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Introduction: The objective of this study was to define prehospital ultra-early neurological deterioration (UND) and to investigate the association with functional outcomes in patients with intracerebral hemorrhage (ICH)., Methods: We conducted a prospective cohort study of consecutive acute ICH patients. The stroke severity at onset and hospital admission was assessed using the Chongqing Stroke Scale (CQSS), and prehospital UND was defined as a CQSS increase of ≥2 points between symptoms onset and admission. Early neurological deterioration (END) was defined as the increase of ≥4 points in NIHSS score within the first 24 h after admission. Poor outcome was defined as a modified Rankin Scale (mRS) of 4-6 at 3 months., Results: Prehospital UND occurred in 29 of 169 patients (17.2%). Patients with prehospital UND had a median admission NIHSS score of 17.0 as opposed to those without prehospital UND with a median NIHSS score of 8.5. There were three patterns of neurological deterioration: prehospital UND only in 21 of 169 patients (12.4%), END but without prehospital UND in 20 of 169 patients (11.8%), and continuous neurological deterioration in both phases in 8 patients (4.7%). Prehospital UND was associated with worse 3-month outcomes (median mRS score, 4.0 vs. 2.0, p = 0.002). After adjusting for age, time from onset to admission, END, and systolic blood pressure, prehospital UND was an independent predictor of poor outcome (odds ratio [OR] 3.27, 95% confidence interval [CI] 1.26-8.48, p = 0.015)., Conclusion: Prehospital UND occurs in approximately 1 in 7 patients between symptom onset and admission and is associated with poor functional outcome in patients with ICH. Further research is needed to investigate the prehospital UND in the prehospital phase in the triage of patients with ICH., (© 2022 S. Karger AG, Basel.)

Background: To promote the shared decision-making (SDM) between patients and doctors in pediatric outpatient departments, this study was designed to validate artificial intelligence (AI) -initiated medical tests for children with fever., Methods: We designed an AI model, named Xiaoyi, to suggest necessary tests for a febrile child before visiting a pediatric outpatient clinic. We calculated the sensitivity, specificity, and F1 score to evaluate the efficacy of Xiaoyi's recommendations. The patients were divided into the rejection and acceptance groups. Then we analyzed the rejected examination items in order to obtain the corresponding reasons., Results: We recruited a total of 11,867 children with fever who had used Xiaoyi in outpatient clinics. The recommended examinations given by Xiaoyi for 10,636 (89.6%) patients were qualified. The average F1 score reached 0.94. A total of 58.4% of the patients accepted Xiaoyi's suggestions (acceptance group), and 41.6% refused (rejection group). Imaging examinations were rejected by most patients (46.7%). The tests being time-consuming were rejected by 2,133 patients (43.2%), including rejecting pathogen studies in 1,347 patients (68.5%) and image studies in 732 patients (31.8%). The difficulty of sampling was the main reason for rejecting routine tests (41.9%)., Conclusion: Our model has high accuracy and acceptability in recommending medical tests to febrile pediatric patients, and is worth promoting in facilitating SDM., Competing Interests: Conflicts of interest: The authors declared no conflicts of interest., (Copyright: © World Journal of Emergency Medicine.)

Objectives: To explore the relationship between total bilirubin (TBil) and stroke risk in older patients with obstructive sleep apnea syndrome (OSAS)., Methods: A total of 1,007 patients with OSAS without stroke history aged ≥ 60 years and with complete serum TBil records were enrolled in this study. The median follow-up was 42 months. Participants were divided into four groups based on the quartile of the baseline serum TBil concentration. Multivariate Cox proportional hazards analysis and restricted cubic spline (RCS) were used to investigate the association of TBil with the incidence of new-onset stroke., Results: The PRIMARY part: the third quantile TBil level group had the lowest prevalence of stroke among the four groups. The RCS functions depicted a J-type curve relationship between TBil (3.3-33.3 µmol/L) and stroke (nonlinear P < 0.05). When the TBil level was in the range of 3.3 to 11.5 µmol/L, the possible protective influence of bilirubin against stroke in patients with OSAS enhanced with an increasing TBil level. However, when the TBil level exceeded 11.5 µmol/L and gradually increased, the effect of TBil on stroke risk became more and more pronounced. The SECONDARY part: for every 1 µmol/L increase in TBil levels in the range of 11.5 to 33.3 µmol/L, the risk of stroke in patients with OSAS increased by 16.2% (P < 0.001). In addition, there was a higher risk in women with OSAS (hazard ratio (HR)=1.292, 95% confidence interval (95%CI): 1.093-1.528; P = 0.003). Moreover, an increased TBil level alone was significantly associated with stroke in subjects aged < 75 years (HR: 1.190, 95%CI: 1.069-1.324), patients with mild-to-moderate OSAS (HR: 1.215, 95%CI: 1.083-1.364), and individuals without atrial fibrillation (AF) (HR: 1.179, 95%CI: 1.083-1.285) within a TBil level in the range of 11.5 to 33.3 µmol/L., Conclusions: Both lower and higher bilirubin levels may increase the risk of stroke in older persons with OSAS, and there was a J-type dose-response relationship. The risk of stroke was lowest when the TBil level was approximately 11.5 µmol/L., Competing Interests: The authors declare that the study was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background and Purpose: The association between infarct location and hemorrhagic transformation of acute ischemic stroke after mechanical thrombectomy is not understood. We aimed to evaluate the association between CTP-based ischemic core variables at admission and hemorrhagic transformation after a successful thrombectomy., Materials and Methods: We retrospectively analyzed patients who underwent endovascular thrombectomy for acute anterior circulation large-vessel occlusion between October 2019 and June 2021. We enrolled 146 patients with visible ischemic core on pretreatment CTP who had successful reperfusion. The ischemic core infarct territories were classified into the cortical and subcortical areas and then qualitatively and quantitatively analyzed by CTP. Logistic regression and receiver operating characteristic curve analyses were performed to determine the association between ischemic core variables and hemorrhagic transformation., Results: Of the 146 patients analyzed, 72 (49.3%) had hemorrhagic transformation and 23 (15.8%) had symptomatic intracerebral hemorrhage. Multivariate analysis showed that subcortical infarcts were independently associated with hemorrhagic transformation (OR, 8.06; 95% CI, 2.31-28.10; P = .001) and subcortical infarct volume was independently linked to symptomatic intracerebral hemorrhage (OR, 1.05; 95% CI, 1.01-1.09; P = .039). The receiver operating characteristic curve indicated that subcortical infarcts can predict hemorrhagic transformation accurately (area under the curve = 0.755; 95% CI, 0.68-0.82; P  < .001) and subcortical infarct volume can predict symptomatic intracerebral hemorrhage (area under the curve = 0.694; 95% CI, 0.61-0.77; P = .002)., Conclusions: Subcortical infarcts seen on CTP at admission are associated with hemorrhagic transformation in patients after successful thrombectomy, and subcortical infarct volume may influence the risk of symptomatic intracerebral hemorrhage., (© 2023 by American Journal of Neuroradiology.)

The transfer of the concept of chirality from molecules to synthesized nanomaterials has attracted attention amongst multidisciplinary teams. Here we demonstrate heterogeneous nucleation and anisotropic accumulation of Au nanoparticles on multilayer MoS 2 planes to form chiroptically functional nanomaterials. Thiol amino acids with chiral conformations modulate asymmetric growth of gold nanoarchitectures on seeds of highly faceted Au/MoS 2 heterostructures. Consequently, dendritic plasmonic nanocrystals with partial chiral morphologies are synthesized. The chirality of dendritic nanocrystals inherited from cysteine molecules refers to the structural characteristics and includes specific recognition of enantiomeric molecules. With integration of the intrinsic photothermal properties and inherited enantioselective characteristics, dendritic Au/MoS 2 heterostructures exhibit chirality-dependent release of antimicrobial drugs from hydrogel substrates when activated by exogenous infrared irradiation. A three-in-one strategy involving synthesis of chiral dendritic heterostructures, enantioselective recognition, and controlled drug release system is presented, which improves nanomaterial synthetic technology and enhances our understanding of crucial chirality information., (© 2022. The Author(s).)

Background: Oculomotor nerve palsy (ONP) may result from posterior communicating artery (PcomA) aneurysms. We aimed to evaluate the resolution of ONP after endovascular treatment with the intention of clarifying predictors of nerve recovery in a relatively large series., Methods: A total of 211 patients with ONP caused by PcomA aneurysms underwent endovascular coiling between May 2010 and December 2020 in four tertiary hospitals. We evaluated the demographics, clinical characteristics, aneurysm morphology parameters and ONP resolution to analyze the predictors of ONP recovery using univariate and multivariate analyses., Results: At the last available clinical follow-up, ONP resolution was complete in 126 (59.7%) patients, partial in 73 (34.6%) patients, and no recovery in 12 (5.7%) patients. The median resolution time after endovascular treatment was 55 days (interquartile range: 40-90 days). In multivariate analysis, degree of ONP (incomplete palsy) on admission (OR 5.396; 95% CI 2.836-10.266; P < 0.001), duration of ONP (≤ 14 days) before treatment (OR 5.940; 95% CI 2.724-12.954; P < 0.001) were statistically significant predictors of complete recovery of ONP. In the subgroup analysis of patients with unruptured aneurysms, aspirin showed a higher complete recovery rate in univariate analysis (OR 2.652; 95% CI 1.057-6.656; P = 0.038)., Conclusion: Initial incomplete ONP and early management might predict better recovery of ONP after endovascular treatment., (© 2022. The Author(s).)

Objective: The standard rescue modality for patients with intracranial atherosclerotic stenosis after failed mechanical thrombectomy (MT) is not well established. We evaluated the safety and efficacy of balloon dilation in combination with tirofiban as the first-line salvage therapy when MT failed in these patients., Methods: We retrospectively analyzed the records of 47 patients admitted between January 2018 and June 2021, with middle cerebral artery atherosclerotic occlusion, who underwent balloon angioplasty in combination with tirofiban as the first-line salvage therapy after the failure of MT. The recanalization outcome, procedure-related complications, symptomatic intracranial hemorrhage, and functional outcome at 90 days were reviewed., Results: Recanalization with a modified Thrombolysis in Cerebral Infarction grade of 2b-3 was achieved in 41 (87.2%) of the 47 patients. Acute stents were deployed in another 6 patients who did not achieve successful re-perfusion after balloon angioplasty. Successful recanalization was achieved in 3 of them. One patient (2.1%, 1/47) experienced re-occlusion several days later due to the withdrawal of antiplatelet therapy for parenchymal hematoma. Seven patients (14.9%, 7/47) underwent stent angioplasty in the stable stage (range: 1-2 months) because severe residual stenosis was detected on follow-up imaging. There was only one event of periprocedural complication, namely ectopic migration of emboli. The good functional outcome rate was 55.3% (26/47), without the events of symptomatic intracranial hemorrhage and mortality., Conclusions: Balloon angioplasty in combination with tirofiban is safe and effective for middle cerebral artery atherosclerotic occlusion after the failure of MT., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Aims: To investigate the association between obstructive sleep apnea (OSA) severity and baseline serum cystatin C (Cys-C) concentration and to explore the association between baseline serum Cys-C and long-term cardiovascular outcomes and mortality in older patients with OSA. Methods: Between January 2015 and October 2017, a total of 1107 consecutive eligible older patients (≥60 years) with OSA were included in this multicenter, prospective cohort study, and baseline demographics, clinical characteristics, sleep parameters, and follow-up outcomes were collected. Participants were divided into different groups based on baseline serum Cys-C levels. The primary end point was major adverse cardiovascular events (MACE) and the secondary end point was all-cause mortality. The correlation between OSA severity and baseline serum Cys-C was evaluated by Spearman correlation analysis. Multivariate Cox regression was used to analyze the association between Cys-C and the incidence of MACE and mortality. Results: Participants included 672 men and 435 women, with a median age of 66 (range, 60-96) years. At baseline, apnea-hypopnea index (AHI) ( r = 0.128, p < 0.05), oxygen desaturation index (ODI) ( r = 0.116, p < 0.05), and the lowest pulse oxygen saturation (LSpO 2 ) ( r = -0.097, p < 0.05) were correlated with serum Cys-C concentration. During the median follow-up period of 42 months, 97 patients (8.8%) experienced MACE and 40 patients (3.6%) experienced death. The association between serum Cys-C levels and the risk of MACE and all-cause mortality was slow rising shaped. The multivariable Cox regression analysis showed patients with a serum Cys-C concentration of ≥1.14 mg/L had higher risks of MACE (HR = 5.30, 95% CI: 2.28-12.30, p < 0.05) and all-cause mortality (HR = 9.66, 95% CI: 2.09-44.72, p < 0.05) compared with patients with serum Cys-C of ≤0.81 mg/L in older patients with OSA. The receiver-operating characteristic curve showed baseline serum Cys-C levels exhibited moderately capable of identifying patients with a long-term risk of clinical adverse events (MACE and mortality). Conclusion: OSA severity was positively correlated with serum Cys-C concentration. High levels of Cys-C were independently associated with increased risks of MACE and all-cause mortality in older patients with OSA, suggesting that lowering Cys-C levels should be considered as a therapeutic target, and monitoring serum Cys-C may be beneficial to the favorable prognosis of older patients with OSA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Gao, Xue, Su, Wang, Lin, Zhao, Zou, Gao, Guo, Shi, Xu, Wang, Qian, Chen, Fan and Liu.)

Aim: To evaluate the prognostic value of the hypoperfusion intensity ratio (HIR) on 90-day clinical outcome in acute ischaemic stroke (AIS) patients with late therapeutic window., Materials and Methods: One hundred and sixty-eight consecutive AIS patients with anterior-circulation large-vessel occlusion who underwent endovascular thrombectomy during the late window were enrolled retrospectively. Clinical data, Alberta Stroke Program Early Computed Tomography Score (ASPECTS) based on unenhanced computed tomography (CT), and perfusion parameters included ischaemic core, hypoperfusion volume, mismatch volume between core and penumbra, and the HIR were assessed and compared between patients with or without favourable outcomes (defined as modified Rankin Scale score of 0-2). Statistical analysis included binary logistic regression and receiver operating characteristic (ROC) analyses., Results: A favourable outcome was achieved in 76 (45.2%) patients. In univariable analysis, age, National Institutes of Health Stroke Scale (NIHSS) score at admission, ASPECTS score, HIR, ischaemic core, and hypoperfusion volume were significantly associated with functional outcome (p<0.05). In multivariate analyses, age (OR 0.95; 95% CI 0.92-0.99), NIHSS score at admission (OR 0.89, 95% CI 0.84-0.96) and HIR (OR 0.018, 95% CI 0.003-0.113) remained as independent outcome predictors (p<0.01). The optimal threshold of HIR was 0.36 (sensitivity 70.7%, specificity 61.8%). The combination of age, NIHSS score at admission, and HIR yield good performance for outcome prediction with an area under the ROC curve of 0.815 (sensitivity 88.2%, specificity 64.1%), significantly higher than individual variable (p<0.05)., Conclusion: Low HIR was a predictor for favourable outcome in AIS patients with late therapeutic window. Integrating HIR with clinical variables improved the ability for outcome classification., (Copyright © 2022 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Aim: To compare the efficacy between contact aspiration thrombectomy and stent retriever thrombectomy in the treatment of acute embolic stroke patients with large vessel occlusion., Materials and Methods: Between January 2019 and June 2020, data from consecutive acute ischaemic stroke patients who underwent either endovascular contact aspiration or stent retriever thrombectomy were analysed at one institution. The primary outcome was the full 90-day modified Rankin Scale (mRS) score. Ordinal logistic regression analysis was used to assess the association between thrombectomy approach and functional outcomes., Results: A total of 156 patients were analysed. Among them, 57 (36.5%) patients underwent primary aspiration thrombectomy, while 99 (63.5%) patients underwent primary stent retriever thrombectomy. The median procedure time was significantly shorter in patients treated with aspiration (37 versus 56 minutes; p<0.001). Compared with those of patients who underwent stent retriever thrombectomy, successful recanalisation rates and favourable functional outcome rates were higher in patients who underwent the aspiration approach (94.7% versus 77.8%, p=0.006; 49.1% versus 27.3%, p=0.006, respectively). Ordinal logistic regression analysis showed that aspiration thrombectomy was independently associated with a good functional outcome (adjusted common odds ratio, 0.30, 95% confidence interval: 0.16-0.60, p<0.001)., Conclusion: Among the specific patients with large vessel occlusion in acute embolic stroke, the use of aspiration thrombectomy compared with stent retriever thrombectomy resulted in a greater likelihood of favourable neurological outcomes; however, because of study limitations, these findings should be interpreted as preliminary and require further study to confirm these results., (Copyright © 2022 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

The synthesis of Co-doped Mn 3 O 4 nanocubes was achieved via galvanic replacement reactions for photo-reduction of CO 2 . Co@Mn 3 O 4 nanocubes could efficiently photo-reduce CO 2 to CO with a remarkable turnover number of 581.8 using [Ru(bpy) 3 ]Cl 2  ⋅ 6H 2 O as photosensitizer and triethanolamine as sacrificial agent in acetonitrile and water. The galvanic replaced Co species are homogeneously distributed at the outer surface of Mn 3 O 4 , providing catalytic active sites during CO 2 reduction reactions, which facilitate the separation and migration of photogenerated charge carriers, further benefiting the outstanding photocatalytic performance of CO 2 reduction. Density functional theory calculations revealed that the decreasing of conduction band maximum in Co@Mn 3 O 4 was beneficial to the electron attachment from the excited sensitized molecule, which promoted photocatalytic reduction of CO 2 ., (© 2022 Wiley-VCH GmbH.)

Objective: To evaluate the safety and efficacy of an overlapped stenting-assisted coiling technique in treating vertebral artery dissecting aneurysm (VADA) via Low-profile Visualized Intraluminal Support (LVIS) stent-within-Neuroform EZ stent., Methods: From January 2017 to June 2019, 18 consecutive patients with VADAs (ruptured : unruptured=5 : 13) were treated with the overlapping stents assisted-coiling technique in our center. The overlapping manner was a Neuroform EZ stent being deployed first, followed by LVIS stents placement using the 'shelf' technique. The patients' clinical characteristics, technical feasibility and safety, and immediate and follow-up angiographic results were retrospectively reviewed., Results: Seventeen (94.4%) procedures were technically successful with an exact deployment of the stents and patent parent or perforator arteries. The immediate angiographies after procedure confirmed Raymond class I, II, and III occlusion of VADAs were in 12 (66.7%), two (11.1%), and four cases (22.2%), respectively. Post-procedural complications developed in one patient (5.6%) with minor brainstem infarctions, which resulted from an in-stent thrombosis during the procedure. Angiographic follow-up at 5.7 months (range 3 to 9 months) demonstrated Raymond class I and II occlusion were in all cases (100%). The modified Rankin Scale scores at 21.3 months (range 15 to 42 months) 0-2 in 17 cases (94.4%) and three in one case (5.6%)., Conclusion: Overlapping stents via LVIS stent-within-Neuroform EZ stent combined with coiling is safe and effective for patients with VADA in the midterm results.

Ruxolitinib (RUX), a small molecule inhibitor of JAK1/JAK2, has been identified as the possible novel targeted agent for the treatment of hemophagocytic lymphohistiocytosis (HLH). However, due to the lack of randomized clinical trials (RCTs), it is extremely difficult to determine the effective therapeutic dose for RUX in HLH patients, especially in pediatric patients. At the same time, the clinical response of pediatric patients to RUX varies greatly among individuals according to several case reports. Therefore, it is imperative to investigate the pharmacokinetic and pharmacodynamic characteristics of RUX in HLH children, and this must be based on a satisfactory method to determine the concentration of RUX. Owing to several limits of published analytical methods, herein, we describe a novel liquid chromatography tandem mass spectrometry (LC-MS/MS) method for monitoring RUX in children's plasma samples. The protein precipitation method using methanol was used for sample cleanup. The analytes were separated by gradient elution in which 2.0 mM ammonium acetate in distilled water and acetonitrile were used as mobile phases. In the positive electrospray ionization (ESI+) mode, the m / z 307.1 → 186.0 and 316.1 → 185.9 ion pair transitions of RUX and RUX-d9 were used for the qualitative and quantitative analysis, respectively. The calibration curves of RUX were linear in the concentration range from 0.5 to 400 ng mL -1 . The intra- and inter-batch precision, accuracy, recovery, dilution completeness, and stability of this method were all within acceptable standards, and no matrix effects or residues were found. This method was successfully applied to the clinical pharmacokinetic study of RUX in 32 children with HLH. The pharmacokinetic parameters of HLH children after a single dose of RUX and the steady state plasma concentration after multiple administrations were proposed through this method. Most importantly, it was found that the age and serum creatinine (SCr) of children with HLH had a significant and complex impact on the in vivo process of RUX after the single as well as multiple administrations of RUX.

Background: The benefit of endovascular thrombectomy for patients with in-hospital stroke remains unclear. Thus, the aim of this study was to compare the endovascular thrombectomy outcomes between in-hospital stroke and community-onset stroke among patients with acute ischemic stroke., Methods: From January 2015 to July 2019, 362 consecutive patients with acute ischemic stroke with large vessel occlusion in the anterior circulation received endovascular thrombectomy in our centre. After propensity score matching with a ratio of 1:2 (in-hospital stroke:community-onset stroke), clinical characteristics and functional outcomes were compared between in-hospital stroke and community-onset stroke groups., Results: Thirty-six patients with in-hospital stroke and 72 patients with community-onset stroke were enrolled. The number of patients with New York Heart Association classification III/IV (41.7% vs. 6.9%, p  < 0.001) and with underlying cancer (25.0% vs. 2.8%, p  < 0.001) was higher in the in-hospital stroke than in the community-onset stroke group. The intravenous thrombolysis rate was lower in the in-hospital stroke group (13.9% vs. 43.1%, p  = 0.002). No significant difference in symptom onset to puncture ( p  = 0.618), symptom onset to recanalisation ( p  = 0.618) or good reperfusion (modified thrombolysis in cerebral infarction ≥2 b ) rates ( p  = 0.852) was found between the groups. The favourable clinical outcome trend (modified Rankin scale ≤2 at 90 days) was inferior, but acceptable, in the in-hospital stroke, group compared to the community-onset stroke group (30.6% vs. 41.7%, p  = 0.262)., Conclusion: Patients with in-hospital stroke had more disadvantageous comorbidities than those with community-onset stroke. Cardiac dysfunction seems to be associated with poor outcomes after thrombectomy. Nevertheless, endovascular thrombectomy still appears to be safe and effective for patients with in-hospital stroke.

Background and Purpose: DIRECT-MT showed that endovascular thrombectomy was noninferior to thrombectomy preceded by intravenous alteplase with regard to functional outcome in patients with acute ischemic stroke. In this post hoc analysis, we examined whether infarct size modified the effect of alteplase., Methods: All patients with baseline Alberta Stroke Program Early Computed Tomography Score (ASPECTS) grades were included. The primary outcome was the 90-day modified Rankin Scale (mRS) score. Multivariate ordinal logistic regression analysis was used to calculate the adjusted common odds ratio (OR) for better functional outcome based on the mRS for thrombectomy alone versus combination therapy. An interaction term was entered to test for an interaction with baseline ASPECTS subgroups: 0-4 versus 5-7 versus 8-10., Results: Of 649 patients, 323 (49.8%) were in the thrombectomy-alone group and 326 (50.2%) in the combination-therapy group. There was no significant treatment-by-trichotomized ASPECTS interaction with alteplase prior to endovascular treatment for the primary endpoint of ordinal mRS (p-value interaction term relative to ASPECTS 8-10: ASPECTS 0-4, p = 0.386; ASPECTS 5-7, p = 0.936). Adjusted common ORs for improvement in the 90-day mRS with thrombectomy alone compared with combination therapy were 1.99 (95% confidence interval = 0.72-5.46) for ASPECTS 0-4, 1.07 (0.62-1.86) for ASPECTS 5-7, and 1.03 (0.74-1.45) for ASPECTS 8-10. There was no significant difference in the safety outcomes between the two groups., Conclusions: Baseline infarct size may not modify the effect of alteplase prior to endovascular thrombectomy with regard to favorable functional outcomes and adverse events., (© 2022 European Academy of Neurology.)

Introduction: This meta-analysis evaluated the efficacy and safety of placebo during the maintenance therapy of ovarian cancer (OC) patients in randomized controlled trials (RCTs)., Methods: A comprehensive literature review was performed for RCTs published up to and including August 2020 from four electronic databases. We analyzed the efficacy and safety in the control arms of the maintenance therapy in advanced OC patients. Hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) of progression-free survival (PFS) and overall survival (OS) were estimated in the placebo arms and the observation arms, respectively, using the Frequency Framework method. We also calculated the incidences of common adverse effects (AEs) in the placebo arms., Results: In total, 41 articles with 20,099 (4,787 in the placebo arms, 3,420 in the observation arms, and 11,892 in the experiment arms) patients were included in this meta-analysis. Compared with observation, placebo did not improve or reduce PFS (HR, 1.02; 95% CI, 0.87-1.20; P = 0.81) and OS (HR, 1.02; 95% CI, 0.89-1.16; P = 0.76) of OC patients, while other treatments, except for radiotherapy, significantly improved PFS and OS (all P < 0.05). The incidences of AEs produced by placebo were 94.03% in all grades and 20.22% in grade ≥3. The incidences of AEs were 29.75% in fatigue, 26.38% in nausea, 24.34% in abdominal pain, 18.92% in constipation, 16.65% in diarrhea, 14.55% in vomiting, 13.89% in hypertension, and 13.14% in headache., Conclusions: Placebo did not improve or reduce the PFS and OS benefits of OC patients in RCTs but increased the incidences of AEs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Zhao, Bin, Zhang, Sun, Wang, Feng, Ji, He, Chen and Li.)

Objective: To investigate the association between cerebral small vessel disease (SVD) and hematoma volume in primary intracerebral hemorrhage (ICH)., Methods: Patients from a prospective ICH cohort were enrolled. Admission and follow-up CT scan within 72 h after onset were reviewed to calculate the final hematoma volume. We evaluated cortical superficial siderosis and the global SVD score, including white matter hyperintensities, lacunes, enlarged perivascular space, and cerebral microbleeds on MRI. We conducted the multivariate logistic regression analyses to explore the association between SVD markers and small ICH, as well as hematoma volume. Hematoma location was stratified into lobar and non-lobar for subgroup analysis., Results: A total of 187 patients with primary ICH (mean age 62.4 ± 13.4 years, 67.9% male) were enrolled. 94 (50.2%) patients had small ICH. The multivariate logistic regression analysis showed an association between global SVD score and small ICH [adjusted odds ratio (aOR) 1.27, 95% CI 1.03-1.57, p = 0.027] and a trend of higher global SVD score towards non-lobar small ICH (aOR 1.23, 95% CI 0.95-1.58, p = 0.122). In the multivariate linear regression analysis, global SVD score was inversely related to hematoma volume of all ICH (β = -0.084, 95% CI -0.142 to -0.025, p = 0.005) and non-lobar ICH (β = -0.112, 95% CI -0.186 to -0.037, p = 0.004). Lacune (β = -0.245, 95% CI -0.487 to -0.004, p = 0.046) was associated with lower non-lobar ICH volume., Conclusion: Global SVD score is associated with small ICH and inversely correlated with hematoma volume. This finding predominantly exists in non-lobar ICH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Zhao, Hu, Yang, Deng, Lv, Li, Cheng, Pu, Tang, Wu, Zhao, Xie and Li.)

Background: To determine the risk factors for intracranial hematoma (ICH) development following ruptured anterior communicating artery (AcomA) aneurysms and to determine prognostic factors associated with unfavorable outcomes after coiling first., Methods: From March 2014 to February 2020, 235 patients with ruptured AcomA aneurysms underwent endovascular treatment in our department. The clinical and radiographic conditions were collected retrospectively. Modified Rankin Scale (mRS) scores of ≤ 2 were accepted as favorable outcomes. Univariate and multivariate logistic regressions were performed to identify significant factors contributing to the incidence of ICHs and to unfavorable outcomes., Results: Of these 235 patients, 68 had additional ICHs. A posterior orientation of ruptured AcomA aneurysms was the independent variable associated with the incidence of ICHs (OR 3.675; p<0.001). Furthermore, having preoperative Hunt-Hess grades Ⅳ-Ⅴ was an independent variable associated with unfavorable outcomes for ICH patients (OR 80.000; p<0.001). Among the 68 patients with ICHs, 40% (27/68) had Hunt-Hess grades IV-V. Four percent of patients (3/68) underwent surgical hematoma evacuation after the coiling procedure and 15% of the patients (10/68) underwent external ventricular drainage. A favorable outcome was achieved in 72% (49/68) of patients with ruptured AcomA aneurysms. The mortality rate was 21% (14/68) at 6 months., Conclusion: A posterior orientation of ruptured AcomA aneurysms was associated with the incidence of ICHs. Coiling first with surgical management if necessary seems to be an acceptable treatment for ruptured AcomA aneurysms with ICHs. The clinical outcome was associated with the clinical neurological status on admission., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Patients with acute ischemic stroke (AIS) caused by large vessel occlusion (LVO) were usually transferred from a primary stroke center (PSC) to a comprehensive stroke center (CSC) for endovascular treatment (drip-and-ship [DS]), while driving the doctor from a CSC to a PSC to perform a procedure is an alternative strategy (drip-and-drive [DD])., Purpose: To compare the efficacy and prognosis of the two strategies., Material and Methods: From February 2017 to June 2019, 62 patients with LVO received endovascular treatment via the DS and DD models and were retrospectively analyzed from the stroke alliance based on our CSC. Primary endpoint was door-to-reperfusion (DTR) time. Secondary endpoints included puncture-to-recanalization (PTR) time, modified Thrombolysis in Cerebral Infarction (mTICI) rates at the end of the procedure, and modified Rankin Scale (mRS) at 90 days., Results: Forty-one patients received the DS strategy and 21 patients received the DD strategy. The DTR time was significantly longer in the DS group compared to the DD group (315.5 ± 83.8 min vs. 248.6 ± 80.0 min; P  < 0.05), and PTR time was shorter (77.2 ± 35.9 min vs. 113.7 ± 69.7 min; P  = 0.033) compared with the DD group. Successful recanalization (mTICI 2b/3) was achieved in 89% (36/41) of patients in the DS group and 86% (18/21) in the DD group ( P  = 1.000). Favorable functional outcomes (mRS 0-2) were observed in 49% (20/41) of patients in the DS group and 71% (15/21) in the DD group at 90 days ( P  = 0.089)., Conclusion: Compared with the DS strategy, the DD strategy showed more effective and a trend of better clinical outcomes for AIS patients with LVO.

Objective: Hyperglycemia is often observed in the patients after acute stroke. This study aims to elucidate the potential effect and mechanism of hyperglycemia by screening microRNAs expression in intracerebral hemorrhage mice., Methods: We employed the collagenase model of intracerebral hemorrhage. Twenty male C57BL/6 mice were used and randomly divided in normo- and hyperglycemic. The hyperglycemia was induced by intraperitoneally injection of 50% of Dextrose (8 mL/kg) 3 hours after intracerebral hemorrhage. The neurologic impairment was investigated by neurologic deficit scale. To study the specific mechanisms of hyperglycemia, microRNAs expression in perihematomal area was investigated by RNA sequencing. MicroRNAs expression in hyperglycemic intracerebral hemorrhage animals were compared normoglycemic mice. Functional annotation analysis was used to indicate potential pathological pathway, underlying observed effects. Finally, polymerase chain reaction validation was administered., Results: Intraperitoneal injection of dextrose significantly increased blood glucose level. That was associated with aggravation of neurological deficits in hyperglycemic compared to normoglycemic animals. A total of 73 differentially expressed microRNAs were identified via transcriptomics analysis. Bioinformatics analyses showed that these microRNAs were significantly altered in several signaling pathways, of which the hedgehog signaling pathway was regarded as the most potential pathway associated with the effect of hyperglycemia on acute intracerebral hemorrhage. Furthermore, polymerase chain reaction results validated the correlation between microRNAs and hedgehog signaling pathway., Conclusions: MicroRNA elevated in hyperglycemia group may be involved in worsening the neurological function via inhibiting the hedgehog signaling, which provides a novel molecular physiological mechanism and lays the foundation for treatment of intracerebral hemorrhage., Competing Interests: Declaration of Competing Interest The authors claim no conflict of interest, (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Higher baseline Alberta Stroke Program Early Computed Tomography Score (ASPECTS) was associated with a lower probability of hemorrhagic transformation in patients with acute ischemic stroke (AIS)., Purpose: To investigate the predictive value of cerebral blood volume (CBV)-ASPECTS of intracranial hemorrhage (ICH) in AIS treated with thrombectomy selected by computed tomographic perfusion (CTP) in an extended time window., Material and Methods: A total of 91 consecutive patients with AIS with large vessel occlusion in the anterior circulation after thrombectomy in an extended time window were enrolled between January 2018 and September 2019. ICH was diagnosed according to Heidelberg Bleeding Classification. CBV-ASPECTS was assessed by evaluating each ASPECTS region for relatively low CBV value compared with the mirror region in the contralateral hemisphere. Demographic characteristics, clinical data, CBV-ASPECTS, and procedure process and results were compared between patients with ICH and those without., Results: ICH occurred in 31/91 (34.1%) patients with AIS. Symptomatic ICH (sICH) was observed in 4 (4.4%) patients, while asymptomatic ICH (aICH) was seen in 27 (29.7%). In univariate analysis, both ICH and aICH were associated with high admission NIHSS score ( P <0.001 and P <0.001, respectively), more passes of retriever ( P  = 0.007 and P  = 0.019, respectively), low NCCT-ASPECTS ( P  = 0.013 and P  = 0.034, respectively), and low CBV-ASPECTS ( P  < 0.001 and P  < 0.001, respectively). After multivariable analysis, low CBV-ASPECTS remained an independent predictor of ICH (odds ratio [OR] 0.521, 95% confidence interval [CI] 0.371-0.732, P  < 0.001) and aICH (OR 0.532, 95% CI 0.376-0.752, P  < 0.001), respectively., Conclusion: Low CBV-ASPECTS independently predicts ICH in patients with AIS treated with thrombectomy selected by CTP in an extended time window.

As a common soil-borne nematode, hookworm is mainly parasitized in the intestine, and the clinical manifestations of hookworm infections mainly include gastrointestinal symptoms and iron-deficiency anemia. In addition, hookworm may be also parasitized in other organs in addition to gastrointestinal system, resulting in development of disorders in other systems. Proteinuria caused by hookworm infections is rare and easy to be misdiagnosed in clinical practices. Hereby, the diagnosis and treatment of a case of proteinuria associated with hookworm infections was reported, in order to increase the understanding of hookworm infection-associated proteinuria among clinicians.

Background: Outcomes regarding the conventional surgical and conservative treatment for the lobar intracerebral hemorrhage (ICH) have not been previously compared. The current meta-analysis was designed to review and compile the evidence regarding the management of patients with lobar intracerebral hemorrhage., Methods: Online electronic databases, including PubMed, Embase, Medline, Cochrane Library, and Google Scholar, were searched for randomized controlled trials (RCTs). Studies were selected on the basis of the inclusion and exclusion criteria. Trials with CT-confirmed lobar intracerebral hemorrhage patients of which treatment regimen was started within 72 h following the stroke were included. Low quality trials were excluded. Death or dependence was defined as primary outcome and death at the end of the follow up was the secondary outcome., Results: One hundred five RCTs were screened and 96 articles were excluded on the basis of abstract. Nine articles were assessed for the eligibility and 7 trials were included that involved 1,102 patients. The Odds ratio (OR) for the primary outcome was 0.80 (95% CI, 0.62-1.04, p = 0.09) and for the secondary outcome was 0.79 (95%CI, 0.60-1.03, p = 0.09)., Conclusion: Our findings suggested that surgical treatments did not significantly improve the functional outcome as compared with the conservative medical management for patients with lobar ICH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Akram, Zhao, Shen, Yang, Deng, Li, Hu, Zhao, Xie and Li.)

Aim: To explore the association between haemorrhagic transformation (HT) subtypes and functional outcome in acute ischaemic stroke (AIS) patients with successful recanalization treated by endovascular thrombectomy (EVT)., Materials and Methods: Consecutive patients with AIS due to large-vessel occlusion in the anterior circulation, who were treated between January 2015 and June 2019 and achieved successful EVT, were enrolled in this retrospective study. HT was categorized according to the Heidelberg Bleeding Classification. Functional outcome was evaluated using the 90-day modified Rankin Scale (mRS) after stroke onset. Ordinal logistic regression analysis was performed to determine the association of HT subtypes with functional outcomes., Results: A total of 243 patients were included for further analysis. Among them, 121 (49.8%) had HT. Ten (4.1%) patients were classified as haemorrhagic infarction (HI) subtype 1, 61 (25.1%) as HI subtype 2, 17 (7.0%) as parenchymal haematoma (PH) subtype 1, and 33 (13.6%) as PH subtype 2. Ordinal logistic regression analysis suggested that HI subtype 2 (adjusted common OR 0.357, 95% CI: 0.192-0.667), PH1 (adjusted common OR 0.254, 95% CI: 0.093-0.696) and PH subtype 2 (adjusted common OR 0.017, 95% CI: 0.006-0.051) were significantly associated with poor functional outcomes., Conclusion: The present study shows that HI subtype 2, PH subtype 1, and PH subtype 2 are independently associated with poor clinical outcomes in AIS patients with successful recanalization after EVT., (Copyright © 2021 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Artificial intelligence (AI) has been deeply applied in the medical field and has shown broad application prospects. Pre-consultation system is an important supplement to the traditional face-to-face consultation. The combination of the AI and the pre-consultation system can help to raise the efficiency of the clinical work. However, it is still challenging for the AI to analyze and process the complicated electronic health record (EHR) data. Our pre-consultation system uses an automated natural language processing (NLP) system to communicate with the patients through the mobile terminals, applying the deep learning (DL) techniques to extract the symptomatic information, and finally outputs the structured electronic medical records. From November 2019 to May 2020, a total of 2,648 pediatric patients used our model to provide their medical history and get the primary diagnosis before visiting the physicians in the outpatient department of the Shanghai Children's Medical Center. Our task is to evaluate the ability of the AI and doctors to obtain the primary diagnosis and to analyze the effect of the consistency between the medical history described by our model and the physicians on the diagnostic performance. The results showed that if we do not consider whether the medical history recorded by the AI and doctors was consistent or not, our model performed worse compared to the physicians and had a lower average F1 score (0.825 vs. 0.912). However, when the chief complaint or the history of present illness described by the AI and doctors was consistent, our model had a higher average F1 score and was closer to the doctors. Finally, when the AI had the same diagnostic conditions with doctors, our model achieved a higher average F1 score (0.931) compared to the physicians (0.92). This study demonstrated that our model could obtain a more structured medical history and had a good diagnostic logic, which would help to improve the diagnostic accuracy of the outpatient doctors and reduce the misdiagnosis and missed diagnosis. But, our model still needs a good deal of training to obtain more accurate symptomatic information., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Qian, Dong, Yuan, Yin, Wang, Wang, Wang, Tian, Li, Zhang, Zhao and Ning.)

Objective: To evaluate the prognostic significance of high-sensitivity cardiac troponin T (hs-cTnT) elevation in acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) in the anterior circulation treated with endovascular thrombectomy (ET) in late time windows and identify the factors associated with hs-cTnT elevation., Methods: A total of 152 AIS patients treated with ET in late time windows between January 2018 and August 2020 were included in this study. Patients were stratified into either normal or elevated hs-cTnT groups according to a cutoff value of 14 ng/L on admission. Baseline demographic features, comorbidities, and imaging data were compared between the elevated hs-cTnT group (＞14 ng/L) and the normal hs-cTnT group (≤14 ng/L). After accounting for these clinical characteristics, the association between hs-cTnT elevation and clinical outcomes was evaluated., Results: 69(45.4%) patients had elevated hs-cTnT levels (>14 ng/L) on admission. The multivariable logistic regression analysis demonstrated that hs-cTnT elevation was independently associated with 3-month all-cause mortality (P = 0.014, OR 3.907, 95% CI 1.313-11.625) and 3-month composite unfavorable outcome (mRS 3-6) (P = 0.001, OR 5.099, 95% CI 1.873-13.888). Old age (P = 0.002, OR 1.053, 95% CI 1.020-1.088), admission NIHSS score (P = 0.015, OR 1.057, 95% CI 1.011-1.106), congestive heart failure (P = 0.016, OR 4.341, 95% CI 1.322-14.257) and coronary artery disease (P = 0.020, OR 2.914, 95% CI 1.183-7.180) were independently associated with hs-cTnT elevation., Conclusion: In AIS patients treated with ET in late time windows, elevated hs-cTnT is independently associated with an increased risk of 3-month poor outcomes. Old age, high admission NIHSS score, coronary artery disease, and congestive heart failure are independent predictors of hs-cTnT elevation., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Global development has been heavily reliant on the overexploitation of natural resources since the Industrial Revolution. With the extensive use of fossil fuels, deforestation, and other forms of land-use change, anthropogenic activities have contributed to the ever-increasing concentrations of greenhouse gases (GHGs) in the atmosphere, causing global climate change. In response to the worsening global climate change, achieving carbon neutrality by 2050 is the most pressing task on the planet. To this end, it is of utmost importance and a significant challenge to reform the current production systems to reduce GHG emissions and promote the capture of CO 2 from the atmosphere. Herein, we review innovative technologies that offer solutions achieving carbon (C) neutrality and sustainable development, including those for renewable energy production, food system transformation, waste valorization, C sink conservation, and C-negative manufacturing. The wealth of knowledge disseminated in this review could inspire the global community and drive the further development of innovative technologies to mitigate climate change and sustainably support human activities., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

Electrochemical reduction of nitrogen to produce ammonia at moderate conditions in aqueous solutions holds great prospect but also faces huge challenges. Considering the high selectivity of Au-based materials to inhibit competitive hydrogen evolution reaction (HER) and high activity of transition metals such as Fe and Mo toward the nitrogen reduction reaction (NRR), it was proposed that Au-based alloy materials could act as efficient catalysts for N 2 fixation based on density functional theory simulations. Only on Mo 3 Au(111) surface the adsorption of N 2 is stronger than H atom. Thermodynamics combined with kinetics studies were performed to investigate the influence of composition and ratio of Au-based alloys on NRR and HER. The binding energy and reorganization energy affected performance for the initial N 2 activation and hydrogenation process. By considering the free-energy diagram, the computed potential-determining step was either the first or the fifth hydrogenation step on metal catalysts. The optimum catalytic activity could be achieved by adjusting atomic proportion in alloys to make all intermediate species exhibit moderate adsorption. Free-energy diagrams of N 2 hydrogenation via Langmuir-Hinshelwood mechanism and hydrogen evolution via Tafel mechanism were compared to reveal that the Mo 3 Au surface showed satisfactory catalytic performance by simultaneously promoting NRR and suppressing HER. Theoretical simulations demonstrated that Au-Mo alloy materials could be applied as high-performance electrocatalysts for NRR., (© 2021 Wiley-VCH GmbH.)

Background: Madelung's disease (MD) is a rare disorder of lipid metabolism, characterized by the growth of unencapsulated masses of adipose tissue symmetrically deposited around the neck, shoulders, or other sites around the body. Its pathological mechanism is not yet known. One of the most common comorbidities in MD patients is liver disease, especially chronic alcoholic liver disease (CALD); however, no reports exist of acute kidney injury (AKI) with MD., Case Summary: We report a 60-year-old man who presented with complaint of edema in the lower limbs that had persisted for 3 d. Physical examination showed subcutaneous masses around the neck, and history-taking revealed the masses to have been present for 2 years and long-term heavy drinking. Considering the clinical symptoms, along with various laboratory test results and imaging characteristics, a diagnosis was made of MD with acute exacerbation of CALD and AKI. The patient was treated with liver function protection and traditional Chinese medicine, without surgical intervention. He was advised to quit drinking. After 10 d, the edema had subsided, renal function indicators returned to normal, liver function significantly improved, and size of subcutaneous masses remained stable., Conclusion: In MD, concomitant liver or kidney complications are possible and monitoring of liver and kidney functions can be beneficial., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The prognostic significance of obstructive sleep apnea (OSA) in elderly patients with type 2 diabetes is unclear. The aim of this study was to determine the risk of cardiovascular disease (CVD) and mortality in elderly patients with OSA complicated with type 2 diabetes compared to patients with OSA without type 2 diabetes., Methods: From January 2015 to October 2017, 1113 eligible elderly patients with OSA, no history of cardiovascular, ≥60 years of age, and complete follow-up records were enrolled in this consecutive multicentre prospective cohort study. All patients had completed polysomnography (PSG) examinations. An apnoea-hypopnoea index of ≥5 events per hour recorded by polysomnography was defined as the diagnostic criterion for OSA. We collected baseline demographics, clinical characteristics, sleep parameters and follow-up outcomes. The primary aim of this study was to identify the risk of incident major adverse cardiovascular events (MACE). Secondary outcomes were all-cause mortality, components of MACE and a composite of all events. Kaplan-Meier survival analysis and Cox proportional hazards models were used to evaluate whether type 2 diabetes was associated with incident events., Results: A total of 266 (23.9%) patients had OSA complicated with type 2 diabetes. MACE occurred in 97 patients during the median 42-month follow-up. Kaplan-Meier survival curves indicated a significant relationship between type 2 diabetes and MACE (log-rank P = 0.003). Multivariable Cox regression analysis showed that type 2 diabetes increased the risk of MACE (HR = 1.64, 95% CI:1.08-2.47, P = 0.019), hospitalisation for unstable angina (HR = 2.11, 95% CI:1.23-3.64, P = 0.007) and a composite of all events in elderly patients with OSA (HR = 1.70, 95% CI:1.17-2.49, P = 0.007). However, there were no significant differences in the incidence of cardiovascular death, all-cause mortality, MI and hospitalisation for heart failure between patients with and without diabetes (P > 0.05). The subgroup analysis demonstrated that females (AHR = 2.46, 95% CI:1.17-5.19, P = 0.018), ≥ 70 years (AHR = 1.95, 95% CI:1.08-3.52, P = 0.027), overweight and obese (AHR = 2.04, 95% CI:1.29-3.33, P = 0.002) with mild OSA (AHR = 2.42, 95% CI: 1.03-5.71, P = 0.044) were at a higher risk for MACE by diabetes., Conclusion: OSA and type 2 diabetes are interrelated and synergistic with MACE, hospitalisation for unstable angina and a composite of all events development. Overweight and obese females, ≥ 70 years with mild OSA combined with type 2 diabetes presented a significantly high MACE risk., (© 2021. The Author(s).)

An efficient method for the Lewis acid promotion of the synthesis 9-phosphoryl fluorenes has been reported. This method focuses on ketone phosphonylation to form a C-P bond and a C-C bond between diphenylmethanone and H-phosphinate esters, H-phosphites, and H-phosphine oxides via phospha-aldol elimination, in which a series of 9-phosphoryl fluorene derivatives were selectively obtained in moderate to excellent yields.

Objectives: Thousands of designated COVID-19 hospitals have been set up in China to fight the ongoing COVID-19 pandemic. Anecdotal reports indicate a falling rate of acute stroke diagnoses in these hospitals during the COVID-19 period. We conducted an exploratory single-center analysis to estimate the change in acute stroke presentation at the designated COVID-19 hospitals. Methods: This retrospective observational study included all patients admitted to Yongchuan Hospital Affiliated to Chongqing Medical University with acute stroke between January 24 and March 10, 2020. Patient demographics, characteristics of the stroke, treatment details, and clinical outcomes were compared with those of patients admitted in the corresponding period in the year before (2019, "the pre-COVID-19 period"). Subgroup analysis was performed in the ischemic and hemorrhagic stroke groups. Results: A total of 110 patients presented with acute stroke symptoms during the COVID-19 pandemic, compared with 173 patients in the pre-COVID-19 period. A higher proportion of stroke patients presented to the hospital via emergency medical services during the pandemic (48.2 vs. 31.8%, p = 0.006). There was a lower proportion of ischemic stroke patients (50.9 vs. 65.3%, p = 0.016) than in the preceding year. There were significantly fewer patients with 90-day modified Rankin Scale score ≥3 in the COVID-19 period compared with the pre-COVID-19 period (17.3 vs. 30.6%, p = 0.012). Among patients with ischemic stroke, the mean time from patient arrival to vessel puncture for emergency endovascular therapy in the COVID-19 period was shorter than that in the pre-COVID-19 period (109.18 ± 71.39 vs. 270.50 ± 161.51 min, p = 0.002). Among patients with hemorrhagic stroke, the rate of emergency surgical operation in the COVID-19 period was higher than that in the pre-COVID-19 period (48.1 vs. 30.0%, p = 0.047). The mean time from patient arrival to emergency surgical operation (15.31 ± 22.89 vs. 51.72 ± 40.47 min, p = 0.002) was shorter in the COVID-19 period than in the pre-COVID-19 period. Conclusions: Although fewer acute stroke patients sought medical care in this designated COVID-19 hospital during the COVID-19 pandemic, this type of hospital was more efficient for timely treatment of acute stroke. Recognizing how acute strokes presented in designated COVID-19 hospitals will contribute to appropriate adjustments in strategy for dealing with acute stroke during COVID-19 and future pandemics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tan, Liu, Fan, Du, Wu, Gong, Wei, Zhao, Lei and Zhao.)

Purpose: Before we enter the era of flow diverter stents (FDS), the standard stent-assisted coiling technique is a well-established treatment option for routine paraclinoid aneurysms. We assess the clinical safety and efficacy of stent-assisted coiling with open-cell stent in the treatment of paraclinoid aneurysms and evaluate the association between clinical factors and follow-up aneurysm occlusion., Methods: The clinical and radiographic data of 110 consecutive patients with 122 paraclinoid aneurysms treated with open-cell stent between April 2015 and April 2019 were analyzed retrospectively at our center. We assessed the immediate and progressive occlusion rates, complications, and clinical outcome. Multivariate analysis was performed to investigate the risk factors of angiographic incomplete occlusion., Results: Among 110 patients, stent-assisted coiling was successfully performed in all cases. Four (3.6%) thromboembolic events were reported during the procedure, which resulted in transient morbidity. Immediate angiography demonstrated complete occlusion in 64 (52.5%) aneurysms and no occlusion of ophthalmic artery. Angiographic follow-up at 6 months demonstrated an increase in the complete occlusion rate to 92.9%. No delayed in-stent stenosis was observed, and three aneurysms recurred. Clinical follow-up was completed in 102 patients (92.7%), and favorable outcomes were achieved in 101 (99%) patients at 6 months. Multivariate analysis showed that aneurysm size (p < 0.001) was associated with incomplete aneurysm occlusion at follow-up., Conclusion: Stent-assisted coil embolization with open-cell stents is safe and effective for the treatment of paraclinoid aneurysms and provides progressive occlusion without significant in-stent stenosis events., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Background/objectives: To propose a novel definition for hydrocephalus growth and to further describe the association between hydrocephalus growth and poor outcome among patients with intracerebral hemorrhage (ICH)., Methods: We analyzed consecutive patients who presented within 6 h after ICH ictus between July 2011 and June 2017. Follow-up CT scans were performed within 36 h after initial CT scans. The degree of hydrocephalus were evaluated by the hydrocephalus score of Diringer et al. The optimal increase of the hydrocephalus scores between initial and follow-up CT scan was estimated to define hydrocephalus growth. Poor long-term outcome was defined as a modified Rankin Scale of 4-6 at 3 months. Multivariate logistic regression analysis was performed to investigate the hydrocephalus growth for predicting 30-day mortality, 90-day mortality, and poor long-term outcome., Results: A total of 321 patients with ICH were included in the study. Of 64 patients with hydrocephalus growth, 34 (53.1%) patients presented with both concurrent hematoma expansion and intraventricular hemorrhage (IVH) growth. After adjusting for potential confounding factors, hydrocephalus growth independently predicted 30-day mortality, 90-day mortality, and 90-day poor long-term outcome in multivariate logistic regression analysis. Hydrocephalus growth showed higher accuracy for predicting 30-day mortality, 90-day mortality, and poor long-term outcome than IVH growth or hematoma expansion, respectively., Conclusions: Hydrocephalus growth is defined by strongly predictive of short- or long-term mortality and poor outcome at 90 days, and might be a potential indicator for assisting clinicians for clinical decision-making., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Purpose: To compare the ischemic core volume estimated by CT Perfusion 4D and Vue PACS with that estimated by RAPID software in acute ischemic stroke (AIS)., Materials and Methods: CT perfusion data from AIS patients were retrospectively post-processed with RAPID, CT Perfusion 4D and Vue PACS software. The Vue PACS application included three different settings: method A (Circular Singular Value Decomposition), method B (Oscillating index Singular Value Decomposition) and method C (Standard Singular Value Decomposition). Bland-Altman analysis, intraclass correlation coefficients (ICCs) and Kappa analysis were used to evaluate concordance between estimated ischemic core values. Final infarct volume (FIV) was measured by follow-up non-contrast CT or MRI 5-7 days after mechanical thrombectomy (MT) in patients with successful recanalization., Results: A total of 82 patients were included in the study. Concordance with RAPID ranged from good (method B: ICC 0.780; method C: ICC 0.852) to excellent (CT perfusion 4D: ICC 0.950; method A: ICC 0.954). The limits of agreement (-32.3, 41.8 mL) were the narrowest with method A. For detecting core volumes ≤ 70 ml, method A and CT perfusion 4D showed almost perfect concordance with RAPID (CT perfusion 4D, kappa=0.87; method A, kappa=0.87), whereas methods B and C showed substantial concordance with RAPID (method B, kappa=0.77; method C, kappa =0.73). Thirty-two patients had good reperfusion after MT. RAPID showed the highest accuracy for predicting FIV, followed by method A., Conclusion: CT perfusion 4D and Vue PACS method A showed excellent concordance with RAPID for quantifying ischemic core volume, which can be considered as alternatives in selecting patients for MT in clinical practice., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: This study aimed to investigate the safety and efficacy of endovascular embolization for very small ruptured anterior communicating artery (AcomA) aneurysms., Methods: From August 2015 to June 2020, 81 patients with very small (≤3 mm) ruptured AcomA aneurysms treated endovascularly were enrolled in this study. Clinical and radiographic data were analyzed retrospectively, including the aneurysm occlusion rate, complications, and clinical outcome., Results: Among 81 patients, simple coiling embolization was performed in 52 cases and stent-assisted embolization in 29 cases. Immediate angiography demonstrated complete occlusion in 59 (72.8%) aneurysms, residual neck in 20 (24.7%) aneurysms, and residual lumen in 2 (2.5%). Procedure-related complications rate was 2.5% (2 of 81), all of which were transient thromboembolic events. Angiographic follow-up outcomes of 60 patients (mean: 6.8 ± 3.2 months) revealed complete occlusion in 91.7% (55 of 60), with recurrence in 1 patient. The mean clinical follow-up time was 22.6 ± 11.4 months and good prognosis rates (6-month modified Rankin Scale score: 0-2) reached 90.2% (73 of 81). The differences in aneurysm occlusion and procedure-related complications between the simple coiling group and the stent-assisted coiling group were not statistically significant., Conclusions: Coiling with or without stent-assisted technique for the treatment of very small ruptured AcomA aneurysms was safe and effective., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Cardiac embolism is the leading etiology of ischemic strokes. There are arguments about the left-right propensity of cardioembolic strokes.This study aimed to reveal the relationship between the different aortic arch types and the location of large vessel occlusion (LVO) in cardioembolic stroke.We retrospectively identified all patients with acute ischemic stroke admitted to our comprehensive stroke center who had medium- to high-risk cardioembolicsources according to the TOAST classification.Only those with LVO and available images of the aortic arch were included. Patients were classified into 3 groups according to the aortic arch types: Type I (n = 44), Type II (n = 105), Type III (n = 36).The thrombus was divided into large thrombus or small thrombus based on the location of LVO.Overall, left-sided strokes (50.8%) were almost equal to right-sided (49.2%). There was a growing tendency for the percentage of left-sided infarcts with advancement of the aortic arch types either in the total cases or in the atrial fibrillation cases, with no statistical difference between the 3 aortic arch types.In type III aortic arch, left-sided strokes (69.0%) were twice than right-sided (31%) in large thrombus (P < 0.05), while right-sided strokes (85.7%) were more common than left-sided (14.3%) in small thrombus (P < 0.05).Conversely, in type Ⅰ and II aortic arches, left-sided strokes were more common than right-sided in small thrombus, while right-sided strokes were more common than left-sided in large thrombus (P < 0.05). The left-right propensity of cardioembolic stroke is related to the proximity of clot lodging in different aortic arch types., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Organic carbonyl compounds are regarded as promising candidates for next-generation rechargeable batteries due to their low cost, environmentally benign nature, and high capacity. The carbonyl utilization is a key issue that limits the practical specific capacity of multi-carbonyl compounds. In this work, a combination of thermodynamic computation and electronic structure analysis is carried out to study the influence of carbonyl type and carbonyl number on the electrochemical performance of a series of multi-carbonyl compounds by using density functional theory (DFT) calculations. By comparing discharge profiles of six tetraone compounds with different carbonyl sites, it is demonstrated that pentacene-5,7,12,14-tetraone (PT) with para-dicarbonyl and pyrene-4,5,9,10-tetraone (PTO) with ortho-dicarbonyl undergo four-lithium transfer while the other four compounds with meta-dicarbonyl fragments show only two-lithium transfer during the discharge process. By further increasing the carbonyl number, the electrochemical performance of molecules with similar para-dicarbonyl sites to PT can not be strongly improved. Among all the studied multi-carbonyl compounds, triphenylene-2,3,6,7,10,11-hexaone (TPHA) and tribenzo[f,k,m]tetraphen-2,3,6,7,11,12,15,16-octaone (TTOA) with similar ortho-dicarbonyl sites to PTO exhibit the best electrochemical performance due to simultaneous high specific capacity and high discharge voltage. Our results offer evidence that conjugated multiple-carbonyl molecules with ortho-dicarbonyl sites are promising in developing high energy-density organic rechargeable batteries.

Background: The prognostic significance of hyperperfusion after reperfusion therapy in patients with acute ischemic stroke (AIS) remains controversial., Purpose: To investigate the clinical factors associated with hyperperfusion, and the 90-day prognostic value of hyperperfusion after mechanical thrombectomy in AIS patients., Study Type: Retrospective., Population/subjects: Fifty-four AIS patients who underwent mechanical thrombectomy., Field Strength/sequence: Time-of-flight MR angiography, pulsed arterial spin labeling (ASL), diffusion-weighted imaging (DWI), and susceptibility-weighted imaging were performed at 3.0T within 1 week after thrombectomy., Assessment: Clinical factors including demographics, risk factors, stroke and treatment characteristics were collected and assessed. Hyperperfusion on ASL was defined as a focal increased cerebral blood flow on the affected side ≥130% of its mirror counterpart. Good clinical outcome at 90 days was defined as modified Rankin Scale score of 0-2., Statistical Tests: The interrater agreement was assessed using Cohen's kappa or the intraclass correlation coefficient. The relationship between hyperperfusion and clinical factors were analyzed by appropriate univariate statistics. Predictors of 90-day functional outcome were assessed by univariate analyses followed by multivariate logistic regression analysis and receiver-operating-characteristic curves., Results: Thirty-six (66.7%) patients developed hyperperfusion on ASL after thrombectomy. Hyperperfusion was significantly correlated with successful recanalization (P < 0.05) and improvement of National Institutes of Health Stroke Scale scores at 24 hours (NIHSS 24h ) (P < 0.05). A higher incidence of hemorrhage transformation was observed in patients with hyperperfusion than those without (63.9% vs. 50.0%), but no significant difference was found (P = 0.327). NIHSS 24h (odds ratio [OR], 0.75, [95% confidence interval [CI] 0.62-0.91], P < 0.05), lesion volume on diffusion-weighted imaging (OR, 0.97, [95% CI 0.95-1.00], P < 0.05), and hyperperfusion on ASL (OR, 9.8, [95% CI 1.7-55.3], P < 0.05) were independent variables for predicting good functional outcomes., Data Conclusion: Hyperperfusion on ASL correlated with successful recanalization and may be an independent prognostic marker for good neurological outcomes at 90 days in AIS patients after mechanical thrombectomy., Level of Evidence: 4 TECHNICAL EFFICACY STAGE: 2., (© 2020 International Society for Magnetic Resonance in Medicine.)

Objectives: The original intracerebral hemorrhage (oICH) score is the severity score most commonly used in clinical intracerebral hemorrhage (ICH) research but may be influenced by hematoma expansion or intraventricular hemorrhage (IVH) growth in acute ICH. Here, we aimed to develop new clinical scores to improve the prediction of functional outcomes in patients with ICH. Methods: Patients admitted to the First Affiliated Hospital of Chongqing Medical University with primary ICH were prospectively enrolled in this study. Hematoma volume was measured using a semiautomated, computer-assisted technique. The dynamic ICH (dICH) score was developed by incorporating hematoma expansion and IVH growth into the oICH score. The ultra-early ICH (uICH) score was developed by adding the independent non-contrast CT markers to the oICH score. Receiver operating characteristic curve analysis was used to compare performance among the oICH score, dICH score, and uICH score. Results: This study included 76 patients (23.3%) with hematoma expansion and 61 patients (18.7%) with IVH growth. Of 31 patients with two or more non-contrast computed tomography markers, 61.3% died, and 96.8% had poor outcomes at 90 days. After adjustment for potential confounding variables, we found that age, baseline Glasgow Coma Scale score, presence of IVH on initial CT, baseline ICH volume, infratentorial hemorrhage, hematoma expansion, IVH growth, blend sign, black hole sign, and island sign could independently predict poor outcomes in multivariate analysis. In comparison with the oICH score, the dICH score and uICH score exhibited better performance in the prediction of poor functional outcomes. Conclusions: The dICH score and uICH score were useful clinical assessment tools that could be used for risk stratification concerning functional outcomes and provide guidance in clinical decision-making in acute ICH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yang, Shen, Wei, Zhao, Liu, Xie, Zhang, Deng, Lv, Zhang, Li, Li and Xie.)

The correlations between hydroxytryptamine receptor 2A (HTR2A) gene polymorphisms (1438A/G, 102T/C, and rs7997012G/A) and the safety and efficacy of antidepressants in depression patients were constantly reported, but conclusions are debatable. This meta-analysis ascertained forty-two studies on the efficacy (including response and remission) and side-effect issued before February 2020. Pooled analyses indicated significant associations of 1438A/G polymorphism (16 studies, 1931 subjects) and higher response within dominant model (OR: 1.40, 95% CI: 1.12-1.76); rs7997012G/A polymorphism (nine studies, 1434 subjects) and higher remission in overall models (dominant model: OR: 1.30, 95% CI: 1.01-1.66; recessive model: OR: 2.20, 95% CI: 1.53-3.16; homozygote model: OR: 2.73, 95% CI: 1.78-4.17); 102T/C polymorphism (eight studies, 804 subjects) and reduced risk of side-effect within recessive (OR: 0.57, 95% CI: 0.4-0.83) and homozygote models (OR: 0.54, 95% CI: 0.29-0.99). For depression patients, genotyping of HTR2A polymorphisms is a promising tool for estimating the outcome and side-effect of antidepressants.

Objective: Lung auscultation plays an important role in the diagnosis of pulmonary diseases in children. The objective of this study was to evaluate the use of an artificial intelligence (AI) algorithm for the detection of breath sounds in a real clinical environment among children with pulmonary diseases. Method: The auscultations of breath sounds were collected in the respiratory department of Shanghai Children's Medical Center (SCMC) by using an electronic stethoscope. The discrimination results for all chest locations with respect to a gold standard (GS) established by 2 experienced pediatric pulmonologists from SCMC and 6 general pediatricians were recorded. The accuracy, sensitivity, specificity, precision, and F1-score of the AI algorithm and general pediatricians with respect to the GS were evaluated. Meanwhile, the performance of the AI algorithm for different patient ages and recording locations was evaluated. Result: A total of 112 hospitalized children with pulmonary diseases were recruited for the study from May to December 2019. A total of 672 breath sounds were collected, and 627 (93.3%) breath sounds, including 159 crackles (23.1%), 264 wheeze (38.4%), and 264 normal breath sounds (38.4%), were fully analyzed by the AI algorithm. The accuracy of the detection of adventitious breath sounds by the AI algorithm and general pediatricians with respect to the GS were 77.7% and 59.9% ( p < 0.001), respectively. The sensitivity, specificity, and F1-score in the detection of crackles and wheeze from the AI algorithm were higher than those from the general pediatricians (crackles 81.1 vs. 47.8%, 94.1 vs. 77.1%, and 80.9 vs. 42.74%, respectively; wheeze 86.4 vs. 82.2%, 83.0 vs. 72.1%, and 80.9 vs. 72.5%, respectively; p < 0.001). Performance varied according to the age of the patient, with patients younger than 12 months yielding the highest accuracy (81.3%, p < 0.001) among the age groups. Conclusion: In a real clinical environment, children's breath sounds were collected and transmitted remotely by an electronic stethoscope; these breath sounds could be recognized by both pediatricians and an AI algorithm. The ability of the AI algorithm to analyze adventitious breath sounds was better than that of the general pediatricians., Competing Interests: H-YZ was employed by Tuoxiao Intelligent Technology Company. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Wang, Zhou, Dong, Zhang, Zhang, Liu, Wu, Yuan, Tang, Dong, Lin, Chen, Tong, Zhao and Yin.)

Background Noncontrast computed tomography (NCCT) markers are the emerging predictors of hematoma expansion in intracerebral hemorrhage. However, the relationship between NCCT markers and the dynamic change of hematoma in parenchymal tissues and the ventricular system remains unclear. Methods and Results We included 314 consecutive patients with intracerebral hemorrhage admitted to our hospital from July 2011 to May 2017. The intracerebral hemorrhage volumes and intraventricular hemorrhage (IVH) volumes were measured using a semiautomated, computer-assisted technique. Revised hematoma expansion (RHE) was defined by incorporating the original definition of hematoma expansion into IVH growth. Receiver operating characteristic curve analysis was used to compare the performance of the NCCT markers in predicting the IVH growth and RHE. Of 314 patients in our study, 61 (19.4%) had IVH growth and 93 (23.9%) had RHE. After adjustment for potential confounding variables, blend sign, black hole sign, island sign, and expansion-prone hematoma could independently predict IVH growth and RHE in the multivariate logistic regression analysis. Expansion-prone hematoma had a higher predictive performance of RHE than any single marker. The diagnostic accuracy of RHE in predicting poor prognosis was significantly higher than that of hematoma expansion. Conclusions The NCCT markers are independently associated with IVH growth and RHE. Furthermore, the expansion-prone hematoma has a higher predictive accuracy for prediction of RHE and poor outcome than any single NCCT marker. These findings may assist in risk stratification of NCCT signs for predicting active bleeding.

The purpose of this study was to explore the effect of the traditional Chinese medicine Fuyou formula on precocious puberty (PP). The Fy formula may exert an effect in female rats with PP and GT-7 cells through the GPR54/GnRH signaling pathway. To confirm the effect of the Fy formula on PP through the GPR54/GnRH signaling pathway, we first treated GT1-7 cells with the Fy formula and observed changes in the expression of related genes and proteins and in GnRH secretion. Then, we randomly divided young female Sprague-Dawley rats into the control group, model group, leuprorelin group and the Fy formula group. A PP model was established by injection of danazol on postnatal day 5, and the Fy formula was administered on PND15. The time of vaginal opening, the wet weights of the ovary and uterus, serum hormone levels and the expression of hypothalamic-related genes were observed. We found that the Fy formula delayed vaginal opening, decreased the wet weights and coefficients of the ovary and uterus, decreased the levels of serum hormones (E2, follicle-stimulating hormone and luteinizing hormone) and the cellular GnRH level, and downregulated the gene expression of Kiss1, GPR54 and GnRH in the hypothalamus and the gene and protein expression of GPR54 and GnRH in GT1-7 cells. In conclusion, the Fy formula may alleviate PP via the GPR54/GnRH signaling pathway., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer PZ declared a shared affiliation with the authors to the handling editor at the time of the review., (Copyright © 2021 Bai, Hu, Huan, Wang, Lei, Zhang, Guo, Chang, Zhao, Liu, Shen, Wang and Ni.)

We aimed to conduct a meta-analysis to evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) in patients with post-stroke depression (PSD). Six relevant electronic databases (PubMed, CENTRAL, Embase, Web of Science, CINAHL, and PsycINFO) were searched. Randomized controlled trials (RCTs) that compared rTMS with control condition for PSD were included. The mean change in depression symptom scores was defined as the primary efficacy outcome. Secondary outcomes included the remission rate of depression, stroke recovery, and cognitive function recovery. In total, 7 RCTs with 351 participants were included. At post-treatment, rTMS was significantly more effective than the control condition, with a standardized mean difference (SMD) of -1.15 (95%CI: -1.62 to -0.69; P<0.001, I2=71%) and remission with an odds ratio (OR) of 3.46 (95%CI: 1.68 to 7.12; P<0.001; I2=11%). As for stroke recovery, rTMS was also better than the control condition (SMD=-0.67, 95%CI: -1.02 to -0.32; P<0.001). However, no significant difference was found for cognitive function recovery between the two groups (SMD=4.07, 95%CI: -1.41 to 9.55; P=0.15). To explore the potential moderators for the primary outcome, a series of subgroup and sensitivity analyses were performed. The results implied that rTMS may be more effective in Asian samples than in North American samples (P=0.03). In conclusion, from the current evidence in this study, rTMS could be an effective treatment for patients with PSD. Further clinical studies with larger sample sizes and clearer subgroup definitions are needed to confirm these outcomes.

Background/objectives: The objective of this study is to propose a definition of intraventricular hemorrhage (IVH) growth and to investigate whether IVH growth is associated with ICH expansion and functional outcome., Methods: We performed a prospective observational study of ICH patients between July 2011 and March 2017 in a tertiary hospital. Patients were included if they had a baseline CT scan within 6 h after onset of symptoms and a follow-up CT within 36 h. IVH growth was defined as either any newly occurring intraventricular bleeding on follow-up CT scan in patients without baseline IVH or an increase in IVH volume ≥ 1 mL on follow-up CT scan in patients with initial IVH. Poor outcome was defined as modified Rankin Scale score of 3-6 at 90 days. The association between IVH growth and functional outcome was assessed by using multivariable logistic regression analysis., Results: IVH growth was observed in 59 (19.5%) of 303 patients. Patients with IVH growth had larger baseline hematoma volume, higher NIHSS score and lower GCS score than those without. Of 44 patients who had concurrent IVH growth and hematoma growth, 41 (93.2%) had poor functional outcome at 3-month follow-up. IVH growth (adjusted OR 4.15, 95% CI 1.31-13.20; P = 0.016) was an independent predictor of poor functional outcome (mRS 3-6) at 3 months in multivariable analysis., Conclusion: IVH growth is not uncommon and independently predicts poor outcome in ICH patients. It may serve as a promising therapeutic target for intervention.

Objective: To investigate the relationship between hematoma ventricle distance (HVD) and clinical outcome in patients with intracerebral hemorrhage (ICH)., Methods: We prospectively enrolled consecutive patients with ICH in a tertiary academic hospital between July 2011 and April 2018. We retrospectively reviewed images for all patients receiving a computed tomography (CT) within 6 h after onset of symptoms and at least one follow-up CT scan within 36 h. The minimum distance of hematoma border to nearest ventricle was measured as HVD. Youden index was used to evaluate the cutoff of HVD predicting functional outcome. Logistic regression model was used to assess the HVD data and clinical poor outcome (modified Rankin Scale 4-6) at 90 days., Results: A total of 325 patients were included in our final analysis. The median HVD was 2.4 mm (interquartile range, 0-5.7 mm), and 119 (36.6%) patients had poor functional outcome at 3 months. After adjusting for age, admission Glasgow coma scale, intraventricular hemorrhage, baseline ICH volume, admission systolic blood pressure, blood glucose, hematoma expansion, withdrawal of care, and hypertension, HVD ≤ 2.5 mm was associated with increased odds of clinical poor outcome [odd ratio, 3.59, (95%CI = 1.72-7.50); p = 0.001] in multivariable logistic regression analysis., Conclusion: Hematoma ventricle distance allows physicians to quickly select and stratify patients in clinical trials and thereby serve as a novel and useful addition to predict ICH prognosis., (Copyright © 2020 Deng, Zhang, Ji, Yang, Wei, Shen, Li, Zhang, Lv, Li, Tang, Wu, Zhao, Xie and Li.)

The electrochemical reduction of N2 is a promising reaction candidate for the ammonia synthesis process. Density functional theory simulations are carried out to study the reaction thermodynamics and kinetics for a better understanding of the catalytic performance of Fe, Mo, Rh, and Ru electrodes. The distal pathway is the most likely reaction pathway for nitrogen reduction on transition metal surfaces according to the computed reaction free energies. The onset potential of nitrogen reduction on Fe(110) (-0.49 V) and Mo(110) (-0.52 V) is determined by the hydrogenation of NH to NH2, which is more positive than the onset potential on the Ru(0001) (-0.76 V) and Rh(111) (-0.98 V) surfaces attributed to the hydrogenation of N2 to NNH. In particular, the initial hydrogenation of N2 on Mo(111) is a spontaneous process due to the strong interaction of N2 and NNH with the Mo(110) surface. Electronic structure analyses including Bader charge analysis and projected crystal orbital Hamilton populations are performed to interpret the difference in adsorption energy of key intermediates on the four metal surfaces. It is found that both N2 and NNH species have the strongest interaction with Mo(110) leading to the initial activation of N2 on the Mo(110) surface being a spontaneous process. A kinetic model based on the Marcus theory is applied to calculate the potential-dependent reaction barrier of electrochemical hydrogenation steps of the N2 reduction reaction. The rate-determining step is the fifth hydrogenation step *NH → *NH2 on Fe(110) and Mo(110) surfaces, and the first hydrogenation step *N2 → *NNH on Rh(111) and Ru(0001) surfaces. The predicted electrocatalytic activity from the potential-dependent rate constant of the rate-determining step on the four metal electrodes decreases in sequence: Fe(110) > Mo(110) > Ru(0001) > Rh(111).

Objective: This study aimed to develop a parent-metabolite joint population pharmacokinetic model to characterize the pharmacokinetic (PK) profile for phosphocreatine (PCr) and its metabolite creatine (Cr) in children with myocarditis and to use this model to study the PK profile of different dosing schemes. Methods: One hundred pediatric patients with myocarditis were enrolled. Blood samples were collected at baseline and approximately 30, 40 or 50, 75, and 180 min after a single dose of phosphocreatine sodium. Plasma PCr and Cr concentrations were determined using an HPLC-MS/MS method. A nonlinear mixed effect model approach was used to build the population pharmacokinetic model. After validation, the model was used for simulations to evaluate the PK profile of different dosing schemes. Results: A total of 997 plasma concentrations (498 for PCr and 499 for Cr) were included in the analysis. A four-compartment chain model (central and peripheral compartments for both PCr and Cr) with the first-order elimination adequately characterized the in vivo process of PCr and Cr. Allometric scaling based on bodyweight was applied to the PK parameters. The covariate analysis identified that the glomerular filtration rate (GFR) was strongly associated with Cr clearance. Bootstrapping and visual predictive checks suggested that a robust and reliable pharmacokinetic model was developed. The simulation results showed that PCr had no accumulation in vivo . With the infusion of PCr, the concentration of Cr increased rapidly. Conclusion: A joint population pharmacokinetic model for PCr and Cr in pediatric patients with myocarditis was successfully developed for the first time., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 He, Zhang, Zhao, Sun, Zhang, Yuan and Wang.)