Development and Validation of a Deep Learning Predictive Model Combining Clinical and Radiomic Features for Short-Term Postoperative Facial Nerve Function in Acoustic Neuroma Patients.

OBJECTIVE: This study aims to construct and validate a predictable deep learning model associated with clinical data and multi-sequence magnetic resonance imaging (MRI) for short-term postoperative facial nerve function in patients with acoustic neuroma. METHODS: A total of 110 patients with acoustic neuroma who underwent surgery through the retrosigmoid sinus approach were included. Clinical data and raw features from four MRI sequences (T1-weighted, T2-weighted, T1-weighted contrast enhancement, and T2-weighted-Flair images) were analyzed. Spearman correlation analysis along with least absolute shrinkage and selection operator regression were used to screen combined clinical and radiomic features. Nomogram, machine learning, and convolutional neural network (CNN) models were constructed to predict the prognosis of facial nerve function on the seventh day after surgery. Receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to evaluate model performance. A total of 1050 radiomic parameters were extracted, from which 13 radiomic and 3 clinical features were selected. RESULTS: The CNN model performed best among all prediction models in the test set with an area under the curve (AUC) of 0.89 (95% CI, 0.84-0.91). CONCLUSION: CNN modeling that combines clinical and multi-sequence MRI radiomic features provides excellent performance for predicting short-term facial nerve function after surgery in patients with acoustic neuroma. As such, CNN modeling may serve as a potential decision-making tool for neurosurgery.

Combined Endovascular and Surgical Treatment for Brain Arteriovenous Malformations in Biplanar Hybrid Operating Room.

OBJECTIVE: Combined surgical and endovascular treatment for vascular disorders has become prevalent in recent years. However, reports on one-session hybrid surgery for arteriovenous malformations (AVMs) are relatively rare. The safety and efficiency of combined treatment for brain AVMs were analyzed in biplanar hybrid operating room (OR) at one stage. METHODS: We retrospectively analyzed 20 patients with AVMs undergoing combined surgical and endovascular treatment from October 2015 to June 2018. The data for resection rate, microcatheter adhesion, surgical position and postoperative outcomes were analyzed. Total resection or near-total resection was achieved in all cases. RESULTS: A total of 13 patients were under combined endovascular and surgical procedures, and 7 experienced surgery with intraoperative digital subtraction angiography. Sitting position was applied in 3 of them; 2 niduses in cerebellum, and 1 in parietal lobe. Compared with admission modified Rankin Scale (mRS) in all patients, postoperative 12-month mRS showed a significant decline. Besides, 3 patients experienced microcatheter adhesion after endovascular embolization, thereafter underwent surgical adhesion removal while nidus resection was done. CONCLUSION: Combined endovascular and surgical modality in a hybrid OR at one stage provides a safe strategy for the treatment of AVMs. The biplanar hybrid neurointerventional suite is endowed with unconstrained operating angle which enables combined endovascular and surgical treatment in sitting position. It also reduces the risk of microcatheter adhesion, which enables interventional radiologists to perform aggressively.

Long Noncoding RNA PVT1 Promotes Stemness and Temozolomide Resistance through miR-365/ELF4/SOX2 Axis in Glioma.

Long non-coding RNA (lncRNA) are a class of non-coding RNAs demonstrated to play pivotal roles in regulating tumor progression. Therefore, deciphering the regulatory role of lncRNA in the development of glioma may offer a promising therapeutic target for treatment of glioma. We performed RT-qPCR analysis on the expression of lncRNA plasmacytoma variant translocation 1 (PVT1) and miR-365 in glioma tissues and cell lines. Cell proliferation and viability was assessed with CCK8 assay. Cell migration was assessed by wound healing assay. Transwell assay was used to assess cell invasion capacity. Expression of CD133+ cells was detected by flow cytometry. Western blot assay was used to detection the expression of ELF4 and stemness-related protein SOX2, Oct4 and Nanog. Bioinformatics and dual-luciferase assay were used to predict and validate the interaction between PVT1 and miR-365. Elevated PVT1 expression was observed in glioma tissues and cells. Knockdown of PVT1 and overexpression of miR-365 inhibited proliferation, migration, invasion and promoted stemness and Temozolomide (TMZ) resistance of glioma cells. PVT1 regulated ELF4 expression by competitively binds to miR-365. PVT1 regulated the stemness and sensitivity of TMZ of glioma cells through miR-365/ELF4/ SOX2 axis. This study identified that PVT1 promoted glioma stemness through miR-365/ELF4/SOX2 axis.

Bisperoxovandium (pyridin-2-squaramide) targets both PTEN and ERK1/2 to confer neuroprotection.

BACKGROUND AND PURPOSE: We and others have shown that inhibiting phosphatase and tensin homolog deleted on chromosome 10 (PTEN) or activating ERK1/2 confer neuroprotection. As bisperoxovanadium compounds are well-established inhibitors of PTEN, we designed bisperoxovandium (pyridin-2-squaramide) [bpV(pis)] and determined whether and how bpV(pis) exerts a neuroprotective effect in cerebral ischaemia-reperfusion injury. EXPERIMENTAL APPROACH: Malachite green-based phosphatase assay was used to measure PTEN activity. A western blot assay was used to measure the phosphorylation level of Akt and ERK1/2 (p-Akt and p-ERK1/2). Oxygen-glucose deprivation (OGD) was used to injure cultured cortical neurons. Cell death and viability were assessed by LDH and MTT assays. To verify the effects of bpV(pis) in vivo, Sprague-Dawley rats were subjected to middle cerebral artery occlusion, and brain infarct volume was measured and neurological function tests performed. KEY RESULTS: bpV(pis) inhibited PTEN activity and increased p-Akt in SH-SY5Y cells but not in PTEN-deleted U251 cells. bpV(pis) also elevated p-ERK1/2 in both SH-SY5Y and U251 cells. These data indicate that bpV(pis) enhances Akt activation through PTEN inhibition but increases ERK1/2 activation independently of PTEN signalling. bpV(pis) prevented OGD-induced neuronal death in vitro and reduced brain infarct volume and promoted functional recovery in stroke animals. This neuroprotective effect of bpV(pis) was blocked by inhibiting Akt and/or ERK1/2. CONCLUSIONS AND IMPLICATIONS: bpV(pis) confers neuroprotection in OGD-induced injury in vitro and in cerebral ischaemia in vivo by suppressing PTEN and activating ERK1/2. Thus, bpV(pis) is a bi-target neuroprotectant that may be developed as a drug candidate for stroke treatment.

Treatment strategies for huge central neurocytomas.

Central neurocytomas (CNs), initially asymptomatic, sometimes become huge before detection. We described and analyzed the clinical, radiological, operational and outcome data of 13 cases of huge intraventricular CNs, and discussed the treatment strategies in this study. All huge CNs (n=13) in our study were located in bilateral lateral ventricle with diameter ≥5.0 cm and had a broad-based attachment to at least one side of the ventricle wall. All patients received craniotomy to remove the tumor through transcallosal or transcortical approach and CNs were of typical histologic and immunohistochemical features. Adjuvant therapies including conventional radiation therapy (RT) or gamma knife radiosurgery (GKRS) were also performed postoperatively. Transcallosal and transcortical approaches were used in 8 and 5 patients, respectively. Two patients died within one month after operation and 3 patients with gross total resection (GTR) were additionally given a decompressive craniectomy (DC) and/or ventriculoperitoneal shunt (VPS) as the salvage therapy. Six patients received GTR(+RT) and 7 patients received subtotal resection (STR)(+GKRS). Eight patients suffered serious complications such as hydrocephalus, paralysis and seizure after operation, and patients who underwent GTR showed worse functional outcome [less Karnofsky performance scale (KPS) scores] than those having STR(+GKRS) during the follow-up period. The clinical outcome of huge CNs seemed not to be favorable as that described in previous reports. Surgical resection for huge CNs should be meticulously considered to guarantee the maximum safety. Better results were achieved in STR(+GKRS) compared with GTR(+RT) for huge CNs, suggesting that STR(+GKRS) may be a better treatment choice. The recurrent or residual tumor can be treated with GKRS effectively.

Stromal cell-derived factor 1α decreases ß-amyloid deposition in Alzheimer's disease mouse model.

ß-amyloid (Aß) aggregates are known to induce neuronal and synaptic dysfunction, and thus are involved in learning and memory deficits in Alzheimer's disease (AD), making Aß deposits a potential target for prevention or treatment. Microglia, especially bone marrow-derived microglia (BMDM), has been recently thought to play important roles in internalizing and phagocytozing Aß. BMDM originate in the bone marrow, migrate into the blood as hematopoietic progenitor cells (HPCs) and enter the brain in a chemokine-dependent manner. An effective chemoattractant for HPCs is stromal cell-derived factor 1 (SDF-1), which is also involved in regulating HPCs differentiation. Therefore, we hypothesize that SDF-1 might have influence on the migration of BMDM from peripheral cycle to brain. To explore whether treatment with SDF-1α can decrease Aß burden, APP/PS1 double transgenic mice were given intracerebroventricular injection of SDF-1α weekly from the age of 28 to 32 weeks (4 weeks of injections) or from 28 to 36 weeks (8 weeks of injections). The results of our study showed that SDF-1α treatment decreased the area and the number of Aß deposits, increased the level of Iba-1, a marker of microglia, and increased the number of plaque associated microglia in the parenchyma of APP/PS1 transgenic mice. These results suggest that SDF-1 could provide a novel and promising target for the purpose of lowering Aß pathology in AD.