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Visible-light-induced three-component 1,2-alkylpyridylation of alkenes with unactivated alkyl iodides and aryl cyanides is reported via a photocatalytic halogen-atom transfer (XAT) strategy. This metal-free protocol utilizes readily available tertiary alkylamine as the terminal reductant to smoothly convert alkyl iodides into the corresponding carbon radical species. The reaction features a broad substrate scope, excellent functional group tolerance, high efficiency, and mild reaction conditions. The practicability of this methodology is further demonstrated in the late-stage difunctionalization of bioactive molecules.
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PURPOSE: To evaluate the association between facet joints cross-sectional area asymmetry (FCAA) and cervical intervertebral disc herniation (CDH). METHODS: Overall, we retrospectively recruited 390 consecutive patients with CDH who underwent surgical treatment at our institution and 50 normal participants. Clinical variables and radiological findings related to CDH were collected. RESULTS: Patients with CDH were more likely to have a higher absolute value of the facet asymmetry factor (FAF) (p < .001), in which the FAF value of the left group was significantly higher than the other groups (p < .001) and the right group was lower than the central group (p < .001). 9.62% (C3/4), 12.19% (C4/5), 8.70% (C5/6), and 8.14% (C6/7) were determined as cutoff values for each variable that maximized sensitivity and specificity. Furthermore, multivariate analysis showed that cross-sectional area asymmetry of the facet joint (FCAA) was an independent risk factor for the occurrence of CDH. Also, the Chi-square test showed a significant difference in the distribution of the degeneration classification of the disc between the facet-degenerated group and the nondegenerated group at C5/6 (p = 0.026) and C6/7 (p = 0.005) in the facet asymmetry (FA) group. CONCLUSIONS: FCAA is evaluated as an independent risk factor for CDH and associated with the orientation of disc herniation. And facet joint orientation may also play a role in cervical spine degeneration rather than facet joint tropism.
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Vértebras Cervicais , Deslocamento do Disco Intervertebral , Articulação Zigapofisária , Humanos , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Deslocamento do Disco Intervertebral/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Articulação Zigapofisária/diagnóstico por imagem , Articulação Zigapofisária/cirurgia , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Adulto , Estudos Retrospectivos , IdosoRESUMO
Immune hemostasis due to an infection plays a vital role in sepsis-induced multiple organ dysfunction. Dendritic cells (DC) and T helper (Th) cells are the key members of the immune system maintaining immune homeostasis. This study aimed to explore the effect and mechanism of CD40L on the activation of DC and activated DC-induced Th2/Th17 differentiation. A CD40L knockout and cecal ligation and puncture (CLP) mouse model was established via cecal ligation. HE staining was used to evaluate the pathological changes. The gene expressions were studied using quantitative real-time polymerase chain reaction (qRT-PCR), while a transwell system was used to perform the co-culture of DC and T-cells. Flow cytometry was performed to detect the subtype of T and DC cells. ELISA was used to assess the amount of inflammatory factors. CD40L was highly expressed in the plasma of CLP mice. Knock out of CD40L inhibited the activation of DC cell and Th17 differentiation while promoting the Th2 differentiation. The mechanistic investigations revealed that CD40L promoted the activation of cGAS-STING pathway. Rescue experiments indicated that CD40L mediated DC activation via cGAS-STING signaling. Moreover, co-culturing of CD and CD+4 T-cells demonstrated that silencing of CD40L in DC suppressed the DC activation and inhibited Th17 differentiation while promoting Th2 differentiation. These findings revealed a relationship between CD40L, DC activation, and Th2/Th17 differentiation balance in sepsis-induced acute lung injury for the first time. These findings are envisaged to provide novel molecular targets for sepsis-induced lung injury treatment.
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This study assesses the status of outcome measures in the randomized controlled trial(RCT) involving the kidney-tonif-ying and blood-activating method for treating knee osteoarthritis(KOA), aiming to establish a theoretical foundation for the development of a core set of outcome measures in traditional Chinese medicine(TCM) treatment of KOA. The relevant articles were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, and Web of Science, in addition to ClinicalTrials.gov and the China Clinical Trial Registration Center, with the time interval from inception to August 2023. The RCT of treating KOA with the kidney-tonifying and blood-activating method was included. Two assessors independently conducted literature screening, data collection, and qualitative analysis to compile the outcome measure results. A total of 350 RCTs were included, involving 165 outcome measures with the total frequency of 1 462. These outcome measures were categorized into six domains: symptom and sign measures(23) with the frequency of 718(49.1%), TCM symptom and syndrome measures(3) with the frequency of 53(3.6%), physical examination measures(130) with the frequency of 506(34.6%), quality of life measures(4) with the frequency of 20(1.3%), long-term efficacy measures(2) with the frequency of 6(0.4%), and safety measures(3) with the frequency of 159(10.9%). Additionally, 53 studies used TCM syndrome and symptom scores as indicators of efficacy, employing eight distinct measurement tools. The RCTs involving the kidney-tonifying and blood-activating method for treating KOA had a variety of problems, such as unclear prio-ritization of outcome measures, diversity in measurement tools, absence of standardized assessment criteria for specific measures, and non-standardized usage. These problems affected the research quality and reliability. Hence, it is advisable to draw upon international expertise, improve research design, and merge TCM efficacy characteristics with clinical research to establish a core set of KOA outcome measures aligned with TCM principles.
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Medicina Tradicional Chinesa , Osteoartrite do Joelho , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Osteoartrite do Joelho/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/administração & dosagem , Rim/fisiopatologia , Avaliação de Resultados em Cuidados de Saúde , Resultado do TratamentoRESUMO
PURPOSE: To report and analyze development trends in the surgical treatment of congenital scoliosis (CS) in a large CS cohort over a 10-year period. METHODS: We retrospectively searched and extracted medical records of CS inpatients receiving posterior instrumented fusion surgery at our institute from January 2010 to December 2019. We analyzed information on demographics and surgical information, including the surgical approach, number of fused segments, use of osteotomy and titanium cage implantation, length of stay, intraoperative blood loss, and rates of complications and readmission. RESULTS: 1207 CS inpatients were included. In the past decade, the proportion of patients younger than 5 years increased from 15.5 to 26.9%. The average number of fused segments decreased from 9.24 to 7.48, and the proportion of patients treated with short-segment fusion increased from 13.4 to 30.3%. The proportion of patients treated with osteotomy and titanium cage implantation increased from 55.65% and 12.03% to 76.5% and 40.22%. The average length of stay and blood loss decreased from 16.5 days and 816.1 ml to 13.5 days and 501.7 ml. The complication and readmission rates also decreased during these ten years. CONCLUSION: During this ten-year period, the surgical treatment of CS at our institute showed trends toward a younger age at fusion, lower number of fused segments, higher rate of osteotomy and titanium cage implantation, reduced blood loss, shorter length of stay and lower rate complications and readmission. These results suggest performing osteotomy combined with titanium cage implantation at an earlier age can achieve fewer fused segments and complications.
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Escoliose , Fusão Vertebral , Humanos , Escoliose/etiologia , Resultado do Tratamento , Estudos Retrospectivos , Titânio , Próteses e Implantes , Fusão Vertebral/métodosRESUMO
The IEEE 802.11 standard provides multi-rate support for different versions. As there is no specification on the dynamic strategy to adjust the rate, different rate adaptation algorithms are applied according to different manufacturers. Therefore, it is often hard to interpret the performance discrepancy of various devices. Moreover, the ever-changing channels always challenge the rate adaptation, especially in the scenario with scarce spectrum and low SNR. As a result, it is important to sense the radio environment cognitively and reduce the unnecessary oscillation of the transmission rate. In this paper, we propose an environment-aware robust (EAR) algorithm. This algorithm employs an occasional small packet, designs a rate scheme adaptive to the environment, and enhances the robustness. We verify the throughput of EAR using network simulator NS-3 in terms of station number, motion speed and node distance. We also compare the proposed algorithm with three benchmark methods: AARF, RBAR and CHARM. Simulation results demonstrate that EAR outperforms other algorithms in several wireless environments, greatly improving the system robustness and throughput.
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Precisely introducing two similar functional groups into bulk chemical alkenes represents a formidable route to complex molecules. Especially, the selective activation of two electrophiles is in crucial demand, yet challenging for cross-electrophile-coupling. Herein, we demonstrate a redox-mediated electrolysis, in which aryl nitriles are both aryl radical precursors and redox-mediators, enables an intermolecular alkene 1,2-diarylation with a remarkable regioselectivity, thereby avoiding the involvement of transition-metal catalysts. This transformation utilizes cyanoarene radical anions for activating various aryl halides (including iodides, bromides, and even chlorides) and affords 1,2-diarylation adducts in up to 83 % yield and >20 : 1 regioselectivity with more than 80 examples, providing a feasible approach to complex bibenzyl derivatives.
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Organic carbamates represent a kind of privileged structures in both organic chemistry and industry. Despite the fact that the synthesis of alcohol-based carbamates has been well studied, an efficient access to hydroxamic acid-based carbamates is less explored due to the nucleophilicity of both O and N atoms in hydroxamic acids. Herein, we report a copper-catalyzed oxidative coupling of quinazoline-3-oxides and formamides for the synthesis of O-quinazolinic carbamates. This protocol is featured with practicability, simple starting materials, and operational simplicity.
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An organic photoredox-catalyzed gem-difluoroallylation of α-trifluoromethyl alkenes with alkyl iodides via C-F bond cleavage for the synthesis of gem-difluoroalkene derivatives is reported. This transition-metal-free transformation utilized a readily available organic dye 4CzIPN as the sole photocatalyst and employed a common chemical N,N,N',N'-tetramethylethylenediamine as the radical activator of alkyl iodides via halogen-atom transfer. In addition, a variety of iodides, including primary, secondary, and tertiary alkyl iodides, were tolerated and provided good to high yields.
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Meningioangiomatosis (MA) is a disease that is extremely rarely reported. Sporadic MA is occasionally combined with meningioma or other lesions (identified as non-pure MA). This retrospective study investigated the difference between pure MA and non-pure MA by exploring clinical manifestations, histopathology characteristics, and outcomes of MA after surgery. We reviewed the medical records of 36 histopathologically confirmed MA patients (18 pure MA and 18 non-pure MA) who received surgery at our institution between 2012 and 2021. We compared differences in demographic, clinical, imaging, pathological features, and surgical outcomes between pure MA and non-pure MA through descriptive statistics. Compared to non-pure MA, pure MA presented with a more prominent male predilection (5:1 vs. 1.57:1, P = 0.264), a higher seizure incidence (83.3% vs 50.0%, P = 0.038), a more seizure type of GTCS (14/15 vs 5/9, P = 0.047), a less prominent enhancement on MRI (27.8% vs 88.9%, P < 0.001) and a preference of temporal and frontal lobe (100% vs 44.4%, P < 0.001). The differences in clinical characteristics between pure MA and non-pure MA demonstrate their disparate biological natures. Pure MA seems to be a non-neoplastic lesion, while non-pure MA is commonly combined with meningioma, which is a neoplastic lesion. A correct differential diagnosis can be achieved via a triad of the type of seizure, the location of lesion and the radiological presentation. MA is curable and the prognosis is excellent as most patients are free of seizure and recurrence after surgical treatment.
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Malformações Vasculares do Sistema Nervoso Central , Neoplasias Meníngeas , Meningioma , China , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/cirurgia , Meningioma/diagnóstico , Meningioma/patologia , Meningioma/cirurgia , Prognóstico , Estudos Retrospectivos , Convulsões/etiologiaRESUMO
Knowing the molecular mechanism of male sterility in alfalfa is important to utilize the heterosis more effectively. However, the molecular mechanisms of male sterility in alfalfa are still unclear. In this study, the bulked segregant analysis (BSA) and bulked segregant RNA-seq (BSR) were performed with F2 separation progeny to study the molecular mechanism of male sterility in alfalfa. The BSA-seq analysis was located in a candidate region on chromosome 5 containing 626 candidate genes which were associated with male sterility in alfalfa, while the BSR-seq analysis filtered seven candidate DEGs related to male sterility, and these candidate genes including EF-Tu, ß-GAL, CESA, PHGDH, and JMT. The conjunctive analyses of BSR and BSA methods revealed that the genes of Msß-GAL and MsJMT are the common detected candidate genes involved in male sterility in alfalfa. Our research provides a theory basis for further study of the molecular mechanism of male sterility in alfalfa and significant information for the genetic breeding of Medicago sativa.
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Infertilidade Masculina , Medicago sativa , Humanos , Masculino , Medicago sativa/genética , Melhoramento Vegetal , Infertilidade das Plantas/genética , RNA-SeqRESUMO
In this paper, the effect of the ethylene vinyl acetate (EVA) copolymer, commonly used in improving rheological behavior of waxy oil, is introduced to investigate its effect on the formation of cyclopentane hydrate in a water-in-waxy oil emulsion system. The wax content studied shows a negative effect on the formation of hydrate by elongating its induction time. Besides, the EVA copolymer is found to elongate the induction time of cyclopentane hydrate through the cocrystallization effect with wax molecules adjacent to the oil-water interface.
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An efficient palladium-catalyzed carbonylation reaction of readily available quaternary ammonium salts with CO is reported for the first time to afford arylacetamides and arylacetic acid esters via benzylic C-N bond cleavage. This protocol features mild reaction conditions under atmospheric pressure of CO, a redox-neutral process without an additional oxidant, and a broad substrate scope for various kinds of amines, alcohols and phenols.
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In this work, the resistance plasticity of Cu/SiO2/W programmable metallization cell devices is experimentally explored for the emulation of biological synapses. PMC devices were fabricated with foundry friendly materials using standard processes. The resistance can be continuously increased or decreased with both dc and voltage pulse programming. Impedance spectroscopy results indicate that the gradual change of resistance is attributable to the expansion or contraction of a Cu-rich layer within the device. Pulse programming experiments further show that the pulse amplitude plays a more important role in resistance change than pulse width, which is consistent with the proposed 'dual-layer' device model. The dense resistance-state distribution, 1 V operating voltage and inherent CMOS-compatibility suggests its potential application as electronic synapse in neuromorphic computing.
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BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive and lethal neurodegenerative disease. Several studies have suggested the involvement of cuproptosis in its pathogenesis. In this research, we intend to explore the cuproptosis-related molecular clusters in ALS and develop a novel cuproptosis-related genes prediction model. METHODS: The peripheral blood gene expression data was downloaded from the Gene Expression Omnibus (GEO) online database. Based on the GSE112681 dataset, we investigated the critical cuproptosis-related genes (CuRGs) and pathological clustering of ALS. The immune microenvironment features of the peripheral blood in ALS patients were also examined using the CIBERSORT algorithm. Cluster-specific hub genes were determined by the WGCNA. The most accurate prediction model was selected by comparing the performance of four machine learning techniques. ROC curves and two independent datasets were applied to validate the prediction accuracy. The available compounds targeting these hub genes were filtered to investigate their efficacy in treating ALS. RESULTS: We successfully determined four critical cuproptosis-related genes and two pathological clusters with various immune profiles and biological characteristics in ALS. Functional analysis showed that genes in Cluster1 were primarily enriched in pathways closely associated with immunity. The Support Vector Machine (SVM) model exhibited the best discrimination properties with a large area under the curve (AUC = 0.862). Five hub prediction genes (BAP1, SMG1, BCLAF1, DHX15, EIF4G2) were selected to establish a nomogram model, suggesting significant risk prediction potential for ALS. The accuracy of this model in predicting ALS incidence was also demonstrated through calibration curves, nomograms, and decision curve analysis. Finally, three drugs targeting BAP1 were determined through drug-gene interactions. CONCLUSION: This study elucidated the complex associations between cuproptosis and ALS and constructed a satisfactory predictive model to explore the pathological characteristics of different clusters in ALS patients.
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Esclerose Lateral Amiotrófica , Doenças Neurodegenerativas , Humanos , Esclerose Lateral Amiotrófica/genética , Algoritmos , Calibragem , Análise por Conglomerados , ApoptoseRESUMO
The production of type I interferon (IFN) is precisely modulated by host to protect against viral infection efficiently without obvious immune disorders. Elucidating the tight control towards type I IFN production would be helpful to get insight into natural immunity and inflammatory diseases. As yet, however, the mechanisms that regulate IFN-ß production, especially the epigenetic regulatory mechanisms, remain poorly explored. This study elucidated the potential function of Peptidylarginine deiminases (PADIs)-mediated citrullination in innate immunity. We identified PADI4, a PADIs family member that can act as an epigenetic coactivator, could repress IFN-ß production upon RNA virus infection. Detailed experiments showed that PADI4 deficiency increased IFN-ß production and promoted antiviral immune activities against RNA viruses. Mechanistically, the increased PADI4 following viral infection translocated to nucleus and recruited HDAC1 upon binding to Ifnb1 promoter, which then led to the deacetylation of histone H3 and histone H4 for repressing Ifnb1 transcription. Taken together, we identify a novel non-classical role for PADI4 in the regulation of IFN-ß production, suggesting its potential as treatment target in inflammatory or autoimmune diseases.
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Histonas , Viroses , Proteína DEAD-box 58/genética , Histona Desacetilase 1/genética , Histona Desacetilase 1/metabolismo , Histonas/metabolismo , Imunidade Inata , Desiminases de Arginina em Proteínas/genética , Desiminases de Arginina em Proteínas/metabolismo , Receptores Imunológicos/metabolismoRESUMO
Carbon storage plays a pivotal role in addressing climate change, maintaining ecological equilibrium, and fostering sustainable development. Gansu Province, situated in the arid to semi-arid region of Northwestern China, is confronted with substantial carbon storage losses as a result of ongoing ecological land desertification processes. However, studies on carbon storage loss under various scenarios in desertified regions are seldom reported. In this study, we delineated the ecological red line using quantified indicators encompassing multiple ecosystem service functions and ecological vulnerability sensitivity. Furthermore, we projected future land use and carbon storage transformations under multiple policy scenarios employing the patch-generating land use simulation (PLUS) model. Lastly, we unveiled spatial disparities in the driving factors behind alterations in carbon storage by geographically weighted regression model. Our findings suggest that: (1) The delineated ecological red line covers an area of 11.8 × 104 km2, approximately 27 % of the total land area of Gansu Province. (2) Quantitative findings reveal that the overall accuracy of the PLUS model reached an impressive 0.975, accompanied by a Kappa coefficient of 0.964, thus affirming the model's exceptional applicability. (3) Under the base line scenario, Gansu Province's carbon storage witnesses a consistent decline from 2000 to 2050, with a substantial total loss of 1.62 × 107 t over the ensuing three decades. The ecological red line scenario, by controlling 27 % of the land area in Gansu Province, achieves a 61.7 % effect of the global ecological scenario by 2050, thus reversing the declining trend in carbon storage. (4) Natural factors primarily influence carbon storage in the southeastern region, while human activity factors are distributed in the central region. This study offers scientifically robust policy recommendations to facilitate the attainment of carbon neutrality objective.
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OBJECTIVE: To conduct a quantitative analysis of published studies on hematoma enlargement after intracerebral hemorrhage. METHODS: Studies on hematoma enlargement after cerebral hemorrhage were retrieved from the Web of Science database on June 30, 2023. Microsoft Excel, VOSviewer, and CiteSpace software were used for bibliometric analysis and visualization, focusing on the quantitative characteristics of the literature. RESULTS: A total of 444 articles were published in 161 journals, with 2161 authors from 41 countries and 717 institutions. The most published authors, countries, and institutions were Goldstein, the USA, and Massachusetts General Hospital. Stroke published the most studies, but the average citation number per year of Lancet Neurology far exceeded that of other journals. The research field of hematoma enlargement is mainly divided into 3 focuses, including mechanisms, identification (computed tomography signs, predictive models), and treatment (hemostasis, antihypertensive therapy). Most bursts in publication number have been since 2010, where the highest burst was from research on spot signs, and the latest burst focused on tranexamic acid. Treatment using tranexamic acid based on different computed tomography signs is a focus of current research, but the effectiveness still requires further exploration. CONCLUSIONS: This bibliometric analysis analyzed the research framework and hotspots on hematoma enlargement after cerebral hemorrhage, which can help researchers better understand this field and provide potential suggestions for collaborations and research.
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Acidente Vascular Cerebral , Ácido Tranexâmico , Humanos , Hemorragia Cerebral/complicações , Hemorragia Cerebral/diagnóstico por imagem , Bibliometria , Hematoma/diagnóstico por imagem , HipertrofiaRESUMO
Heart failure (HF) is a life-threatening syndrome. Timely and accurate bedside monitoring of the occurrence and progression of HF via measurements of multiple HF-related biomarkers remains a challenge. Here, we report a triple cascade quantum-strip (TCQS) sensing strategy for the rapid and selective multiplex-tracing of three clinically validated HF biomarkers (BNP/NT-proBNP/ST2) in serum. High selectivity to the three biomarkers is achieved by controlling the individual recognition ability of three target-specific quantum immunoprobes and tuning their simultaneous use to BNP/NT-proBNP/ST2 recognition without mutual interference, which allows the three biomarkers to be directly enriched from serum samples. Benefiting from the fast release-binding kinetics of target-bound immunoprobes on TCQS, recognizable fluorescent signals can be rapidly read out through combining with a self-designed smartphone-based portable reader. This rapid and simple profiling strategy results in good specificity and sensitivity with LODs of 0.097, 0.072, and 0.948 ng/mL for BNP, NT-proBNP, and ST2, respectively, which match the need of clinical applications. Real serum samples are tested with an accuracy of 92.86% for HF diagnosis, validating the capability of the smartphone-read TCQS for practical applications. In particular, the simultaneous detection of the TCQS sensing strategy for BNP/NT-proBNP/ST2 will facilitate the accurate monitoring of HF occurrence, risk stratification, progression, and prognosis as a powerful POCT tool.
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Insuficiência Cardíaca , Proteína 1 Semelhante a Receptor de Interleucina-1 , Humanos , Insuficiência Cardíaca/diagnóstico , Peptídeo Natriurético Encefálico , Prognóstico , Biomarcadores , Limite de DetecçãoRESUMO
OBJECTIVES: Delirium is a significant health concern in acute stroke patients. We aim to systematically summarize existing evidence to conduct a meta-analysis to quantify the occurrence and risk factors for delirium after acute stroke. METHOD: PubMed, EMBASE and MEDLINE were searched from inception to Feb. 2023 for prospective observational studies that reported the incidence or prevalence of post-stroke delirium and/or evaluated potential risk factors. The search strategy was created using controlled vocabulary terms and text words for stroke and delirium. We performed a meta-analysis of the estimates for occurrence and risk factors using random-effects models. Meta-regression and subgroup meta-analyses were conducted to explore the sources of heterogeneity. Study quality and quality of evidence were assessed using the customized Newcastle-Ottawa Scale and GRADE, respectively. RESULTS: Forty-nine studies that enrolled 12383 patients were included. The pooled occurrence rate of post-stroke delirium was 24.4â¯% (95â¯%CI, 20.4â¯%-28.9â¯%, I2=96.2â¯%). The pooled occurrence of hyperactive, hypoactive, and mixed delirium was 8.5â¯%, 5.7â¯% and 5.0â¯%, respectively. Study location, delirium assessment method and stroke type independently affected the heterogeneity of the pooled estimate of delirium. Statistically significant risk factors were older age, low education level, cigarette smoking, alcohol drinking, atrial fibrillation, lower ADL level, higher pre-stroke mRS score, premorbid cognitive impairment or dementia, aphasia, total anterior circulation impairment, higher National Institute of Health Stroke Scale score and infection. CONCLUSIONS: Delirium affected 1 in 4 acute stroke patients, although reported rates may depend on assessment method and stroke type. Timely prevention, recognition and intervention require prioritizing patients with dominant risk factors.