Peripheral inflammation and trajectories of depressive symptomology after ischemic stroke: A prospective cohort study.

BACKGROUND: Understanding the association of peripheral inflammation and post-stroke depressive symptomology (PSDS) might provide further insights into the complex etiological mechanism of organic depression. However, studies focusing on the longitudinal patterns of PSDS were limited and it remained unclear whether peripheral inflammation influences the occurrence and development of PSDS. METHODS: A total of 427 prospectively enrolled and followed ischemic stroke patients were included in the analytical sample. Depressive symptomology was assessed on four occasions during 1 year after ischemic stroke. Peripheral inflammatory proteins on admission and repeated measures of peripheral immune markers in three stages were collected. Latent class growth analysis (LCGA) was employed to delineate group-based trajectories of peripheral immune markers and PSDS. Multinomial regression was performed to investigate the association of peripheral inflammation with PSDS trajectories. RESULTS: Four distinct trajectories of PSDS were identified: stable-low (n = 237, 55.5 %), high-remitting (n = 120, 28.1 %), late-onset (n = 44, 10.3 %), and high-persistent (n = 26, 6.1 %) PSDS trajectories. The elevation of peripheral fibrinogen on admission increased the risk of high-persistent PSDS in patients with early high PSDS. Additionally, chronic elevation of innate immune levels might not only increase the risk of high-persistent PSDS in patients with early high PSDS but also increase the risk of late-onset PSDS in patients without early high PSDS. The elevation of adaptive immune levels in the convalescence of ischemic stroke may contribute to the remission of early high PSDS. CONCLUSIONS: Peripheral immunity could influence the development of PSDS, and this influence might have temporal heterogeneity. These results might provide vital clues for the inflammation hypothesis of PSD.

Exploring the potential molecular intersection of stroke and major depression disorder.

Stroke and major depression disorder are common neurological diseases, and a large number of clinical studies have shown that there is a close relationship between the two diseases, but whether the two diseases are linked at the genetic level needs to be further explored. The purpose of this study was to explore the comorbidity mechanism of stroke and major depression by using bioinformatics technology and animal experiments. From the GEO database, we gathered transcriptome data of stroke and depression mice (GSE104036, GSE131712, GSE81672, and GSE146845) and identified comorbid gene set through edgR and WGCNA analyses. Further analysis revealed that these genes were enriched in pathways associated with cell death. Programmed cell death gene sets (PCDGs) are generated from genes related to apoptosis, necroptosis, pyroptosis and autophagy. The intersection of PCDGs and comorbid gene set resulted in two hub genes, Mlkl and Nlrp3. Single-cell sequencing analysis indicated that Mlkl and Nlrp3 are mainly influential on endothelial cells and microglia, suggesting that the impairment of these two cell types may be a factor in the relationship between stroke and major depression. This was experimentally confirmed by RT-PCR and immunofluorescence staining. Our research revealed that two specific genes, namely, Mlkl and Nlrp3, play crucial roles in the complex mechanism that links stroke and major depression. Additionally, we have predicted six possible therapeutic agents and the outcomes of docking simulations of target proteins and drug molecules.

Endovascular Therapy and Outcomes Among Patients With Very Large Ischemic Core Stroke.

Importance: The association of endovascular therapy (EVT) with outcomes is unclear for patients with very low Alberta Stroke Program Early Computed Tomography Score (ASPECTS) within 24 hours of stroke onset. Objective: To explore the association of EVT with functional and safety outcomes among patients with ASPECTS of 0 to 2 scored with noncontrast computed tomography. Design, Setting, and Participants: This cohort study used data from an ongoing, prospective, observational, nationwide registry including all patients treated at 38 stroke centers in China with an occlusion in the internal carotid artery or M1 or M2 segment of the middle cerebral artery within 24 hours of witnessed symptom onset. Patients with ASPECTS of 0 to 2 between November 1, 2021, and February 8, 2023, were included in analysis. Data were analyzed October to November 2023. Exposures: EVT vs standard medical treatment (SMT). Main Outcomes and Measures: The primary outcome was favorable functional outcome, defined as modified Rankin Scale score (mRS) of 0 to 3, at 90 days. Safety outcomes included symptomatic intracerebral hemorrhage (sICH) within 48 hours and mortality at 90 days. Results: A total of 245 patients (median [IQR] age, 71 [63-78] years; 118 [48%] women) with ASPECTS of 0 to 2 were included, of whom 111 patients (45.1%) received SMT and 135 patients (54.9%) received EVT. The EVT group had significantly greater odds of favorable functional outcome at 90 days than the SMT group (30 patients [22.2%] vs 11 patients [9.9%]; P = .01; adjusted odds ratio [aOR], 3.07 [95% CI, 1.29-7.31]; P = .01). Patients in the EVT group, compared with the SMT group, had significantly greater odds of any ICH (56 patients [41.5%] vs 16 patients [11.4%]; P < .001; aOR, 4.27 [95% CI, 2.19-8.35]; P < .001) and sICH (24 patients [17.8%] vs 1 patient [0.9%]; P < .001; aOR, 23.07 [95% CI, 2.99-177.79]; P = .003) within 48 hours. There were no differences between groups for 90-day mortality (80 patients [59.3%] vs 59 patients [53.2%]; P = .34; aOR, 1.38 [95% CI, 0.77-2.47]; P = .28). The results remained robust in the propensity score-matched analysis. Conclusions and Relevance: In this cohort study of patients with very low ASPECTS based on NCCT within 24 hours of stroke onset, those treated with EVT had higher odds of a favorable functional outcome compared with those who received SMT. Randomized clinical trials are needed to assess these findings.

The Association Between National Institutes of Health Stroke Scale Score and Clinical Outcome in Patients with Large Core Infarctions Undergoing Endovascular Treatment.

INTRODUCTION: This study aimed to analyze the association between baseline National Institutes of Health Stroke Scale (NIHSS) scores and clinical outcomes in patients with large core infarctions undergoing endovascular treatment (EVT), a relationship that remains unclear. METHODS: Data were obtained from the MAGIC study, a prospective multicenter cohort study focusing on patients with acute large core ischemic stroke. This analysis evaluated the impact of NIHSS scores on EVT outcomes in patients with large core infarctions. Primary outcome metrics included favorable outcomes (modified Rankin Scale [mRS] of 0-3 at 90 days), while secondary outcomes encompassed shifts in mRS scores, functional independence (mRS score of 0-2), mRS score of 0-4, and successful recanalization rates. Adverse events considered were symptomatic intracranial hemorrhage (sICH) and mortality. RESULTS: A total of 490 patients were enrolled in this study. Higher baseline NIHSS scores were inversely correlated with favorable outcomes (adjusted odds ratio [OR] in model 3, 0.848 [0.797-0.903], P < 0.001), particularly in patients with NIHSS scores above 20 (adjusted OR in model 3, 0.518 [0.306-0.878] vs. 0.290 [0.161-0.523]). Regarding adverse events, higher baseline NIHSS scores significantly correlated with increased 90-day mortality rates (adjusted OR in model 3, 1.129 [1.072-1.189], P < 0.001). This correlation became insignificant when baseline NIHSS scores exceeded 22. Additionally, baseline NIHSS scores partially mediated the association between age (indirect effect = - 0.0005, 19.39% mediated) and sex (indirect effect = 0.0457, 25.08% mediated) with the primary outcome. CONCLUSIONS: The findings indicate that higher baseline NIHSS scores correlate with poorer outcomes and increased mortality, particularly when scores exceed 20. Moreover, age and sex indirectly influence favorable outcomes through their association with baseline NIHSS scores.

High mono-rhamnolipids production by a novel isolate Pseudomonas aeruginosa LP20 from oily sludge: characterization, optimization, and potential application.

This study aims to isolate microbial strains for producing mono-rhamnolipids with high proportion. Oily sludge is rich in petroleum and contains diverse biosurfactant-producing strains. A biosurfactant-producing strain LP20 was isolated from oily sludge, identified as Pseudomonas aeruginosa based on phylogenetic analysis of 16S rRNA. High-performance liquid chromatography-mass spectrometry results indicated that biosurfactants produced from LP20 were rhamnolipids, mainly containing Rha-C8-C10, Rha-C10-C10, Rha-Rha-C8-C10, Rha-Rha-C10-C10, Rha-C10-C12:1, and Rha-C10-C12. Interestingly, more mono-rhamnolipids were produced by strain LP20 with a relative abundance of 64.5%. Pseudomonas aeruginosa LP20 optimally produced rhamnolipids at a pH of 7.0 and a salinity of 0.1% using glycerol and nitrate. The culture medium for rhamnolipids by strain LP20 was optimized by response surface methodology. LP20 produced rhamnolipids up to 6.9 g L-1, increased by 116%. Rhamnolipids produced from LP20 decreased the water surface tension to 28.1 mN m-1 with a critical micelle concentration of 60 mg L-1. The produced rhamnolipids emulsified many hydrocarbons with EI24 values higher than 56% and showed antimicrobial activity against Staphylococcus aureus and Cladosporium sp. with inhibition rates 48.5% and 17.9%, respectively. Pseudomonas aeruginosa LP20 produced more proportion of mono-rhamnolipids, and the LP20 rhamnolipids exhibited favorable activities and promising potential in microbial-enhanced oil recovery, bioremediation, and agricultural biocontrol.

Neuro-bone tissue engineering: emerging mechanisms, potential strategies, and current challenges.

The skeleton is a highly innervated organ in which nerve fibers interact with various skeletal cells. Peripheral nerve endings release neurogenic factors and sense skeletal signals, which mediate bone metabolism and skeletal pain. In recent years, bone tissue engineering has increasingly focused on the effects of the nervous system on bone regeneration. Simultaneous regeneration of bone and nerves through the use of materials or by the enhancement of endogenous neurogenic repair signals has been proven to promote functional bone regeneration. Additionally, emerging information on the mechanisms of skeletal interoception and the central nervous system regulation of bone homeostasis provide an opportunity for advancing biomaterials. However, comprehensive reviews of this topic are lacking. Therefore, this review provides an overview of the relationship between nerves and bone regeneration, focusing on tissue engineering applications. We discuss novel regulatory mechanisms and explore innovative approaches based on nerve-bone interactions for bone regeneration. Finally, the challenges and future prospects of this field are briefly discussed.

Corrigendum to "Photocatalytic oxygen evolution and antibacterial biomimetic repair membrane for diabetes wound repair via HIF1-α pathway" [Mater. Today Bio 20 (2023) 100616].

[This corrects the article DOI: 10.1016/j.mtbio.2023.100616.].

Longitudinal relationships between depressive symptoms and cognitive function after stroke: A cross-lagged panel design.

OBJECTIVE: Stroke is a leading cause of mortality and disability. This study aimed to investigate the temporal and directional relationships between post-stroke depressive symptoms and cognitive impairment using a cross-lagged panel design. Depressive symptoms and cognitive impairment are two common post-stroke complications. However, the precise underlying mechanism remains unclear despite their close relationship. Therefore, elucidating the causal relationship between these two issues is of great clinical significance for improving the poor prognosis of stroke. METHODS: This study employed a hospital-based multicenter prospective cohort design. A total of 610 patients with ischemic stroke were eligible. Depressive symptoms (measured using the seventeen-item Hamilton Rating Scale for Depression) and cognitive function (measured using the Montreal Cognitive Assessment) were assessed at baseline and the 12-month follow-up. Spearman's correlation was used to examine the correlation between cognitive function and depressive symptoms. Additionally, a cross-lagged panel analysis was employed to elucidate the causal relationship between these factors after adjusting for potential covariates. RESULTS: The results of a four-iteration cross-lagged panel analysis substantiated a bidirectional relationship between post-stroke depressive symptoms and cognitive function over time. Specifically, higher scores for early depressive symptoms were associated with lower scores for later cognitive function; additionally, higher baseline cognitive function scores were associated with lower depressive symptom scores at a later point. CONCLUSION: This study establishes a reciprocally causal long-term relationship between depressive symptoms and cognitive function after an ischemic stroke. Therefore, interventions aimed at improving cognitive function and ameliorating depressive symptoms may positively affect both cognition and mood. TRIAL REGISTRATION: ChiCTR-ROC-17013993.

Depressive symptom dimensions predict the treatment effect of repetitive transcranial magnetic stimulation for post-stroke depression.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) has attracted considerable attention because of its non-invasiveness, minimal side effects, and treatment efficacy. Despite an adequate duration of rTMS treatment, some patients with post-stroke depression (PSD) do not achieve full symptom response or remission. METHODS: This was a prospective randomized controlled trial. Participants receiving rTMS were randomly assigned to the ventromedial prefrontal cortex (VMPFC), left dorsolateral prefrontal cortex (DLPFC), or contralateral motor area (M1) groups in a ratio of 1:1:1. Enrollment assessments and data collection were performed in weeks 0, 2, 4, and 8. The impact of depressive symptom dimensions on treatment outcomes were tested using a linear mixed-effects model fitted with maximum likelihood. Univariate analysis of variance (ANOVA) and back-testing were used to analyze the differences between the groups. RESULTS: In total, 276 patients were included in the analysis. Comparisons across groups showed that 17-item Hamilton Rating Scale for Depression (HAMD-17) scores of the DLPFC group significantly differed from those of the VMPFC and M1 groups at 2, 4, and 8 weeks after treatment (p < 0.05). A higher observed mood score (ß = -0.44, 95% confidence interval [CI]: -0.85-0.04, p = 0.030) could predict a greater improvement in depressive symptoms in the DLPFC group. Higher neurovegetative scores (ß = 0.60, 95% CI: 0.25-0.96, p = 0.001) could predict less improvement of depressive symptoms in the DLPFC group. CONCLUSION: Stimulation of the left DLPFC by high-frequency rTMS (HF-rTMS) could significantly improve depressive symptoms in the subacute period of subcortical ischemic stroke, and the dimension of depressive symptoms at admission might predict the treatment effect.

Ultrasonic-assisted extraction of flavonoids from Nitraria sibirica leaf using response surface methodology and their anti-proliferative activity on 3T3-L1 preadipocytes and antioxidant activities.

As both an edible and medicinal plant, Nitraria sibirica has been used as a natural remedy for indigestion and hypertension since ancient times in Central Asia. The ethanolic extract of N. sibirica leaves lowers blood pressure and blood lipids. We assume that these bioactivities are most likely related to the composition of flavonoids due to their dominant content. Therefore, we investigated bioactivity-oriented extraction parameters of flavonoids from N. sibirica. In this study, the ultrasonic-assisted extraction variables were optimized using a response surface methodology for optimal recoveries of total flavonoid content (TFC), anti-proliferative activity on 3T3-L1 preadipocytes and antioxidant capacities (DPPH) of N. sibirica leaf extract (NLE). The optimal extraction conditions of NLEs were as follows: ethanol concentration of 71.33%, feed-to-solvent ratio of 30.36 mL/g, extraction temperature of 69.48°C, extraction time of 25.27 min, extraction number of two times, the TFCs were 1.73 ± 0.01 mg RE/g d.w. (n = 4), IC50 value of preadipocytes was 259.42 ± 3.62 µg/mL (n = 4), and antioxidant capacity of 86.55 ± 3.71% (n = 4). After the purification of NLEs, the TFCs were 7.52 mg RE/g d.w., the inhibition capacity of IC50 was 143.50 µg/mL, and DPPH scavenging rate was 86.99%, which were approximately 4.34, 1.81, and 1.01 folds higher than before the purification of NLEs, respectively. Bioactive-oriented extraction of NLEs possessed the potential lipid lowering and antioxidant activities, which hold high research value for the development of natural medicines or new functional foods to treat or prevent metabolic diseases such as obesity.

Photocatalytic oxygen evolution and antibacterial biomimetic repair membrane for diabetes wound repair via HIF1-α pathway.

Diabetic wounds always have puzzled patients and caused serious social problems. Due to the lack of local blood vessels, severe hypoxia is generated in the defect area, which is an essential reason for the difficulty of wound healing. We have constructed a photocatalytic oxygen evolution and antibacterial biomimetic repair membrane to solve the problems of wound repair. A scanning electron microscope and transmission electron microscope characterized the biomimetic repair membrane. The oxygen evolution of the biomimetic membrane was tested by an oxygen meter. The excellent antibacterial performance of the biomimetic repair membrane was also verified by co-culture with Staphylococcus aureus and Escherichia coli. It was confirmed that the expression of collagen and HIF1-α in fibroblasts was significantly increased in vitro. And the mitochondrial activity of the vascular and nerve was increased considerably. In vivo, the healing time of diabetes wounds treated with the biomimetic repair membrane was significantly reduced, the collagen and the number of pores were increased considerably, and vascular regeneration was enhanced. The biomimetic repair membrane has an excellent performance in photocatalytic oxygen evolution and antibacterial and can significantly promote the repair of diabetes wounds. This will provide a promising treatment for diabetes wound repair.

Incremental Value of Stroke-Induced Structural Disconnection in Predicting Global Cognitive Impairment After Stroke.

BACKGROUND: Poststroke cognitive impairment (PSCI) is highly prevalent in stroke survivors and correlated with unfavorable clinical outcomes. This study aimed to identify the neural substrate of PSCI using atlas-based disconnectome analysis and assess the value of disconnection score, a baseline measure for stroke-induced structural disconnection, in PSCI prediction. METHODS: A multicenter prospective cohort of 676 first-ever patients with acute ischemic stroke was enrolled from 3 independent hospitals in China. Sociodemographic, clinical, and neuroimaging data were collected at acute stage of stroke. Cognitive assessment was performed at 3 months after stroke. Voxel-wise and tract-wise disconnectome analysis were performed to uncover the strategic structural disconnection pattern for global PSCI. Disconnection score was calculated for each participant in leave-one-dataset-out cross-validation. Multivariable logistic regression was performed for the association between disconnection score and PSCI. Prediction models with and without disconnection score were developed, cross-validated, and compared in terms of discrimination and goodness-of-fit. RESULTS: Compared with lesions of non-PSCI, those of PSCI were more likely to have fiber connections with left prefrontal cortex and left deep structures (thalamus and basal ganglia). Disconnection score could predict the risk and severity of PSCI during cross-validation, and was independently associated with PSCI after controlling for all baseline covariates (odds ratio, 1.38 [95% CI, 1.17-1.64]; P<0.001). Incorporating disconnection score into a reference model with 6 known predictors resulted in significant improvement in both discrimination and goodness-of-fit throughout cross-validation. CONCLUSIONS: A strategic structural disconnection pattern centered on left prefrontal cortex, thalamus, and basal ganglia is identified for global PSCI using indirect disconnectome analysis. The baseline disconnection score is independently predictive of PSCI and has significant incremental value to preexisting sociodemographic, clinical, and neuroimaging predictors. REGISTRATION: URL: http://www.chictr.org.cn/enIndex.aspx; Unique identifier: ChiCTR-ROC-17013993.

Nomogram including indirect bilirubin for the prediction of post-stroke depression at 3 months after mild acute ischemic stroke onset.

Background: Post-stroke depression (PSD) has been proven to be associated with stroke severity. Thus, we hypothesized that the prevalence of PSD would be lower in patients with mild stroke. We aim to explore predictors of depression at 3 months after mild acute ischemic stroke (MAIS) onset and to develop a practical and convenient prediction model for the early identification of patients at high risk. Methods: A total of 519 patients with MAIS were consecutively recruited from three hospitals in Wuhan city, Hubei province. MAIS was defined as a National Institute of Health Stroke Scale (NIHSS) score of ≤5 at admission. Meeting the DSM-V diagnostic criteria and a 17-item Hamilton Rating Scale for Depression (HAMD-17) score of >7 at their 3-month follow-up were considered the primary outcomes. A multivariable logistic regression model was used to determine the factors adjusted for potential confounders, and all independent predictors were brought into the construction of a nomogram to predict PSD. Results: The prevalence of PSD is up to 32% at 3 months after MAIS onset. After adjusting for potential confounders, indirect bilirubin (p = 0.029), physical activity (p = 0.001), smoking (p = 0.025), hospitalization days (p = 0.014), neuroticism (p < 0.001), and MMSE (p < 0.001) remained independently and significantly related with PSD. The concordance index (C-index) of the nomogram jointly constructed by the aforementioned six factors was 0.723 (95% CI: 0.678-0.768). Conclusion: The prevalence of PSD seems equally high even if the ischemic stroke is mild, which calls for great concern from clinicians. In addition, our study found that a higher level of indirect bilirubin can lower the risk of PSD. This finding may provide a potential new approach to PSD treatment. Furthermore, the nomogram including bilirubin is convenient and practical to predict PSD after MAIS onset.

Psychopathological network for early-onset post-stroke depression symptoms.

BACKGROUND: Post-stroke depression (PSD) can be conceptualized as a complex network where PSD symptoms (PSDS) interact with each other. The neural mechanism of PSD and interactions among PSDS remain to be elucidated. This study aimed to investigate the neuroanatomical substrates of, as well as the interactions between, individual PSDS to better understand the pathogenesis of early-onset PSD. METHODS: A total of 861 first-ever stroke patients admitted within 7 days poststroke were consecutively recruited from three independent hospitals in China. Sociodemographic, clinical and neuroimaging data were collected upon admission. PSDS assessment with Hamilton Depression Rating Scale was performed at 2 weeks after stroke. Thirteen PSDS were included to develop a psychopathological network in which central symptoms (i.e. symptoms most strongly correlated with other PSDS) were identified. Voxel-based lesion-symptom mapping (VLSM) was performed to uncover the lesion locations associated with overall PSDS severity and severities of individual PSDS, in order to test the hypothesis that strategic lesion locations for central symptoms could significantly contribute to higher overall PSDS severity. RESULTS: Depressed mood, Psychiatric anxiety and Loss of interest in work and activities were identified as central PSDS at the early stage of stroke in our relatively stable PSDS network. Lesions in bilateral (especially the right) basal ganglia and capsular regions were found significantly associated with higher overall PSDS severity. Most of the above regions were also correlated with higher severities of 3 central PSDS. The other 10 PSDS could not be mapped to any certain brain region. CONCLUSIONS: There are stable interactions among early-onset PSDS with Depressed mood, Psychiatric anxiety and Loss of interest as central symptoms. The strategic lesion locations for central symptoms may indirectly induce other PSDS via the symptom network, resulting in higher overall PSDS severity. TRIAL REGISTRATION: URL: http://www.chictr.org.cn/enIndex.aspx ; Unique identifier: ChiCTR-ROC-17013993.

Explore the influencing factors and construct random forest models of post-stroke depression at 3 months in males and females.

BACKGROUND: Post-stroke depression (PSD) is one of the most common neuropsychiatric complications after stroke. The occurrence, development and prognosis of PSD have long been different between males and females. The main purpose of this study was to explore the influencing factors of PSD at 3 months in males and females, and construct random forest (RF) models to rank the influencing factors. METHODS: This is a prospective multicenter cohort study (Registration number: ChiCTR-ROC-17013993). Stroke patients hospitalized in the department of Neurology of three hospitals in Wuhan were enrolled from May 2018 to August 2019. Scale assessments were performed 24 hours after admission and 3 months after stroke onset. Binary logistic regression analysis was used for univariate and multivariate (stepwise backward method) analysis, when p was less than 0.05, the difference between groups was considered statistically significant. Lastly, the RF models were constructed according to the results of multivariate regression analysis. RESULTS: This study found that several baseline variables were associated with PSD at 3 months in males and females. RF model ranked them as stroke severity (OR [odds ratio] =1.17, p < 0.001, 95%CI [confidence interval]:1.11-1.24), neuroticism dimension (OR = 1.06, p = 0.002, 95%CI:1.02-1.10), physical exercise (OR = 0.62, p = 0.007, 95%CI:0.44-0.88), sleeping time < 5 h (OR = 1.91, p = 0.006, 95% CI:1.20-3.04) and atrial fibrillation (OR = 4.18, p = 0.012, 95%CI:1.38-12.68) in males. In females, RF model ranked them as psychological resilience (OR = 0.98, p = 0.015, 95%CI:0.96-1.00), ability of daily living (OR = 0.98, p = 0.001, 95%CI:0.97-0.99), neuroticism dimension (OR = 1.11, p = 0.002, 95%CI:1.04-1.18) and subjective support (OR = 1.11, p < 0.001, 95%CI:1.05-1.78). CONCLUSION: The study found influencing factors of PSD at 3 months were different in males and females, and construct RF models to rank them according to their importance. This suggests that clinicians should focus their interventions on sex-specific influencing factors in order to improve the prognosis of PSD patients. TRIAL REGISTRATION: ChiCTR-ROC-17013993.

Structural disconnection-based prediction of poststroke depression.

Poststroke depression (PSD) is a common complication of stroke. Brain network disruptions caused by stroke are potential biological determinants of PSD but their conclusive roles are unavailable. Our study aimed to identify the strategic structural disconnection (SDC) pattern for PSD at three months poststroke and assess the predictive value of SDC information. Our prospective cohort of 697 first-ever acute ischemic stroke patients were recruited from three hospitals in central China. Sociodemographic, clinical, psychological and neuroimaging data were collected at baseline and depression status was assessed at three months poststroke. Voxel-based disconnection-symptom mapping found that SDCs involving bilateral temporal white matter and posterior corpus callosum, as well as white matter next to bilateral prefrontal cortex and posterior parietal cortex, were associated with PSD. This PSD-specific SDC pattern was used to derive SDC scores for all participants. SDC score was an independent predictor of PSD after adjusting for all imaging and clinical-sociodemographic-psychological covariates (odds ratio, 1.25; 95% confidence interval, 1.07, 1.48; P = 0.006). Split-half replication showed the stability and generalizability of above results. When added to the clinical-sociodemographic-psychological prediction model, SDC score significantly improved the model performance and ranked the highest in terms of predictor importance. In conclusion, a strategic SDC pattern involving multiple lobes bilaterally is identified for PSD at 3 months poststroke. The SDC score is an independent predictor of PSD and may improve the predictive performance of the clinical-sociodemographic-psychological prediction model, providing new evidence for the brain-behavior mechanism and biopsychosocial theory of PSD.

Corrigendum: Large-scale preparation of highly stable recombinant human acidic fibroblast growth factor in Escherichia coli BL21(DE3) plysS strain.

[This corrects the article DOI: 10.3389/fbioe.2021.641505.].

Calibration of sightseeing tour choices considering multiple decision criteria with diminishing reward.

For an increasing number of cities, managing tourism becomes an important task and accordingly better understanding of touristic travel patterns is required. We model the sightseeing-tour choice within a city as a utility maximization problem. For this, attractions and their intrinsic utilities as well as tourists' preferences are evaluated over multiple dimensions in order to explain the variance in tourists' choice of POIs (points of interest) including the visiting order. Furthermore, the choice of destinations is considered "history-dependent" in that there is diminishing marginal utility gained by visiting additional POIs. Given the many potential sights, this leads to a large combinatorial problem. We solve this with a variant of a TTDP (tourist trip design problem) with the modified distance that evaluates omitted POIs and geographical distance between estimated and observed tours. The approach is applied to revealed-preference survey data from Kyoto, Japan, where tourists stated their visited attractions among 37 touristic areas. We discuss model fit and scenarios with the existing and a modified transport network.

Neural Substrates of Poststroke Depression: Current Opinions and Methodology Trends.

Poststroke depression (PSD), affecting about one-third of stroke survivors, exerts significant impact on patients' functional outcome and mortality. Great efforts have been made since the 1970s to unravel the neuroanatomical substrate and the brain-behavior mechanism of PSD. Thanks to advances in neuroimaging and computational neuroscience in the past two decades, new techniques for uncovering the neural basis of symptoms or behavioral deficits caused by focal brain damage have been emerging. From the time of lesion analysis to the era of brain networks, our knowledge and understanding of the neural substrates for PSD are increasing. Pooled evidence from traditional lesion analysis, univariate or multivariate lesion-symptom mapping, regional structural and functional analyses, direct or indirect connectome analysis, and neuromodulation clinical trials for PSD, to some extent, echoes the frontal-limbic theory of depression. The neural substrates of PSD may be used for risk stratification and personalized therapeutic target identification in the future. In this review, we provide an update on the recent advances about the neural basis of PSD with the clinical implications and trends of methodology as the main features of interest.

Higher Concentration of Adrenocorticotropic Hormone Predicts Post-Stroke Depression.

Background: Post-stroke depression (PSD) is the most common neuropsychiatric complication after stroke, seriously affecting the quality of survivors' life. As one of the important causes of PSD, neuroendocrine mechanism has been widely studied in recent years. The main objective of this study was to investigate the relationship between adrenocorticotropic hormone (ACTH) on admission and PSD at 3 months. Methods: This is a hospital-based prospective cohort study, which was conducted at three independent hospitals (Tongji Hospital, Wuhan First Hospital and Wuhan Central Hospital) between August 2018 and June 2019. A total of 768 ischemic stroke patients were finally eligible for analysis and categorized into equal tertiles according to the distribution of ACTH and the number of patients. The χ 2-test, Mann-Whitney U-test and Kruskal-Wallis test were used to check for statistical significance. And restricted cubic spline (RCS) regression model was used to explore the non-linear relationship between continuous ACTH levels and PSD at 3 months. Results: The optimal cut-off points of ACTH were as follows: (T1) 0.32-20.55 pg/mL, (T2) 20.56-39.79 pg/mL, (T3) 39.80-143.40 pg/mL. A total of 305 patients (39.7%) were diagnosed as PSD at 3 months follow-up. Significant differences were found between the PSD and non-PSD groups in ACTH concentration (P = 0.001). After adjustment for all conventional confounders, the odds ratios of PSD were 1.735 (95% CI = 1.176-2.560, P = 0.005) for the highest tertile of ACTH and 1.496 (95% CI = 1.019-2.194, P = 0.040) for the middle tertile of ACTH, as compared with the lowest tertile. In multiple-adjusted RCS regression, continuous ACTH showed saturation effect relation with PSD risk after 31.02 pg/mL (P for nonlinear = 0.0143). Conclusion: Higher ACTH level on admission is a significant and independent biomarker to predict the development of PSD at 3 months follow-up. Besides, saturation effect was revealed even if the underlying mechanism is unclear. For stroke patients, doctors should pay attention to the baseline ACTH for screening high-risk PSD in clinical practice.