A Protocol for a Single-Centered, Pragmatic, Randomized, Controlled, Parallel Trial Comparing Comprehensive Nonsurgical Therapy Options for Individuals with Lumbar Spinal Stenosis.

Aim: Lumbar spinal stenosis (LSS) is a long-term degenerative disease. Considering the risks and advantages of the patient's age range and the characteristics of the condition, non-surgical treatment is recommended. To determine the best first-line non-surgical therapy for LSS, few studies have examined different non-surgical therapies. Therefore, the main objective of this study is to determine whether the selection of comprehensive Chinese medicine (CM) treatment for LSS is more successful than non-surgical conservative treatment. Patients and Methods: In this two-armed, parallel, single-centered, pragmatic randomized controlled study, 94 LSS participants will be randomized to receive 24 sessions of comprehensive CM therapy or conservative treatment for 3 months, with follow-up assessments at 6, 9, 12, and 15 months. The primary outcome will be based on the success rate of the Zurich Claudication Questionnaire (ZCQ) for the most clinical important difference (MCID) at 3 and 15 months. Secondary outcomes include Numerical Rating Scale (NRS) scores for back and leg pain, ZCQ scores, Oswestry Disability Index scores for lumbar dysfunction, and Short-Form 12 scores for health-related quality of life at 3, 6, 9, 12, and 15 months. Adverse events and incidences of surgery will be reported anytime during the trial and follow-up. Conclusion: This protocol examines the comparative efficacy of comprehensive CM therapy compared with conventional care through a pragmatic randomized controlled trial to present data to facilitate clinical or policy decision-making. The outcomes will make it easier to decide which patient-centered treatments to prioritize for LSS.

Modified Skin Incision and Location of Burr-Hole Surgery via a Retrosigmoid Approach: An Anatomical Study.

Objective This study aims to reduce the tissue damage during craniotomy with retrosigmoid approach. A modified sickle-shaped skin incision was developed, and a new burr-hole positioning method was proposed. Methods Five adult cadaveric heads (10 sides) were used in this study. The sickle-shaped skin incision was performed during craniotomy. The nerves, blood vessels, and muscles were observed and measured under a microscope. Additionally, 62 dry adult skull specimens (left sided, n = 35; right sided, n = 27) were used to measure the distance between the most commonly used locating point (asterion [Ast] point) and the posteroinferior point of the transverse sigmoid sinus junction (PSTS) (Ast-PSTS), as well as the distance between the new locating O point and the PSTS (O-PSTS). Then, the reliability of the new locating O point was validated on the same five adult cadaveric heads (10 sides) used for the sickle-shaped skin incision. Results The sickle-shaped skin incision reduced the damage to the occipital nerves, blood vessels, and muscles during the surgery via a retrosigmoid approach. The dispersion and variability of O-PSTS were smaller than those of Ast-PSTS. Conclusion The sickle-shaped skin incision of the retrosigmoid approach can reduce the tissue damage and can completely expose the structures in the cerebellopontine angle. The modified O point is a more reliable locating point for a burr-hole surgery than the Ast point.

Horospherical Decision Boundaries for Large Margin Classification in Hyperbolic Space.

Hyperbolic spaces have been quite popular in the recent past for representing hierarchically organized data. Further, several classification algorithms for data in these spaces have been proposed in the literature. These algorithms mainly use either hyperplanes or geodesics for decision boundaries in a large margin classifiers setting leading to a non-convex optimization problem. In this paper, we propose a novel large margin classifier based on horospherical decision boundaries that leads to a geodesically convex optimization problem that can be optimized using any Riemannian gradient descent technique guaranteeing a globally optimal solution. We present several experiments depicting the competitive performance of our classifier in comparison to SOTA.

Inhibition of TRPA1 Attenuates Oxidative Stress-induced Damage After Traumatic Brain Injury via the ERK/AKT Signaling Pathway.

Neuron apoptosis is a feature of secondary injury after traumatic brain injury (TBI). Evidence implies that excess calcium (Ca2+) ions and reactive oxidative species (ROS) play critical roles in apoptosis. In reaction to increased ROS, the anti-oxidative master transcription factor, Transient receptor potential Ankyrin 1 (TRPA1) allows Ca2+ ions to enter cells. However, the effect of TBI on the expression of TRPA1 and the role of TRPA1 in TBI are unclear. In the present study, TBI in the mouse brain was simulated using the weight-drop model. The process of neuronal oxidative stress was simulated in HT22 neuronal cells by treatment with hydrogen peroxide. We found that TRPA1 was significantly upregulated in neurons at 24 h after TBI. Neuronal apoptosis was increased in the in vivo and in vitro models; however, this increase was reduced by the functional inhibition of TRPA1 in both models. After TBI, TRPA1 was upregulated via nuclear factor, erythroid 2 like 2 (Nrf2) in neurons. TRPA1-mediated neuronal apoptosis after TBI might be achieved in part through the CaMKII/AKT/ERK signaling pathway. To sum up, TBI-triggered TRPA1 upregulation in neurons is mediated by Nrf2 and the functional blockade of TRPA1 attenuates neuronal apoptosis and improves neuronal dysfunction, partially mediated through the activation of the calcium/calmodulin dependent protein kinase II (CaMKII) extracellular regulated kinase (ERK)/protein kinase B (AKT) signaling pathway. Our results suggest that functional blockade of TRPA1 might be a promising therapeutic intervention related to ROS and Nrf2 in TBI.

Nested Hyperbolic Spaces for Dimensionality Reduction and Hyperbolic NN Design.

Hyperbolic neural networks have been popular in the recent past due to their ability to represent hierarchical data sets effectively and efficiently. The challenge in developing these networks lies in the nonlinearity of the embedding space namely, the Hyperbolic space. Hyperbolic space is a homogeneous Riemannian manifold of the Lorentz group which is a semi-Riemannian manifold, i.e. a manifold equipped with an indefinite metric. Most existing methods (with some exceptions) use local linearization to define a variety of operations paralleling those used in traditional deep neural networks in Euclidean spaces. In this paper, we present a novel fully hyperbolic neural network which uses the concept of projections (embeddings) followed by an intrinsic aggregation and a nonlinearity all within the hyperbolic space. The novelty here lies in the projection which is designed to project data on to a lower-dimensional embedded hyperbolic space and hence leads to a nested hyperbolic space representation independently useful for dimensionality reduction. The main theoretical contribution is that the proposed embedding is proved to be isometric and equivariant under the Lorentz transformations, which are the natural isometric transformations in hyperbolic spaces. This projection is computationally efficient since it can be expressed by simple linear operations, and, due to the aforementioned equivariance property, it allows for weight sharing. The nested hyperbolic space representation is the core component of our network and therefore, we first compare this representation - independent of the network - with other dimensionality reduction methods such as tangent PCA, principal geodesic analysis (PGA) and HoroPCA. Based on this equivariant embedding, we develop a novel fully hyperbolic graph convolutional neural network architecture to learn the parameters of the projection. Finally, we present experiments demonstrating comparative performance of our network on several publicly available data sets.

De-differentiation associated with drop metastasis of a recurrent intracranial solitary fibrous tumor: a case report and literature review.

BACKGROUND: Central nervous system is a rare occurring location of solitary fibrous tumors (SFTs). SFTs have a potential for recurrence, which is the leading cause of death in patients with these disease entities. De-differentiation phenomenon combined with cerebrospinal fluid (CSF) dissemination through drop metastasis of STFs from intracranial to intraspinal has only been reported in extremely limited cases. CASE DESCRIPTION: Herein, we present a case of SFT in a 54-year old male. MRI showed characteristic of mixed high and low signal with 6.3 cm × 6.5 cm × 5.9 cm. After radical surgical resection, the pathology indicated benign SFT. However, MRI re-examination of 22 months later detected local recurrence, concomitant with spreading of intracranial and intraspinal through CSF dissemination. And interestingly, the second pathology found de-differentiation phenomenon and malignance of SFT, in which some areas transformed to rhabdomyosarcoma. CONCLUSION: This is the first case report of recurrent intracranial SFT de-differentiating to rhabdomyosarcoma concurrent with CSF pathway drop metastasis. Benign intracranial SFTs have the potential of de-differentiation, which may play an important role in its distant metastasis. The underlying molecular biological and pathological mechanisms of benign SFT malignance transformation still warrant further exploration.

S100A8 Promotes Inflammation via Toll-Like Receptor 4 After Experimental Traumatic Brain Injury.

INTRODUCTION: S100 calcium-binding protein A8 (S100A8) is also known as macrophage-related protein 8, which is involved in various pathological processes in the central nervous system post-traumatic brain injury (TBI), and plays a critical role in inducing inflammatory cytokines. Accumulating evidences have indicated that toll-like receptor 4 (TLR4) is considered to be involved in inflammatory responses post TBI. The present study was designed to analyze the hypothesis that S100A8 is the key molecule that induces inflammation via TLR4 in TBI. METHODS: The weight-drop TBI model was used and randomly implemented on mice that were categorized into six groups: Sham, NS, S100A8, S100A8+TAK-242, TBI, and TBI+TAK-242 groups. In the S100A8+TAK-242 and TBI+TAK-242 groups, at half an hour prior to the intracerebroventricular administration of S100A8 or TBI, mice were intraperitoneally treated with TAK-242 that acts as a selective antagonist and inhibitor of TLR4. Furthermore, the protein recombinant of S100A8 was injected into the lateral ventricle of the brain of mice in the S100A8 and S100A8+TAK-242 groups. Sterile normal saline was injected into the lateral ventricle in the NS group. To evaluate the association between S100A8 and TLR4, Western blot, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and Nissl staining were employed. Simultaneously, the neurological score and brain water content were assessed. In the in vitro analysis, BV-2 microglial cells were stimulated with lipopolysaccharide LPS or S100A8 recombinant protein, with or without TAK-242. The expression of the related proteins was subsequently detected by Western blot or enzyme-linked immunosorbent assay. RESULTS: The levels of S100A8 protein and pro-inflammatory cytokines were significantly elevated after TBI. There was a reduction in the neurological scores of non-TBI animals with remarkable severe brain edema after the intracerebroventricular administration of S100A8. Furthermore, the TLR4, p-p65, and myeloid differentiation factor 88 (MyD88) levels were elevated after the administration of S100A8 or TBI, which could be restored by TAK-242. Meanwhile, in the in vitro analysis, due to the stimulation of S100A8 or LPS, there was an upregulation of p-p65 and MyD88, which could also be suppressed by TAK-242. CONCLUSION: The present study demonstrated that the TLR4-MyD88 pathway was activated by S100A8, which is essential for the development of inflammation in the brain after TBI.