Initial CT-based radiomics nomogram for predicting in-hospital mortality in patients with traumatic brain injury: a multicenter development and validation study.

OBJECTIVE: To develop and validate a radiomic prediction model using initial noncontrast computed tomography (CT) at admission to predict in-hospital mortality in patients with traumatic brain injury (TBI). METHODS: A total of 379 TBI patients from three cohorts were categorized into training, internal validation, and external validation sets. After filtering the unstable features with the minimum redundancy maximum relevance approach, the CT-based radiomics signature was selected by using the least absolute shrinkage and selection operator (LASSO) approach. A personalized predictive nomogram incorporating the radiomic signature and clinical features was developed using a multivariate logistic model to predict in-hospital mortality in patients with TBI. The calibration, discrimination, and clinical usefulness of the radiomics signature and nomogram were evaluated. RESULTS: The radiomic signature consisting of 12 features had areas under the curve (AUCs) of 0.734, 0.716, and 0.706 in the prediction of in-hospital mortality in the internal and two external validation cohorts. The personalized predictive nomogram integrating the radiomic and clinical features demonstrated significant calibration and discrimination with AUCs of 0.843, 0.811, and 0.834 in the internal and two external validation cohorts. Based on decision curve analysis (DCA), both the radiomic features and nomogram were found to be clinically significant and useful. CONCLUSION: This predictive nomogram incorporating the CT-based radiomic signature and clinical features had maximum accuracy and played an optimized role in the early prediction of in-hospital mortality. The results of this study provide vital insights for the early warning of death in TBI patients.

GNG5 is an unfavourable independent prognostic indicator of gliomas.

Gliomas are the most common primary brain tumours, and glioblastomas (GBMs) are subgrouped into four distinct molecular subtypes. This study aimed to identify the potential gene related to glioma progression. Weighted gene co-expression network analysis (WGCNA) was used to explore the related gene. Correlation, ROC, survival and Cox regression analyses were performed. Blue module was strongly associated with WHO grade (r = .65, P = 1e-19). GNG5 in gliomas was overexpressed compared with normal samples and associated with clinicopathologic characteristics. GNG5 was frequent in Mesenchymal subtype and lowly expressed in Proneural subtype of GBMs. Survival and Cox regression analyses showed that glioma patients with GNG5 overexpression had shorter survival time, and GNG5 was an independent prognostic indicator of overall survival. Overall, GNG5 expression is closely associated with clinicopathologic characteristics and is an independent prognostic indicator for glioma patients, as well as a promising subtype-associated biomarker in molecular classification of gliomas.

The length and width of diatoms in drowning cases as the evidence of diatoms penetrating the alveoli-capillary barrier.

Forensic diatom test has been considered as a significant tool for diagnosis of drowning. Most of the studies in this field discussed the methodology of extracting, enriching and detecting diatoms from different tissues and drowning media. There are few studies on the basic principle of diatom test which was based on the theory developed by forensic scientists many years ago. This study was designed to analyze the length and width of diatoms in different organs and drowning medium samples of drowning cases. This study is designed to find evidence of diatoms penetrating the alveoli-capillary barrier. Samples from 100 drowning cases were analyzed using the methodology we developed: the Microwave Digestion-Vacuum Filtration-Automated Scanning Electron Microscopy method (MD-VF-Auto SEM method). The results showed that the length and width of diatoms in the liver and kidney tissues are smaller than that of the lung tissues and water samples. Our studies also found that the pennate diatoms are easier to penetrate through the alveoli-capillary barrier, travel in the blood stream and finally deposit in the distant tissues including liver and kidney. These findings provided evidences to support the process of diatoms penetrating the alveoli-capillary barrier.

Unique Phase Diagram and Superconductivity of Calcium Hydrides at High Pressures.

Structure prediction studies on Ca-H binary systems under high pressures were carried out, and the structures of calcium hydrides in earlier works were reproduced. The previously unreported composition of CaH9 was found to be stable and experienced the phase transition series Cm → P21/ m → C2/ m from 100 to 400 GPa. To the best of our knowledge, CaH9 may be the only alkaline earth hydride with an odd H content. At 400 GPa, the metastable R3̅ m-CaH10 phase shares the same space group with the R3̅ m-SrH10 phase with puckered honeycomb H layers. The C2/ m phase of CaH9 and the R3̅ m phase of CaH10 are excellent superconductors with Tc values of about 240-266 and 157-175 K at 300 and 400 GPa, respectively. The high contributions of H-derived states at the Fermi level play an important role in the superconductivity of calcium hydrides.

High-Pressure Formation of Cobalt Polyhydrides: A First-Principle Study.

The high-pressure phase diagram, crystal structures, and electronic properties of cobalt hydrides are systematically investigated in the pressure range of 1 atm to 300 GPa by first-principle calculations. Except for the experimentally found CoH, two new cobalt polyhydrides CoH2 and CoH3 are discovered at 10 and 30 GPa, respectively. The crystal structure of CoH2 is determined to have cubic symmetry with the space group Fm3̅m and then transforms into the I4/mmm phase above 42 GPa. In addition, CoH3 with Pm3̅m is stable between 30 and 300 GPa, which can be used as a potential hydrogen storage material with a high volumetric hydrogen density of 425 g H2/L. All the cobalt polyhydrides exhibit metallic and ionic characteristics at high pressure. Furthermore, application of the Allen-Dynes-modified McMillan equation estimated no superconductivity for cobalt polyhydrides.

Stable structures and superconductivity of an At-H system at high pressure.

The phase diagram, electronic properties and superconductivity of an At-H system at high pressure are investigated through first principles calculation considering the effect of spin-orbit coupling (SOC). The Cmcm-AtH2, Pnma-AtH2, P6/mmm-AtH4, and Cmmm-AtH4 phases are uncovered above 50 GPa. Metallization is realized at 50 GPa for AtH2 and 60 GPa for AtH4, with Tc values of approximately 5-10 K and 30-50 K, respectively. In P6/mmm-AtH4, phonon softening induced by Fermi surface nesting occurs as the pressure increases, which is closely related to the structural phase transition of P6/mmm → Cmmm and plays a crucial role in the superconductivity of the P6/mmm phase. In addition, the spin-orbit coupling effect considerably influences the energy of ground states, pressure points of phase transitions, electronic structures, and even the electron-phonon coupling of the At-H system. Such an influence may also occur in other heavy atomic hydrides.

Betulinic acid induces apoptosis and ultrastructural changes in MDA-MB-231 breast cancer cells.

The aim of this study is to investigate the effects of betulinic acid (BA) on triple-negative breast cancer MDA-MB-231 cells and observe the ultrastructural changes. The concentration of BA required to induce apoptosis in MDA-MB-231 cells has been previously reported. In this study, a cell counting kit-8 proliferation assay was used to measure cell viability and the apoptosis rate. Western blotting was performed to observe the protein expression levels of Bcl-2. Cell morphology and changes in cell density were observed by microscopy. Electron microscopy revealed pyknotic nuclei as well as vacuoles. Collectively, our results showed the morphological mechanisms by which BA impairs the ultrastructure of MDA-MB-231 cells.

Large animal models of traumatic brain injury.

Purpose/Aim: Animal models of traumatic brain injury (TBI) provide powerful tools to study TBI in a controlled, rigorous and cost-efficient manner. The mostly used animals in TBI studies so far are rodents. However, compared with rodents, large animals (e.g. swine, rabbit, sheep, ferret, etc.) show great advantages in modeling TBI due to the similarity of their brains to human brain. The aim of our review was to summarize the development and progress of common large animal TBI models in past 30 years. MATERIALS AND METHODS: Mixed published articles and books associated with large animal models of TBI were researched and summarized. RESULTS: We majorly sumed up current common large animal models of TBI, including discussion on the available research methodologies in previous studies, several potential therapies in large animal trials of TBI as well as advantages and disadvantages of these models. CONCLUSIONS: Large animal models of TBI play crucial role in determining the underlying mechanisms and screening putative therapeutic targets of TBI.

Pressure-Stabilized Superconductive Ionic Tantalum Hydrides.

High-pressure structures of tantalum hydrides were investigated over a wide pressure range of 0-300 GPa by utilizing evolutionary structure searches. TaH and TaH2 were found to be thermodynamically stable over this entire pressure range, whereas TaH3, TaH4, and TaH6 become thermodynamically stable at pressures greater than 50 GPa. The dense Pnma (TaH2), R3̅m (TaH4), and Fdd2 (TaH6) compounds possess metallic character with a strong ionic feature. For the highly hydrogen-rich phase of Fdd2 (TaH6), a calculation of electron-phonon coupling reveals the potential high-Tc superconductivity with an estimated value of 124.2-135.8 K.

Prediction of superconducting ternary hydride MgGeH6: from divergent high-pressure formation routes.

Invigorated by the high temperature superconductivity in some binary hydrogen-dominated compounds, we systematically explored high-pressure phase diagrams and superconductivity of a ternary Mg-Ge-H system using ab initio methods. Stoichiometric MgGeH6 with high hydrogen content exhibiting Pm3[combining macron] symmetry was predicted from a series of high-pressure synthesis paths. We performed an in-depth study on three distinct formation routes to MgGeH6, i.e., Mg + Ge + 3H2 → MgGeH6, MgGe + 3H2 → MgGeH6 and MgH2 + GeH4 → MgGeH6 at high pressures. By directly squeezing three elemental solids Mg + Ge + 3H2, we obtained ternary MgGeH6 at 200 GPa. By adding a little bit of the MgGe alloy into hydrogen, we found that MgGeH6 can form and stabilize at about 200 GPa. More intriguingly, upon compressing MgH2 and GeH4 to 250 GPa, we also predicted the same MgGeH6. Electron structure calculations reveal that the cubic MgGeH6 is a good metal and takes on ionic character. Electron-phonon coupling calculation reveals a large λ = 1.16 for MgGeH6 at 200 GPa. In particular, we found that ternary MgGeH6 could be a potential high temperature superconductor with a superconducting transition temperature Tc of ∼67 K at 200 GPa.

Stability and properties of the Ru-H system at high pressure.

We report on a first-principles study of the phase diagram, structures and properties of the Ru-H system in the H-rich regime over a wide range of pressures. The results show that RuH is thermodynamically stable and can coexist with RuH3 and RuH6 under pressure. RuH and RuH3 stoichiometries exhibit metallic character as a result of notable band structures, while RuH6 is a semiconductor. Strikingly, some hydrogen atoms pairwise couple into H2 units in the RuH6 compound. An estimation of superconducting transition temperature Tc is carried out by applying the Allen-Dynes modified McMillan equation for Fm3[combining macron]m (RuH), Pm3[combining macron]m (RuH3), and Pm3[combining macron]n (RuH3) structures and the resulting Tc reaches 0.41, 3.57 and 1.25 K at different pressures, respectively.

Sodium butyrate-induced apoptosis and ultrastructural changes in MCF-7 breast cancer cells.

This study investigated the effects of sodium butyrate (NaB) on Michigan Cancer Foundation-7 (MCF-7) breast cancer cells and analyzed the relevant mechanism. Here, we demonstrated that a certain concentration of NaB effectively induced MCF-7 cell apoptosis. Cell counting kit-8 (CCK-8) assay was used to detect cell viability and the apoptosis rate. Western blotting was used to detect changes in the Bcl-2 expression level. We observed cell shape changes with microscopy. Immunofluorescence revealed some apoptotic nuclei. Electron microscopy revealed thick nucleoli, chromatin margination, reduced mitochondria, and dramatic vacuoles. Collectively, our findings elucidated the morphological mechanism by which NaB changed the ultrastructure of MCF-7 cells.

Pressure-Induced Structures and Properties in Indium Hydrides.

The structures, electron properties, and potential superconductivity of indium hydrides are systematically studied under high pressure by first-principles density functional calculations. Upon compression, two stable stoichiometries (InH3 and InH5) are predicted to be thermodynamically stable. Particularly, in the two compounds, all hydrogen atoms exist in the form of H2 or H3 units. The stable phases present metallic features with the overlap between the conduction and the valence bands. The Bader analysis indicates that charges transfer from In atoms to H atoms. Electron-phonon calculations show that the estimated transition temperatures (Tc) of InH3 and InH5 are 34.1-40.5 and 22.4-27.1 K at 200 and 150 GPa, respectively.

Enhancement of T(c) in the atomic phase of iodine-doped hydrogen at high pressures.

The high-pressure structures and superconductivity of iodine-doped hydrogen have been studied by ab initio calculations. Above 100 GPa, we discover a stable phase with Pnma symmetry in the H2I stoichiometry that consists of a monatomic iodine tube trapping hydrogen molecular units. Interestingly, H2 molecular units dissociate and form a novel atomic phase with R3̄m symmetry at 246 GPa. Further electron-phonon coupling calculations predict the critical temperature of superconductivity T(c) to be 3.8 K for the Pnma phase and 33 K for the R3̄m phase at 240 GPa. Significantly, the T(c) of the R3̄m phase is enhanced approximately 8 times that of the Pnma phase, which is mainly attributed to the reason that H2 molecules are broken exhibiting an atomic character in the R3̄m phase.

Inhibition of human glioma U251 cells growth in vitro and in vivo by hydroxyapatite nanoparticle-assisted delivery of short hairpin RNAs against SATB1.

Special AT-rich sequence-binding protein-1 (SATB1) has been reported to be over-expressed in many human tumors and knockdown of SATB1 can inhibit tumor growth. The present study was designed to determine the role of SATB1 in the growth of human glioma U251 cells using the plasmid-based SATB1 short hairpin RNA (shRNA) delivered by hydroxyapatite nanoparticles in vitro and in vivo. The in vitro growth, invasion and angiogenesis assays of human glioma U251 cells were done. U251 cells tumor blocks were transplanted into the nude mice. CaCl2-modified hydroxyapatite nanoparticles carrying shRNA-SATB1 plasmids were injected into the tumors. The apoptosis of the tumor U251 cells was examined with TUNEL assay and flow cytometer (FCM). The tumor growth and immunohistochemistry were measured. The expression level of SATB1 mRNA was investigated by RT-PCR. The expression levels of SATB1, Cyclin D1, MMP-2, VEGF, Bax and Caspase-9 protein were determined by western blot analysis. The results showed that hydroxyapatite nanoparticles-delivered shRNA-SATB1 could significantly inhibit the growth, invasion and angiogenesis of U251 cells in vitro and the growth of U251 cells in vivo. FCM results showed that Nano HAP-shRNA-SATB1-induced apoptosis (up to 67.8 %). SATB1 expression was strongly down-regulated in the tumor U251 cells. Cyclin D1, MMP-2 and VEGF were also down-regulated in the tumor tissues that also displayed significant increased in Bax expression and Caspase-9 activity. These results show that Nano HAP-shRNA-SATB1 can inhibit the growth of human glioma U251 cells in vitro and in vivo, and hydroxyapatite nanoparticles can be used for the in vitro and in vivo delivery of plasmid-based shRNAs into U251 cells.

Where are we in the modelling of traumatic brain injury? Models complicated by secondary brain insults.

BACKGROUND: Traumatic brain injury (TBI) contributes to a substantial number of deaths and cases of disability. Despite well-established experimental models and years of carefully conducted research, a clinical therapeutic breakthrough in TBI has lagged. This may be due, in part, to the discrepancies between commonly used experimental models and clinical scenarios. METHOD: Secondary insults, such as hypotension and hypoxemia, have been well demonstrated as powerful determinants of outcomes from TBI. Despite the frequency of secondary insults in patients with TBI, they are rarely incorporated into most existing models of TBI. This review focuses on the combined injury models, especially coupled with systemic secondary insults, and aims to provide a new view to guiding future research endeavors in this field. RESULTS: A growing number of experimental models of TBI complicated by certain secondary insult have been gradually introduced and characterized. Correspondingly, the pathophysiological changes following combined injuries and the interactive effects of primary injury with secondary insults can be studied more in-depth. CONCLUSION: A more complete understanding of the interactions between the injured brain and secondary insults represents a potentially fruitful avenue that may increase the likelihood of developing effective therapies. Experimental models of TBI should not only attempt to model the focal or diffuse changes resulting from external forces, but also integrate, when appropriate, secondary insults reminiscent of human situations.

Ternary superconducting hydrides stabilized via Th and Ce elements at mild pressures.

The discovery of covalent H3S and clathrate structure LaH10 with excellent superconducting critical temperatures at high pressures has facilitated a multitude of research on compressed hydrides. However, their superconducting pressures are too high (generally above 150 GPa), thereby hindering their application. In addition, making room-temperature superconductivity close to ambient pressure in hydrogen-based superconductors is challenging. In this work, we calculated the chemically "pre-compressed" Be-H by heavy metals Th and Ce to stabilize the superconducting phase near ambient pressure. An unprecedented ThBeH8 (CeBeH8) with a "fluorite-type" structure was predicted to be thermodynamically stable above 69 GPa (76 GPa), yielding a T c of 113 K (28 K) decompressed to 7 GPa (13 GPa) by solving the anisotropic Migdal-Eliashberg equations. Be-H vibrations play a vital role in electron-phonon coupling and structural stability of these ternary hydrides. Our results will guide further experiments toward synthesizing ternary hydride superconductors at mild pressures.

Design and Optimization of NR-Based Stretchable Conductive Composites Filled with MoSi2 Nanoparticles and MWCNTs: Perspectives from Experimental Characterization and Molecular Dynamics Simulations.

Stretchable conductive composites play a pivotal role in the development of personalized electronic devices, electronic skins, and artificial implant devices. This article explores the fabrication and characterization of stretchable composites based on natural rubber (NR) filled with molybdenum disilicide (MoSi2) nanoparticles and multi-walled carbon nanotubes (MWCNTs). Experimental characterization and molecular dynamics (MD) simulations are employed to investigate the static and dynamic properties of the composites, including morphology, glass transition temperature (Tg), electrical conductivity, and mechanical behavior. Results show that the addition of MoSi2 nanoparticles enhances the dispersion of MWCNTs within the NR matrix, optimizing the formation of a conductive network. Dynamic mechanical analysis (DMA) confirms the Tg reduction with the addition of MWCNTs and the influence of MoSi2 content on Tg. Mechanical testing reveals that the tensile strength increases with MoSi2 content, with an optimal ratio of 4:1 MoSi2:MWCNTs. Electrical conductivity measurements demonstrate that the MoSi2/MWCNTs/NR composites exhibit enhanced conductivity, reaching optimal values at specific filler ratios. MD simulations further support experimental findings, highlighting the role of MoSi2 in improving dispersion and mechanical properties. Overall, the study elucidates the synergistic effects of nanoparticles and nanotubes in enhancing the properties of stretchable conductive composites.

Predictive value of the SLC22A18 protein expression in glioblastoma patients receiving temozolomide therapy.

BACKGROUND: Our previous study showed that SLC22A18 downregulation and promoter methylation were associated with the development and progression of glioma and the elevated expression of SLC22A18 was found to increase the sensitivity of glioma U251 cells to the anticancer drug 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). In this study, we investigated the predictive value of SLC22A18 promoter methylation and protein expression in glioblastoma multiforme (GBM) patients receiving temozolomide (TMZ) therapy. PATIENTS AND METHODS: SLC22A18 promoter methylation and protein expression were examined by methylation-specific polymerase chain reaction (MSP) and Western blotting respectively, then we compared SLC22A18 promoter methylation and protein expression in tumor cell explants in regard to prediction of TMZ response and survival time of 86 GBM patients. RESULTS: SLC22A18 promoter methylation was detected in 61 of 86 (71%) samples, whereas 36 of 86 (42%) cases were scored positive for SLC22A18 protein expression. Overall SLC22A18 promoter methylation was significantly related to SLC22A18 protein expression, but a subgroup of cases did not follow this association. Multivariate Cox regression analysis indicated that SLC22A18 protein expression, but not promoter methylation, was significantly correlated with TMZ therapy. SLC22A18 protein expression predicted a significantly shorter overall survival in 51 patients receiving TMZ therapy, whereas no differences in overall survival were observed in 35 patients without TMZ therapy. CONCLUSIONS: These results show that lack of SLC22A18 protein expression is superior to promoter methylation as a predictive tumor biomarker in GBM patients receiving temozolomide therapy.

Foot-and-mouth disease virus carrier status in Bos grunniens yaks.

BACKGROUND: The carrier status of foot-and-mouth disease virus (FMDV) is complicated, and the role of carrier animals in virus transmission is controversial. To investigate the carrier status of FMDV in animals that live in high altitude, Bos grunniens yaks were infected experimentally with FMDV O/Akesu/58. RESULTS: All of the yaks showed clinical signs of foot-and-mouth disease (FMD). Total antibody levels against FMDV measured by liquid-phase blocking enzyme-linked immunosorbent assay (LPB-ELISA) and antibody levels against nonstructural proteins (NSP) showed dynamic changes. Three of the five yaks were indentified as carrier animals by RT-PCR method, and the OP fluids from carrier yaks can cause cytopathic effect (CPE) on BHK-21 cells. At last, five persistent infection strains were isolated. Nucleotide mutations of VP1 gene were analyzed. CONCLUSIONS: After infected with FMDV, all of the yaks showed typical clinical signs. Yaks can keep carrier status for at least 8 months. Total antibody levels against FMDV measured by LPB-ELISA and antibody levels against NSP were at high level for carrier yaks. Sequence alignment of the five isolated strains showed obvious gene and protein mutations.