Automatic classification of MSA subtypes using Whole-brain gray matter function and Structure-Based radiomics approach.

BACKGROUND: This study aims to develop a radiomics method based on the function and structure of whole-brain gray matter to accurately classify multiple system atrophy with predominant Parkinsonism (MSA-P) or predominant cerebellar ataxia (MSA-C). METHODS: We enrolled 30 MSA-C and 41 MSA-P cases for the internal cohort and 11 MSA-C and 10 MSA-P cases for the external test cohort. We extracted 7,308 features, including gray matter volume (GMV), mean amplitude of low-frequency fluctuation (mALFF), mean regional homogeneity (mReHo), degree of centrality (DC), voxel-mirrored homotopic connectivity (VMHC), and resting-state functional connectivity (RSFC) from 3D-T1 and Rs-fMR data. Feature selection was conducted with t-test and least absolute shrinkage and selection operator (Lasso). Classification was performed using the support vector machine with linear and RBF kernel (SVM-linear/SVM-RBF), random forest and logistic regression. Model performance was assessed via receiver operating characteristic (ROC) curve and compared with DeLong's test. RESULTS: Feature selection resulted in 12 features, including 1 ALFF, 1 DC and 10 RSFC. All the classifiers showed remarkable classification performance, especially the RF model which exhibited AUC values of 0.91 and 0.80 in the validation and test datasets, respectively. The brain functional activity and connectivity in the cerebellum, orbitofrontal lobe and limbic system were important features to distinguish MSA subtypes with the same disease severity and duration. CONCLUSION: Radiomics approach has the potential to support clinical diagnostic systems and to achieve high classification accuracy for distinguishing between MSA-C and MSA-P patients at the individual level.

Functional connectome automatically differentiates multiple system atrophy (parkinsonian type) from idiopathic Parkinson's disease at early stages.

Differentiating the parkinsonian variant of multiple system atrophy (MSA-P) from idiopathic Parkinson's disease (IPD) is challenging, especially in the early stages. This study aimed to investigate differences and similarities in the brain functional connectomes of IPD and MSA-P patients and use machine learning methods to explore the diagnostic utility of these features. Resting-state fMRI data were acquired from 88 healthy controls, 76 MSA-P patients, and 53 IPD patients using a 3.0 T scanner. The whole-brain functional connectome was constructed by thresholding the Pearson correlation matrices of 116 regions, and topological properties were evaluated through graph theory approaches. Connectome measurements were used as features in machine learning models (random forest [RF]/logistic regression [LR]/support vector machine) to distinguish IPD and MSA-P patients. Regarding graph metrics, early IPD and MSA-P patients shared network topological properties. Both patient groups showed functional connectivity disruptions within the cerebellum-basal ganglia-cortical network, but these disconnections were mainly in the cortico-thalamo-cerebellar circuits in MSA-P patients and the basal ganglia-thalamo-cortical circuits in IPD patients. Among the connectome parameters, t tests combined with the RF method identified 15 features, from which the LR classifier achieved the best diagnostic performance on the validation set (accuracy = 92.31%, sensitivity = 90.91%, specificity = 93.33%, area under the receiver operating characteristic curve = 0.89). MSA-P and IPD patients show similar whole-brain network topological alterations. MSA-P primarily affects cerebellar nodes, and IPD primarily affects basal ganglia nodes; both conditions disrupt the cerebellum-basal ganglia-cortical network. Moreover, functional connectome parameters showed outstanding value in the differential diagnosis of early MSA-P and IPD.

Three-layer core-shell structure of polypyrrole/polydopamine/poly(l-lactide) nanofibers for wound healing application.

Poor wound healing is a very common clinical problem, so far there is no completely satisfactory treatment. Electropsun nanofibrous wound dressings may provide an ideal structure to improve wound healing. Therefore, development of nanofibrous wound dressings with rapid hemostasis, antibacterial and tissue regenerative multi-functions has been a hotspot in the field of skin tissue engineering. In this work, polydopamine (PDA) and polypyrrole (PPy) were uniformly coated onto the surface of poly(l-lactide) (PLLA) nanofibers by in-situ polymerization, forming a novel PPy/PDA/PLLA three-layer core-shell structure. The homogeneously coated PPy and PDA two layers could significantly increase the hydrophilicity, conductivity, near-infrared photothermal antibacterial property, the speed of wound hemostasis, antioxidant capacity and reactive oxygen species (ROS) scavenging capacity, respectively. In addition, PPy/PDA/PLLA nanofibers showed good biocompatibility. Rat wound healing model confirmed that PPy/PDA/PLLA nanofibers could significantly accelerate wound repair in vivo. Thus, this novel nanofibrous wound dressing is a promising candidate for clinical wound healing.

White matter structural network alterations in congenital bilateral profound sensorineural hearing loss children: A graph theory analysis.

Functional magnetic resonance imaging (fMRI) studies have revealed a functional reorganization in patients with sensorineural hearing loss (SNHL). The structural basement of functional changes has also been investigated recently. Graph theory analysis brings a new understanding of the structural connectome and topological features in central neural system diseases. However, little is known about the structural network connectome changes in SNHL patients, especially in children. We explored the differences in topologic organization, rich-club organization, and structural connection between children with congenital bilateral profound SNHL and normal hearing under the age of three using graph theory analysis and probabilistic tractography. Compared with the normal-hearing (NH) group, the SNHL group showed no difference in global and nodal topological parameters. Increased structural connection strength were found in the right cortico-striatal-thalamus-cortical circuity. Decreased cross-hemisphere connections were found between the right precuneus and the left auditory cortex as well as the left subcortical regions. Rich-club organization analysis found increased local connection in the SNHL group. These results revealed structural organizations after hearing deprivation in congenital bilateral profound SNHL children.

Altered resting-state functional network connectivity in profound sensorineural hearing loss infants within an early sensitive period: A group ICA study.

Data from both animal models and deaf children provide evidence for that the maturation of auditory cortex has a sensitive period during the first 2-4 years of life. During this period, the auditory stimulation can affect the development of cortical function to the greatest extent. Thus far, little is known about the brain development trajectory after early auditory deprivation within this period. In this study, independent component analysis (ICA) technique was used to detect the characteristics of brain network development in children with bilateral profound sensorineural hearing loss (SNHL) before 3 years old. Seven resting-state networks (RSN) were identified in 50 SNHL and 36 healthy controls using ICA method, and further their intra-and inter-network functional connectivity (FC) were compared between two groups. Compared with the control group, SNHL group showed decreased FC within default mode network, while enhanced FC within auditory network (AUN) and salience network. No significant changes in FC were found in the visual network (VN) and sensorimotor network (SMN). Furthermore, the inter-network FC between SMN and AUN, frontal network and AUN, SMN and VN, frontal network and VN were significantly increased in SNHL group. The results implicate that the loss and the compensatory reorganization of brain network FC coexist in SNHL infants. It provides a network basis for understanding the brain development trajectory after hearing loss within early sensitive period.

Altered Functional Network in Infants With Profound Bilateral Congenital Sensorineural Hearing Loss: A Graph Theory Analysis.

Functional magnetic resonance imaging (fMRI) studies have suggested that there is a functional reorganization of brain areas in patients with sensorineural hearing loss (SNHL). Recently, graph theory analysis has brought a new understanding of the functional connectome and topological features in central neural system diseases. However, little is known about the functional network topology changes in SNHL patients, especially in infants. In this study, 34 infants with profound bilateral congenital SNHL and 28 infants with normal hearing aged 11-36 months were recruited. No difference was found in small-world parameters and network efficiency parameters. Differences in global and nodal topologic organization, hub distribution, and whole-brain functional connectivity were explored using graph theory analysis. Both normal-hearing infants and SNHL infants exhibited small-world topology. Furthermore, the SNHL group showed a decreased nodal degree in the bilateral thalamus. Six hubs in the SNHL group and seven hubs in the normal-hearing group were identified. The left middle temporal gyrus was a hub only in the SNHL group, while the right parahippocampal gyrus and bilateral temporal pole were hubs only in the normal-hearing group. Functional connectivity between auditory regions and motor regions, between auditory regions and default-mode-network (DMN) regions, and within DMN regions was found to be decreased in the SNHL group. These results indicate a functional reorganization of brain functional networks as a result of hearing loss. This study provides evidence that functional reorganization occurs in the early stage of life in infants with profound bilateral congenital SNHL from the perspective of complex networks.

Alterations of structural and functional connectivity in profound sensorineural hearing loss infants within an early sensitive period: A combined DTI and fMRI study.

Due to heightened level of neuroplasticity, there is a sensitive period (2-4 years after birth) that exists for optimal central auditory development. Using diffusion tensor imaging combined with resting-state functional connectivity (rsFC) analysis, this study directly investigates the structural connectivity alterations of the whole brain white matter (WM) and the functional reorganization of the auditory network in infants with sensorineural hearing loss (SNHL) during the early sensitive period. 46 bilateral profound SNHL infants prior to cochlear implantation (mean age, 17.59 months) and 33 healthy controls (mean age, 18.55 months) were included in the analysis. Compared with controls, SNHL infants showed widespread WM alterations, including bilateral superior longitudinal fasciculus, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, right corticospinal tract, posterior thalamic radiation and left uncinate fasciculus. Moreover, SNHL infants demonstrated increased rsFC between left/right primary auditory cortex seeds and right insula and superior temporal gyrus. In conclusion, this study suggests that SNHL in the early sensitive period is associated with diffuse WM alterations that mainly affect the auditory and language pathways. Furthermore, increased rsFC in areas mainly associated with auditory and language networks may potentially reflect reorganization and compensatory activation in response to auditory deprivation during the early sensitive period.

GmRFP1 encodes a previously unknown RING-type E3 ubiquitin ligase in Soybean (Glycine max).

RING-finger proteins with E3 ubiquitin ligase activity play important roles in the regulation of plant growth and development. In this study, a cDNA clone encoding a novel RING-finger protein, designated as GmRFP1, was isolated and characterized from soybean. GmRFP1 was an intronless gene encoding a predicted protein product of 392 amino acid residues with a molecular mass of ~43 kDa. The protein contained a RING-H2 motif and an N-terminal transmembrane domain. The transcript was observed in all detected organs and was up-regulated by abscisic acid (ABA) and salt stress, but down-regulated by cold and drought treatments. We further expressed and purified both wild type and mutant version of GmRFP1 in E. coli. In vitro assays showed that the purified GmRFP1 induced the formation of polyubiquitin chains while mutation within the RING-finger region abolished the ubiquitination activity. These findings suggest that GmRFP1 is a previously unknown E3 ubiquitin ligase in soybean and that the RING domain is required for its activity. It may play unappreciated roles in ABA signaling and stress responses via mediating the ubiquitination and degradation of target proteins through the ubiquitin-proteasome pathway.