Border Zone Maybe Correlated with Radiation Necrosis After Radiosurgery in Metastatic Brain Tumor.

BACKGROUND: Radiation necrosis (RN) after stereotactic radiosurgery (SRS) in brain metastases has been extensively evaluated, and RN is correlated with various risk factors. However, no study comprehensively analyzed the correlation between RN and the border zones of the brain that are vulnerable to ischemia. We hypothesized that patients with tumors in the border zone are at high risk of RN. Hence, the current study aimed to assess the correlation between border zone lesions and RN, with consideration of other predetermined factors. METHODS: This retrospective study included 117 patients with 290 lesions who underwent Gamma Knife SRS. Radiological and clinical analyses were performed to identify factors possibly correlated with RN. Notably, the lesion location was classified into 2 groups (border zone and nonborder zone) based on the blood supply. RESULTS: In total, 22 (18.8%) patients with 22 (7.5%) lesions developed RN. Univariate analysis revealed a significant correlation between RN and external border zone lesions, second course of SRS administered at the same site of the previous SRS, prescribed dose, and tumor volume. Multivariate analysis showed that border zone lesions, second course of SRS at the same site of the previous SRS, and tumor volume were significantly correlated with RN. CONCLUSIONS: Patients with tumors in the border zone are at high risk of RN. The potential risks of RN can be attributed hypothetically to hypoperfusion. Hence, the association between RN and border zone lesions seems reasonable.

Full-range stress-strain curve estimation of aluminum alloys using machine learning-aided ultrasound.

Full-range stress-strain (SS) curves are crucial in understanding mechanical properties of a material such as the yield strength, ultimate tensile strength, and elongation. In this study, a full-range SS-curve was nondestructively estimated by applying machine learning to the ultrasonic amplitude-scan signal propagated through the material. The performance of the developed technique was validated using five-hundred aluminum alloy specimens with a wide spectrum of mechanical properties. The analyses of various ultrasonic properties, including nonlinearity and attenuation, with respect to the elements in the SS curves revealed how ultrasonics can be used to predict the SS curves without conventional destructive tensile testing. The proposed technique has significant potential for new applications in the fields of materials science and engineering, such as inline SS curve estimation during manufacturing.

Venous ectasia preceding intra-tumoral hemorrhage in a case of gliosarcoma with transverse sinus involvement.

Although intratumoral hemorrhage is common in patients with malignant brain tumors, reports on its clinical course are scarce. This report presents a rare case of a patient with intratumoral hemorrhage with gliosarcoma invading the venus sinus. This invasion and a small draining vein were observed at diagnosis. Magnetic resonance imaging performed 1 week later showed new-onset venous ectasia, which caused intratumoral hemorrhage. This case provides insight into the mechanisms underlying intratumoral hemorrhage and highlights the emergence of new intratumoral vasculature as a potential warning sign for hemorrhage.

Development of an Angiography Guide Indicator for Stereotactic Radiosurgery for High Precision.

BACKGROUND: Stereotactic radiosurgery (SRS) is effectively used for treating various cerebrovascular diseases, including arteriovenous malformations. As image-based surgery is the gold standard technique in SRS, the quality of stereotactic angiography images greatly influences the surgical approach for cerebrovascular diseases. Despite several studies in the relevant literature, research on auxiliary devices, including angiography indicators used for cerebrovascular disease surgeries, is limited. Thus, the development of angiographic indicators may provide meaningful data for stereotactic surgery. METHODS: A centerline was drawn, and a guideline was attached such that the "+" and "X" centers of the existing angiography guide indicator intersect. Further, a guideline wire connecting "+" and "X" was fixed using a tape. Based on the presence or absence of the guide indicator, angiography anterior-posterior (AP) and lateral (LAT) images were taken 10 times each, and statistical analysis was performed. RESULTS: The average and standard deviation of the conventional AP and LAT indicators were 10.22 ± 0.53 mm and 9.02 ± 0.33 mm, and those of the developed AP and LAT indicators were 10.3 ± 0.57 mm and 8.92 ± 0.23 mm, respectively. CONCLUSIONS: The results confirmed that the use of the lead indicator developed in this study provides higher accuracy and precision compared to that of the use of the conventional indicator. Furthermore, the developed guide indicator may provide meaningful information during SRS.

Ganglioside GD1a enhances osteogenesis by activating ERK1/2 in mesenchymal stem cells of Lmna mutant mice.

Mutations in Lmna usually cause a series of human disorders, such as premature aging syndrome (progeria) involving the skeletal system. Gangliosides are known to be involved in cell surface differentiation and proliferation of stem cells. However, the role of gangliosides in Lmna dysfunctional mesenchymal stem cells (MSCs) is unclear. Therefore, Ganglioside's role in osteogenesis of Lmna dysfunctional MSCs analyzed. As a result of the analysis, it was confirmed that the expression of ganglioside GD1a was significantly reduced in MSCs derived from LmnaDhe/+ mice and in MSCs subjected to Lamin A/C knockdown using siRNA. Osteogenesis-related bone morphogenetic protein-2 and Osteocalcin protein, and gene expression were significantly decreased due to Lmna dysfunction. A result of treating MSCs with Lmna dysfunction with ganglioside GD1a (3 µg/ml), significantly increased bone differentiation in ganglioside GD1a treatment to Lmna-mutated MSCs. In addition, the level of pERK1/2, related to bone differentiation mechanisms was significantly increased. Ganglioside GD1a was treated to Congenital progeria LmnaDhe/+ mice. As a result, femur bone volume in ganglioside GD1a-treated LmnaDhe/+ mice was more significantly increased than in the LmnaDhe/+ mice. Therefore, it was confirmed that the ganglioside GD1a plays an important role in enhancing osteogenic differentiation in MSC was a dysfunction of Lmna.

Identification of Novel Nucleocapsid Chimeric Proteins Inhibiting HIV-1 Replication.

The positive transcription elongation factor b (P-TEFb) is an essential factor that induces transcription elongation and is also negatively regulated by the cellular factor HEXIM1. Previously, the chimeric protein HEXIM1-Tat (HT) was demonstrated to inhibit human immunodeficiency virus-1 (HIV)-1 transcription. In this study, we attempted to develop an improved antiviral protein that specifically binds viral RNA (vRNA) by fusing HT to HIV-1 nucleocapsid (NC). Thus, we synthesized NC-HEXIM1-Tat (NHT) and HEXIM1-Tat-NC (HTN). NHT and HTN inhibited virus proliferation more effectively than HT, and they did not attenuate the function of HT. Notably, NHT and HTN inhibited the infectivity of the progeny virus, whereas HT had no such effect. NHT and HTN selectively and effectively interacted with vRNA and inhibited the proper packaging of the HIV-1 genome. Taken together, our results illustrated that the novel NC-fused chimeric proteins NHT and HTN display novel mechanisms of anti-HIV effects by inhibiting both HIV-1 transcription and packaging.

Recent Progress in Development and Applications of Ionic Polymer-Metal Composite.

Electroactive polymer (EAP) is a polymer that reacts to electrical stimuli, such as voltage, and can be divided into electronic and ionic EAP by an electrical energy transfer mechanism within the polymer. The mechanism of ionic EAP is the movement of the positive ions inducing voltage change in the polymer membrane. Among the ionic EAPs, an ionic polymer-metal composite (IPMC) is composed of a metal electrode on the surface of the polymer membrane. A common material for the polymer membrane of IPMC is Nafion containing hydrogen ions, and platinum, gold, and silver are commonly used for the electrode. As a result, IPMC has advantages, such as low voltage requirements, large bending displacement, and bidirectional actuation. Manufacturing of IPMC is composed of preparing the polymer membrane and plating electrode. Preparation methods for the membrane include solution casting, hot pressing, and 3D printing. Meanwhile, electrode formation methods include electroless plating, electroplating, direct assembly process, and sputtering deposition. The manufactured IPMC is widely demonstrated in applications such as grippers, micro-pumps, biomedical, biomimetics, bending sensors, flow sensors, energy harvesters, biosensors, and humidity sensors. This paper will review the overall field of IPMC by demonstrating the categorization, principle, materials, and manufacturing method of IPMC and its applications.

Development of an Animal Stereotactic Device for Preclinical Research on Tumor Response After Stereotactic Radiosurgery.

BACKGROUND: In gamma knife radiosurgery, the tumor response to radiation is an important predictor of clinical treatment results. Since brain tumors have different characteristics and growth patterns, depending on the type, the tumors' response to radiation are also different. Compared with various other clinical treatments, there is a dearth of research on the development of gamma knife-magnetic resonance imaging (MRI) preclinical experimental equipment. Hence, the identification of preclinical equipment necessity for experimental animals will provide meaningful data for the provision of clinical assistance to humans. OBJECTIVES: A device for stereotactic radiosurgery capable of MRI in small animals was developed. The feasibility of creating a preplan by means of small animal images was then assessed. METHODS: A device for stereotaxic surgery of small animals using a 48-channel MRI coil was developed using a 3 dimensional printer. Rat brain-MRI images were obtained with a 3.0 T MRI scanner using a multi-channel coil. The acquired MRI images were transferred to a GammaPlan workstation to establish a preplan. RESULTS: To gamma rays to the targeted site on animals, a positioning device combined with a G-frame was mounted on a gamma knife. Planning of radiosurgery based on MRI images became possible with GammaPlan workstations. CONCLUSIONS: Preclinical experiments using small animals are possible with the use of stereotactic devices. In clinical treatment, preclinical experimental results will provide meaningful information.

Microstructural Characterization of Additively Manufactured Metal Components Using Linear and Nonlinear Ultrasonic Techniques.

Metal additive manufacturing (AM) is an innovative manufacturing technology that uses a high-power laser for the layer-by-layer production of metal components. Despite many achievements in the field of AM, few studies have focused on the nondestructive characterization of microstructures, such as grain size and porosity. In this study, various microstructures of additively manufactured metal components were characterized non-destructively using linear/nonlinear ultrasonic techniques. The contributions of this study are as follows: (1) presenting correlation analyses of various microstructures (grain size and texture, lack of fusion, and porosity) and ultrasonic properties (ultrasonic velocity, attenuation, and nonlinearity parameters), (2) development of nondestructive microstructural characterization techniques for additively manufactured components; and (3) exploring the potential for the online monitoring of AM processes owing to the nondestructive nature of the proposed technique. The performance of the proposed technique was validated using additively manufactured samples under varying laser beam speed conditions. The characteristics of the target microstructures characterized using the proposed technique were consistent with the results obtained using destructive optical microscopy and electron back-scattered diffraction methods.

Is Conservative Treatment Better than Surgical Treatment for Basal Ganglia Hemorrhage in a Conventionally Non-Surgical Indication Group with Poor Motor Function?

Background: The treatment options for basal ganglia intracerebral hemorrhage (ICH), either surgical or conservative, remain controversial. A previous study developed "A new modified ICH (MICH) score" that suggests which treatment option will be better for basal ganglia ICH. According to this scoring system, a MICH score of 0 or 1 indicates that conservative treatment is better than surgical treatment. The purpose of this study was to determine whether conservative treatment is still a better option for a basal ganglia hemorrhage in patients with MICH scores of 0 and 1, with initial poor motor grades. Methods: This retrospective study was comprised of 41 patients with a spontaneous basal ganglia hemorrhage. These patient groups had no previous brain lesions, their initial MICH score was 0 or 1, and the manual muscle test (MMT) of their hand was grade 2+ or lower in the initial evaluation. All patients were transferred to the Department of Rehabilitation Medicine and received rehabilitation treatment. Ten patients had an operative intervention, which was burr-hole aspiration or craniotomy with hematoma removal. The control group included 31 patients who underwent conservative treatment. Outcome evaluations used the Berg Balance Scale (BBS), Modified Barthel Index (MBI), and Brunnstrom recovery stage (BRS) which were evaluated at initial and regular follow-ups after 1, 3, and 6 months. We defined an improvement state if the BRS of their hand became 4 or more in 6 months, which means an escape from the synergic pattern. Results: Demographic characteristics showed no significant differences in age, sex, hemiplegic side, initial GCS score, presence of IVH and hydrocephalus, or distribution of MICH scores 0 and 1. There was only a significant difference in the distribution of hematoma volume between groups of less than 20 mL and groups from 21 to 50 mL (p = 0.049). There were no significant differences in MBI values in 1 month or improvement of BRS of their hand in 6 months between the two groups. Conclusions: Even in the group classified as predominantly conservative in basal ganglia hemorrhage patients, if the initial muscle strength is low, it is necessary to reconsider whether conservative treatment is superior to surgical treatment in terms of functional improvement.

Human pluripotent stem cell-derived myogenic progenitors undergo maturation to quiescent satellite cells upon engraftment.

Human pluripotent stem cell (hPSC)-derived myogenic progenitor cell (MPC) transplantation is a promising therapeutic approach for a variety of degenerative muscle disorders. Here, using an MPC-specific fluorescent reporter system (PAX7::GFP), we demonstrate that hPSC-derived MPCs can contribute to the regeneration of myofibers in mice following local injury and in mice deficient of dystrophin (mdx). We also demonstrate that a subset of PAX7::GFP MPCs engraft within the basal lamina of regenerated myofibers, adopt a quiescent state, and contribute to regeneration upon reinjury and in mdx mouse models. This subset of PAX7::GFP MPCs undergo a maturation process and remodel their molecular characteristics to resemble those of late-stage fetal MPCs/adult satellite cells following in vivo engraftment. These in-vivo-matured PAX7::GFP MPCs retain a cell-autonomous ability to regenerate and can repopulate in the niche of secondary recipient mice, providing a proof of principle for future hPSC-based cell therapy for muscle disorders.

Retrospective 6 month-outcomes and prognostic factors following spontaneous angiogram-negative non-perimesencephalic subarachnoid hemorrhage.

Our objective was to analyze functional outcomes and prognostic factors in patients suffering from angiogram-negative non-perimesencephalic subarachnoid hemorrhage (non-PMH). In total, 1601 patients presenting with spontaneous SAH between January 2009 to December 2019 admitted to our institution were reviewed. Among them, 51 patients with angiogram negative non-perimesencephalic subarachnoid hemorrhage were analyzed. We divided patients into groups according to hemorrhage pattern and duration. Prognostic factors were assessed according to initial neurologic grade, early hydrocephalus, fisher grade, and duration of hemorrhage. Outcomes were assessed according to the modified Rankin Scale after 6 months. Overall, 41 patients (80.3%) with angiogram-negative non-PMH achieved a favorable outcome. In univariate analysis, good initial neurologic grade, absence of early hydrocephalus, non-Fisher-type 3 bleeding pattern, and short term hemorrhage (blood wash out <7 days after onset) duration were significantly associated with a favorable outcome. In multivariate analysis, a non-Fisher-type 3 hemorrhagic pattern (p < 0.05) and good initial neurologic state (p < 0.01) were independent predictors of favorable outcomes in angiogram-negative non-PMH patients. Patients with angiogram-negative non-PMH generally had favorable outcomes. A non-Fisher-type 3 hemorrhagic pattern and good initial neurologic state were prognostic factors of a favorable outcome in non-PMH. Furthermore, patients with long-term SAH were more likely to develop hydrocephalus. Evaluating the pattern and duration of subarachnoid hemorrhage may allow better prediction of outcomes in patients with angiogram negative and non-PMH.

Multi-omic analysis of selectively vulnerable motor neuron subtypes implicates altered lipid metabolism in ALS.

Amyotrophic lateral sclerosis (ALS) is a devastating disorder in which motor neurons degenerate, the causes of which remain unclear. In particular, the basis for selective vulnerability of spinal motor neurons (sMNs) and resistance of ocular motor neurons to degeneration in ALS has yet to be elucidated. Here, we applied comparative multi-omics analysis of human induced pluripotent stem cell-derived sMNs and ocular motor neurons to identify shared metabolic perturbations in inherited and sporadic ALS sMNs, revealing dysregulation in lipid metabolism and its related genes. Targeted metabolomics studies confirmed such findings in sMNs of 17 ALS (SOD1, C9ORF72, TDP43 (TARDBP) and sporadic) human induced pluripotent stem cell lines, identifying elevated levels of arachidonic acid. Pharmacological reduction of arachidonic acid levels was sufficient to reverse ALS-related phenotypes in both human sMNs and in vivo in Drosophila and SOD1G93A mouse models. Collectively, these findings pinpoint a catalytic step of lipid metabolism as a potential therapeutic target for ALS.

Effect of Cadherin-11 Expression on the Prognosis of a Newly Diagnosed Primary Glioblastoma.

BACKGROUND: Cadherin-11, a cell-to-cell adhesion molecule, is associated with higher tumor grade and decreased patient survival. The purpose of this study was to investigate the clinical significance of cadherin-11 expression in the progression and prognosis of a newly diagnosed primary glioblastoma (GBL). METHODS: Between 2007 and 2016, 52 out of 178 patients diagnosed with a GBL and satisfied the following criteria: 1) a new primary GBL, 2) gross-total resection, 3) immunohistochemically-available tissue, and 4) standardized adjuvant treatment. RESULTS: In terms of staining intensity, the low-intensity cadherin-11 group showed longer progression-free survival (PFS) than the high-intensity cadherin-11 group (median PFS, 12.0 months [95% CI, 11.1-12.9] vs. median PFS, 6.0 months [95% CI, 3.7-8.3]; p<0.001). The low-intensity cadherin-11 group revealed longer overall survival (OS) than the high-intensity cadherin-11 group (median OS, 20.0 months [95% CI, 11.8-16.6] vs. median OS, 15.0 months [95% CI, 11.8-18.2]; p=0.003). The staining intensity of cadherin-11 was a statistically significant factor in PFS and OS in terms of univariate and multivariate analyses (univariate analysis: p<0.001 and p=0.005; multivariate analysis: p<0.001 and p=0.005). CONCLUSION: Our clinical study demonstrates high cadherin-11 expression may be associated with poor PFS and OS for a newly diagnosed primary GBL.

Wetting Behavior of a Surface with Dual-Scale Structures.

Theoretical and numerical studies were conducted to investigate the transitional interpillar spacing for dual-scale structures, where wetting transition between the Wenzel and Cassie-Baxter states occurs in the primary and secondary pillars. A theoretical formula was derived for the transitional interpillar spacing based on the continuum picture of water. Molecular dynamics (MD) simulations were carried out by varying the interpillar spacing for the primary pillars for single- and dual-scale structures with various pillar heights. The results obtained from the theoretical formula agreed reasonably well with the results obtained from MD simulations, especially when the primary pillar height was relatively high. The transitional interpillar spacing increases as the pillar height and the number of secondary pillars increase. The effect of the secondary pillars on the transitional interpillar spacing was also evaluated using the difference in the grand potentials between the Wenzel and Cassie-Baxter states. These results show that the dual-scale structures increase the transitional interpillar spacing with an increase in the surface hydrophobicity.

Transversus abdominis plane block for lumboperitoneal shunt surgery in idiopathic normal pressure hydrocephalus: a case report.

The transversus abdominis plane (TAP) block is an ideal pain control method used in surgeries that require abdominal wall incisions through the injection of an anesthetic solution into the plane between the internal oblique muscle and transversus abdominis muscle. Herein, we report an 83-year-old man who was diagnosed with idiopathic normal pressure hydrocephalus (iNPH) and underwent lumboperitoneal shunt surgery (LPS). The TAP block was performed before LPS, and the numerical rating scale for pain was 0 at day 1 after the surgery. The patient was discharged early at day 3 after surgery despite the patient being extremely old, as he reported quick relief from the postoperative abdominal pain. The TAP block can hence be considered for use before LPS in elderly patients with iNPH.

Neuromyelitis Optica Spectrum Disorders Mimicking Multiple Brain Tumors.

We report a rare case of neuromyelitis optica spectrum disorders (NMOSD), mimicking multiple brain tumors. A 53-year-old woman presented with weakness and paresthesia in her right arm and leg. Upon admission, brain MRI showed about 10 multiple brain tumors, which had to be differentiated from multiple brain metastases, lymphoma, and high-grade glioma in both hemispheres. No primary cancer was found in the chest-abdomen-pelvis CT. Subsequent spine MRI revealed multifocal cord signal change involving C2-T7, suggesting myelitis. A decrease in visual acuity was noted when taking a medical history, and optic neuritis was diagnosed upon ophthalmologic examination. With clinical and radiological appearances, multiple brain and spinal cord lesions have been diagnosed as NMOSD. Steroid and immunosuppressive drugs were administered. We should consider the possibility of an autoimmune disease, such as NMOSD, involving the optic nerve, spinal cord, and central nervous system when multiple hemispheric tumefactive lesions are observed.

Arrested Pneumatization of the Sphenoid Sinus in the Skull Base.

We report 2 cases of arrested pneumatization of the sphenoid sinus, a normal variant commonly misdiagnosed as a serious condition of the skull base. A 65-year-old man visited a local clinic for regular checkups. Brain CT showed a non-expansile lesion of the soft tissue with a well-defined sclerotic margin in the clivus but without destruction or mass effect on the surrounding bony structures. Subsequent brain MRI revealed that the lesion within the clivus was a high-signal lesion on the T2-weighted image, containing a low-signal round mass seen on a high-intensity signal on the T1-weighted image without contrast enhancement. Thus, the lesion was considered to contain internal fat. A 70-year-old woman diagnosed with a tumor in the greater sphenoid bone visited our hospital. Her brain CT revealed a non-expansile lesion of mixed density and a well-demarcated lesion and internal curvilinear calcification in the left greater wing of the sphenoid bone. The margin was osteosclerotic and the adjacent bony structure was intact. Her brain MRI showed that the lesion within the greater sphenoid bone had multiple low-signal lesions within a high-signal lesion on the T2-weighted image, suggesting internal fat contents. The lesions were diagnosed as arrested pneumatization of the sphenoid sinus and no further examination or treatment was performed. Arrested pneumatization of the sphenoid sinus should be considered in the presence of non-expansile lesion with an osteosclerotic boundary and internal fat component in the skull base.