Prediction of poststroke independent walking using machine learning: a retrospective study.

BACKGROUND: Accurately predicting the walking independence of stroke patients is important. Our objective was to determine and compare the performance of logistic regression (LR) and three machine learning models (eXtreme Gradient Boosting (XGBoost), Support Vector Machines (SVM), and Random Forest (RF)) in predicting walking independence at discharge in stroke patients, as well as to explore the variables that predict prognosis. METHODS: 778 (80% for the training set and 20% for the test set) stroke patients admitted to China Rehabilitation Research Center between February 2020 and January 2023 were retrospectively included. The training set was used for training models. The test set was used to validate and compare the performance of the four models in terms of area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and F1 score. RESULTS: Among the three ML models, the AUC of the XGBoost model is significantly higher than that of the SVM and RF models (P < 0.001, P = 0.024, respectively). There was no significant difference in the AUCs between the XGBoost model and the LR model (0.891 vs. 0.880, P = 0.560). The XGBoost model demonstrated superior accuracy (87.82% vs. 86.54%), sensitivity (50.00% vs. 39.39%), PPV (73.68% vs. 73.33%), NPV (89.78% vs. 87.94%), and F1 score (59.57% vs. 51.16%), with only slightly lower specificity (96.09% vs. 96.88%). Together, the XGBoost model and the stepwise LR model identified age, FMA-LE at admission, FAC at admission, and lower limb spasticity as key factors influencing independent walking. CONCLUSION: Overall, the XGBoost model performed best in predicting independent walking after stroke. The XGBoost and LR models together confirm that age, admission FMA-LE, admission FAC, and lower extremity spasticity are the key factors influencing independent walking in stroke patients at hospital discharge. TRIAL REGISTRATION: Not applicable.

Effects of Mobile Intelligent Cognitive Training for Patients with Post-Stroke Cognitive Impairment: A 12-Week, Multicenter, Randomized Controlled Study.

Background: The current application effects of computerized cognitive intervention are inconsistent and limited to hospital rehabilitation settings. Objective: To investigate the effect of mobile intelligent cognitive training (MICT) on patients with post-stroke cognitive impairment (PSCI). Methods: This study was a multicenter, prospective, open-label, blinded endpoint, cluster-randomized controlled trial (RCT). 518 PSCI patients were stratified and assigned to four rehabilitation settings, and then patients were randomized into experimental and control groups in each rehabilitation setting through cluster randomization. All patients received comprehensive management for PSCI, while the experimental group additionally received MICT intervention. Treatment was 30 minutes daily, 5 days per week, for 12 weeks. Cognitive function, activities of daily living (ADL), and quality of life (QOL) were assessed before the treatment, at weeks 6 and 12 post-treatment, and a 16-week follow-up. Results: Linear Mixed Effects Models showed patients with PSCI were better off than pre-treatment patients on each outcome measure (p < 0.05). Additionally, the improvement of these outcomes in the experimental group was significantly better than in the control group at week 6 post-treatment and 16-week follow-up (p < 0.05). The rehabilitation setting also affected the cognitive efficacy of MICT intervention in improving PSCI patients, and the degree of improvement in each outcome was found to be highest in hospital, followed by community, nursing home, and home settings. Conclusions: Long-term MICT intervention can improve cognition, ADL, and QOL in patients with PSCI, with sustained effects for at least one month. Notably, different rehabilitation settings affect the cognitive intervention efficacy of MICT on PSCI patients. However, this still needs to be further determined in future studies.

Exploring the therapeutic efficacy and pharmacological mechanism of Guizhi Fuling Pill on ischemic stroke: a meta-analysis and network pharmacology analysis.

The role of Guizhi Fuling Pill (GZFL) in the treatment of ischemic stroke (IS) is still controversial, and its pharmacological mechanism remains unclear. To evaluate the efficacy and potential pharmacological mechanisms of GZFL on IS, a comprehensive method integrating meta-analysis, network pharmacology, and molecular docking was employed. Eight electronic databases were searched from inception to November 2023. Review Manager 5.4.1 software was used for meta-analysis. Active compounds and targets of GZFL were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database, Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine, and Encyclopaedia of Traditional Chinese Medicine. Relevant targets of IS were obtained from the DisGeNet, Genecards, and DrugBank databases. GO biological function analysis and KEGG enrichment analysis were performed in the Metascape database. AutoDock Tools and PyMOL software were employed for Molecular docking. The intervention group significantly increased the total effective rate and decreased the NIHSS score. Administration of GZFL also improved the whole blood viscosity (low and high shear rates) and levels of fibrinogen, TNF-α, and IL-6. The key active compounds included quercetin, kaempferol, catechin, and beta-sitosterol, and the core target proteins included SRC, MAPK1, TP53, JUN, RELA, AKT1, and TNF. GO analysis mainly involved inflammation response, cellular response to lipids, and regulation of ion transport. The core pathways were lipid and atherosclerosis, cAMP, calcium, IL-17, and MAPK signaling pathways. Key active compounds showed good affinity with the core targets. The underlying mechanisms of GZFL in IS treatment are primarily related to its anti-inflammatory, anti-atherosclerosis, and neuroprotective effects.

Insights into the structure and function of the hippocampus: implications for the pathophysiology and treatment of autism spectrum disorder.

The hippocampus is one of the brain areas affected by autism spectrum disorder (ASD). Individuals with ASD typically have impairments in hippocampus-dependent learning, memory, language ability, emotional regulation, and cognitive map creation. However, the pathological changes in the hippocampus that result in these cognitive deficits in ASD are not yet fully understood. In the present review, we will first summarize the hippocampal involvement in individuals with ASD. We will then provide an overview of hippocampal structural and functional abnormalities in genetic, environment-induced, and idiopathic animal models of ASD. Finally, we will discuss some pharmacological and non-pharmacological interventions that show positive impacts on the structure and function of the hippocampus in animal models of ASD. A further comprehension of hippocampal aberrations in ASD might elucidate their influence on the manifestation of this developmental disorder and provide clues for forthcoming diagnostic and therapeutic innovation.

Interactions between circulating inflammatory factors and autism spectrum disorder: a bidirectional Mendelian randomization study in European population.

Background: Extensive observational studies have reported an association between inflammatory factors and autism spectrum disorder (ASD), but their causal relationships remain unclear. This study aims to offer deeper insight into causal relationships between circulating inflammatory factors and ASD. Methods: Two-sample bidirectional Mendelian randomization (MR) analysis method was used in this study. The genetic variation of 91 circulating inflammatory factors was obtained from the genome-wide association study (GWAS) database of European ancestry. The germline GWAS summary data for ASD were also obtained (18,381 ASD cases and 27,969 controls). Single nucleotide polymorphisms robustly associated with the 91 inflammatory factors were used as instrumental variables. The random-effects inverse-variance weighted method was used as the primary analysis, and the Bonferroni correction for multiple comparisons was applied. Sensitivity tests were carried out to assess the validity of the causal relationship. Results: The forward MR analysis results suggest that levels of sulfotransferase 1A1, natural killer cell receptor 2B4, T-cell surface glycoprotein CD5, Fms-related tyrosine kinase 3 ligand, and tumor necrosis factor-related apoptosis-inducing ligand are positively associated with the occurrence of ASD, while levels of interleukin-7, interleukin-2 receptor subunit beta, and interleukin-2 are inversely associated with the occurrence of ASD. In addition, matrix metalloproteinase-10, caspase 8, tumor necrosis factor-related activation-induced cytokine, and C-C motif chemokine 19 were considered downstream consequences of ASD. Conclusion: This MR study identified additional inflammatory factors in patients with ASD relative to previous studies, and raised a possibility of ASD-caused immune abnormalities. These identified inflammatory factors may be potential biomarkers of immunologic dysfunction in ASD.

Therapeutic efficacy and pharmacological mechanism of Yindan Xinnaotong soft capsule on acute ischemic stroke: a meta-analysis and network pharmacology analysis.

Yindan Xinnaotong soft capsule (YDXNT), a traditional Chinese medicine preparation, has shown a promising effect in the treatment of acute ischemic stroke (AIS). The goal of this study was to investigate the therapeutic effects and pharmacological mechanisms of YDXNT on AIS. Randomized controlled trials were searched and screened. Review Manager 5.4 was used for a meta-analysis. Active ingredients and targets of YDXNT were extracted from the Traditional Chinese Medicine Systems Pharmacology Database, Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine, and Encyclopaedia of Traditional Chinese Medicine. AIS-related targets were retrieved from GeneCards, OMIM, and DrugBank databases. We constructed PPI and ingredient-target networks, performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and conducted molecular docking. The YDXNT group had a higher total effective rate and a higher Barthel Index score. YDXNT reduced the low-density lipoprotein cholesterol and the whole blood viscosity at high and shear rates. Our study identified 313 ingredients and 1196 common targets. The key ingredients were mainly quercetin, neocryptotanshinone II, miltionone I, neotanshinone C, and tanshiquinone B, and the key targets were mainly SRC, MAPK3, AKT1, MAPK1, and JUN. GO analysis showed that the core targets mainly involved in atherosclerosis and neural apoptosis. The core pathways were lipid and atherosclerosis, PI3K-Akt, MAPK, and other pathways. Key ingredients exhibited robust binding interactions with core targets. YDXNT could effectively improve the total effective rate, ability of daily life, blood lipids, and blood viscosity. Antiatherosclerotic and neuroprotective effects are the main pharmacological mechanisms.Registration number: CRD42023400127.

Bibliometric analysis of global research trends on regulatory T cells in neurological diseases.

This bibliometric study aimed to summarize and visualize the current research status, emerging trends, and research hotspots of regulatory T (Treg) cells in neurological diseases. Relevant documents were retrieved from the Web of Science Core Collection. Tableau Public, VOSviewer, and CiteSpace software were used to perform bibliometric analysis and network visualization. A total of 2,739 documents were included, and research on Treg cells in neurological diseases is still in a prolific period. The documents included in the research were sourced from 85 countries/regions, with the majority of them originating from the United States, and 2,811 organizations, with a significant proportion of them coming from Harvard Medical School. Howard E Gendelman was the most prolific author in this research area. Considering the number of documents and citations, impact factors, and JCR partitions, Frontiers in Immunology was the most popular journal in this research area. Keywords "multiple sclerosis," "inflammation," "regulatory T cells," "neuroinflammation," "autoimmunity," "cytokines," and "immunomodulation" were identified as high-frequency keywords. Additionally, "gut microbiota" has recently emerged as a new topic of interest. The study of Treg cells in neurological diseases continues to be a hot topic. Immunomodulation, gut microbiota, and cytokines represent the current research hotspots and frontiers in this field. Treg cell-based immunomodulatory approaches have shown immense potential in the treatment of neurological diseases. Modifying gut microbiota or regulating cytokines to boost the numbers and functions of Treg cells represents a promising therapeutic strategy for neurological diseases.

Effect of different constraint-induced movement therapy protocols on recovery of stroke survivors with upper extremity dysfunction: a systematic review and network meta-analysis.

We aimed to assess and rank comparative efficacy of different constraint-induced movement therapy (CIMT) protocols on motor function of upper extremity and activities of daily living (ADL) in stroke survivors. A comprehensive search was conducted in PubMed, EMBASE, Web of Science and Cochrane Library to identify randomized controlled trials on CIMT. Included studies were evaluated using the revised Cochrane risk of bias tool. Then a random-effects network meta-analysis was performed within a frequentist framework using Stata v16.0. Of the 1150 studies retrieved, 44 studies with 1779 participants were included. In terms of motor recovery of upper extremity, CIMT combined with trunk restraint, in which the less affected arm was constrained at least 4 h but no more than 6 h per day, ranked as the most effective intervention for the improvement of the Fugl-Meyer Assessment-Upper Extremity and the Action Research Arm Test score. In terms of ADL improvement, constraining the less affected arm for at least 4 h but no more than 6 h per day in CIMT combined with trunk restraint, was found to significantly improve the Motor Activity Log of quality of movement scale and amount of use scale score. The protocol of CIMT combined with trunk restraint, in which the less affected arm was constrained at least 4 h but no more than 6 h per day, ranked the highest in this analysis and might be considered in practice.

Music-based interventions for unilateral spatial neglect: A systematic review.

This study aimed to evaluate the effects of music-based interventions on unilateral spatial neglect. Five databases were retrieved prior to May 5, 2022. A range of study designs were considered, including randomized controlled trials, controlled clinical trials, cohorts, and case series/reports. Types of music-based interventions were not limited. Methodological quality of randomized trials were evaluated using the RoB 2 tool, and the RoBiNT scale was utilized to assess the quality of case studies. Two authors independently summarized main results for assessments. Search strategies identified 186 potentially relevant articles, and 10 articles were collected for in-depth analysis. Preliminary results showed that USN patients performed better in cancellation tests than bisection tests after music-based intervention. In summary, pleasant music listening may have a beneficial effect on the visual attention of USN patients, and it can be hypothesized that this is related to the positive mood and emotions of patients induced by music. Music with a dynamic auditory stimulus as a new music listening programme in USN rehabilitation is worthy of further investigation. Instrument playing intervention can be considered as a multisensory stimulation to ameliorate neglect performance via multiple mechanisms. However, current results only support the short-term positive effects of music-based interventions on USN.

Nattokinase Supplementation and Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: As a fibrinolytic enzyme from fermented soybean, nattokinase has been shown to be potentially beneficial for cardiovascular health, but current clinical evidences regarding the nattokinase supplementation on cardiovascular risk factors are various. This study aims to evaluate the cardiovascular efficacy of nattokinase. Methods: Four electronic databases were systematically searched to collect eligible randomized controlled trials. Data were extracted and summarized in a pre-designed form by two independent reviewers. Review Manager 5.4 software (Cochrane Library Software, Oxford, U.K.) was used for meta-analysis and bias risk assessment. Results: Six studies were eligible for quantitative analysis with 546 participants. The overall methodological quality of included studies was high. Relatively low total dosage of nattokinase had a negative effect on blood total cholesterol (MD [mean difference] = 5.27, 95% CI [confidence intervals]: 3.74 to 6.81, p < 0.00001), high-density lipoprotein cholesterol (MD = -2.76, 95% CI: -3.88 to -1.64, p < 0.00001), and low-density lipoprotein cholesterol (MD = 6.49, 95% CI: 0.83 to 12.15, p = 0.02). Nattokinase supplementation significantly reduced systolic blood pressure (MD = -3.45, 95% CI: -4.37 to -2.18, p < 0.00001) and diastolic blood pressure (MD = -2.32, 95% CI: -2.72 to -1.92, p < 0.00001), and led a slight increase in blood glucose (MD = 0.40, 95% CI: 0.20 to 0.60, p < 0.0001) as compared to placebo. Nattokinase group with relatively high total dosage also had a higher total cholesterol (MD = 3.18, 95% CI: 2.29 to 4.06, p < 0.00001) than control interventions, but no significant differences were found in levels of high-density lipoprotein cholesterol and low-density lipoprotein cholesterol. No significant correlation was found between nattokinase supplementation and triglyceride (p = 0.71). No notable adverse events were reported in all studies due to intake of nattokinase. Conclusions: This study further supports that nattokinase can be used as an effective adjunctive therapy for hypertension, but relatively low-dose supplementation of nattokinase may have no significant lipid-lowering effect. More work will need to be done to determine whether the positive efficacy of nattokinase on cardiovascular risk factors is dose-dependent. Systematic Review Registration: This work has been registered on PROSPERO (CRD42022315020).

Exosomes in the Field of Neuroscience: A Scientometric Study and Visualization Analysis.

Exosomes have received great attention for their diagnostic, therapeutic, and prognostic roles in the field of neuroscience over the past decade. This scientometric study aimed to quantitatively and qualitatively evaluate knowledge structure, hot topics, and research trends of studies about exosomes in the field of neuroscience using visualization tools. Web of Science Core collection databases were searched for relevant publications between 2005 and 2021. The Carrot2 online system, BICOMB, gCLUTO, and Ucinet software were utilized for key word analysis, and co-citations analyses were conducted in Citespace and VOSviewer. Altogether, 21 high-frequency key words were collected from 856 included articles, and 5 clusters were identified through biclustering analyses. The strategic diagram and social network analysis further determined research hotspots and trends. Co-citation analysis results revealed a few crucial works that contributed to the development of research on exosomes in the field of neuroscience. Moreover, the important sources that had contributed to the development of this field were identified. Our findings suggested that Alzheimer's disease-related research remained a hot topic in this field till now, and recent researchers had extended their scopes to more cognitive impairments. Importantly, researches related to exosomes in multiple sclerosis and Parkinson's disease were promising. While exosomes in acute central nervous system injury had not been sufficiently investigated, with continuous improvement in exosome-based delivery technology, this subject might make a breakthrough in terms of therapeutic innovations in the immediate future.

Exploring Active Compounds and Mechanisms of Angong Niuhuang Wan on Ischemic Stroke Based on Network Pharmacology and Molecular Docking.

Methods: The chemical ingredients of ANW were retrieved from TCMSP, TCMID, and literature. We predicted the potential targets of active ingredients by PubChem, Swiss Target Prediction, and STITCH databases. The targets related to ischemic stroke were retrieved using GeneCards, DisGeNET, DrugBank, TTD, and GEO databases. Subsequently, Venn diagrams were used to identify common targets of active ingredients and ischemic stroke. Protein-protein interaction (PPI) network was structured with STRING platform and Cytoscape 3.8.2. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of key targets were performed in the Metascape database. Finally, molecular docking was conducted by AutoDock Tools and PyMOL software. Results: A total of 2391 targets were identified for 230 active ingredients of ANW, and 1386 of them overlapped with ischemic stroke targets. The key active ingredients were mainly quercetin, ß-estradiol, berberine, wogonin, and ß-sitosterol, and the key targets were also identified, including IL-6, AKT1, MAPK3, PIK3CA, and TNF. The biological process (BP) results indicated that ANW may have therapeutic effects through response oxidative stress, inflammatory response, cellular response to lipid, and response to nutrient levels. Furthermore, the ingredients of ANW were predicted to have therapeutic effects on ischemic stroke via the HIF-1 signaling pathway, FoxO signaling pathway, chemokine signaling pathway, fluid shear stress and atherosclerosis, and neurotrophin signaling pathway. The molecular docking results all showed that the core ingredients were strong binding activity with the core targets. Conclusion: In conclusion, the bioinformatics and pharmacological results reveal that counteracting oxidative stress, suppressing inflammation, inhibiting the development of AS, and even protecting neurological function are critical pathways for ANW in the treatment of ischemic stroke. These results may help to elucidate the mechanism of ANW on ischemic stroke for experimental studies and clinical applications.

Effects of sling exercise therapy on post-stroke walking impairment: a systematic review and meta-analysis.

Walking impairment is a common consequence of stroke, resulting in long-term disability. Trunk muscle strength has been proven to be associated with post-stroke walking performance. As a type of trunk training, sling exercise therapy (SET) has been widely used to improve the trunk function in stroke patients. The purpose of this systematic review was to investigate the efficacy of SET on post-stroke walking impairment. Seven databases were systematically searched for eligible studies from their inception to 1 August 2021. Review Manager 5.3 software was used for this meta-analysis. The overall quality of included studies was evaluated by the physiotherapy evidence database scale. Twenty-five randomized controlled trials involving 1504 patients were included (23 in China and two in South Korea). In summary, SET more effectively improved the walking ability of post-stroke patients than conventional physical therapy or trunk training. The pooled analysis demonstrated that SET had positive effects on the 10 m maximum walking speed, integrated electromyography value of rectus femoris, biceps femoris and gastrocnemius, functional ambulation category, timed up and go test, and step length. At least in East Asia, our findings support SET to manage the post-stroke walking impairment.

Effect of probiotics on the nutritional status of severe stroke patients with nasal feeding that receive enteral nutrition: A protocol for systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Malnutrition is commonly observed after stroke and is closely associated with poor clinical outcomes. So, early nutrition support is particularly crucial for severe stroke patients. However, a significant number of critically ill patients are intolerant to enteral nutrition (EN). Probiotics have been widely used in malnutrition by various diseases and have a low incidence of enteral intolerance. So, we aim to elucidate the efficacy of probiotics in EN in improving the nutritional status and clinical prognosis of severe stroke patients with nasal feeding. METHOD: Embase, PubMed, Sinomed, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang database, and Vip Journal Integration Platform were searched from inception to March 31, 2021. Randomized controlled trials that applied probiotics in patients with severe stroke were included. The data were extracted and the risk of bias was assessed independently by 2 evaluators. RESULTS: Twenty-four studies comprising 2003 participants of randomized controlled trials were included. The result of pooled analyses showed that probiotics in EN were associated with better outcomes than EN alone on Glasgow Coma Scale score (mean difference [MD] = 1.03, 95% confidence intervals [CI]: 0.78-1.27; P < .00001), infection events (odds ratio [OR] = 0.25, 95% CI: 0.15-0.43; P < .00001), rate of intestinal flora dysbiosis (OR = 0.24, 95% CI: 0.12-0.48; P < .0001), gastrointestinal complications (OR = 0.25, 95% CI: 0.16-0.37, P < .00001), time to reach target nutrition (MD = -1.80, 95% CI: -2.42 to 1.18, P < .00001), prealbumin content (MD = 25.83, 95% CI: 13.68-37.99, P < .0001). CONCLUSION: Our results demonstrated that probiotics supplementation might be an effective intervention for improving the clinical prognosis in severe stroke patients with nasal feeding, but no significant effect on increasing muscle circumference.