Better efficacy in differentiating WHO grade II from III oligodendrogliomas with machine-learning than radiologist's reading from conventional T1 contrast-enhanced and fluid attenuated inversion recovery images.

BACKGROUND: The medical imaging to differentiate World Health Organization (WHO) grade II (ODG2) from III (ODG3) oligodendrogliomas still remains a challenge. We investigated whether combination of machine leaning with radiomics from conventional T1 contrast-enhanced (T1 CE) and fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) offered superior efficacy. METHODS: Thirty-six patients with histologically confirmed ODGs underwent T1 CE and 33 of them underwent FLAIR MR examination before any intervention from January 2015 to July 2017 were retrospectively recruited in the current study. The volume of interest (VOI) covering the whole tumor enhancement were manually drawn on the T1 CE and FLAIR slice by slice using ITK-SNAP and a total of 1072 features were extracted from the VOI using 3-D slicer software. Random forest (RF) algorithm was applied to differentiate ODG2 from ODG3 and the efficacy was tested with 5-fold cross validation. The diagnostic efficacy of radiomics-based machine learning and radiologist's assessment were also compared. RESULTS: Nineteen ODG2 and 17 ODG3 were included in this study and ODG3 tended to present with prominent necrosis and nodular/ring-like enhancement (P < 0.05). The AUC, ACC, sensitivity, and specificity of radiomics were 0.798, 0.735, 0.672, 0.789 for T1 CE, 0.774, 0.689, 0.700, 0.683 for FLAIR, as well as 0.861, 0.781, 0.778, 0.783 for the combination, respectively. The AUCs of radiologists 1, 2 and 3 were 0.700, 0.687, and 0.714, respectively. The efficacy of machine learning based on radiomics was superior to the radiologists' assessment. CONCLUSIONS: Machine-learning based on radiomics of T1 CE and FLAIR offered superior efficacy to that of radiologists in differentiating ODG2 from ODG3.

A DAAM1 3'-UTR SNP mutation regulates breast cancer metastasis through affecting miR-208a-5p-DAAM1-RhoA axis.

BACKGROUND: Dishevelled-associated activator of morphogenesis 1 (DAAM1) is a member of microfilament-related formins and mediates cell motility in breast cancer (BrCa). However, the genetic mutation status of DAAM1 mRNA and its correlation with pathological characteristics are still unclearly. Methods: A patient cohort and BrCa cells were recruited to demonstrate the role of functional SNP in microRNA-208a-5p binding site of DAAM1 3'-UTR and underlying mechanism in BrCa metastasis. METHODS: A patient cohort and BrCa cells were recruited to demonstrate the role of functional SNP in microRNA-208a-5p binding site of DAAM1 3'-UTR and underlying mechanism in BrCa metastasis. RESULTS: The expression and activation of DAAM1 increased markedly in lymphnode metastatic tissues. A genetic variant (rs79036859 A/G) was validated in the miR-208a-5p binding site of DAAM1 3'-UTR. The G genotype (AG/GG) was a risk genotype for the metastasis of BrCa by reducing binding affinity of miR-208a-5p for the DAAM1 3'-UTR. Furthermore, the miR-208a-5p expression level was significantly suppressed in lymphnode metastatic tissues compared with that in non-lymphnode metastatic tissues. Overexpression of miR-208a-5p inhibited DAAM1/RhoA signaling pathway, thereby leading to the decrease of the migratory ability. CONCLUSION: Overall, the rs79036859 G variant of DAAM1 3'-UTR was identified as a relevant role in BrCa metastasis via the diversity of miR-208a-5p binding affinity.

Prevalence of and factors affecting malocclusion in primary dentition among children in Xi'an, China.

BACKGROUND: This study aimed to investigate the prevalence and associated factors of malocclusion among children with primary dentition in Xi'an, China. METHODS: A total of 2,974 subjects were selected from local schools in Xi'an city using a stratified cluster sampling method from January to September 2015. After screening samples according to the inclusion criteria, the final sample size comprised 2,235 pre-school children, with a mean age of 4.82 (SD, 1.76; range, 2.63-6.12) years. Malocclusion traits were assessed by trained clinicians followed by the evaluation of associated factors through clinical examination and a precisely designed questionnaire including data regarding gender, birth place, parental education level, monthly familial income, parental attitude toward the problem of malocclusion, feeding methods of the children, feeding postures, pacifier use, and delivery methods. Data were analyzed using the Chi-square test and logistic regression analysis. RESULTS: The most common type of malocclusion was increased overjet (34.99 %) in the sagittal direction, deep overbite (37.58 %), and midline deviation (25.32 %) in the vertical and transverse directions, respectively. The prevalence of posterior crossbite, anterior crossbite, and anterior open bite was 7.56, 6.80 and 6.98 %, respectively. The prevalence of the anterior edge-to-edge occlusion was the lowest (2.46 %). The variables associated with malocclusion (P < 0.05) were birth place (odds ratio [OR] = 1.741 with 95 % CI of 1.384-2.162), insufficient abrasion of primary canines (OR = 1.465; 95 % CI of 1.153-1.894), caries in primary teeth (OR = 2.045; 95 % CI of 1.665-2.539), tongue thrusting (OR = 2.833; 95 % CI of 1.640-3.649), mandibular prognathism (OR = 2.621; 95 % CI of 1.574-3.689), and finger sucking (OR = 1.573 with 95 % CI of 1.098-2.014). The feeding methods (OR = 3.614 with 95 % CI of 3.087-4.596) along with the method of delivery (OR = 1.847 with 95 % CI of 1.323-2.451) have been observed to play an important role in the morbidity of malocclusion (P < 0.05). CONCLUSIONS: The prevalence of malocclusion among pre-school children in Xi'an is higher compared to that in other geographical parts of China. Therefore, early attention to the development of occlusion and necessary interventions toward the associated factors are important to reduce its prevalence and further adverse effects.

Direct time-resolved observation of surface-bound carbon dioxide radical anions on metallic nanocatalysts.

Time-resolved identification of surface-bound intermediates on metallic nanocatalysts is imperative to develop an accurate understanding of the elementary steps of CO2 reduction. Direct observation on initial electron transfer to CO2 to form surface-bound CO2•- radicals is lacking due to the technical challenges. Here, we use picosecond pulse radiolysis to generate CO2•- via aqueous electron attachment and observe the stabilization processes toward well-defined nanoscale metallic sites. The time-resolved method combined with molecular simulations identifies surface-bound intermediates with characteristic transient absorption bands and distinct kinetics from nanosecond to the second timescale for three typical metallic nanocatalysts: Cu, Au, and Ni. The interfacial interactions are further investigated by varying the important factors, such as catalyst size and the presence of cation in the electrolyte. This work highlights fundamental ultrafast spectroscopy to clarify the critical initial step in the CO2 catalytic reduction mechanism.

CKIP-1 contributes to osteogenic differentiation of mouse bone marrow mesenchymal stem cells.

Background: Osteogenesis greatly depends on the differentiation of bone marrow mesenchymal stem cells (BMSCs). CKIP-1 is considered to be a negative regulator of BMSCs. Methods: We established a CKIP-1 knockout mouse model, then isolated and cultured BMSCs from wild-type and knockout groups. Results: Our data demonstrated that CKIP-1 knockout significantly increased bone structure in the experimental mouse model and enhanced BMSC proliferation. CKIP-1 knockout contributed to osteoblastic and adipogenic differentiation. Furthermore, CKIP-1 regulated osteogenesis in BMSCs via the MAPK signaling pathway, and BMSCs from the CKIP-1 knockout mice were effective in repairing the skull defect null mice. Conclusion: Our results concluded that silencing of CKIP-1 promoted osteogenesis in experimental mice and increased BMSCs differentiation via upregulation of the MAPK signaling pathway.

Establishing a Prognostic Signature Based on Epithelial-Mesenchymal Transition-Related Genes for Endometrial Cancer Patients.

Backgrounds: Epithelial-mesenchymal transition (EMT) is a sequential process where tumor cells develop from the epithelial state to the mesenchymal state. EMT contributes to various tumor functions including initiation, propagating potential, and resistance to therapy, thus affecting the survival time of patients. The aim of this research is to set up an EMT-related prognostic signature for endometrial cancer (EC). Methods: EMT-related gene (ERG) expression and clinical data were acquired from The Cancer Genome Atlas (TCGA). The entire set was randomly divided into two sets, one for contributing the risk model (risk score) and the other for validating. Univariate and multivariate Cox proportional hazards regression analyses were applied to the training set to select the prognostic ERGs. The expression of 10 ERGs was confirmed by qRT-PCR in clinical samples. Then, we developed a nomogram predicting 1-/3-/5-year survival possibility combining the risk score and clinical factors. The entire set was stratified into the high- and low-risk groups, which was used to analyze the immune infiltrating, tumorigenesis pathways, and response to drugs. Results: A total of 220 genes were screened out from 1,316 ERGs for their differential expression in tumor versus normal. Next, 10 genes were found to be associated with overall survival (OS) in EC, and the expression was validated by qRT-PCR using clinical samples, so we constructed a 10-ERG-based risk score to distinguish high-/low-risk patients and a nomogram to predict survival rate. The calibration plots proved the predictive value of our model. Gene Set Enrichment Analysis (GSEA) discovered that in the low-risk group, immune-related pathways were enriched; in the high-risk group, tumorigenesis pathways were enriched. The low-risk group showed more immune activities, higher tumor mutational burden (TMB), and higher CTAL4/PD1 expression, which was in line with a better response to immune checkpoint inhibitors. Nevertheless, response to chemotherapeutic drugs turned out better in the high-risk group. The high-risk group had higher N6-methyladenosine (m6A) RNA expression, microsatellite instability level, and stemness indices. Conclusion: We constructed the ERG-related signature model to predict the prognosis of EC patients. What is more, it might offer a reference for predicting individualized response to immune checkpoint inhibitors and chemotherapeutic drugs.

Increased resting state functional irregularity of T2DM brains with high HbA1c: sign for impaired verbal memory function?

Glycosylated hemoglobin A1c (HbA1c) has been considered as a key contributor to impaired cognition in type 2 diabetes mellitus (T2DM) brains. However, how does it affect the brain and whether the glucose controlling can slow down the process are still unknown. In the current study, T2DM patients with high glycosylated hemoglobin level (HGL) and controls with normal glycosylated hemoglobin level (NGL) were enrolled to investigate the relationships between HbA1c, brain imaging characteristics and cognitive function. First, a series of cognitive tests including California Verbal Learning Test (CVLT) were conducted. Then, the functional irregularity based on resting state functional magnetic resonance imaging data was evaluated via a new data-driven brain entropy (BEN) mapping analysis method. We found that the HGLs exhibited significantly increased BEN in the right precentral gyrus (PreCG.R), the right middle frontal gyrus (MFG.R), the triangular and opercular parts of the right inferior frontal gyrus (IFGtriang.R and IFGoperc.R). The strengths of the functional connections of PreCG.R with the brainstem/cerebellum were decreased. Partial correlation analysis showed that HbA1c had a strong positive correlation to regional BEN and negatively correlated with some CVLT scores. Negative correlations also existed between the BEN of PreCG.R/IFGoperc.R and some CVLT scores, suggesting the correspondence between higher HbA1c, increased BEN and decreased verbal memory function. This study demonstrated the potential of BEN in exploring the functional alterations affected by HbA1c and interpreting the verbal memory function decline. It will help understanding the neurophysiological mechanism of T2DM-induced cognitive decline and taking effective prevention or treatment measures.

Spinal CCL2 Promotes Pain Sensitization by Rapid Enhancement of NMDA-Induced Currents Through the ERK-GluN2B Pathway in Mouse Lamina II Neurons.

Previous studies have shown that CCL2 (C-C motif chemokine ligand 2) induces chronic pain, but the exact mechanisms are still unknown. Here, we established models to explore the potential mechanisms. Behavioral experiments revealed that an antagonist of extracellular signal-regulated kinase (ERK) inhibited not only CCL2-induced inflammatory pain, but also pain responses induced by complete Freund's adjuvant. We posed the question of the intracellular signaling cascade involved. Subsequent experiments showed that CCL2 up-regulated the expression of phosphorylated ERK (pERK) and N-methyl D-aspartate receptor [NMDAR] subtype 2B (GluN2B); meanwhile, antagonists of CCR2 and ERK effectively reversed these phenomena. Whole-cell patch-clamp recordings revealed that CCL2 enhanced the NMDAR-induced currents via activating the pERK pathway, which was blocked by antagonists of GluN2B and ERK. In summary, we demonstrate that CCL2 directly interacts with CCR2 to enhance NMDAR-induced currents, eventually leading to inflammatory pain mainly through the CCL2-CCR2-pERK-GluN2B pathway.

Fabrication of piezoelectric porous BaTiO3 scaffold to repair large segmental bone defect in sheep.

Porous titanium scaffolds can provide sufficient mechanical support and bone growth space for large segmental bone defect repair. However, they fail to restore the physiological environment of bone tissue. Barium titanate (BaTiO3) is considered a smart material that can produce an electric field in response to dynamic force. Low-intensity pulsed ultrasound stimulation (LIPUS), as a kind of micromechanical wave, can not only promote bone repair but also induce BaTiO3 to generate an electric field. In our studies, BaTiO3 was coated on porous Ti6Al4V and LIPUS was externally applied to observe the influence of the piezoelectric effect on the repair of large bone defects in vitro and in vivo. The results show that the piezoelectric effect can effectively promote the osteogenic differentiation of bone marrow stromal cells (BMSCs) in vitro as well as bone formation and growth into implants in vivo. This study provides an optional alternative to the conventional porous Ti6Al4V scaffold with enhanced osteogenesis and osseointegration for the repair of large bone defects.

Bivariate optimization of orthodontic mini-implant thread height and pitch.

PURPOSE: Mini-implants have been used as anchorage for years, but failure is common in clinical practice. Mini-implant design is a critical factor affecting its stability. The aim of this study was to evaluate the effect of continuous and simultaneous variations of thread height and pitch on the biomechanical properties of an orthodontic mini-implant. METHOD: A 3D finite element model, composed of a posterior maxilla section and an orthodontic mini-implant, was created. Mini-implant thread height ranged from 0.10 to 0.40 mm, and thread pitch ranged from 0.50 to 2.00 mm. Effects of the implant thread height and pitch on the maximum Von Mises stresses in maxilla and mini-implant, as well as maximum displacements in the mini-implant, were evaluated by a finite element method. Bivariate analysis was used to determine the optimal range of thread height and pitch. RESULTS: Variation of thread height and pitch decreased the maximum Von Mises stresses in cortical bone, cancellous bone and mini-implant by 54.9, 78.4 and 23.6 %, respectively. The maximum displacement in the mini-implant decreased by 21.8 %. CONCLUSION: Maxillary stress and mini-implant stability were influenced by mini-implant thread height and pitch. Increased thread height with a thread pitch of 1.20 mm was better for orthodontic mini-implant in the maxillary posterior region. Thread height played a more significant role than the thread pitch in reducing maxillary stress and enhancing orthodontic mini-implant stability.

Bone mesenchymal stem cell functions on the hierarchical micro/nanotopographies of the Ti-6Al-7Nb alloy.

We investigated the response of rat bone mesenchymal stem cells (BMSC) placed on the titanium-6aluminium-7niobiuim (Ti-6Al-7Nb) alloy modified by hydrofluoric acid etch combined with subsequent anodic oxidation. Pure titanium (Ti) discs and Ti-6Al-7Nb discs were treated by hydrofluoric acid etch and anodic oxidation, and polished pure Ti discs and Ti-6Al-7Nb discs without surface modification served as controls (n=35 in each group). Scanning electron microscopy, atomic force microscopy, and radiographic photoelectron spectroscopy assays were used to detect the properties of the samples' surface. The morphology, adhesion, proliferation, and alkaline phosphatase activity of BMSC were examined using various techniques of microscopic and biological characterisation. The results showed that both Ti-6Al-7Nb samples and the pure Ti samples showed hierarchical micro/nanotopographies, and fluorine emerged on the surfaces of the samples after modification. The hierarchical micro/nanotopographies significantly increased the spreading, adhesion, and proliferation of BMSC and activity of alkaline phosphatase. In addition, modified samples of Ti-6Al-7Nb showed significantly higher alkaline phosphatase activity than modified pure Ti samples (p<0.05). The experiment successfully confirmed that Ti-6Al-7Nb alloy with hierarchical micro/nanotopographies treated by hydrofluoric acid etch and anodic oxidation possessed good biocompatibility, and may be a promising candidate for dental implants.