Dual Antiplatelet Treatment up to 72 Hours after Ischemic Stroke.

BACKGROUND: Dual antiplatelet treatment has been shown to lower the risk of recurrent stroke as compared with aspirin alone when treatment is initiated early (≤24 hours) after an acute mild stroke. The effect of clopidogrel plus aspirin as compared with aspirin alone administered within 72 hours after the onset of acute cerebral ischemia from atherosclerosis has not been well studied. METHODS: In 222 hospitals in China, we conducted a double-blind, randomized, placebo-controlled, two-by-two factorial trial involving patients with mild ischemic stroke or high-risk transient ischemic attack (TIA) of presumed atherosclerotic cause who had not undergone thrombolysis or thrombectomy. Patients were randomly assigned, in a 1:1 ratio, within 72 hours after symptom onset to receive clopidogrel (300 mg on day 1 and 75 mg daily on days 2 to 90) plus aspirin (100 to 300 mg on day 1 and 100 mg daily on days 2 to 21) or matching clopidogrel placebo plus aspirin (100 to 300 mg on day 1 and 100 mg daily on days 2 to 90). There was no interaction between this component of the factorial trial design and a second part that compared immediate with delayed statin treatment (not reported here). The primary efficacy outcome was new stroke, and the primary safety outcome was moderate-to-severe bleeding - both assessed within 90 days. RESULTS: A total of 6100 patients were enrolled, with 3050 assigned to each trial group. TIA was the qualifying event for enrollment in 13.1% of the patients. A total of 12.8% of the patients were assigned to a treatment group no more than 24 hours after stroke onset, and 87.2% were assigned after 24 hours and no more than 72 hours after stroke onset. A new stroke occurred in 222 patients (7.3%) in the clopidogrel-aspirin group and in 279 (9.2%) in the aspirin group (hazard ratio, 0.79; 95% confidence interval [CI], 0.66 to 0.94; P = 0.008). Moderate-to-severe bleeding occurred in 27 patients (0.9%) in the clopidogrel-aspirin group and in 13 (0.4%) in the aspirin group (hazard ratio, 2.08; 95% CI, 1.07 to 4.04; P = 0.03). CONCLUSIONS: Among patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause, combined clopidogrel-aspirin therapy initiated within 72 hours after stroke onset led to a lower risk of new stroke at 90 days than aspirin therapy alone but was associated with a low but higher risk of moderate-to-severe bleeding. (Funded by the National Natural Science Foundation of China and others; INSPIRES ClinicalTrials.gov number, NCT03635749.).

Exosomal miR-23a-3p derived from human umbilical cord mesenchymal stem cells promotes remyelination in central nervous system demyelinating diseases by targeting Tbr1/Wnt pathway.

Oligodendrocyte precursor cells are present in the adult central nervous system, and their impaired ability to differentiate into myelinating oligodendrocytes can lead to demyelination in patients with multiple sclerosis, accompanied by neurological deficits and cognitive impairment. Exosomes, small vesicles released by cells, are known to facilitate intercellular communication by carrying bioactive molecules. In this study, we utilized exosomes derived from human umbilical cord mesenchymal stem cells (HUMSCs-Exos). We performed sequencing and bioinformatics analysis of exosome-treated cells to demonstrate that HUMSCs-Exos can stimulate myelin gene expression in oigodendrocyte precursor cells. Functional investigations revealed that HUMSCs-Exos activate the Pi3k/Akt pathway and regulate the Tbr1/Wnt signaling molecules through the transfer of miR-23a-3p, promoting oligodendrocytes differentiation and enhancing the expression of myelin-related proteins. In an experimental autoimmune encephalomyelitis model, treatment with HUMSCs-Exos significantly improved neurological function and facilitated remyelination. This study provides cellular and molecular insights into the use of cell-free exosome therapy for central nervous system demyelination associated with multiple sclerosis, demonstrating its great potential for treating demyelinating and neurodegenerative diseases.

Serum lipidome reveals lipid metabolic dysregulation in severe fever with thrombocytopenia syndrome.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a rapidly progressing infectious disease with a high fatality rate caused by a novel bunyavirus (SFTSV). The role of lipids in viral infections is well-documented; however, the specific alterations in lipid metabolism during SFTSV infection remain elusive. This study aims to elucidate the lipid metabolic dysregulations in the early stages of SFTS patients. METHODS: This study prospectively collected peripheral blood sera from 11 critical SFTS patients, 37 mild SFTS patients, and 23 healthy controls during the early stages of infection for lipidomics analysis. A systematic bioinformatics analysis was conducted from three aspects integrating lipid differential expressions, lipid differential correlations, and lipid-clinical indices correlations to reveal the serum lipid metabolic dysregulation in SFTSV-infected individuals. RESULTS: Our findings reveal significant lipid metabolic dysregulation in SFTS patients. Specifically, compared to healthy controls, SFTS patients exhibited three distinct modes of lipid differential expression: increased levels of lipids including phosphatidylserine (PS), hexosylceramide (HexCer), and triglycerides (TG); decreased levels of lipids including lysophosphatidylcholine (LPC), acylcarnitine (AcCa), and cholesterol esters (ChE); and lipids showing "dual changes" including phosphatidylcholine (PC) and phosphatidylethanolamine (PE). Finally, based on lipid metabolic pathways and literature analysis, we systematically elucidated the potential mechanisms underlying lipid metabolic dysregulation in the early stage of SFTSV infection. CONCLUSIONS: Our study presents the first global serum lipidome profile and reveals the lipid metabolic dysregulation patterns in the early stage of SFTSV infection. These findings provide a new basis for the diagnosis, treatment, and further investigation of the disease.

Implementation of early prophylaxis for deep-vein thrombosis in intracerebral hemorrhage patients: an observational study from the Chinese Stroke Center Alliance.

BACKGROUND: There is substantial evidence to support the use of several methods for preventing deep-vein thrombosis (DVT) following intracerebral hemorrhage (ICH). However, the extent to which these measures are implemented in clinical practice and the factors influencing patients' receipt of preventive measures remain unclear. Therefore, we aimed to evaluate the rate of the early implementation of DVT prophylaxis and the factors associated with its success in patients with ICH. METHODS: This study enrolled 49,950 patients with spontaneous ICH from the Chinese Stroke Center Alliance (CSCA) between August 2015 and July 2019. Early DVT prophylaxis implementation was defined as an intervention occurring within 48 h after admission. Univariate and multivariate logistic regression analyses were conducted to identify the rate and factors associated with the implementation of early prophylaxis for DVT in patients with ICH. RESULTS: Among the 49,950 ICH patients, the rate of early DVT prophylaxis implementation was 49.9%, the rate of early mobilization implementation was 29.49%, and that of pharmacological prophylaxis was 2.02%. Factors associated with an increased likelihood of early DVT prophylaxis being administered in the multivariable model included receiving early rehabilitation therapy (odds ratio [OR], 2.531); admission to stroke unit (OR 2.231); admission to intensive care unit (OR 1.975); being located in central (OR 1.879) or eastern regions (OR 1.529); having a history of chronic obstructive pulmonary disease (OR 1.292), ischemic stroke (OR 1.245), coronary heart disease or myocardial infarction (OR 1.2); taking antihypertensive drugs (OR 1.136); and having a higher Glasgow Coma Scale (GCS) score (OR 1.045). Conversely, being male (OR 0.936), being hospitalized in tertiary hospitals (OR 0.778), and having a previous intracranial hemorrhage (OR 0.733) were associated with a lower likelihood of early DVT prophylaxis being administered in patients with ICH. CONCLUSIONS: The implementation rate of early DVT prophylaxis among Chinese patients with ICH was subpar, with pharmacological prophylaxis showing the lowest prevalence. Various controllable factors exerted an impact on the implementation of early DVT prophylaxis in this population.

Effects of subthalamic nucleus deep brain stimulation using different frequency programming paradigms on axial symptoms in advanced Parkinson's disease.

BACKGROUND: In advanced Parkinson's disease (PD), axial symptoms are common and can be debilitating. Although deep brain stimulation (DBS) significantly improves motor symptoms, conventional high-frequency stimulation (HFS) has limited effectiveness in improving axial symptoms. In this study, we investigated the effects on multiple axial symptoms after DBS surgery with three different frequency programming paradigms comprising HFS, low-frequency stimulation (LFS), and variable-frequency stimulation (VFS). METHODS: This study involved PD patients who had significant preoperative axial symptoms and underwent bilateral subthalamic nucleus (STN) DBS. Axial symptoms, motor symptoms, medications, and quality of life were evaluated preoperatively (baseline). One month after surgery, HFS was applied. At 6 months post-surgery, HFS assessments were performed, and HFS was switched to LFS. A further month later, we conducted LFS assessments and switched LFS to VFS. At 8 months after surgery, VFS assessments were performed. RESULTS: Of the 21 PD patients initially enrolled, 16 patients were ultimately included in this study. Regarding HFS, all axial symptoms except for the Berg Balance Scale (p < 0.0001) did not improve compared with the baseline (all p > 0.05). As for LFS and VFS, all axial symptoms improved significantly compared with both the baseline and HFS (all p < 0.05). Moreover, motor symptoms and medications were significantly better than the baseline (all p < 0.05) after using LFS and VFS. Additionally, the quality of life of the PD patients after receiving LFS and VFS was significantly better than at the baseline and with HFS (all p < 0.0001). CONCLUSION: Our findings indicate that HFS is ineffective at improving the majority of axial symptoms in advanced PD. However, both the LFS and VFS programming paradigms exhibit significant improvements in various axial symptoms.

In-hospital outcomes of intravenous recombinant tissue plasminogen activator treatment for acute ischemic stroke in patients aged >80 years: Findings from the Chinese Stroke Center Alliance.

BACKGROUND: Intravenous (IV) recombinant plasminogen activator (rt-PA) within 4.5 hours of symptom onset has established benefit for patients with acute ischemic stroke (AIS); however, evidence on the use of IV rt-PA in elderly Chinese patients is limited. This study evaluated the patient characteristics and in-hospital clinical outcomes of Chinese patients aged >80 years who received IV rt-PA within 4.5 hours of symptom onset, using patients aged 18-80 years as a reference group. (NCT05395351). METHODS: This study analyzed adult Chinese patients with AIS who arrived at the hospital within 4.5 hours of symptom onset between August 2015 and July 2019 and were registered in the nationwide, hospital-based Chinese Stroke Center Alliance platform. Patients were categorized by treatment (IV rt-PA versus no IV rt-PA) and age (>80 years versus 18-80 years). In-hospital outcomes were evaluated in IV rt-PA-treated patients. Primary outcome was all-cause mortality during hospitalization; secondary outcomes included proportion of patients with intracranial hemorrhage (ICH) during hospitalization, change in National Institutes of Health Stroke Scale (NIHSS) before and 24 hours after IV rt-PA, modified Rankin Scale (mRS) at discharge, proportion of patients with stroke recurrence during hospitalization, and duration of hospital stay. RESULTS: Of 113035 patients with AIS included in the study, 31,418 patients received IV rt-PA within 4.5 hours after symptom onset (aged >80 years: n=3,332; 18-80 years: n=28,086). Among IV rt-PA-treated patients, all-cause mortality was 2.6% (95% CI 2.1-3.2%) and 0.8% (95% CI 0.7-0.9%) in patients aged >80 years and 18-80 years, respectively. Intracranial hemorrhage occurred in 6.7% (95% CI 5.8-7.5%) and 3.1% (95% CI 2.9-3.3%) of patients; mean±SD change in NIHSS score was 2.8±5.0 and 2.5±4.3; mRS 0-1 at discharge in 42.8% (95% CI 40.8%-44.8%) and 63.6% (95% CI 62.9%-64.3%); stroke recurrence in 11.1% (95% CI 10.0-12.1%) and 7.3% (95% CI 7.0-7.6%). Median duration of hospital stay was 11 days in both age groups. CONCLUSIONS: Chinese patients aged >80 years with AIS who received IV rt-PA within 4.5 hours after symptom onset had higher all-cause mortality during hospitalization than those aged 18-80 years.

10-year Temporal Trends of Intravenous Thrombolysis in Acute Ischemic Stroke: Analysis of the China National Stroke Registry I-â ¢.

OBJECTIVES: To investigate the 10-year trend in healthcare quality of intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator in acute ischemic stroke (AIS) in China. MATERIALS AND METHODS: We analyzed 42,188 AIS within 7 days of onset from the China National Stroke Registry (CNSR) Ⅰ-Ⅲ. Primary outcomes were temporal changes in the proportion of patients arriving at the hospital within 3.5 hours (and 2 hours) of onset and receiving IVT within 4.5 hours (and 3 hours), stratified by region and hospital tier. Secondary outcomes included temporal changes in door-to-needle time (DNT), DNT ≤60 min and favorable outcome defined as a 90-day modified Rankin Scale (mRS) of 0-1. RESULTS: Among patients arriving at the hospital within 3.5 hours of onset, 13.5%, 7.1% and 33.4% patients received IVT within 4.5 hours in CNSR Ⅰ, Ⅱ and Ⅲ, respectively, including a higher proportion from eastern China (37.0%) and tertiary hospitals (36.5%). The median DNT was shorter in CNSR Ⅲ (60.0 min) than those in Ⅱ (95.0 min) and I (94.0 min). The proportion of patients with DNT ≤60 min was greater in Ⅲ (53.4%) than those in Ⅱ (26.7%) and Ⅰ (13.4%). The proportion of favorable outcomes was higher in CNSR Ⅲ (72.8%) than those in Ⅱ (49.6%) and Ⅰ (49.4%). Similar trends were observed for patients arriving at the hospital within 2 hours and receiving IVT within 3 hours of onset. CONCLUSIONS: The healthcare quality of IVT has improved remarkably in the past decade, notably in eastern China and tertiary hospitals.

Integrative Genomics and Bioactivity-Guided Isolation of Novel Antimicrobial Compounds from Streptomyces sp. KN37 in Agricultural Applications.

Actinomycetes have long been recognized as an important source of antibacterial natural products. In recent years, actinomycetes in extreme environments have become one of the main research directions. Streptomyces sp. KN37 was isolated from the cold region of Kanas in Xinjiang. It demonstrated potent antimicrobial activity, but the primary active compounds remained unclear. Therefore, we aimed to combine genomics with traditional isolation methods to obtain bioactive compounds from the strain KN37. Whole-genome sequencing and KEGG enrichment analysis indicated that KN37 possesses the potential for synthesizing secondary metabolites, and 41 biosynthetic gene clusters were predicted, some of which showed high similarity to known gene clusters responsible for the biosynthesis of antimicrobial antibiotics. The traditional isolation methods and activity-guided fractionation were employed to isolate and purify seven compounds with strong bioactivity from the fermentation broth of the strain KN37. These compounds were identified as 4-(Diethylamino)salicylaldehyde (1), 4-Nitrosodiphenylamine (2), N-(2,4-Dimethylphenyl)formamide (3), 4-Nitrocatechol (4), Methylsuccinic acid (5), Phenyllactic acid (6) and 5,6-Dimethylbenzimidazole (7). Moreover, 4-(Diethylamino)salicylaldehyde exhibited the most potent inhibitory effect against Rhizoctonia solani, with an EC50 value of 14.487 mg/L, while 4-Nitrosodiphenylamine showed great antibacterial activity against Erwinia amylovora, with an EC50 value of 5.715 mg/L. This study successfully isolated several highly active antimicrobial compounds from the metabolites of the strain KN37, which could contribute as scaffolds for subsequent chemical synthesis. On the other hand, the newly predicted antibiotic-like substances have not yet been isolated, but they still hold significant research value. They are instructive in the study of active natural product biosynthetic pathways, activation of silent gene clusters, and engineering bacteria construction.

Comparative assessment of orthodontic clear aligner versus fixed appliance for anterior retraction: a finite element study.

BACKGROUND: The aim of this study is to conduct a comparative evaluation of different designs of clear aligners and examine the disparities between clear aligners and fixed appliances. METHODS: 3D digital models were created, consisting of a maxillary dentition without first premolars, maxilla, periodontal ligaments, attachments, micro-implant, 3D printed lingual retractor, brackets, archwire and clear aligner. The study involved the creation of five design models for clear aligner maxillary anterior internal retraction and one design model for fixed appliance maxillary anterior internal retraction, which were subsequently subjected to finite element analysis. These design models included: (1) Model C0 Control, (2) Model C1 Posterior Micro-implant, (3) Model C2 Anterior Micro-implant, (4) Model C3 Palatal Plate, (5) Model C4 Lingual Retractor, and (6) Model F0 Fixed Appliance. RESULTS: In the clear aligner models, a consistent pattern of tooth movement was observed. Notably, among all tested models, the modified clear aligner Model C3 exhibited the smallest differences in sagittal displacement of the crown-root of the central incisor, vertical displacement of the central incisor, sagittal displacement of the second premolar and second molar, as well as vertical displacement of posterior teeth. However, distinct variations in tooth movement trends were observed between the clear aligner models and the fixed appliance model. Furthermore, compared to the fixed appliance model, significant increases in tooth displacement were achieved with the use of clear aligner models. CONCLUSIONS: In the clear aligner models, the movement trend of the teeth remained consistent, but there were variations in the amount of tooth displacement. Overall, the Model C3 exhibited better torque control and provided greater protection for posterior anchorage teeth compared to the other four clear aligner models. On the other hand, the fixed appliance model provides superior anterior torque control and better protection of the posterior anchorage teeth compared to clear aligner models. The clear aligner approach and the fixed appliance approach still exhibit a disparity; nevertheless, this study offers a developmental direction and establishes a theoretical foundation for future non-invasive, aesthetically pleasing, comfortable, and efficient modalities of clear aligner treatment.

Ferroptosis and central nervous system demyelinating diseases.

Ferroptosis is a newly discovered programmed cell death caused by intracellular iron excess and glutathione (GSH) system imbalance, resulting in fatal lipid peroxidation. It is different from necrosis, apoptosis, autophagy, and other forms of cell death. Accumulating evidences suggest that brain iron overload is involved in the pathogenesis of demyelinating diseases of the central nervous system (CNS), such as multiple sclerosis (MS), neuromyelitis optica (NMO), and acute disseminated encephalomyelitis (ADEM). The study of ferroptosis may provide a new understanding of demyelinating diseases and provide a novel therapeutic target for clinical treatment. Herein, we reviewed recent discoveries on mechanisms of ferroptosis, the effects of metabolic pathways on ferroptosis, and its involvement in CNS demyelinating diseases.

The effects of lingual buttons, precision cuts, and patient-specific attachments during maxillary molar distalization with clear aligners: Comparison of finite element analysis.

INTRODUCTION: This study aimed to analyze the biomechanical effects of the combined use of clear aligners (CA) and auxiliaries (precision cuts, lingual buttons, and patient-specific attachments) on mesial tipping and extrusion of the premolars during maxillary molars distalization. METHODS: Three-dimensional finite element method was employed to simulate clinical scenarios of CA with different auxiliaries for molar distalization. As such, 200 g of distal force was applied to the microimplants from the notches, lingual buttons, and hooks. Orthodontic tooth movement and the hydrostatic pressure in the periodontal ligament were compared. RESULTS: Adding auxiliaries can provide the maxillary arch anchorage and promote the distal tipping of premolars and retroclination of maxillary incisors. In contrast, this effect was more pronounced in patient-specific attachment applications than in other types of auxiliaries. The independent application of the CA caused mesial tipping and extrusion of the premolar and also caused the incisor proclination. CONCLUSIONS: The anchorage loss caused by the CA alone could be alleviated with the assistance of auxiliaries. Notably, patient-specific attachments further reinforce the anchorage of the anterior arch by incorporating anchor teeth as 1 anchorage unit.

Effects of different designs of orthodontic clear aligners on the maxillary central incisors in the tooth extraction cases: a biomechanical study.

BACKGROUND: Controlling the 3D movement of central incisors during tooth extraction cases with clear aligners is important but challenging in invisible orthodontic treatment. This study aimed to explore the biomechanical effects of central incisors in tooth extraction cases with clear aligners under different power ridge design schemes and propose appropriate advice for orthodontic clinic. METHODS: A series of Finite Element models was constructed to simulate anterior teeth retraction or no retraction with different power ridge designs. These models all consisted of maxillary dentition with extracted first premolars, alveolar bone, periodontal ligaments and clear aligner. And the biomechanical effects were analysed and compared in each model. RESULTS: For the model of anterior teeth retraction without power ridge and for the model of anterior teeth no retraction with a single power ridge, the central incisors exhibited crown lingual inclination and relative extrusion. For the model of anterior teeth no retraction with double power ridges, the central incisors tended to have crown labial inclination and relative intrusion. For the model of anterior tooth retraction with double power ridges, the central incisors exhibited a similar trend to the first kind of model, but as the depth of the power ridge increased, there was a gradual decrease in crown retraction value and an increase in crown extrusion value. The simulated results showed that von-Mises stress concentration was observed in the cervical and apical regions of the periodontal ligaments of the central incisors. The clear aligner connection areas of adjacent teeth and power ridge areas also exhibited von-Mises stress concentration and the addition of power ridge caused the clear aligner to spread out on the labial and lingual sides. CONCLUSIONS: The central incisors are prone to losing torque and extruding in tooth extraction cases. Double power ridges have a certain root torque effect when there are no auxiliary designs, but they still cannot rescue tooth inclination during tooth retraction period. For tooth translation, it may be a better clinical procedure to change the one-step aligner design to two-step process: tilting retraction and root control.

Sex Differences in Short-Term and Long-Term Outcomes Among Patients With Acute Ischemic Stroke in China.

BACKGROUND: Sex differences in stroke outcomes are crucial to secondary prevention, but previous reports showed inconsistent results. We aimed to explore the sex differences in stroke outcomes in the Third China National Stroke Registry, a prospective multicenter registry study. METHODS: Among the 15 166 patients enrolled between 2015 and 2018, 9038 patients with acute ischemic stroke (AIS) were included. The primary outcomes were stroke recurrence, mortality, and unfavorable functional outcome (modified Rankin Scale > 2) at 3, 6, and 12 months. Cox regression model was used for stroke recurrence and mortality and logistic regression was used for the unfavorable functional outcome, and adjusted as follows: (1) Model 1: without adjustment; (2) Model 2: adjusted for potential risk factors, National Institutes of Health Stroke Scale at admission, prestroke modified Rankin Scale, tPA (tissue-type plasminogen activator) treatment, TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification, and onset-to-door time; (3) Model 3: adjusted for covariates from model 2 in addition to blood pressure and blood serum covariates. Multiple imputation was used for missing values, and sensitivity analyses were conducted to describe sex differences by age groups. RESULTS: One-third (2802/9038) of the patients were women. Women were significantly older than men (64.78±10.84 versus 61.26±11.42, P<0.001). In the fully adjusted model, female patients were more likely to have unfavorable functional outcomes at 3 months (odds ratio, 1.28 [1.09-1.50]), especially among patients aged 65 years or older (odds ratio, 1.39 [1.14-1.70]), but no difference was discovered in patients aged <65 years. There were no sex differences in stroke recurrence and mortality at 3, 6, or 12 months or unfavorable functional outcomes at 6 or 12 months after adjustment. CONCLUSIONS: Compared with men, women with AIS were less likely to have favorable outcomes at 3 months in China, especially among those over 65 years of age. Experts should aim to tailor secondary prevention strategies for high-risk patients.

ICH-LR2S2: a new risk score for predicting stroke-associated pneumonia from spontaneous intracerebral hemorrhage.

PURPOSE: We develop a new risk score to predict patients with stroke-associated pneumonia (SAP) who have an acute intracranial hemorrhage (ICH). METHOD: We applied logistic regression to develop a new risk score called ICH-LR2S2. It was derived from examining a dataset of 70,540 ICH patients between 2015 and 2018 from the Chinese Stroke Center Alliance (CSCA). During the training of ICH-LR2S2, patients were randomly divided into two groups - 80% for the training set and 20% for model validation. A prospective test set was developed using 12,523 patients recruited in 2019. To further verify its effectiveness, we tested ICH-LR2S2 on an external dataset of 24,860 patients from the China National Stroke Registration Management System II (CNSR II). The performance of ICH-LR2S2 was measured by the area under the receiver operating characteristic curve (AUROC). RESULTS: The incidence of SAP in the dataset was 25.52%. A 24-point ICH-LR2S2 was developed from independent predictors, including age, modified Rankin Scale, fasting blood glucose, National Institutes of Health Stroke Scale admission score, Glasgow Coma Scale score, C-reactive protein, dysphagia, Chronic Obstructive Pulmonary Disease, and current smoking. The results showed that ICH-LR2S2 achieved an AUC = 0.749 [95% CI 0.739-0.759], which outperforms the best baseline ICH-APS (AUC = 0.704) [95% CI 0.694-0.714]. Compared with the previous ICH risk scores, ICH-LR2S2 incorporates fasting blood glucose and C-reactive protein, improving its discriminative ability. Machine learning methods such as XGboost (AUC = 0.772) [95% CI 0.762-0.782] can further improve our prediction performance. It also performed well when further validated by the external independent cohort of patients (n = 24,860), ICH-LR2S2 AUC = 0.784 [95% CI 0.774-0.794]. CONCLUSION: ICH-LR2S2 accurately distinguishes SAP patients based on easily available clinical features. It can help identify high-risk patients in the early stages of diseases.

Study on Droplet Impact and Spreading and Deposition Behavior of Harvest Aids on Cotton Leaves.

The deposition and spreading of pesticide droplets on the surface of plants is a severe challenge to precise pesticide application, which directly affects the pesticide utilization rate and efficacy. Cotton harvest aids are widely used in machine-picked cotton but the effect of formulation and concentration on the droplet behavior and defoliation effect of cotton defoliants is not clear. To clarify the influence of formulation and concentration on the droplet behavior of cotton defoliants, four formulations (suspension concentrate (SC), water dispersible granule (WG), oil dispersion (OD), and wettable powder (WP)) of cotton defoliants were used to prepare different concentrations of harvest aid solutions, according to the spraying volume. The physicochemical properties, droplet impact, and spreading and deposition behavior were studied. The results indicated that the four kinds of harvest aids have good physicochemical properties and can be wet and spread on cotton leaves. The surface tension of the high-concentration harvest aid solution (the spraying volume was less than 1.2 L/667 m2) was increased, which increased the contact angle and reduced the adhesion tension, adhesion work, and the spreading area. Once the harvest aid solution systems impacted the cotton leaves, it could spread to the maximum in a short time (10 ms). The field experiment showed that the droplet spectrum of harvest aids changed slightly, the coefficient of variation (CV) did not exceed 50%, and the defoliation rate was better when the spraying volume was 1.5 L/667 m2. The correlation and principal component analysis showed that the spraying volume (concentration) and coverage were negatively correlated with the defoliation rate, while the viscosity, diffusion factor, and spreading rate were positively correlated with the defoliation rate. Overall, the use of appropriate spraying volume application in cotton fields can improve the performance of spray, increase the effective deposition and wetting spread of defoliants on cotton leaves, further reduce the dosage of defoliants, and improve pesticide utilization. These results can provide a theoretical basis for the scientific preparation and spraying of cotton harvest aid solutions.

Sex differences in vascular risk factors, in-hospital management, and outcomes of patients with acute ischemic stroke in China.

BACKGROUND: Previous assessments of sex differences for patients with acute ischemic stroke were limited in a specific region or population, narrow scope, or small sample size. METHODS: Patients with acute ischemic stroke hospitalized in the China Stroke Center Alliance hospitals were analyzed. Absolute standardized differences (ASDs) were used to assess sex differences in vascular risk factors, guideline-recommended in-hospital management measures and outcomes, including stroke severity (National Institutes of Health Stroke Scale≥16), death/discharge against medical advice, major adverse cardiovascular events, pneumonia, and disability (modified Rankin Scale≥3). RESULTS: Of 838,229 patients analyzed, 524351 (62.6%) were men and 313,878 (37.4%) were women. Compared with men, women were older (68.6 vs. 64.7 years), had higher prevalence of hypertension (67.7% vs. 62.4%), diabetes (24.7% vs. 19.5%), and atrial fibrillation (7.1% vs. 4.3%), but lower prevalence of smoking (4.5% vs. 56.6%) and drinking (2.6% vs 35.8%) (ASDs >10%). No sex differences were seen in guideline-directed management measures, indicated by risk-adjusted individual measures and the all-or-null summary measure (34.5% vs 34.9%, ASD = 1.0%). Compared to men, women tended to have strokes that were more severe at presentation (6.5% vs. 4.5%, ASD = 8.8%) and more disabilities at discharge (34.9% vs 30.5%, ASD =9.4%). However, all sex-related differences in outcomes were attenuated to null after risk adjustments (ASDs<2%). CONCLUSIONS: Compared to male patients, female patients had more vascular risk factors and received similar in-hospital care. They had strokes that were more severe at presentation and more disabilities at discharge, both of which may be explained by worse vascular risk profiles.

Identifying stroke diagnosis-related features from medical imaging reports to improve clinical decision-making support.

BACKGROUND: Medical imaging reports play an important role in communication of diagnostic information between radiologists and clinicians. Head magnetic resonance imaging (MRI) reports can provide evidence that is widely used in the diagnosis and treatment of ischaemic stroke. The high-signal regions of diffusion-weighted imaging (DWI) images in MRI reports are key evidence. Correctly identifying high-signal regions of DWI images is helpful for the treatment of ischaemic stroke patients. Since most of the multiple signals recorded in head MRI reports appear in the same part, it is challenging to identify high-signal regions of DWI images from MRI reports. METHODS: We developed a deep learning model to automatically identify high-signal regions of DWI images from head MRI reports. We proposed a fine-grained entity typing model based on machine reading comprehension that transformed the traditional two-step fine-grained entity typing task into a question-answering task. RESULTS: To prove the validity of the model proposed, we compared it with the fine-grained entity typing model, of which the F1 measure was 5.9% and 3.2% higher than the F1 measures of the models based on LSTM and BERT, respectively. CONCLUSION: In this study, we explore the automatic identification of high-signal regions of DWI images from the description part of a head MRI report. We transformed the identification of high-signal regions of DWI images to an FET task and proposed an MRC-FET model. Compared with the traditional two-step FET method, the model we proposed not only simplifies the task but also has better performance. The comparable result shows that the work in this study can contribute to improving the clinical decision support system.

Influence of bone morphology on the mechanobiological stimuli distribution of maxillary anterior labial bone: A biomechanical study.

OBJECTIVE: This study intended to ascertain the dimensional effects of labial bone thickness and height on the mechanobiological stimuli distribution of maxillary anterior labial bone through biomechanical analysis. MATERIAL AND METHODS: Twelve 3D finite element models of an anterior maxillary region with an implant were computer-simulated, including four levels of labial bone thicknesses (2, 1.5, 1.0, and 0.5 mm) and three levels of labial bone heights (normal, reduced by 1/3, reduced by 1/2). A 45° buccolingual oblique load of 100 N was applied to the implant restoration. RESULTS: Equivalent stress and principal strain mainly concentrated on crestal bone around the implant neck. The maximum equivalent stress in bone decreased as labial bone mass decreased, while the maximum principal strain and the displacement of dental implant increased as labial bone mass decreased. No significant difference of these three indicators was observed, when the labial bone thickness changed in the range of 2.0-1.0 mm with sufficient labial bone height. CONCLUSIONS: In terms of biomechanics, the thickness of labial bone plate was recommended ≥1 mm. Sufficient labial bone height was warranted to prevent the stability of the implants from being seriously affected. The labial bone heights were more effective than thicknesses on the mechanobiological stimuli response of the dental implant-bone system. CLINICAL SIGNIFICANCE: For this 3D finite element study, the biomechanical responses under different bone mass conditions were explored, in order to predict the process of bone remodeling and provide valid clinical recommendations for the decision-making process regarding the choices of tissue augmentation for some specific esthetic implantation cases for future clinical applications.

Non-High-Density Lipoprotein Cholesterol Predicts Adverse Outcomes in Acute Ischemic Stroke.

Background and Purpose: Non­high-density lipoprotein cholesterol (non­HDL-C) was significantly related to adverse outcomes in patients with cardiovascular disease. We aim to investigate the associations of non-HDL-C and adverse outcomes in acute ischemic stroke. Methods: Among 19 604 patients with acute ischemic stroke admitted to the China National Stroke Registry II, 16 113 with both total cholesterol and HDL-C were analyzed. Patients were classified into 5 groups by quintiles of non-HDL-C. The outcomes included recurrent ischemic stroke, intracranial hemorrhage, and all-cause death within 1 year. The relationship of non-HDL-C with the risk of outcomes was analyzed by Cox regression models. Results: Among the 16 113 patients, the median (interquartile range) of non-HDL-C was 3.41 (2.78­4.10) mmol/L. After adjustment for confounding variables, patients in the top quintile of non-HDL-C were associated with higher risk of recurrent ischemic stroke within 1 year (adjusted hazard ratio, 1.46 [95% CI, 1.20­1.77]), compared with those in the third quintile. Patients in the bottom and top quintile of non-HDL-C were associated with higher risk of all-cause death within 1 year (adjusted hazard ratio, 1.22 [95% CI, 1.01­1.47] and adjusted hazard ratio, 1.40 [95% CI, 1.15­1.70], respectively), compared with those in the third quintile. However, non-HDL-C levels were not significantly predictive in intracranial hemorrhage. Conclusions: Non-HDL-C may be a qualified predictor for recurrent ischemic stroke and all-cause death within 1 year in patients with acute ischemic stroke.

Clinical Characteristics and In-Hospital Outcomes of Varying Definitions of Minor Stroke: From a Large-Scale Nation-Wide Longitudinal Registry.

BACKGROUND AND PURPOSE: A variety of definitions for minor stroke have been proposed. We aimed to compare the clinical characteristics and outcomes of minor stroke defined as the National Institutes of Health Stroke Scale (NIHSS) score ≤5 versus ≤3. METHODS: We retrieved acute ischemic stroke patients with NIHSS score ≤5 in the CSCA study (China Stroke Center Alliance) between August 2015 and 2019. In-hospital clinical outcomes including all-cause mortality, stroke, and myocardial infarction were compared between the NIHSS score ≤5 and NIHSS score ≤3 groups using absolute standardized differences (ASD). RESULTS: A total of 1 006 798 patients were registered in the CSCA program from 1476 hospitals, 472 352 patients had NIHSS score ≤5, of whom 356 314 patients had NIHSS score ≤3. The in-hospital composite events of death, myocardial infarction, or recurrent stroke were not significantly different between the NIHSS score ≤5 and NIHSS score ≤3 groups (5.6% [26 346/472 352] versus 5.2% [18 682/356 314]; ASD, 1.8). The in-hospital all-cause mortality (0.1% [443/472 352] versus 0.1% [255/356 314]; ASD, <0.01), recurrent ischemic stroke (5.3% [25 026/472 352] versus 5.0% [17 777/356 314]; ASD, 1.4), and hemorrhagic stroke (0.5% [2151/472 352] versus 0.4% [1475/356 314]; ASD, 1.5) were not significantly different between both the NIHSS score ≤5 and NIHSS score ≤3 groups. CONCLUSIONS: Our large-scale study identified that minor stroke using NIHSS scores ≤5 and ≤3 as the definition was comparable with each other regarding in-hospital all-cause mortality, recurrent stroke, and hemorrhagic stroke. This observation may be useful for future comparison studies and clinical trial design.