and mismatch volume ≥10 ml (mismatch+, n = 395; mismatch-, n = 31) and mismatch ratio ≥1.8 and mismatch volume ≥15 ml groups (mismatch+, n = 346; mismatch-, n = 80), better 90-day modified Rankin Scale outcomes were found in the endovascular treatment group compared with the MM group (4 [2-5] vs 4 [3-5], common odds ratio [cOR], 1.9, 95% confidence interval [CI] 1.3-2.7, p = 0.001; 4 [2-5] vs 4 [3-5], cOR, 1.9, 95% CI 1.3-2.8, p = 0.001, respectively), but not in patients without mismatch ratio ≥1.2 and mismatch volume ≥10 ml (5 [3-6] vs 5 [4-6], cOR, 1.2, 95% CI 0.3-4.1, p = 0.83), and mismatch ratio ≥1.8 and mismatch volume ≥15 ml (4 [3-6] vs 5 [3-6], cOR, 1.2, 95% CI 0.6-2.7, p = 0.60). However, no interaction effect was found in both subgroups (p interaction >0.10). CONCLUSION: Endovascular treatment was more efficacious than MM in patients with mismatch profiles, but no treatment effect or interaction was noted in the no mismatch profile patients. However, the small sample size of patients with no mismatch may have underpowered our analysis. A pooled analysis of large core trials stratified by mismatch is warranted. ANN NEUROL 2024.

Association of Mean Upper Cervical Spinal Cord Cross-Sectional Area With Cerebral Small Vessel Disease: A Community-Based Cohort Study.

BACKGROUND: The purpose of this study was to investigate the association between the mean upper cervical spinal cord cross-sectional area (MUCCA) and the risk and severity of cerebral small vessel disease (CSVD). METHODS: Community-dwelling residents in Lishui City, China, from the cross-sectional survey in the PRECISE cohort study (Polyvascular Evaluation for Cognitive Impairment and Vascular Events) conducted from 2017 to 2019. We included 1644 of 3067 community-dwelling adults in the PRECISE study after excluding those with incorrect, incomplete, insufficient, or missing clinical or imaging data. Total and modified total CSVD scores, as well as magnetic resonance imaging features, including white matter hyperintensity, lacunes, cerebral microbleeds, enlarged perivascular spaces, and brain atrophy, were assessed at the baseline. The Spinal Cord Toolbox was used to measure the upper cervical spinal cord cross-sectional area of the C1 to C3 segments of the spinal cord and its average value was taken as MUCCA. Participants were divided into 4 groups according to quartiles of MUCCA. Associations were analyzed using linear regression models adjusted for age, sex, current smoking and drinking, medical history, intracranial volume, and total cortical volume. RESULTS: The means±SD age of the participants was 61.4±6.5 years, and 635 of 1644 participants (38.6%) were men. The MUCCA was smaller in patients with CSVD than those without CSVD. Using the total CSVD score as a criterion, the MUCCA was 61.78±6.12 cm2 in 504 of 1644 participants with CSVD and 62.74±5.94 cm2 in 1140 of 1644 participants without CSVD. Using the modified total CSVD score, the MUCCA was 61.81±6.04 cm2 in 699 of 1644 participants with CSVD and 62.91±5.94 cm2 in 945 of 1644 without CSVD. There were statistical differences between the 2 groups after adjusting for covariates in 3 models. The MUCCA was negatively associated with the total and modified total CSVD scores (adjusted ß value, -0.009 [95% CI, -0.01 to -0.003] and -0.007 [95% CI, -0.01 to -0.0006]) after adjustment for covariates. Furthermore, the MUCCA was negatively associated with the white matter hyperintensity burden (adjusted ß value, -0.01 [95% CI, -0.02 to -0.003]), enlarged perivascular spaces in the basal ganglia (adjusted ß value, -0.005 [95% CI, -0.009 to -0.001]), lacunes (adjusted ß value, -0.004 [95% CI, -0.007 to -0.0007]), and brain atrophy (adjusted ß value, -0.009 [95% CI, -0.01 to -0.004]). CONCLUSIONS: The MUCCA and CSVD were correlated. Spinal cord atrophy may serve as an imaging marker for CSVD; thus, small vessel disease may involve the spinal cord in addition to being intracranial.

Associations of life's essential 8 with extent of multi-territorial atherosclerotic plaques and stenosis: a cross-sectional study.

BACKGROUND: Life's Essential 8 (LE8), the recently updated construct for quantifying cardiovascular health, is related to the risks of cardiovascular events. The present study aimed to evaluate associations of LE8 score with the multi-territorial extent of atherosclerosis in a community-dwelling population. METHODS: Data were derived from the baseline cross-sectional survey of the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study in Lishui City. The LE8 included overall, medical and behavior LE8 scores, and were categorized as low (< 60), moderate (60-<80), and high (≥ 80) groups. Vascular magnetic resonance imaging was used to evaluate intracranial and extracranial arteries; thoracoabdominal computed tomography angiography to evaluate coronary, subclavian, aorta, renal, ilio-femoral arteries; and ankle-brachial index to evaluate peripheral arteries. The presence of atherosclerotic plaque or stenosis in any territory was defined as plaque or vascular stenosis with 1 territory affected or more in these arteries. The extent of atherosclerotic plaques or stenosis was assessed according to the number of these 8 vascular sites affected, and graded as four grades (none, single territory, 2-3 territories, 4-8 territories). RESULTS: Of 3065 included participants, the average age was 61.2 ± 6.7 years, and 53.5% were women (n = 1639). The moderate and high overall LE8 groups were associated with lower extent of multi-territorial plaques [common odds ratio (cOR) 0.44, 95% confidence interval (CI), 0.35-0.55; cOR 0.16, 95%CI, 0.12-0.21; respectively] and stenosis (cOR 0.51, 95%CI, 0.42-0.62; cOR 0.16, 95%CI, 0.12-0.21; respectively) after adjustment for potential covariates. Similar results were observed for medical LE8 score with the extent of multi-territorial plaques and stenosis (P < 0.05). We also found the association between behavior LE8 score and the extent of multi-territorial stenosis (P < 0.05). CONCLUSIONS: The higher LE8 scores, indicating healthier lifestyle, were associated with lower presence and extent of atherosclerotic plaque and stenosis in southern Chinese adults. Prospective studies are needed to further validate these findings.

Comparison of Caries and Gingival Status in Patients with Type 2 Diabetes and Healthy Children.

Background: Oral health problems often occur in patients with type 2 diabetes (T2D), and the incidences of dental caries and gingivitis increase as blood glucose (BG) levels rise. This work compared caries and gingival status of patients with T2D and healthy children to improve the understanding and attention of patients with T2D to oral health. Methods: Clinical data of 60 patients with T2D under the age of 10 from May 2020 to September 2022 were retrospectively collected and assigned to the diabetes group. Those 60 healthy children with the same physical examination were collected and assigned to the healthy group. Children in both groups underwent periodontal examination, dental caries examination, and gingival index examination. The prevalence, decayed, missed, and filled teeth (DMFT), caries average (CA), plaque index (PI), gingival crevicular bleeding index (GCBI), attachment loss (AL), and tooth looseness (TL) were observed and compared. Results: The prevalence of dental plaque (DP) (91.67%) and moderate to severe DP (45%) in the diabetes group was much higher based on those in the healthy group (73.33% and 23.33%) [1.25, 95% CI (0.96, 1.63), P < .001]. The prevalence of caries and CA was greatly higher in the diabetes group (75% vs. 21.67%, 2.88 vs. 1.06), and the incidence of gingivitis was higher (63.33% vs. 16.67%) [1.93, 95% CI (1.38, 2.70), P < .001]. Meanwhile, the diabetes group exhibited much higher PI (2.31 ± 0.13), GCBI (2.45 ± 0.28), AL (5.62 ± 0.47 mm), and TL (0.85 ± 0.17 mm) and exhibited obvious difference to those in the healthy group (0.92 ± 0.21, 0.86 ± 0.23, 1.65 ± 0.46mm, 0.36 ± 0.08 mm) [3.46, 95% CI (2.33, 5.15), P < .001]. Conclusion: The prevalence of dental caries and gingivitis in patients with T2D was higher than those in healthy children. Based on these findings, it is suggested that patients with T2D should be educated and encouraged to prioritize their oral health. Regular dental check-ups, proper oral hygiene practices, and preventive measures, such as professional cleanings and fluoride treatments, should be emphasized. Maintaining optimal blood glucose control is also crucial, as it may help reduce the risk and severity of oral health complications associated with diabetes.

Mediation of Systemic Inflammation on Insulin Resistance and Prognosis of Nondiabetic Patients With Ischemic Stroke.

BACKGROUND: Insulin resistance is associated with stroke recurrence and poor functional outcomes of nondiabetic patients with ischemic stroke. The study aimed to investigate whether the association between insulin resistance and the prognosis of nondiabetic patients with ischemic stroke was mediated by systematic inflammation. METHODS: Patients with ischemic stroke but without a history of diabetes who were enrolled in CNSR-III (Third China National Stroke Registry) were included in the study and followed up for 1 year after stroke onset. Insulin resistance was determined by using the homeostasis model assessment for insulin resistance (HOMA-IR) method. hs-CRP (high-sensitivity C-reactive protein) and Lp-PLA2 (lipoprotein-associated phospholipase A2) activity were measured at baseline. The primary outcome was stroke recurrence, and other outcomes included composite vascular events, mortality, and poor functional outcome (modified Rankin Scale score, 3-6). Multivariable Cox or logistic regression analyses were performed to estimate the association between HOMA-IR and the study outcomes. A mediation analysis was performed to examine the relationship between insulin resistance and the study outcomes mediated by systemic inflammation. RESULTS: Among a total of 3808 nondiabetic patients with ischemic stroke who were included in the study, the median HOMA-IR was 1.79 (interquartile range, 1.05-2.97). After adjustments for potential confounders, higher HOMA-IR quartiles were associated with higher risks of stroke recurrence, ischemic stroke, and composite vascular events, especially in the large artery atherosclerosis subtype. hs-CRP partially mediated the association between the HOMA-IR index and the prognosis of ischemic stroke (mediation proportion, 5.9% for stroke recurrence and 7.5% for composite vascular events). No evidence of Lp-PLA2 activity mediating the association of insulin resistance with stroke outcomes was observed. CONCLUSIONS: Our study found that insulin resistance was associated with poor clinical outcomes in nondiabetic patients with ischemic stroke, which was partially mediated by hs-CRP with a modest amount.

Association of metabolic dysfunction-associated fatty liver disease with systemic atherosclerosis: a community-based cross-sectional study.

BACKGROUND: Data are limited on the association of metabolic dysfunction-associated fatty liver disease (MAFLD) with systemic atherosclerosis. This study aimed to examine the relationship between MAFLD and the extent of atherosclerotic plaques and stenosis, and presence of polyvascular disease (PolyVD). METHODS: In this cross-sectional study, MAFLD was diagnosed based on the presence of metabolic dysfunction (MD) and fatty liver disease (FLD). MAFLD was divided into three subtypes: MAFLD with diabetes mellitus (DM), MAFLD with overweight or obesity (OW), as well as MAFLD with lean/normal weight and at least two metabolic abnormalities. Atherosclerosis was evaluated, with vascular magnetic resonance imaging for intracranial and extracranial arteries, thoracoabdominal computed tomography angiography for coronary, subclavian, aorta, renal, iliofemoral arteries, and ankle-brachial index for peripheral arteries. The extent of plaques and stenosis was defined according to the number of these eight vascular sites affected. PolyVD was defined as the presence of stenosis in at least two vascular sites. RESULTS: This study included 3047 participants, with the mean age of 61.2 ± 6.7 years and 46.6% of male (n = 1420). After adjusting for potential confounders, MAFLD was associated with higher extent of plaques (cOR, 2.14, 95% CI 1.85-2.48) and stenosis (cOR, 1.47, 95% CI 1.26-1.71), and higher odds of presence of PolyVD (OR, 1.55, 95% CI 1.24-1.94) as compared with Non-MAFLD. In addition, DM-MAFLD and OW-MAFLD were associated with the extent of atherosclerotic plaques and stenosis, and presence of PolyVD (All P < 0.05). However, lean-MAFLD was only associated with the extent of atherosclerotic plaques (cOR, 1.63, 95% CI 1.14-2.34). As one component of MAFLD, FLD per se was associated with the extent of plaques and stenosis in participants with MAFLD. Furthermore, FLD interacted with MD to increase the odds of presence of systemic atherosclerosis (P for interaction ≤ 0.055). CONCLUSIONS: MAFLD and its subtypes of DM-MAFLD and OW-MAFLD were associated with the extent of atherosclerotic plaques and stenosis, and presence of PolyVD. This study implicated that FLD might be a potential target of intervention for reducing the deleterious effects of MAFLD on systemic atherosclerosis.

Association between Fibrinogen-to-Albumin Ratio and Adverse Stroke Outcomes among Patients with Acute Ischemic Stroke.

INTRODUCTION: Fibrinogen-to-albumin ratio (FAR) is implicated in prothrombotic states and is associated with an increased risk of acute ischemic stroke (AIS). However, studies investigating whether the prothrombotic effect of FAR is associated with long-term adverse outcomes in patients with AIS are lacking. Therefore, we aimed to investigate the association based on The Third China National Stroke Registry (CNSR-III). METHODS: Patients with AIS with complete laboratory data for fibrinogen and albumin in the CNRS-III were included in this study. The primary outcomes were poor functional outcomes (modified Rankin scale score 3-6) at 12 months, including disability (modified Rankin scale score 3-5), all-cause death, recurrent stroke, and combined vascular events within 1 year. Univariate and multivariate logistic or Cox regression analyses were used to investigate the association between FAR quartiles and adverse outcomes. RESULTS: A total of 8984 patients with AIS were enrolled in this study. After one-year follow-up, 238 patients were lost to follow-up. A total of 1230(14.06%) patients had poor functional outcomes; 932(10.37%) and 981(10.92%) experienced stroke recurrence and combined vascular events, respectively. The adjusted odds ratios/hazard ratios and 95% confidence intervals of the highest quartile of the FAR(>11.44) were 1.64(1.35-2.00) for poor functional outcomes, 1.68(1.34-2.10) for disability, 1.40(1.02-1.94) for all-cause death, 1.11(0.92-1.34) for stroke recurrence, and 1.11(0.92-1.33) for combined vascular event, respectively. CONCLUSION: High FAR(>11.44) increased the risk of short- and long-term poor functional outcomes, including disability and all-cause death among patients with AIS. The FAR may play an important role in the early stratification of patients with AIS.

Prevalence and Prognostic Significance of Malnutrition Risk in Patients With Acute Ischemic Stroke: Results From the Third China National Stroke Registry.

BACKGROUND AND PURPOSE: To investigate the prevalence of malnutrition risk in patients with acute ischemic stroke (AIS) at admission, the association between malnutrition risk and long-term outcomes, and whether the predictive ability would be improved after adding to previous prognostic models for poor outcomes. METHODS: Based on the Third China National Stroke Registry data from August 2015 to March 2018, we evaluated malnutrition risk using objective scores, including the controlling nutritional status score, geriatric nutritional risk index, and prognostic nutritional index. The primary outcome was death or major disability (modified Rankin Scale score ≥3) at 1 year after stroke onset. We calculated the crude prevalence of malnutrition risk and investigated the association between malnutrition risk and clinical outcomes. Prognostic performance of 3 objective malnutrition scores for poor outcomes was assessed. RESULTS: Moderate to severe malnutrition risk was identified in 5.89%, 5.30%, and 1.95% of the Third China National Stroke Registry AIS patients according to the controlling nutritional status score, geriatric nutritional risk index, and prognostic nutritional index, respectively. At 1-year follow-up, 1143 participants (13.5%) experienced death or major disability. After adjustment for traditional risk factors, moderate to severe malnutrition risk was associated with high risk of composite events (odds ratio, 2.25 [95% CI, 1.75-2.90], for controlling nutritional status score; odds ratio, 2.10 [95% CI, 1.63-2.69], for geriatric nutritional risk index; odds ratio, 3.36 [95% CI, 2.33-4.84], for prognostic nutritional index; all P<0.01). Addition of the 3 malnutrition scores to different predicted scales (iScore and Acute Stroke Registry and Analysis of Lausanne) improved predictive ability for long-term poor outcomes validated by the integrated discrimination index (all P<0.05). CONCLUSIONS: The prevalence of moderate or severe malnutrition risk in Chinese patients with AIS ranged from 1.95% to 5.89%. Malnutrition risk in patients with AIS was associated with increased risk of long-term death and major disability. Our study provides evidence supporting the prognostic significance of objective malnutrition scores after AIS.

Genome-wide identification, expression analysis and evolutionary relationships of the IQ67-domain gene family in common wheat (Triticum aestivum L.) and its progenitors.

BACKGROUND: The plant-specific IQ67-domain (IQD) gene family plays an important role in plant development and stress responses. However, little is known about the IQD family in common wheat (Triticum aestivum L), an agriculturally important crop that provides more than 20% of the calories and protein consumed in the modern human diet. RESULTS: We identified 125 IQDs in the wheat genome and divided them into four subgroups by phylogenetic analysis. The IQDs belonging to the same subgroup had similar exon-intron structure and conserved motif composition. Polyploidization contributed significantly to the expansion of IQD genes in wheat. Characterization of the expression profile of these genes revealed that a few T. aestivum (Ta)IQDs showed high tissue-specificity. The stress-induced expression pattern also revealed a potential role of TaIQDs in environmental adaptation, as TaIQD-2A-2, TaIQD-3A-9 and TaIQD-1A-7 were significantly induced by cold, drought and heat stresses, and could be candidates for future functional characterization. In addition, IQD genes in the A, B and D subgenomes displayed an asymmetric evolutionary pattern, as evidenced by their different gain or loss of member genes, expression levels and nucleotide diversity. CONCLUSIONS: This study elucidated the potential biological functions and evolutionary relationships of the IQD gene family in wheat and revealed the divergent fates of IQD genes during polyploidization.

Interleukin-6 and YKL-40 predicted recurrent stroke after ischemic stroke or TIA: analysis of 6 inflammation biomarkers in a prospective cohort study.

OBJECTIVE: Contribution of individual and combined inflammatory markers in prognosis after stroke was still undefined. We aimed to investigate the association of systemic and local vascular inflammatory markers and recurrent stroke as well as impact on poor functional outcome. METHODS: In this pre-specified substudy of the Third China National Stroke Registry (CNSR-III), 10,472 consecutive acute ischemic stroke or TIA patients with available centralized-measured levels of Interleukin-6 (IL-6), high sensitive C-reactive protein (hsCRP), IL-1 receptor antagonist (IL-1Ra), lipoprotein-associated phospholipase A2 mass (Lp-PLA2) and activity (Lp-PLA2-A), and YKL-40 from 171 sites were enrolled. The primary outcomes consisted of stroke recurrence and poor functional outcome defined as modified Rankin Scale (mRS) score of 2-6 within 1 year. RESULTS: There were 1026 (9.8%) and 2395 (23.4%) patients with recurrent stroke and poor functional outcome within 1 year. The highest quartiles of IL-6 (adjusted HR, 1.36; 95% CI 1.13-1.64; P = 0.001), hsCRP (adjusted HR, 1.41; 95% CI 1.17-1.69; P = 0.0003) and YKL-40 (adjusted HR, 1.28; 95% CI 1.06-1.56; P = 0.01) were associated with increased risk of recurrent stroke; and the highest quartiles of IL-6 (adjusted OR 1.93; 95% CI 1.64-2.27; P < 0.0001), IL-1Ra (adjusted OR 1.60; 95% CI 1.37-1.87; P < 0.0001), hsCRP (adjusted OR 1.60; 95% CI 1.37-1.86; P < 0.0001) and YKL-40 (adjusted OR 1.21; 95% CI 1.03-1.42; P = 0.02) were correlated with increased risk of poor functional outcome. In the multivariate stepwise regression analysis including all markers with backward selection, elevated levels of IL-6 or YKL-40 were associated with recurrent stroke (IL6: OR, 1.34; 95% CI 1.19-1.52; P < 0.0001; YKL-40: OR, 1.01; 95% CI 1.01-1.03; P = 0.004) and poor functional outcome (IL6: OR, 1.68; 95% CI 1.46-1.93; P < 0.0001; YKL-40: OR, 1.02; 95% CI 1.01-1.03; P = 0.0001). Adding IL-6 and YKL-40 significantly increased the area under the receiver operating characteristic curves for the prediction models of Essen Stroke Risk Score (0.03, P < 0.0001) and Totaled Health Risks in Vascular Events Score (0.07, P < 0.0001), and yielded continuous net reclassification improvement (19.0%, P < 0.0001; 33.0, P < 0.0001). CONCLUSIONS: In the patients with ischemic stroke or TIA, IL-6 and YKL-40 were independently associated with recurrent stroke and poor functional outcome, and improved risk classification of clinical risk algorithms.

Gender differences in brain response to infant emotional faces.

Infant emotional stimuli can preferentially engage adults' attention and provide valuable information essential for successful interaction between adults and infants. Exploring the neural processes of recognizing infant stimuli promotes better understandings of the mother-infant attachment mechanisms. Here, combining task-functional magnetic resonance imaging (Task-fMRI) and resting-state fMRI (rs-fMRI), we investigated the effects of infants' faces on the brain activity of adults. Two groups including 26 women and 25 men were recruited to participate in the current study. During the task-fMRI, subjects were exposed to images of infant emotional faces (including happy, neutral, and sad) randomly. We found that the brains of women and men reacted differently to infants' faces, and these differential areas are in facial processing, attention, and empathetic networks. The rs-fMRI further showed that the connectivity of the default-mode network-related regions increased in women than in men. Additionally, brain activations in regions related to emotional networks were associated with the empathetic abilities of women. These differences in women might facilitate them to more effective and quick adjustments in behaviors and emotions during the nurturing infant period. The findings provide special implications and insights for understanding the neural processing of reacting to infant cues in adults.

Association between triglyceride glucose index and atherosclerotic plaques and Burden: findings from a community-based study.

BACKGROUND: Insulin resistance is an important cause of cardiovascular events and cerebral infarction development. We aimed to investigate the association of the triglyceride glucose (TyG) index with atherosclerotic burden and plaques in coronary, intra- and extracranial arteries in participants with non-diabetes, and compared the results with that of the homeostasis model assessment of insulin resistance (HOMA-IR). METHODS: Participants without diabetes in the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study were included. We categorized participants by tertiles of the TyG index and the concordance/discordance of the TyG index and HOMA-IR. Discordance was defined as a TyG index equal to or greater than the median and HOMA-IR less than the median, or vice versa. The atherosclerosis plaques and burden in coronary, intra- and extracranial arteries were evaluated. The association of HOMA-IR and TyG index with the presence of atherosclerotic plaques and atherosclerotic burden was assessed by binary and ordinal logistic regression models, respectively. RESULTS: Among 2,719 included participants, the average age was 60.9 (± 6.6) years, and 53.0% were female. Both TyG index and HOMA-IR were associated with increased odds of coronary/intra- and extracranial atherosclerotic plaques and burden after adjustment for age, sex, currenting smoking and drinking (all P < 0.05). However, the association between HOMA-IR and intracranial atherosclerosis was not statistically significant after adjustment for all potential confounders. Discordantly high TyG index with HOMA-IR had a higher odd of extracranial plaque (odds ratio [OR]: 1.34, 95% confidence interval [CI]: 1.04-1.71), extracranial atherosclerotic burden (common odds ratio [cOR]: 1.35, 95% CI 1.06-1.71), coronary plaque (OR: 1.30, 95% CI 1.01-1.68) and segment stenosis score (cOR: 1.39, 95% CI 1.09-1.78) as compared with concordantly low TyG index with HOMA-IR. The TyG index had a better net reclassification improvement ability than HOMA-IR for atherosclerotic plaques when adding to baseline model. CONCLUSION: Elevated TyG index was associated with increased odds of atherosclerosis in coronary/intra- and extracranial arteries. Compared with HOMA-IR, the TyG index was more strongly associated with intracranial atherosclerosis. Moreover, discordantly high TyG index with HOMA-IR was also important for atherosclerosis identification.

Association of residual inflammatory risk with stroke recurrence in patients with acute ischaemic stroke or transient ischaemic attack.

BACKGROUND AND PURPOSE: The aim was to explore the association of residual inflammatory risk (RIR) with stroke recurrence after an index acute ischaemic stroke or transient ischaemic attack. METHODS: This study was based on the Third China National Stroke Registry. A total of 5840 patients with two high sensitivity C-reactive protein (hsCRP) measurements at baseline and at 3 months were included in the analysis. High RIR was defined as an hsCRP ≥3 mg/l. Patients were divided into four groups: persistent high RIR (first high then high hsCRP), attenuated RIR (first high then low hsCRP), increased RIR (first low then high hsCRP) and persistent low RIR (first low then low hsCRP). The primary outcome was new stroke onset during the 1-year follow-up. Secondary outcomes included composite vascular events, all-cause mortality and poor functional outcome (modified Rankin Scale score 3-6). RESULTS: During the 1-year follow-up, 523 (9.0%) patients had stroke recurrence. Patients with persistent high RIR had an increased risk of stroke recurrence (hazard ratio with 95% confidence interval 1.39, 1.08-1.78), compared with those with persistent low RIR. Similar results were found for the outcome of composite vascular events, mortality and poor functional outcome. An increased risk of stroke recurrence was further found in patients with persistent high RIR and intracranial artery stenosis or large-artery atherosclerosis stroke subtype. CONCLUSIONS: In patients with acute ischaemic stroke or transient ischaemic attack, persistent high RIR increased the risks of 1-year stroke recurrence, especially in those with intracranial artery stenosis or large-artery atherosclerosis subtype, composite vascular events, mortality and poor functional outcome.

Genetically predicted childhood obesity and adult atrial fibrillation: A mendelian randomization study.

BACKGROUND AND AIMS: It is unclear whether the association of childhood obesity with adult atrial fibrillation observed in observational studies reflects causal effects. The aim of this study was to evaluate the association of childhood obesity with adult atrial fibrillation using genetic instruments. METHODS AND RESULTS: We used a two-sample Mendelian randomization (MR) design to evaluate the association between childhood obesity and adult atrial fibrillation. Two sets of genetic variants (15 single nucleotide polymorphisms [SNPs] for childhood body mass index [BMI] and 12 SNPs for dichotomous childhood obesity) were selected as instruments. Summary data on SNP-childhood obesity and SNP-atrial fibrillation associations were obtained from recently published genome-wide association studies. Effect estimates were evaluated using inverse-variance weighted (IVW) methods. Other MR analyses, including MR-Egger, simple and weighted median, weighted MBE and MR-PRESSO methods were performed in sensitivity analyses. The IVW models showed that both a genetically predicted one-standard deviation increase in childhood BMI (kg/m2) and higher log-odds of childhood obesity were associated with a substantial increase in the risk of atrial fibrillation (OR = 1.22, 95% CI: 1.11-1.34, P < 0.001; OR = 1.09, 95% CI: 1.04-1.14, P < 0.001). MR-Egger regression showed no evidence of genetic pleiotropy for childhood BMI (intercept = 0.000, 95% CI: -0.024 to 0.023), but for childhood obesity (intercept = -0.036, 95% CI: -0.057 to -0.015). Similar results were observed using leave-one-out and other MR methods in sensitivity analyses. CONCLUSIONS: This MR analysis found a consistent association between genetically predicted childhood obesity and an increased risk of adult atrial fibrillation. Further research is warranted to validate our findings.

A novel nutritional index and adverse outcomes in ischemic stroke: Results from the third China National Stroke Registry.

BACKGROUND AND AIMS: Few studies have applied the triglyceride, cholesterol, body weight index (TCBI) in acute ischemic stroke (AIS). We investigated the association between the TCBI and adverse clinical outcomes in patients with AIS. METHODS AND RESULTS: Based on the Third China National Stroke Registry (CNSR-III) data from August 2015 to March 2018, we evaluated the nutritional status of patients with AIS using the TCBI. Patients were categorized according to quartile levels of the TCBI. The main outcomes were poor functional outcomes and recurrent stroke at 1-year and secondary outcomes were adverse outcomes at 3 and 6 months after stroke onset. Poor functional outcomes consisted of all-cause mortality and major disabilities. Multivariate analyses with logistic or Cox regression analysis and restricted cubic splines determined the association between the TCBI and adverse outcomes. We included 9708 patients. At the 1-year follow-up, 1323 patients (13.6%) had died or experienced major disability. The adjusted odds ratios/hazard ratios and 95% confidence intervals of the lowest quartile at 1-year were 1.47 (1.22-1.78) for poor functional outcomes, 1.46 (1.18-1.81) for major disability, and 1.34 (0.94-1.86) for all-cause mortality. Kaplan-Meier analysis demonstrated an inverse relationship between all-cause mortality and the TCBI (log-rank p < 0.05). An approximately L-shaped relationship between TCBI levels and poor functional outcomes and major disability was observed at 1-year. CONCLUSION: The novel TCBI was associated with short- and long-term adverse outcomes in AIS. Thus, it may be useful for predicting adverse outcomes in patients with AIS.

Residual Inflammatory Risk Predicts Poor Prognosis in Acute Ischemic Stroke or Transient Ischemic Attack Patients.

Background and Purpose: It is still unclear whether the residual cholesterol and inflammatory risk in the acute phase is associated with prognosis of stroke. We aimed to investigate the proportion and relative contribution of residual cholesterol and inflammatory risk, determined by baseline low-density lipoprotein cholesterol (LDL-C) and high-sensitivity C-reactive protein (hsCRP) levels, to the risk of recurrent stroke and poor functional outcome at 1 year. Methods: In this prospective multicenter cohort study, 10 499 consecutive acute ischemic stroke and transient ischemic attack patients with levels of LDL-C and hsCRP were enrolled. Patients were divided into 4 groups: residual cholesterol risk only (LDL-C ≥2.6 mmol/L and hsCRP <3 mg/L), residual inflammatory risk (RIR) only (LDL-C <2.6 mmol/L and hsCRP ≥3 mg/L), both risk (LDL-C ≥2.6 mmol/L and hsCRP ≥3 mg/L), and neither risk (LDL-C <2.6 mmol/L and hsCRP <3 mg/L). The primary outcomes consisted of stroke recurrence and a modified Rankin Scale score of 2 to 6 within 1 year. Results: The relative proportions of patients with RIR only, residual cholesterol risk only, both risk, and neither were 21.3%, 23.7%, 14.4%, and 40.6%, respectively. RIR only was independently associated with recurrent stroke (adjusted hazard ratio, 1.18 [95% CI, 1.00­1.40]; P=0.05). The association was slightly attenuated after further adjusting for usage of antiplatelet agent and statin during 1-year follow-up in addition to the traditional risk factors (hazard ratio, 1.31 [95% CI, 0.99­1.76]; P=0.07). When applying the LDL-C cutoff value of 1.8 mmol/L in the sensitivity analyses, such association in large-artery atherosclerosis subtype was more significant (adjusted hazard ratio, 1.69 [95% CI, 1.06­2.67]; P=0.03). Patients with RIR only also had increased risk of poor functional outcome (adjusted odds ratio, 1.43 [95% CI, 1.24­1.64]; P<0.0001). Conclusions: In the patients with acute ischemic stroke or transient ischemic attack, RIR only could be predictive for recurrent stroke, especially for those with large-artery atherosclerosis, and poor functional outcome.

Does the unified protocol really change neuroticism? Results from a randomized trial.

BACKGROUND: Neuroticism is associated with the onset and maintenance of a number of mental health conditions, as well as a number of deleterious outcomes (e.g. physical health problems, higher divorce rates, lost productivity, and increased treatment seeking); thus, the consideration of whether this trait can be addressed in treatment is warranted. To date, outcome research has yielded mixed results regarding neuroticism's responsiveness to treatment, perhaps due to the fact that study interventions are typically designed to target disorder symptoms rather than neuroticism itself. The purpose of the current study was to explore whether a course of treatment with the unified protocol (UP), a transdiagnostic intervention that was explicitly developed to target neuroticism, results in greater reductions in neuroticism compared to gold-standard, symptom focused cognitive behavioral therapy (CBT) protocols and a waitlist (WL) control condition. METHOD: Patients with principal anxiety disorders (N = 223) were included in this study. They completed a validated self-report measure of neuroticism, as well as clinician-rated measures of psychological symptoms. RESULTS: At week 16, participants in the UP condition exhibited significantly lower levels of neuroticism than participants in the symptom-focused CBT (t(218) = -2.17, p = 0.03, d = -0.32) and WL conditions(t(207) = -2.33, p = 0.02, d = -0.43), and these group differences remained after controlling for simultaneous fluctuations in depression and anxiety symptoms. CONCLUSIONS: Treatment effects on neuroticism may be most robust when this trait is explicitly targeted.

Genomic mapping and identification of candidate genes encoding nulliplex-branch trait in sea-island cotton (Gossypium barbadense L.) by multi-omics analysis.

Nulliplex branch is a key architectural trait in sea-island cotton (Gossypium barbadense L.), but its genetic basis is not well understood. Here we investigated the genetic basis of the nulliplex-branch trait in cotton by combining newly created bulked segregant analysis (BSA)-seq data, published RNA-seq data, and published whole-genome resequencing (WGR) data. We delimited the nulliplex-branch locus (qD07-NB) to D07, region 14.8-17.1 Mb, using various BSA methods and markers. We integrated our BSA data with WGR data of sea-island cotton varieties and detected a missense single-nucleotide polymorphism in the candidate gene (Gbar_D07G011870) of qD07-NB. This gene was under positive selection during sea-island cotton breeding in the Xinjiang Uygur Autonomous Region, China. Notably, the nulliplex-branch varieties possessed a better fiber quality than the long-branch varieties, and a set of high-quality molecular markers was identified for molecular breeding of the nulliplex-branch trait in cotton. We combined BSA-seq and RNA-seq data to compare gene expression profiles between two elite sea-island cotton varieties during three developmental stages. We identified eleven relevant candidate genes, five downregulated and six upregulated, in the qD07-NB locus. This research will expand our understanding of the genetic basis of the nulliplex-branch trait and provide guidance for architecture-focused breeding in cotton. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-021-01229-w.

The improved assembly of 7DL chromosome provides insight into the structure and evolution of bread wheat.

Wheat is one of the most important staple crops worldwide and also an excellent model species for crop evolution and polyploidization studies. The breakthrough of sequencing the bread wheat genome and progenitor genomes lays the foundation to decipher the complexity of wheat origin and evolutionary process as well as the genetic consequences of polyploidization. In this study, we sequenced 3286 BACs from chromosome 7DL of bread wheat cv. Chinese Spring and integrated the unmapped contigs from IWGSC v1 and available PacBio sequences to close gaps present in the 7DL assembly. In total, 8043 out of 12 825 gaps, representing 3 491 264 bp, were closed. We then used the improved assembly of 7DL to perform comparative genomic analysis of bread wheat (Ta7DL) and its D donor, Aegilops tauschii (At7DL), to identify domestication signatures. Results showed a strong syntenic relationship between Ta7DL and At7DL, although some small rearrangements were detected at the distal regions. A total of 53 genes appear to be lost genes during wheat polyploidization, with 23% (12 genes) as RGA (disease resistance gene analogue). Furthermore, 86 positively selected genes (PSGs) were identified, considered to be domestication-related candidates. Finally, overlapping of QTLs obtained from GWAS analysis and PSGs indicated that TraesCS7D02G321000 may be one of the domestication genes involved in grain morphology. This study provides comparative information on the sequence, structure and organization between bread wheat and Ae. tauschii from the perspective of the 7DL chromosome, which contribute to better understanding of the evolution of wheat, and supports wheat crop improvement.

Diffuse Tract Damage in CADASIL Is Correlated with Global Cognitive Impairment.

INTRODUCTION: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy -(CADASIL) is the most common familial cerebral small vessel disease caused by notch homolog protein 3 gene mutations and is strongly associated with ischemic stroke and dementia. Patients are characterized by cognitive impairment and widespread white matter (WM) lesions. However, the relationship between WM lesions and cognitive impairment is not very clear. The aim of this study was to investigate WM microstructural abnormalities by diffusion tensor imaging (DTI) and the relationship between WM alterations and cognitive impairment in patients with CADASIL. METHODS: In the present study, we evaluated WM degeneration in 18 patients with CADASIL and 18 controls by fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) based on DTI. RESULTS: Compared with healthy controls, patients with CADASIL showed extensive and significant reductions in FA and increased RD, AD, and MD. These alterations were distributed throughout the entire brain (mainly the inferior and superior longitudinal fasciculus, inferior fronto-occipital fasciculus, corpus callosum, internal capsule, external capsule, corona radiata, thalamic radiation, and cingulum). Furthermore, these WM microstructural alterations were significantly correlated with cognitive scores and stroke scale scores. CONCLUSION: Patients with -CADASIL showed widespread WM abnormalities, and WM microstructural integrity and cognitive impairment were significantly correlated. Our results indicated that damage to WM tracts plays an important role in cognitive impairment in CADASIL.