STN localization using local field potentials based on wavelet packet features and stacking ensemble learning.

BACKGROUND: DBS entails the insertion of an electrode into the patient brain, enabling Subthalamic nucleus (STN) stimulation. Accurate delineation of STN borders is a critical but time-consuming task, traditionally reliant on the neurosurgeon experience in deciphering the intricacies of microelectrode recording (MER). While clinical outcomes of MER have been satisfactory, they involve certain risks to patient safety. Recently, there has been a growing interest in exploring the potential of local field potentials (LFP) due to their correlation with the STN motor territory. METHOD: A novel STN detection system, integrating LFP and wavelet packet transform (WPT) with stacking ensemble learning, is developed. Initial steps involve the inclusion of soft thresholding to increase robustness to LFP variability. Subsequently, non-linear WPT features are extracted. Finally, a unique ensemble model, comprising a dual-layer structure, is developed for STN localization. We harnessed the capabilities of support vector machine, Decision tree and k-Nearest Neighbor in conjunction with long short-term memory (LSTM) network. LSTM is pivotal for assigning adequate weights to every base model. RESULTS: Results reveal that the proposed model achieved a remarkable accuracy and F1-score of 89.49% and 91.63%. COMPARISON WITH EXISTING METHODS: Ensemble model demonstrated superior performance when compared to standalone base models and existing meta techniques. CONCLUSION: This framework is envisioned to enhance the efficiency of DBS surgery and reduce the reliance on clinician experience for precise STN detection. This achievement is strategically significant to serve as an invaluable tool for refining the electrode trajectory, potentially replacing the current methodology based on MER.

Visual Cluster Grounding for Image Captioning.

Attention mechanisms have been extensively adopted in vision and language tasks such as image captioning. It encourages a captioning model to dynamically ground appropriate image regions when generating words or phrases, and it is critical to alleviate the problems of object hallucinations and language bias. However, current studies show that the grounding accuracy of existing captioners is still far from satisfactory. Recently, much effort is devoted to improving the grounding accuracy by linking the words to the full content of objects in images. However, due to the noisy grounding annotations and large variations of object appearance, such strict word-object alignment regularization may not be optimal for improving captioning performance. In this paper, to improve the performance of both grounding and captioning, we propose a novel grounding model which implicitly links the words to the evidence in the image. The proposed model encourages the captioner to dynamically focus on informative regions of the objects, which could be either discriminative parts or full object content. With slacked constraints, the proposed captioning model can capture correct linguistic characteristics and visual relevance, and then generate more grounded image captions. In addition, we propose a novel quantitative metric for evaluating the correctness of the soft attention mechanism by considering the overall contribution of all object proposals when generating certain words. The proposed grounding model can be seamlessly plugged into most attention-based architectures without introducing inference complexity. We conduct extensive experiments on Flickr30k (Young et al., 2014) and MS COCO datasets (Lin et al., 2014), demonstrating that the proposed method consistently improves image captioning in both grounding and captioning. Besides, the proposed attention evaluation metric shows better consistency with the captioning performance.

Cerebral venous sinus thrombosis secondary to tonsillectomy.

Cerebral venous sinus thrombosis(CVST) is considered to be a rare, high-risk, easily misdiagnosed disease with a mortality rate of 9.4%. Early diagnosis and timely anticoagulant thrombolytic therapy can reduce the mortality and disability rate and improve the prognosis of patients. This report describes the situation of a young male patient with bilateral tonsillectomy who, after going under low temperature plasma and general anesthesia surgery, presented with headache on the 4th day after the operation, and was diagnosed to be CVST by computed tomography(CT) and Magnetic Resonance Imaging(MRI). Due to severe pharynx swallowing pain after the surgery, his total daily intake was less than 2000 ml. After treatment, his prognosis was optimistic. The rarity and high risk of CVST after tonsillectomy suggest that we should pay attention to the related problems in the perioperative management of tonsillectomy include Bacterial infections, high condensation state of dehydration, using hemostatic drugs sparingly, etc.

Deep convolutional neural network for the automated detection of Subthalamic nucleus using MER signals.

BACKGROUND: Deep brain stimulation (DBS) surgery has been extensively conducted for treating advanced Parkinson's disease (PD) patient's symptoms. DBS hinges on the localization of the subthalamic nucleus (STN) in which a permanent electrode should be accurately placed to produce electrical current. Microelectrode recording (MER) signals are routinely recorded in the procedure of DBS surgery to validate the planned trajectories. However, manual MER signals interpretation with the goal of detecting STN borders requires expertise and prone to inter-observer variability. Therefore, a computerized aided system would be beneficial to automatic detection of the dorsal and ventral borders of the STN in MER. NEW METHOD: In this study, a new deep learning model based on convolutional neural system for automatic delineation of the neurophysiological borders of the STN along the electrode trajectory was developed. COMPARISON WITH EXISTING METHODS: The proposed model does not involve any conventional standardization, feature extraction or selection steps. RESULTS: Promising results of 98.67% accuracy, 99.03% sensitivity, 98.11% specificity, 98.79% precision and 98.91% F1-score for subject based testing were achieved using the proposed convolutional neural network (CNN) model. CONCLUSIONS: This is the first study on the analysis of MER signals to detect STN using deep CNN. Traditional machine learning (ML) algorithms are often cumbersome and suffer from subjective evaluation. Though, the developed 10-layered CNN model has the capability of extracting substantial features at the convolution stage. Hence, the proposed model has the potential to deliver high performance on STN region detection which shows perspective in aiding the neurosurgeon intraoperatively.

Brainstem atrophy in the early stage of Alzheimer's disease: a voxel-based morphometry study.

Postmortem studies on patients with Alzheimer's disease (AD) have confirmed that the dorsal raphe nucleus (DRN) in the brainstem is the first brain structure affected in the earliest stage of AD. The present study examined the brainstem in the early stage of AD using magnetic resonance (MR) imaging. T1-weighted MR images of the brains of 81 subjects were obtained from the publicly available Open Access Series of Imaging Studies (OASIS) database, including 27 normal control (NC) subjects, 27 patients with very mild AD (AD-VM) and 27 patients with mild AD (AD-M). The brainstem was interactively segmented from the MR images using ITK-SNAP. The present voxel-based morphometry (VBM) study was designed to investigate the brainstem differences between the AD-VM/AD-M groups and the NC group. The results showed bilateral loss in the pons and the left part of the midbrain in the AD-M group compared to the NC group. The AD-M group showed greater loss in the left midbrain than the AD-VM group (PFWEcorrected < 0.05). The results revealed that brainstem atrophy occurs in the early stages of AD (Clinical Dementia Rating = 0.5 and 1.0). Most of these findings were also investigated in a multicenter dataset. This is the first VBM study that provides evidence of brainstem alterations in the early stage of AD.

Effects of Salvia miltiorrhiza and Radix astragali on the TGF-ß/Smad/Wnt pathway and the pathological process of liver fibrosis in rats.

Traditional Chinese medicine has made some progress in the study of liver fibrosis, and provides valuable experience for clinical treatment of liver fibrosis. The aim of this study was to investigate the rationality of compatibility use of Salvia miltiorrhiza and Radix astragali on liver fibrosis in rats. For this purpose, the rat model of liver fibrosis was treated with single or different compatibilities of herbals extracts for 4 weeks. Saline and colchicine were set as a negative and positive control, respectively. Liver histopathology, liver function, and expressions of key proteins in the TGF-ß/Smad/Wnt pathway were assessed. Results showed that compared with colchicine, herbal extracts showed better ability to reduce deposition of α-SMA and type I collagen, and improve liver function. The effect of R. astragali extracts and 1:1 compound on improving liver fibrosis and liver function was relatively better than other treatment options. The compound groups showed a particularly significant effect on reducing Cyclin D1 expression. It was concluded that the 1:1 compatibility use of S. miltiorrhiza extracts and R. astragali extracts can preferably attenuate liver fibrosis by regulating the expression of TGF-ß1 and Cyclin D1.

Spy1, a unique cell cycle regulator, alters viability in ALS motor neurons and cell lines in response to mutant SOD1-induced DNA damage.

Increasing evidence indicates that DNA damage and p53 activation play major roles in the pathological process of motor neuron death in amyotrophic lateral sclerosis (ALS). Human SpeedyA1 (Spy1), a member of the Speedy/Ringo family, enhances cell proliferation and promotes tumorigenesis. Further studies have demonstrated that Spy1 promotes cell survival and inhibits DNA damage-induced apoptosis. We showed that the Spy1 expression levels were substantially decreased in ALS motor neurons compared with wild-type controls both in vivo and in vitro by qRT-PCR, western blotting, and Immunoassay tests. In addition, we established that over-expression of human SOD1 mutant G93A led to a decreased expression of Spy1. Furthermore, DNA damage response was activated in SOD1G93A-transfected cells (mSOD1 cells). Moreover, decreased Spy1 expression reduced cell viability and further activated the DNA damage response in mSOD1 cells. In contrast, increased Spy1 expression improved cell viability and inhibited the DNA damage response in mSOD1 cells. These results suggest that Spy1 plays a protective role in ALS motor neurons. Importantly, these findings provide a novel direction for therapeutic options for patients with ALS as well as for trial designs, such as investigating the role of oncogenic proteins in ALS.

Automatic Extraction of the Centerline of Corpus Callosum from Segmented Mid-Sagittal MR Images.

The centerline, as a simple and compact representation of object shape, has been used to analyze variations of the human callosal shape. However, automatic extraction of the callosal centerline remains a sophisticated problem. In this paper, we propose a method of automatic extraction of the callosal centerline from segmented mid-sagittal magnetic resonance (MR) images. A model-based point matching method is introduced to localize the anterior and posterior endpoints of the centerline. The model of the endpoint is constructed with a statistical descriptor of the shape context. Active contour modeling is adopted to drive the curve with the fixed endpoints to approximate the centerline using the gradient of the distance map of the segmented corpus callosum. Experiments with 80 segmented mid-sagittal MR images were performed. The proposed method is compared with a skeletonization method and an interactive method in terms of recovery error and reproducibility. Results indicate that the proposed method outperforms skeletonization and is comparable with and sometimes better than the interactive method.

Cyclophilin A Maintains Glioma-Initiating Cell Stemness by Regulating Wnt/ß-Catenin Signaling.

Purpose: Glioma-initiating cells (GIC) are glioma stem-like cells that contribute to glioblastoma (GBM) development, recurrence, and resistance to chemotherapy and radiotherapy. They have recently become the focus of novel treatment strategies. Cyclophilin A (CypA) is a cytosolic protein that belongs to the peptidyl-prolyl isomerase (PPIase) family and the major intracellular target of the immunosuppressive drug cyclosporin A (CsA). In this study, we investigate the functions of CypA and its mechanism of action in GICs' development.Experimental Design: We analyzed differences in CypA expression between primary tumors and neurospheres from the GDS database, both before and after GIC differentiation. A series of experiments was conducted to investigate the role of CypA in GIC stemness, self-renewal, proliferation, radiotherapy resistance, and mechanism. We then designed glutathione S-transferase (GST) pulldown and coimmunoprecipitation assays to detect signaling activity.Results: In this study, we demonstrated that CypA promotes GIC stemness, self-renewal, proliferation, and radiotherapy resistance. Mechanistically, we found that CypA binds ß-catenin and is recruited to Wnt target gene promoters. By increasing the interaction between ß-catenin and TCF4, CypA enhances transcriptional activity.Conclusions: Our results demonstrate that CypA enhances GIC stemness, self-renewal, and radioresistance through Wnt/ß-catenin signaling. Due to its promotive effects on GICs, CypA is a potential target for future glioma therapy. Clin Cancer Res; 23(21); 6640-9. ©2017 AACR.

miRNA-214 Inhibits Cellular Proliferation and Migration in Glioma Cells Targeting Caspase 1 Involved in Pyroptosis.

Pyroptosis is a type of proinflammatory programmed cell death mediated by caspase 1 activity and occurs in several types of eukaryotic tumor cells, including gliomas. MicroRNAs (miRNAs), small endogenous noncoding RNAs, have been demonstrated to be advantageous in glioma therapy. However, the question of whether miRNAs regulate pyroptosis in glioma remains unknown. The current study found that caspase 1 expression was substantially increased in both glioma tissues and glioma cell lines, U87 and T98G, while miR-214 expression was significantly downregulated. Luciferase reporter assay recognized caspase 1 as a target gene of miR-214. These findings demonstrate that miR-214 could inhibit cell proliferation and migration through the regulation of pyroptosis intermediated by caspase 1 in glioma U87 and T98G cells and may suggest a novel therapeutic for the intervention of glioma.

Centrosomal Protein of 55 Regulates Glucose Metabolism, Proliferation and Apoptosis of Glioma Cells via the Akt/mTOR Signaling Pathway.

INTRODUCTION: Glioma is one of the most common and most aggressive brain tumors in humans. The molecular and cellular mechanisms responsible for the onset and the progression of glioma are elusive and controversial. Centrosomal protein of 55 (CEP55) was initially described as a highly coiled-coil protein that plays critical roles in cell division, but was recently identified as being overexpressed in many human cancers. The function of CEP55 has not previously been characterized in glioma. We aim to discover the effect and mechanism of CEP55 in glioma development. METHOD: qRT-PCR and immunohistochemistry were used to analyze CEP55 expression. Glucose uptake, western blot, MTS, CCK-8, Caspase-3 activity and TUNEL staining assays were performed to investigate the role and mechanism of CEP55 on glioma cell process. RESULTS: We found that the levels of CEP55 expression were upregulated in glioma. In addition, CEP55 appeared to regulate glucose metabolism of glioma cells. Furthermore, knockdown of CEP55 inhibited cell proliferation and induced cell apoptosis in glioma. Finally, we provided preliminary evidence that knockdown of CEP55 inhibited glioma development via suppressing the activity of Akt/mTOR signaling. CONCLUSIONS: Our results demonstrated that CEP55 regulates glucose metabolism, proliferation and apoptosis of glioma cells via the Akt/mTOR signaling pathway, and its promotive effect on glioma tumorigenesis can be a potential target for glioma therapy in the future.

TUSC3 suppresses glioblastoma development by inhibiting Akt signaling.

Glioblastoma multiform is one of the most common and most aggressive brain tumors in humans. The molecular and cellular mechanisms responsible for the onset and progression of GBM are elusive and controversial. The function of tumor suppressor candidate 3 (TUSC3) has not been previously characterized in GBM. TUSC3 was originally identified as part of an enzyme complex involved in N-glycosylation of proteins, but was recently implicated as a potential tumor suppressor gene in a variety of cancer types. In this study, we demonstrated that the expression levels of TUSC3 were downregulated in both GBM tissues and cells, and also found that overexpression of TUSC3 inhibits GBM cell proliferation and invasion. In addition, the effects of increased levels of methylation on the TUSC3 promoter were responsible for decreased expression of TUSC3 in GBM. Finally, we determined that TUSC3 regulates proliferation and invasion of GBM cells by inhibiting the activity of the Akt signaling pathway.

Identification of two novel critical mutations in PCNT gene resulting in microcephalic osteodysplastic primordial dwarfism type II associated with multiple intracranial aneurysms.

Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) is a highly detrimental human autosomal inherited recessive disorder. The hallmark characteristics of this disease are intrauterine and postnatal growth restrictions, with some patients also having cerebrovascular problems such as cerebral aneurysms. The genomic basis behind most clinical features of MOPD II remains largely unclear. The aim of this work was to identify the genetic defects in a Chinese family with MOPD II associated with multiple intracranial aneurysms. The patient had typical MOPD II syndrome, with subarachnoid hemorrhage and multiple intracranial aneurysms. We identified three novel mutations in the PCNT gene, including one single base alteration (9842A>C in exon 45) and two deletions (Del-C in exon 30 and Del-16 in exon 41). The deletions were co-segregated with the affected individual in the family and were not present in the control population. Computer modeling demonstrated that the deletions may cause drastic changes on the secondary and tertiary structures, affecting the hydrophilicity and hydrophobicity of the mutant proteins. In conclusion, we identified two novel mutations in the PCNT gene associated with MOPD II and intracranial aneurysms, and the mutations were expected to alter the stability and functioning of the protein by computer modeling.

Corpus callosum atrophy associated with the degree of cognitive decline in patients with Alzheimer's dementia or mild cognitive impairment: a meta-analysis of the region of interest structural imaging studies.

Individual structural neuroimaging studies of the corpus callosum (CC) in Alzheimer's disease (AD) and mild cognitive impairment (MCI) with the region of interest (ROI) analysis have yielded inconsistent findings. The aim of this study was to conduct a meta-analysis of structural imaging studies using ROI technique to measure the CC midsagittal area changes in patients with AD or MCI. Databases of PubMed, the Cochrane Library, the ISI Web of Science, and Science Direct from inception to June 2014 were searched with key words "corpus callosum" or "callosal", plus "Alzheimer's disease" or "mild cognitive impairment". Twenty-three studies with 603 patients with AD, 146 with MCI, and 638 healthy controls were included in this meta-analysis. Effect size was used to measure the difference between patients with AD or MCI and healthy controls. Significant callosal atrophy was found in MCI patients with an effect size of -0.36 (95% CI, -0.57 to -0.14; P = 0.001). The degree of the CC atrophy in mild AD was less severe than that in moderate AD with a mean effect size -0.69 (95% CI, -0.89 to -0.49) versus -0.92 (95% CI, -1.16 to -0.69), respectively. Comparing with healthy controls, patients with MCI had atrophy in the anterior portion of the CC (i.e., rostrum and genu). In contrast, patients with AD had atrophy in both anterior and posterior portions (i.e., splenium). These results suggest that callosal atrophy may be related to the degree of cognitive decline in patients with MCI and AD, and it may be used as a biomarker for patients with cognitive deficit even before meeting the criteria for AD.

miR-603 promotes glioma cell growth via Wnt/ß-catenin pathway by inhibiting WIF1 and CTNNBIP1.

Gliomas are the most common and deadly type of brain tumor. In spite of progressive treatments, patient prognosis has not improved significantly. MicroRNAs are considered promising candidates for glioma therapy. MiR-603 was found overexpressed in both glioma tissues and cell lines. MiR-603 promoted cell proliferation, cell cycle progression and neurosphere formation. Conversely, inhibition of miR-603 remarkably reduced these effects. We confirmed that WIF1 and CTNNBIP1 are bona fide targets of miR-603. The negative correlation between miR-603 and these molecules' expression was shown by Pearson correlation in 50 primary glioma tissue samples. Furthermore, overexpression of miR-603 promoted nuclear ß-catenin levels and TOPflash luciferase activity, indicating that miR-603 activates the Wnt/ß-catenin signaling pathway. Our in vivo results confirmed the positive role of miR-603 in glioma development. We demonstrate that miR-603 regulates glioma development via its WIF1 and CTNNBIP1 targets, which suggests that miR-603 may be a promising candidate for therapeutic applications in glioma treatment.

Long-term seizure outcome for international consensus classification of hippocampal sclerosis: a survival analysis.

PURPOSE: Surgery is regarded as a common treatment option for patients with mesial temporal lobe epilepsy (MTLE) as a result of hippocampal sclerosis (HS). However, approximately one-third of patients with intractable epilepsy did not become seizure-free after tailored resection strategies. It would be compelling to identify predictive factors of postoperative seizure outcomes. Our aim was to assess the correlation between HS classification and long-term postoperative seizure outcome in patients with MTLE due to HS. METHODS: To investigate HS classification, semi-quantitative analysis and immunohistochemical staining of neuronal nuclei (NeuN) were performed on 100 postoperative hippocampal specimens. All patients had a 1-7 year postoperative follow-up. The postoperative seizure outcome was evaluated using International League Against Epilepsy (ILAE) outcome classification. RESULTS: Three types of HS were recognized. The highest incidence of initial precipitating injury (IPI) was noted in the HS ILAE type 1 group (53.1%). The most favorable long-term seizure outcome was also noted in the HS ILAE type 1 group. The shortest epilepsy duration was recorded in the HS ILAE type 2 group (mean epilepsy duration=6.64 ± 5.83 years). The completely seizure free rate of patients in all groups declined with an increase in time. CONCLUSIONS: Our study for the first time demonstrated a significant correlation between HS ILAE types and long-term postoperative seizure outcome in patients with MTLE due to HS. Therefore, HS ILAE types have predictive value in long-term seizure outcome following epilepsy surgery.

Corpus callosum atrophy and cognitive decline in early Alzheimer's disease: longitudinal MRI study.

BACKGROUND: We investigated the rate of corpus callosum (CC) atrophy and its association with cognitive decline in early Alzheimer's disease (AD). METHODS: We used publicly available longitudinal MRI data corresponding to 2 or more visits from 137 subjects characterized using the Clinical Dementia Rating (CDR) score. We classified these subjects into 3 groups according to the progression of their cognitive status: a healthy control group (CDR 0→0, n = 72), a decliner group (CDR 0→0.5, n = 14) and an AD group (CDR 0.5→0.5/1, n = 51). We measured the CC area on the midsagittal plane and calculated the atrophy rate between 2 or more visits. The correlation between the CC atrophy rate and annualized Mini Mental State Examination (MMSE) change was also analyzed. RESULTS: The results indicated that the baseline CC area was larger in the healthy control group compared to the AD group, whereas the CC atrophy rate was higher in the AD group relative to the control and decliner groups. The CC atrophy rate was also correlated with the annualized MMSE change in AD patients (p < 0.05). CONCLUSION: Callosal atrophy is present even in early AD and subsequently accelerates, such that the rate of CC atrophy is associated with cognitive decline in AD patients.

Progression of corpus callosum atrophy in early stage of Alzheimer's disease: MRI based study.

RATIONALE AND OBJECTIVES: Magnetic resonance imaging (MRI) studies reveal that atrophy of the corpus callosum (CC) is involved in early Alzheimer's disease (AD). The aim of this study was to investigate when and how callosal changes occur in the early course of AD. MATERIALS AND METHODS: The Open Access Series of Imaging Studies data sets were used in this study to investigate callosal change. High-resolution structural MRI was performed in 196 older patients. Subjects were characterized using the Clinical Dementia Rating (CDR); 98 healthy controls were not demented (CDR 0), and 98 patients had clinical diagnosis of AD in the very mild dementia stage (CDR 0.5; n = 70) and the mild dementia stage (CDR 1; n = 28). A semiautomatic segmentation method was used to extract the CC in the midsagittal plane. The total and regional areas of the CC were measured. RESULTS: The results indicated that callosal atrophy occurred in when subjects' CDRs were 0.5. The area of the genu and rostral body of the CC in the healthy controls (CDR 0) was significantly different from that of the subjects with very mild dementia (CDR 0.5) (P < .05). A significant difference could also be found in the area of the rostral body and midbody of the CC between subjects with very mild dementia (CDR 0.5) and those with mild dementia (CDR 1) (P < .05). CONCLUSIONS: Callosal atrophy can be detected in subjects with CDRs of 0.5. The change in the CC in the early stage of AD indicates an anterior-to-posterior atrophic process as the degree of dementia assessed by the CDR (from 0 to 0.5 to 1) increases.