Emerging Therapies for Glioblastoma.

Glioblastoma is most commonly a primary brain tumor and the utmost malignant one, with a survival rate of approximately 12-18 months. Glioblastoma is highly heterogeneous, demonstrating that different types of cells from the same tumor can manifest distinct gene expression patterns and biological behaviors. Conventional therapies such as temozolomide, radiation, and surgery have limitations. As of now, there is no cure for glioblastoma. Alternative treatment methods to eradicate glioblastoma are discussed in this review, including targeted therapies to PI3K, NFKß, JAK-STAT, CK2, WNT, NOTCH, Hedgehog, and TGFß pathways. The highly novel application of oncolytic viruses and nanomaterials in combating glioblastoma are also discussed. Despite scores of clinical trials for glioblastoma, the prognosis remains poor. Progress in breaching the blood-brain barrier with nanomaterials and novel avenues for targeted and combination treatments hold promise for the future development of efficacious glioblastoma therapies.

Downregulation of SERINC5 expression in buffy coats of HIV-1-infected patients with detectable or undetectable viral load.

Among the host restriction factors against HIV, SERINC5 has been described in vitro, but the mRNA level of SERINC5 in vivo has been little studied. We compare SERINC5 expression in subjects with HIV-1 (highly active antiretroviral treatment (HAART) and HAART-naïve) with and without suppression of viral load. A cross-sectional study was performed with 107 individuals distributed as follows: 24 with HAART-naïve and detectable viral load (> 50 copies/mL), 13 with HAART and detectable viral load (> 50 copies/mL), 50 with HAART and undetectable viral load (≤ 50 copies/mL), and 20 without HIV-1. SERINC5 expression in buffy coats was determined using RT-qPCR. The viral load was determined using real-time PCR and the amount of CD4 + and CD8 + T-lymphocytes was measured using flow cytometry. The data were normalized with the Shapiro-Wilk test and the Kruskal-Wallis test was subsequently performed. The relative expression was compared with a T-test and the remaining data with the Mann-Whitney U-test. ANCOVA multiple linear regression analysis was performed between characteristics of patients with SERINC5 expression. The mean and SD of the SERINC5 expression in the three groups with HIV-1 was 0.9 ± 0.2 and without HIV-1 was 1.7 ± 0.14 (P < 0.001). Multiple linear regression did not show the participation of CD4 +, CD8 + , viral load, infection time, or treatment time. No differences in the SERINC5 expression were found among the studied groups of patients with HIV-1. When comparing the groups with and without HIV-1 infection, SERINC5 was downregulation in the HIV-1 groups.

Archean continental crust formed by magma hybridization and voluminous partial melting.

Archean (4.0-2.5 Ga) tonalite-trondhjemite-granodiorite (TTG) terranes represent fragments of Earth's first continents that formed via high-grade metamorphism and partial melting of hydrated basaltic crust. While a range of geodynamic regimes can explain the production of TTG magmas, the processes by which they separated from their source and acquired distinctive geochemical signatures remain uncertain. This limits our understanding of how the continental crust internally differentiates, which in turn controls its potential for long-term stabilization as cratonic nuclei. Here, we show via petrological modeling that hydrous Archean mafic crust metamorphosed in a non-plate tectonic regime produces individual pulses of magma with major-, minor-, and trace-element signatures resembling-but not always matching-natural Archean TTGs. Critically, magma hybridization due to co-mingling and accumulation of multiple melt fractions during ascent through the overlying crust eliminates geochemical discrepancies identified when assuming that TTGs formed via crystallization of discrete melt pulses. We posit that much Archean continental crust is made of hybrid magmas that represent up to ~ 40 vol% of partial melts produced along thermal gradients of 50-100 °C/kbar, characteristic of overthickened mafic Archean crust at the head of a mantle plume, crustal overturns, or lithospheric peels.

Evaluating lubricant performance to reduce COVID-19 PPE-related skin injury.

BACKGROUND: Healthcare workers around the world are experiencing skin injury due to the extended use of personal protective equipment (PPE) during the COVID-19 pandemic. These injuries are the result of high shear stresses acting on the skin, caused by friction with the PPE. This study aims to provide a practical lubricating solution for frontline medical staff working a 4+ hours shift wearing PPE. METHODS: A literature review into skin friction and skin lubrication was conducted to identify products and substances that can reduce friction. We evaluated the lubricating performance of commercially available products in vivo using a custom-built tribometer. FINDINGS: Most lubricants provide a strong initial friction reduction, but only few products provide lubrication that lasts for four hours. The response of skin to friction is a complex interplay between the lubricating properties and durability of the film deposited on the surface and the response of skin to the lubricating substance, which include epidermal absorption, occlusion, and water retention. INTERPRETATION: Talcum powder, a petrolatum-lanolin mixture, and a coconut oil-cocoa butter-beeswax mixture showed excellent long-lasting low friction. Moisturising the skin results in excessive friction, and the use of products that are aimed at 'moisturising without leaving a non-greasy feel' should be prevented. Most investigated dressings also demonstrate excellent performance.

Digital rock physics and laboratory considerations on a high-porosity volcanic rock.

Digital rock physics combines microtomographic imaging with advanced numerical simulations of effective material properties. It is used to complement laboratory investigations with the aim to gain a deeper understanding of relevant physical processes related to transport and effective mechanical properties. We apply digital rock physics to reticulite, a natural mineral with a strong analogy to synthetic open-cell foams. We consider reticulite an end-member for high-porosity materials with a high stiffness and brittleness. For this specific material, hydro-mechanical experiments are very difficult to perform. Reticulite is a pyroclastic rock formed during intense Hawaiian fountaining events. The honeycombed network of bubbles is supported by glassy threads and forms a structure with a porosity of more than 80%. Comparing experimental with numerical results and theoretical estimates, we demonstrate the high potential of in situ characterization with respect to the investigation of effective material properties. We show that a digital rock physics workflow, so far applied to conventional rocks, yields reasonable results for high-porosity rocks and can be adopted for fabricated foam-like materials with similar properties. Numerically determined porosities, effective elastic properties, thermal conductivities and permeabilities of reticulite show a fair agreement to experimental results that required exeptionally high experimental efforts.

Catastrophic shear-removal of subcontinental lithospheric mantle beneath the Colorado Plateau by the subducted Farallon slab.

The causes of Cenozoic uplift of the Colorado Plateau, southwestern USA, are strongly debated, though most hypotheses acknowledge the importance of northwest-directed subduction of the Farallon oceanic plate beneath North America since c. 100 Ma. Existing thermomechanical models suggest that the Farallon slab underthrust the proto-plateau region at ~200 km depth, removing the basal portions of its subcontinental lithospheric mantle (SCLM) root, although such small-volume subduction erosion cannot fully account for the degree of uplift observed today. Here we show via petrological modeling of lawsonite-bearing eclogite xenoliths exposed in diatremes in the center of the plateau that the Farallon slab surface penetrated through the proto-plateau SCLM at much shallower depths (~120 km) than these previous estimates, allowing shear-removal of ~80 km of SCLM - a volume up to three-times greater than previously suggested. This removal led to asthenospheric upwelling and isostatic rebound of the plateau region during the late Cretaceous to the Eocene. We posit that similar shear-removal of SCLM likely played a major role in inhibiting cratonic growth and stabilization in the Neoarchean and Paleoproterozoic - when low-angle subduction of oceanic lithosphere was more prevalent than today - accounting for the atypically thin roots existing below many ancient cratons worldwide.

Tactile sensor-based real-time clustering for tissue differentiation.

PURPOSE: Reliable intraoperative delineation of tumor from healthy brain tissue is essentially based on the neurosurgeon's visual aspect and tactile impression of the considered tissue, which is-due to inherent low brain consistency contrast-a challenging task. Development of an intelligent artificial intraoperative tactile perception will be a relevant task to improve the safety during surgery, especially when-as for neuroendoscopy-tactile perception will be damped or-as for surgical robotic applications-will not be a priori existent. Here, we present the enhancements and the evaluation of a tactile sensor based on the use of a piezoelectric tactile sensor. METHODS: A robotic-driven piezoelectric bimorph sensor was excited using multisine to obtain the frequency response function of the contact between the sensor and fresh ex vivo porcine tissue probes. Based on load-depth, relaxation and creep response tests, viscoelastic parameters E1 and E2 for the elastic moduli and η for the viscosity coefficient have been obtained allowing tissue classification. Data analysis was performed by a multivariate cluster algorithm. RESULTS: Cluster algorithm assigned five clusters for the assignment of white matter, basal ganglia and thalamus probes. Basal ganglia and white matter have been assigned to a common cluster, revealing a less discriminatory power for these tissue types, whereas thalamus was exclusively delineated; gray matter could even be separated in subclusters. CONCLUSIONS: Bimorph-based, multisine-excited tactile sensors reveal a high sensitivity in ex vivo tissue-type differentiation. Although, the sensor principle has to be further evaluated, these data are promising.

Visualization of Bubble Formation in Porous Media.

We present a visualization approach for the analysis of CO2 bubble-induced attenuation in porous rock formations. As a basis for this, we introduce customized techniques to extract CO2 bubbles and their surrounding porous structure from X-ray computed tomography data (XCT) measurements. To understand how the structure of porous media influences the occurrence and the shape of formed bubbles, we automatically classify and relate them in terms of morphology and geometric features, and further directly support searching for promising porous structures. To allow for the meaningful direct visual comparison of bubbles and their structures, we propose a customized registration technique considering the bubble shape as well as its points of contact with the porous media surface. With our quantitative extraction of geometric bubble features, we further support the analysis as well as the creation of a physical model. We demonstrate that our approach was successfully used to answer several research questions in the domain, and discuss its high practical relevance to identify critical seismic characteristics of fluid-saturated rock that govern its capability to store CO2.

Piezoelectric self-sensing system for tactile intraoperative brain tumor delineation in neurosurgery.

Mechanical characteristics of tumor and healthy tissue in the brain differ but slightly. The task of designing a system that is able to differentiate tissue dignity with high sensitivity is of great importance in neurosurgery. Even when localization of tumor by use of preoperative imaging techniques provides the surgeon with valuable information to decide where and what to resect, the brain shift due to change in pressure during skull opening demands the surgeon to define the limits of the tumor using tactile and visual differentiation. This paper contains a general description of the tactile sensor system based on a piezoelectric bimorph. The main parts of the measurement system are described and the selection of the electrical parameters for tactile differentiation is justified. Results are discussed for a series of measurements at different concentrations in gelatin phantoms.