Radiomics Analysis of Diffusion-Weighted Imaging and Long-Term Unfavorable Outcomes Risk for Acute Stroke.

BACKGROUND: Diffusion-weighted imaging radiomics could be used as prognostic biomarkers in acute ischemic stroke. We aimed to identify a clinical and diffusion-weighted imaging radiomics model for individual unfavorable outcomes risk assessment in acute ischemic stroke. METHODS: A total of 1716 patients with acute ischemic stroke from 2 centers were divided into a training cohort and a validation cohort. Patient outcomes were measured with the modified Rankin Scale score. An unfavorable outcome was defined as a modified Rankin Scale score greater than 2. The primary end point was all-cause mortality or outcomes 1 year after stroke. The MRI-DRAGON score was calculated based on previous publications. We extracted and selected the infarct features on diffusion-weighted imaging to construct a radiomic signature. The clinic-radiomics signature was built by measuring the Cox proportional risk regression score (CrrScore) and compared with the MRI-DRAGON score and the ClinicScore. CrrScore model performance was estimated by 1-year unfavorable outcomes prediction. RESULTS: A high radiomic signature predicted a higher probability of unfavorable outcomes than a low radiomic signature in the training (hazard ratio, 3.19 [95% CI, 2.51-4.05]; P<0.0001) and validation (hazard ratio, 3.25 [95% CI, 2.20-4.80]; P<0.0001) cohorts. The diffusion-weighted imaging Alberta Stroke Program Early CT Score, age, glucose level before therapy, National Institutes of Health Stroke Scale score on admission, glycated hemoglobin' radiomic signature, hemorrhagic infarction, and malignant cerebral edema were associated with an unfavorable outcomes risk after multivariable adjustment. A CrrScore nomogram was developed to predict outcomes and had the best performance in the training (area under the curve, 0.862) and validation cohorts (area under the curve, 0.858). The CrrScore model time-dependent areas under the curve of the probability of unfavorable outcomes at 1 year in the training and validation cohorts were 0.811 and 0.801, respectively. CONCLUSIONS: The CrrScore model allows the accurate prediction of patients with acute ischemic stroke outcomes and can potentially guide rehabilitation therapies for patients with different risks of unfavorable outcomes.

Alterations of brain network topology and structural connectivity-functional connectivity coupling in capsular versus pontine stroke.

BACKGROUND AND PURPOSE: This study was conducted to investigate whether capsular stroke (CS) and pontine stroke (PS) have different topological alterations of structural connectivity (SC) and functional connectivity (FC), as well as correlations of SC-FC coupling with movement assessment scores. METHODS: Resting-state functional magnetic resonance imaging and diffusion tensor imaging were prospectively acquired in 46 patients with CS, 36 with PS, and 29 healthy controls (HCs). Graph theoretical network analyses of SC and FC were performed. Patients with left and right lesions were analyzed separately. RESULTS: With regard to FC, the PS and CS groups both showed higher local efficiency than the HCs, and the CS group also had a higher clustering coefficient (Cp) than the HCs in the right lesion analysis. With regard to SC, the PS and CS groups both showed different normalized clustering coefficient (γ), small-worldness (σ), and characteristic path length (Lp) compared with the HC group. Additionally, the CS group showed higher normalized characteristic path length (λ) and a lower Cp than the HCs and the PS group showed higher λ and lower global efficiency than the HCs in the right-lesion analysis. However, γ, σ, Cp and Lp were only significantly different in the PS and CS groups compared with the HC group in the right-lesion analysis. Importantly, the CS group was found to have a weaker SC-FC coupling than the PS group and the HC group in the right-lesion analysis. In addition, both patient groups had weaker structural-functional connectome correlation than the HCs. CONCLUSIONS: The CS and PS groups both showed FC and SC disruption and the CS group had a weaker SC-FC coupling than the PS group in the right lesion analysis. This may provide useful information for individualized rehabilitative strategies.

The apheresis platelet donation was increased after a nationwide ban on family/replacement donation in China.

BACKGROUND: A nationwide ban on family/replacement donation (FRD) went into effect on April 1, 2018 in China. To date, no reports relevant to the trend of plateletpheresis donations before and after a nationwide ban on FRD were found. METHODS: We used two independent full samples, consisting of 135,851 and 82,129 plateletpheresis donors from Guangzhou and Chengdu between October 2012 and September 2019, respectively. A pseudo-panel data approach was applied by grouping three time-invariant covariates - gender, blood donation history, and birth year across 14 cross-sections (a 6-month interval each) to form a total of 24 cohort groups (14 × 24 = 336 cohorts, i.e., cells) with each having common covariates. The outcome was average apheresis platelet units per donor in each cell. We performed a two-piecewise linear mixed model with the cross-section (i.e., time) just right before the ban as a time breakpoint (i.e., 11th cross-section) to examine the trend of outcome with the adjustment of three time-invariant covariates. We removed the FRDs in each of the first 11 cross-sections to detect its possible influence on the trend. RESULTS: The final model for the samples from Guangzhou presented a two-piecewise linear trend of the outcome over time with a horizontal line to the left of the breakpoint (ßtimeBefore11 = 0.0111, p = 0.0976) and a significantly positive linear trend to the right (ßtimeAfter11 = 0.0404, p < 0.0001). The male donors and the donors with plateletpheresis donation history had an increased baseline outcome and a significant outcome change over time after the ban. Such a two-piecewise linear trend pattern can be replicated using the samples from Chengdu with some minor variations. Removing the FRD before the ban can change the pattern. CONCLUSION: The significant increase of the average apheresis platelet units per donor over time after the FRD ban may be related to the implement of the FRD ban and the improved donation behavior of male donors and/or donors with platelet donation history after the ban. Our findings may potentially motivate the policymakers in other countries where the FRD for plateletpheresis donation is still legitimate to phase out their FRD strategy and ultimately achieve 100% voluntary plateletpheresis donation.

Altered static and dynamic functional network connectivity in post-traumatic headache.

BACKGROUND: Post-traumatic headache (PTH) is a very common symptom following mild traumatic brain injury (mTBI), yet much remains unknown about the underlying pathophysiological mechanisms of PTH. Neuroimaging studies suggest that aberrant functional network connectivity (FNC) may be an important factor in pain disorders. The present study aimed to investigate the functional characteristics of static FNC (sFNC) and dynamic FNC (dFNC) in mTBI patients with PTH. METHODS: With Institutional Review Board (IRB) approval, we prospectively recruited 50 mTBI patients with PTH, who were diagnosed with ICHD-3 beta diagnostic criteria and 39 mTBI without PTH who were well matched for age, gender and education. Resting-state functional magnetic resonance imaging (fMRI) scanning (3.0 T, Philips Medical Systems, Netherlands), Montreal Cognitive Assessment (MoCA) and headache symptom measurement (headache frequency and headache intensity) were performed. The resting-state fMRI sequence took 8 min and 10 s. Independent component analysis and sliding window method were applied to examine the FNC on the basis of nine resting-state networks, namely, default mode network (DMN), sensorimotor network (SMN), executive control network (ECN), auditory network (AuN), attention network (AN), salience network (SN), visual network (VN), and cerebellum network (CN). The differences in sFNC and dFNC were determined and correlated with clinical variables using Pearson rank correlation. RESULTS: For sFNC, compared with mTBI patients without PTH, mTB with PTH group showed four altered interactions, including decreased interactions in SN-SMN and VN-DMN pairs, increased sFNC in SN-ECN and SMN-DMN pairs. For dFNC, significant group differences were found in State 2, including increased connectivity alteration in the DMN with CN, DMN with SMN, and AuN with CN. Significant reduced connectivity changes in the DMN with VN was found in State 4. Furthermore, the number of transitions (r=0.394, p=0.005) between states was positively associated with headache frequency. Additionally, dwell time (r=-0.320, p=0.025) in State 1 was negatively correlated with MoCA score. CONCLUSIONS: MTBI patients with PTH are characterized with altered sFNC and dFNC, which could provide new perspective to understand the neuropathological mechanism underlying the PTH to determine more appropriate management, and may be a useful imaging biomarker for identifying and predicting mTBI with PTH.

Inheritance patterns of leukocyte gene expression under heat stress in F1 hybrid cattle and their parents.

Crossbreeding capitalizes on heterosis effects and results in increased performance of crossbred animals. Dominance hypothesis and overdominance hypothesis are 2 common models proposed to explain heterosis. Differential gene expression between parents and hybrids is hypothesized to be responsible for heterosis. This study aimed to investigate the heat tolerance and inheritance patterns of leukocyte transcriptomics in F1 hybrid cattle (Angus males × Droughtmaster females) and their parents Red Angus (AN) and Droughtmaster (DR) under heat stress. According to the respiratory rate and heat tolerance coefficient index, DR was better adapted to heat stress than AN. The physiological responses to heat stress of F1 hybrids were similar to AN. We identified 802 differentially expressed genes in leukocytes between AN and DR under heat stress using mRNA sequencing. Compared with AN, upregulated genes in DR were enriched in biological processes of response to stress, external and chemical stimulus, and cytokine, cell surface receptor signaling pathway, and cardiovascular system development. In contrast, upregulated genes in AN were enriched in B cell activation and regulation of B cell activation. Gene expression levels can be inherited additively or nonadditively and are classified into additive (35%), dominance (44%), and overdominance and underdominance (18%) modes in F1 hybrids and their parents. Inheritance patterns of gene expression showed that 97% (249/255) of the dominant genes were classified as paternal AN dominant in hybrids. The paternal imprinted PEG10 gene and its regulatory transcription factor MYC showed an AN dominant expression pattern. The MYC interacted with most AN dominant genes. These transcriptomic analyses revealed that DR and AN had specific cellular and humoral immunity and cardiovascular systems development function under heat stress. Inheritance pattern analyses from gene expression partly explained phenotypic differences between parents and F1 hybrids. The paternal imprinted PEG10 gene interaction with transcription factor MYC may contribute to explaining paternal dominant gene expression in hybrids.

Cerebral Blood Flow and Its Connectivity Deficits in Mild Traumatic Brain Injury at the Acute Stage.

Objective: The influence of cognitive impairment after mild traumatic brain injury (mTBI) on cerebral vascular perfusion has been widely concerned, yet the resting-state cerebral blood flow (CBF) connectivity alterations based on arterial spin labeling (ASL) in mild traumatic brain injury (mTBI) remain unclear. This study investigated region CBF and CBF connectivity features in acute mTBI patients, as well as the associations between CBF changes and cognitive impairment. Materials and Methods: Forty-five acute mTBI patients and 42 health controls underwent pseudocontinuous arterial spin labeling (pCASL) perfusion magnetic resonance imaging (MRI). The alterations in regional CBF and relationship between the CBF changes and cognitive impairment were detected. The ASL-CBF connectivity of the brain regions with regional CBF significant differences was also compared between two groups. Neuropsychological tests covered seven cognitive domains. Associations between the CBF changes and cognitive impairment were further investigated. Results: Compared with the healthy controls, the acute mTBI patients exhibited increased CBF in the bilateral inferior temporal gyrus (ITG) and decreased CBF in the right middle frontal gyrus (MFG), the bilateral superior frontal gyrus (SFG), and the right cerebellum posterior lobe (CPL). In the mTBI patients, significant correlations were identified between the CBF changes and cognitive impairment. Importantly, the acute mTBI patients exhibited CBF disconnections between the right CPL and right fusiform gyrus (FG) as well as bilateral ITG, between the left SFG and left middle occipital gyrus (MOG), and between the right SFG and right FG as well as right parahippocampal gyrus. Conclusion: Our results suggest that acute mTBI patients exhibit both regional CBF abnormalities and CBF connectivity deficits, which may underlie the cognitive impairment of the acute mTBI patients.

Altered hypothalamic functional connectivity in post-traumatic headache after mild traumatic brain injury.

BACKGROUND: Post-traumatic headache (PTH) is one of the most frequent symptoms following mild traumatic brain injury (mTBI). Neuroimaging studies implicate hypothalamic function connectivity (FC) disruption as an important factor in pain disorders. However, it is unknown whether there are alterations in the hypothalamus-based resting state FC within PTH following mTBI at the acute stage and its relationship with headache symptom measurement. METHODS: Forty-four mTBI patients with PTH, 27 mTBI patients without PTH and 43 healthy controls who were well matched for age, gender, and years of education were enrolled in this study. All participants underwent resting-state functional magnetic resonance imaging (fMRI) scanning as well as headache symptom measurement and cognitive assessment. Hypothalamic resting state networks were characterized by using a standard seed-based whole-brain correlation method. The bilateral hypothalamic FC was compared among the three groups. Furthermore, the correlations between hypothalamic resting state networks and headache frequency, headache intensity and MoCA scores was investigated in mTBI patients with PTH using Pearson rank correlation. RESULTS: Compared with mTBI patients without PTH, mTBI patients with PTH at the acute stage presented significantly decreased left hypothalamus-based FC with the right middle frontal gyrus (MFG) and right medial superior frontal gyrus (mSFG), and significantly decreased right hypothalamus-based FC with the right MFG. Decreased FC of the right MFG was significantly positively associated with headache frequency and headache intensity (r = 0.339, p = 0.024; r = 0.408, p = 0.006, respectively). Decreased FC of the right mSFG was significantly positively associated with headache frequency and headache intensity (r = 0.740, p < 0.0001; r = 0.655, p < 0.0001, respectively). CONCLUSION: Our data provided evidence of disrupted hypothalamic FC in patients with acute mTBI with PTH, while abnormal FC significantly correlated with headache symptom measurement. Taken together, these changes may play an essential role in the neuropathological mechanism of mTBI patients with PTH.

FLAIR vascular hyperintensity in acute stroke is associated with collateralization and functional outcome.

PURPOSE: Fluid-attenuated inversion recovery vascular hyperintensity (FVH) is frequently found in stroke patients after intracranial arterial occlusion, but the prognostic value of FVH findings is unclear. We assessed whether FVH is associated with cerebral collateral status and functional outcome in patients with acute stroke patients receiving endovascular therapy. METHODS: FVH score, American Society of Interventional and Therapeutic Neuroradiology (ASITN) grade, the functional outcome at 3 months (modified Rankin Scale (mRS)), and other clinical data were collected for 37 acute stroke patients with large vessel occlusion (LVO) receiving MRI before and after endovascular therapy. Statistical analysis was performed to predict functional outcome after stroke. RESULTS: The good functional outcome group (n = 16) had a higher FVH1 (FVH before therapy) score (4.63 ± 1.20 vs 3.14 ± 1.15; p = 0.001) and ASITN grade (3.31 ± 0.48 vs 2.00 ± 1.22; p < 0.001) and a lower FVH2 (FVH after therapy) score than the poor functional outcome group (n = 21; 0.125 ± 0.50 vs 1.44 ± 2.16; p = 0.030). mRS at 3 months was negatively correlated with FVH1 (r = - 0.525, p = 0.001) and the ASITN grade (r = - 0.478, p = 0.003) and positively correlated with FVH2 (r = 0.376, p = 0.034). FVH1 (OR, 0.085; 95% CI, 0.013-0.577; p = 0.012) and FVH2 (OR, 2.724; 95% CI, 1.061-6.996; p = 0.037) were independently associated with functional outcome in multivariable logistic regression analysis. CONCLUSIONS: Assessing FVH before and after therapy in acute stroke patients with LVO might be useful for predicting functional outcome after stroke. KEY POINTS: • Fluid-attenuated inversion recovery vascular hyperintensity is a circular or serpentine brightening in the brain parenchyma or cortical surface bordering the subarachnoid space on MR imaging. • A prospective study showed that fluid-attenuated inversion recovery vascular hyperintensity is associated with cerebral collateral circulation and prognosis. • Fluid-attenuated inversion recovery vascular hyperintensity helps clinicians to predict the prognosis of patients with acute stroke.

Different Patterns of Functional Connectivity Alterations Within the Default-Mode Network and Sensorimotor Network in Basal Ganglia and Pontine Stroke.

BACKGROUND The aim of this study was to investigate whether patients with basal ganglia stroke and patients with pontine stroke have different types of functional connectivity (FC) alterations in the early chronic phase. MATERIAL AND METHODS We included 14 patients with pontine stroke, 17 patients with basal ganglia stroke, and 20 well-matched healthy controls (HCs). All of them underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning. The independent component analysis (ICA) approach was applied to extract information regarding the default-mode network (DMN), including anterior DMN (aDMN) and posterior DMN (pDMN) components and the sensorimotor network (SMN). RESULTS Compared with HCs, patients with basal ganglia stroke exhibited significantly reduced FC in the left precuneus of the pDMN, right supplementary motor area (SMA), and right superior frontal gyrus (SFG) of the SMN. Additionally, FC in the left medial prefrontal gyrus (MFG) of the aDMN, right precuneus and right posterior cingulate cortex (PCC) of the pDMN, and left middle cingulate gyrus (mid-CC) of the SMN decreased in patients with pontine stroke. CONCLUSIONS The different patterns of FC damage in patients with basal ganglia stroke and patients with pontine stroke in the early chronic phase may provide a new method for investigating lesion-induced network plasticity.

Decreased Spontaneous Brain Activity and Functional Connectivity in Type 1 Diabetic Patients Without Microvascular Complications.

BACKGROUND/AIMS: Type 1 diabetes mellitus (T1DM) has been proven to be associated with an increased risk of cognitive dysfunction. In this study, we aimed to investigate whether disrupted spontaneous activity and functional connectivity (FC) exist in T1DM patients using resting-state functional magnetic resonance imaging (rs-fMRI) and to detect the relationships of these parameters with cognitive impairment. METHODS: T1DM patients (n=35) were compared with age-, sex-, and education level-matched healthy controls (n=50) through rs-fMRI. Using rs-fMRI professional software, we calculated the amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and seed-based FC in the posterior cingulate cortex (PCC) to measure the spontaneous neural activity in the groups. The relationship between rs-fMRI data and cognitive performance was further investigated. RESULTS: Compared with the healthy controls, T1DM patients showed significantly decreased ALFF values in the PCC and right inferior frontal gyrus (IFG), decreased ReHo values in the right middle frontal gyrus (MFG) and reduced FC between the PCC and the right MFG. Furthermore, a positive correlation was found between decreased ALFF values in the PCC and Rey-Osterrieth Complex Figure Test (CFT)-delay scores in T1DM patients (r=0.394, p=0.026). Moreover, the Trail Making Test-B (TMT-B) scores showed negative correlations with decreased ReHo values in the right MFG (r=-0.468, p=0.007) and reduced FC between the PCC and right MFG (r=-0.425, p=0.015). CONCLUSION: Our combined analyses revealed decreased spontaneous activity and FC mainly within the default mode network, which was correlated with specific impaired cognitive functioning in T1DM. This study thus elucidates the neurophysiological mechanisms underlying T1DM-related cognitive impairment and may serve as a reference for future clinical diagnosis.

Corticospinal tract changes in acute brainstem ischemic stroke patients: A diffusion kurtosis imaging study.

PURPOSE: The present study aimed to investigate the corticospinal tract (CST) changes in patients with brainstem ischemic stroke by using the diffusion kurtosis imaging (DKI) approach.. MATERIALS AND METHODS: Twenty-one patients with brainstem stroke and 21 group-matched healthy controls underwent brain DKI with 3.0 T magnetic resonance imaging (MRI). The DKI was obtained by using three b values of 0, 1,000, 2,000 s/mm2 with 15 diffusion directions. Regions of interest (ROIs) were placed at four levels: the pons, posterior limb of the internal capsule (PLIC), corona radiata, and precentral gyrus. The DKI parameters, including fractional anisotropy (FA), mean diffusivity (MD), and mean kurtosis (MK) values, in these regions were measured from the contralateral to the ipsilateral side of patients and both the left and right sides of healthy controls at all the four selected levels. RESULTS: The ipsilateral side of the ischemic lesion showed a decrease in FA and MD and an increase in MK when compared with the contralateral normal region at all the four selected levels with statistically differences (P < 0.05). At these four selected levels, there were no differences between the left and right sides in healthy controls with MD, FA, and MK (P > 0.05). The MD values of the contralateral side of the ischemic lesion in patients at the four selected levels were significantly higher than those in the corresponding side of the healthy controls (P < 0.05). Compared to the healthy controls, there was a decrease at the posterior limb of the internal capsule (PLIC) in FA of the contralateral side of the ischemic lesion in stroke patients (P < 0.05). However, no significant differences were observed for MK values between the groups (P > 0.05). CONCLUSION: The current results suggest that the DKI technique could identify the early microstructural changes along the motor pathway and that these changes were not limited to the ipsilateral side of the ischemic lesion; in fact, the contralateral changes also occurred, especially at the PLIC.

Tinnitus distress is linked to enhanced resting-state functional connectivity from the limbic system to the auditory cortex.

The phantom sound of tinnitus is believed to be triggered by aberrant neural activity in the central auditory pathway, but since this debilitating condition is often associated with emotional distress and anxiety, these comorbidities likely arise from maladaptive functional connections to limbic structures such as the amygdala and hippocampus. To test this hypothesis, resting-state functional magnetic resonance imaging (fMRI) was used to identify aberrant effective connectivity of the amygdala and hippocampus in tinnitus patients and to determine the relationship with tinnitus characteristics. Chronic tinnitus patients (n = 26) and age-, sex-, and education-matched healthy controls (n = 23) were included. Both groups were comparable for hearing level. Granger causality analysis utilizing the amygdala and hippocampus as seed regions were used to investigate the directional connectivity and the relationship with tinnitus duration or distress. Relative to healthy controls, tinnitus patients demonstrated abnormal directional connectivity of the amygdala and hippocampus, including primary and association auditory cortex, and other non-auditory areas. Importantly, scores on the Tinnitus Handicap Questionnaires were positively correlated with increased connectivity from the left amygdala to left superior temporal gyrus (r = 0.570, P = 0.005), and from the right amygdala to right superior temporal gyrus (r = 0.487, P = 0.018). Moreover, enhanced effective connectivity from the right hippocampus to left transverse temporal gyrus was correlated with tinnitus duration (r = 0.452, P = 0.030). The results showed that tinnitus distress strongly correlates with enhanced effective connectivity that is directed from the amygdala to the auditory cortex. The longer the phantom sensation, the more likely acute tinnitus becomes permanently encoded by memory traces in the hippocampus. Hum Brain Mapp 38:2384-2397, 2017. © 2017 Wiley Periodicals, Inc.

Disrupted Effective Connectivity within the Fronto-Thalamic Circuit in Pontine Infarction: A Spectral Dynamic Causal Modeling Study.

This study aims to investigate alterations in effective connectivity (EC) within the fronto-thalamic circuit and their associations with motor and cognitive declines in pontine infarction (PI). A total of 33 right PI patients (RPIs), 38 left PI patients (LPIs), and 67 healthy controls (HCs) were recruited. The spectral dynamic causal modeling (spDCM) approach was used for EC analysis within the fronto-thalamic circuit, including the thalamus, caudate, supplementary motor area (SMA), medial prefrontal cortex (mPFC), and anterior cingulate cortex (ACC). The EC differences between different sides of the patients and HCs were assessed, and their correlations with motor and cognitive dysfunctions were analyzed. The LPIs showed increased EC from the mPFC to the R-SMA and decreased EC from the L-thalamus to the ACC, the L-SMA to the R-SMA, the R-caudate to the R-thalamus, and the R-thalamus to the ACC. For RPIs, the EC of the R-caudate to the mPFC, the L-thalamus and L-caudate to the L-SMA, and the L-caudate to the ACC increased obviously, while a lower EC strength was shown from the L-thalamus to the mPFC, the LSMA to the R-caudate, and the R-SMA to the L-thalamus. The EC from the R-caudate to the mPFC was negatively correlated with the MoCA score for RPIs, and the EC from the R-caudate to the R-thalamus was negatively correlated with the FMA score for LPIs. The results demonstrated EC within the fronto-thalamic circuit in PI-related functional impairments and reveal its potential as a novel imaging marker.

Aberrant Brain Triple-Network Effective Connectivity Patterns in Type 2 Diabetes Mellitus.

INTRODUCTION: Aberrant brain functional connectivity network is thought to be related to cognitive impairment in patients with type 2 diabetes mellitus (T2DM). This study aims to investigate the triple-network effective connectivity patterns in patients with T2DM within and between the default mode network (DMN), salience network (SN), and executive control network (ECN) and their associations with cognitive declines. METHODS: In total, 92 patients with T2DM and 98 matched healthy controls (HCs) were recruited and underwent resting-state functional magnetic resonance imaging (rs-fMRI). Spectral dynamic causal modeling (spDCM) was used for effective connectivity analysis within the triple network. The posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC), lateral prefrontal cortex (LPFC), supramarginal gyrus (SMG), and anterior insula (AINS) were selected as the regions of interest. Group comparisons were performed for effective connectivity calculated using the fully connected model, and the relationships between effective connectivity alterations and cognitive impairment as well as clinical parameters were detected. RESULTS: Compared to HCs, patients with T2DM exhibited increased or decreased effective connectivity patterns within the triple network. Furthermore, diabetes duration was significantly negatively correlated with increased effective connectivity from the r-LPFC to the mPFC, while body mass index (BMI) was significantly positively correlated with increased effective connectivity from the l-LPFC to the l-AINS (r = - 0.353, p = 0.001; r = 0.377, p = 0.004). CONCLUSION: These results indicate abnormal effective connectivity patterns within the triple network model in patients with T2DM and provide new insight into the neurological mechanisms of T2DM and related cognitive dysfunction.

Bioactive components and potential mechanisms of Biqi Capsule in the treatment of osteoarthritis: based on chondroprotective and anti-inflammatory activity.

Cartilage damage and synovial inflammation are vital pathological changes in osteoarthritis (OA). Biqi Capsule, a traditional Chinese medicine formula used for the clinical treatment of arthritis in China, yields advantages in attenuating OA progression. The drawback here is that the bioactive components and pharmacological mechanisms by which Biqi Capsule exerts its anti-inflammatory and chondroprotective effects have yet to be fully clarified. For in vivo studies, a papain-induced OA rat model was established to explore the pharmacological effects and potential mechanisms of Biqi Capsule against OA. Biqi Capsule alleviated articular cartilage degeneration and chondrocyte damage in OA rats and inhibited the phosphorylation of NF-κB and the expression of pro-inflammatory cytokines in synovial tissue. Network pharmacology analysis suggested that the primary biological processes regulated by Biqi Capsule are inflammation and oxidative stress, and the critical pathway regulated is the PI3K/AKT signaling pathway. The result of this analysis was later verified on SW1353 cells. The in vitro studies demonstrated that Glycyrrhizic Acid and Liquiritin in Biqi Capsule attenuated H2O2-stimulated SW1353 chondrocyte damage via activation of PI3K/AKT/mTOR pathway. Moreover, Biqi Capsule alleviated inflammatory responses in LPS-stimulated RAW264.7 macrophages via the NF-κB/IL-6 pathway. These observations were suggested to have been facilitated by Brucine, Liquiritin, Salvianolic Acid B, Glycyrrhizic Acid, Cryptotanshinone, and Tanshinone ⅡA. Put together, this study partially clarifies the pharmacological mechanisms and the bioactive components of Biqi capsules against OA and suggests that it is a promising therapeutic option for the treatment of OA. Chemical compounds studied in this article. Strychnine (Pubchem CID:441071); Brucine (Pubchem CID:442021); Liquiritin (Pubchem CID:503737); Salvianolic Acid B (Pubchem CID:6451084); Glycyrrhizic Acid (Pubchem CID:14982); Cryptotanshinone (Pubchem CID:160254); Tanshinone ⅡA (Pubchem CID:164676).

Disrupted resting-state functional connectivity and network topology in mild traumatic brain injury: an arterial spin labelling study.

Mild traumatic brain injury can cause different degrees of cognitive impairment and abnormal brain structure and functional connectivity, but there is still a lack of research on the functional connectivity and topological organization of cerebral blood flow fluctuations. This study explored the cerebral blood flow, functional connectivity and topological organization of the cerebral blood flow network in acute mild traumatic brain injury patients. In total, 48 mild traumatic brain injury patients and 46 well-matched healthy controls underwent resting-state arterial spin labelling perfusion MRI and neuropsychological assessments. The functional connectivity and topological organization of the cerebral blood flow network were analysed. Then, the correlation between the changes in cerebral blood flow network characteristics and cognitive function was explored. Acute mild traumatic brain injury patients showed decreased cerebral blood flow in the right insula and increased cerebral blood flow in the right inferior temporal gyrus and left superior temporal gyrus. Abnormal cerebral blood flow network connection patterns mainly occur in sensorimotor network, default mode network, cingulo-opercular network and occipital network-related regions. Furthermore, mild traumatic brain injury disrupted the topological organization of the whole brain, which manifested as (i) reduced global efficiency; (ii) abnormal degree centrality, betweenness centrality, nodal clustering coefficient and nodal efficiency; and (iii) decreased intermodular connectivity between the occipital network and sensorimotor network. Finally, the change in network topology was correlated with the cognitive score of the mild traumatic brain injury. This study provided evidence of abnormal functional connectivity and network topology based on cerebral blood flow in acute mild traumatic brain injury patients, revealing their potential use as early markers for mild traumatic brain injury, which may contribute to both disease diagnosis and assessment.

A deep learning-based model for prediction of hemorrhagic transformation after stroke.

Hemorrhagic transformation (HT) is one of the most serious complications after endovascular thrombectomy (EVT) in acute ischemic stroke (AIS) patients. The purpose of this study is to develop and validate deep-learning (DL) models based on multiparametric magnetic resonance imaging (MRI) to automatically predict HT in AIS patients. Multiparametric MRI and clinical data of AIS patients with EVT from two centers (data set 1 for training and testing: n = 338; data set 2 for validating: n = 54) were used in the DL models. The acute infarction area of diffusion-weighted imaging (DWI) and hypoperfusion of perfusion-weighted imaging (PWI) was labeled manually. Two forms of data sets (volume of interest [VOI] data sets and slice data sets) were analyzed, respectively. The models based on single parameter and multiparameter models were developed and validated to predict HT in AIS patients after EVT. Performance was evaluated by area under the receiver-operating characteristic curve (AUC), accuracy (ACC), sensitivity, specificity, negative predictive value, and positive predictive value. The results showed that the performance of single parameter model based on MTT (VOI data set: AUC = 0.933, ACC = 0.843; slice data set: AUC = 0.945, ACC = 0.833) and TTP (VOI data set: AUC = 0.916, ACC = 0.873; slice data set: AUC = 0.889, ACC = 0.818) were better than the other single parameter model. The multiparameter model based on DWI & MTT & TTP & Clinical (DMTC) had the best performance for predicting HT (VOI data set: AUC = 0.948, ACC = 0.892; slice data set: AUC = 0.932, ACC = 0.873). The DMTC model in the external validation set achieved similar performance with the testing set (VOI data set: AUC = 0.939, ACC = 0.884; slice data set: AUC = 0.927, ACC = 0.871) (p > 0.05). The proposed clinical, DWI, and PWI multiparameter DL model has great potential for assisting the periprocedural management in the early prediction HT of the AIS patients with EVT.

Aberrant Static and Dynamic Functional Network Connectivity in Acute Mild Traumatic Brain Injury with Cognitive Impairment.

PURPOSE: This study aimed to investigate differences in static and dynamic functional network connectivity (FNC) and explore their association with neurocognitive performance in acute mild traumatic brain injury (mTBI). METHODS: A total of 76 patients with acute mTBI and 70 age-matched and sex-matched healthy controls were enrolled (age 43.79 ± 10.22 years vs. 45.63 ± 9.49 years; male/female: 34/42 vs. 38/32; all p > 0.05) and underwent resting-state functional magnetic resonance imaging (fMRI) scan (repetition time/echo time = 2000/30 ms, 230 volumes). Independent component analysis was conducted to evaluate static and dynamic FNC patterns on the basis of nine resting-state networks, namely, auditory network (AUDN), dorsal attention network (dAN), ventral attention network (vAN), default mode network (DMN), left frontoparietal network (LFPN), right frontoparietal network (RFPN), somatomotor network (SMN), visual network (VN), and salience network (SN). Spearman's correlation among aberrances in FNC values, and Montreal cognitive assessment (MoCA) scores was further measured in mTBI. RESULTS: Compared with controls, patients with mTBI showed wide aberrances of static FNC, such as reduced FNC in DMN-vAN and VN-vAN pairs. The mTBI patients exhibited aberrant dynamic FNC in state 2, involving reduced FNC aberrance in the vAN with AUDN, VN with DMN and dAN, and SN with SMN and vAN. Reduced dFNC in the SN-vAN pair was negatively correlated with the MoCA score. CONCLUSION: Our findings suggest that aberrant static and dynamic FNC at the acute stage may contribute to cognitive symptoms, which not only may expand knowledge regarding FNC cognition relations from the static perspective but also from the dynamic perspective.

Reduced functional network connectivity is associated with upper limb dysfunction in acute ischemic brainstem stroke.

This study aimed to detect alterations in intra- and inter-network functional connectivity (FC) of multiple networks in acute brainstem ischemic stroke patients, and the relationship between FC and movement assessment scores to assess their ability to predict upper extremity motor impairment. Resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from acute brainstem ischemic stroke patients (n = 50) and healthy controls (HCs) (n = 45). Resting-state networks (RSNs) were established based on independent component analysis (ICA) and the functional network connectivity (FNC) analysis was performed. Subsequently, correlation analysis was subsequently used to explore the relationship between FNC abnormalities and upper extremity motor impairment. Altered FC within default mode network (DMN), executive control network (ECN), the salience network (SN), auditory network (AN), and cerebellum network (CN) were found in the acute brainstem ischemic stroke group relative to HCs. Moreover, different patterns of altered network interactions were found between the patients and HCs, including the SN-CN, SN-AN, and ECN-DMN connections. Correlations between functional disconnection and upper limb dysfunction measurements in acute brainstem ischemic stroke patients were also found. This study intimated that widespread FNC impairment and altered integration existed in brainstem ischemic stroke at acute stage, suggesting that FNC disruption may be applied for early diagnosis and prediction of upper limb dysfunction in acute brainstem ischemic stroke.