281 research outputs found

    The association between post-stroke depression, aphasia, and physical independence in stroke patients at 3-month follow-up

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    Objective: Few studies have examined the association between post-stroke depression (PSD), aphasia, and physical independence in Chinese patients. This study investigated the above association in stroke patients in China at 3-month follow-up. Methods: Altogether 270 patients within 14 days after ischemic stroke were recruited and followed up at 3 months. PSD, aphasia, and physical functional status were measured using the Stroke Aphasia Depression Questionnaire (SADQ), Western Aphasia Battery (WAB), and modified Rankin Scale (mRS), respectively. Patients with mRS total score \u3e2 were considered as having “physical dependence.” Results: Out of 248 patients at 3-month follow up, 119 (48%) were rated as having physical dependence. Multiple logistic regression analyses revealed that female (p = 0.04; OR = 2.2; 95% CI: 1.0–5.1), more severe stroke at admission (p \u3c 0.01; OR = 1.4; 95% CI: 1.3–1.5), and more severe PSD at 3 months (p = 0.01; OR = 1.05; 95% CI: 1.01–1.1) were independently associated with physical dependence at 3 months. Conclusions: Greater PSD and stroke severity were independently associated with physical dependence at 3months after stroke. Aphasia was also associated with physical dependence but the relationship was not significant. Early and effective depression screening, treatment and stroke rehabilitation appear to be important to improve the physical outcome and reduce the burden of stroke survivors

    Molecular landscape of IDH-mutant primary astrocytoma Grade IV/glioblastomas

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    WHO 2016 classified glioblastomas into IDH-mutant and IDH-wildtype with the former having a better prognosis but there was no study on IDH-mutant primary glioblastomas only, as previous series included secondary glioblastomas. We recruited a series of 67 IDH-mutant primary glioblastomas/astrocytoma IV without a prior low-grade astrocytoma and examined them using DNA-methylation profiling, targeted sequencing, RNA sequencing and TERT promoter sequencing, and correlated the molecular findings with clinical parameters. The median OS of 39.4 months of 64 cases and PFS of 25.9 months of 57 cases were better than the survival data of IDH-wildtype glioblastomas and IDH-mutant secondary glioblastomas retrieved from datasets. The molecular features often seen in glioblastomas, such as EGFR amplification, combined +7/-10, and TERT promoter mutations were only observed in 6/53 (11.3%), 4/53 (7.5%), and 2/67 (3.0%) cases, respectively, and gene fusions were found only in two cases. The main mechanism for telomere maintenance appeared to be alternative lengthening of telomeres as ATRX mutation was found in 34/53 (64.2%) cases. In t-SNE analyses of DNA-methylation profiles, with an exceptional of one case, a majority of our cases clustered to IDH-mutant high-grade astrocytoma subclass (40/53; 75.5%) and the rest to IDH-mutant astrocytoma subclass (12/53; 22.6%). The latter was also enriched with G-CIMP high cases (12/12; 100%). G-CIMP-high status and MGMT promoter methylation were independent good prognosticators for OS (p = 0.022 and p = 0.002, respectively) and TP53 mutation was an independent poor prognosticator (p = 0.013) when correlated with other clinical parameters. Homozygous deletion of CDKN2A/B was not correlated with OS (p = 0.197) and PFS (p = 0.278). PDGFRA amplification or mutation was found in 16/59 (27.1%) of cases and was correlated with G-CIMP-low status (p = 0.010). Aside from the three well-known pathways of pathogenesis in glioblastomas, chromatin modifying and mismatch repair pathways were common aberrations (88.7% and 20.8%, respectively), the former due to high frequency of ATRX involvement. We conclude that IDH-mutant primary glioblastomas have better prognosis than secondary glioblastomas and have major molecular differences from other commoner glioblastomas. G-CIMP subgroups, MGMT promoter methylation, and TP53 mutation are useful prognostic adjuncts

    CatNorth: An Improved Gaia DR3 Quasar Candidate Catalog with Pan-STARRS1 and CatWISE

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    A complete and pure sample of quasars with accurate redshifts is crucial for quasar studies and cosmology. In this paper, we present CatNorth, an improved Gaia DR3 quasar candidate catalog with more than 1.5 million sources in the 3π\pi sky built with data from Gaia, Pan-STARRS1, and CatWISE2020. The XGBoost algorithm is used to reclassify the original Gaia DR3 quasar candidates as stars, galaxies, and quasars. To construct training/validation datasets for the classification, we carefully built two different master stellar samples in addition to the spectroscopic galaxy and quasar samples. An ensemble classification model is obtained by averaging two XGBoost classifiers trained with different master stellar samples. Using a probability threshold of pQSO_mean>0.95p_{\mathrm{QSO\_mean}}>0.95 in our ensemble classification model and an additional cut on the logarithmic probability density of zero proper motion, we retrieved 1,545,514 reliable quasar candidates from the parent Gaia DR3 quasar candidate catalog. We provide photometric redshifts for all candidates with an ensemble regression model. For a subset of 89,100 candidates, accurate spectroscopic redshifts are estimated with the Convolutional Neural Network from the Gaia BP/RP spectra. The CatNorth catalog has a high purity of > 90% while maintaining high completeness, which is an ideal sample to understand the quasar population and its statistical properties. The CatNorth catalog is used as the main source of input catalog for the LAMOST phase III quasar survey, which is expected to build a highly complete sample of bright quasars with i<19.5i < 19.5.Comment: 24 pages, 13 figures, submitted to AAS journals. Table 4 (The CatNorth quasar candidate catalog) is available at https://nadc.china-vo.org/res/r101313

    (NZ)CH...O Contacts assist crystallization of a ParB-like nuclease

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    BACKGROUND: The major bottleneck for determination of 3 D structures of proteins using X-rays is the production of diffraction quality crystals. Often proteins are subjected to chemical modification to improve the chances of crystallization RESULTS: Here, we report the successful crystallization of a nuclease employing a reductive methylation protocol. The key to crystallization was the successful introduction of 44 new cohesive (NZ) CH...O contacts (3.2 – 3.7 Å) by the addition of 2 methyl groups to the side chain amine nitrogen (NZ) of 9 lysine residues of the nuclease. The new contacts dramatically altered the crystallization properties of the protein, resulting in crystals that diffracted to 1.2 Å resolution. Analytical ultracentrifugation analysis and thermodynamics results revealed a more compact protein structure with better solvent exclusion of buried Trp residues in the folded state of the methylated protein, assisting crystallization. CONCLUSION: In this study, introduction of novel cohesive (NZ)CH...O contacts by reductive methylation resulted in the crystallization of a protein that had previously resisted crystallization in spite of extensive purification and crystallization space screening. Introduction of (NZ)CH...O contacts could provide a solution to crystallization problems for a broad range of protein targets

    Large-Scale Fabrication of Boron Nitride Nanotubes via a Facile Chemical Vapor Reaction Route and Their Cathodoluminescence Properties

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    Cylinder- and bamboo-shaped boron nitride nanotubes (BNNTs) have been synthesized in large scale via a facile chemical vapor reaction route using ammonia borane as a precursor. The structure and chemical composition of the as-synthesized BNNTs are extensively characterized by X-ray diffraction, scanning electron microscopy, high-resolution transmission electron microscopy, and selected-area electron diffraction. The cylinder-shaped BNNTs have an average diameter of about 100 nm and length of hundreds of microns, while the bamboo-shaped BNNTs are 100–500 nm in diameter with length up to tens of microns. The formation mechanism of the BNNTs has been explored on the basis of our experimental observations and a growth model has been proposed accordingly. Ultraviolet–visible and cathodoluminescence spectroscopic analyses are performed on the BNNTs. Strong ultraviolet emissions are detected on both morphologies of BNNTs. The band gap of the BNNTs are around 5.82 eV and nearly unaffected by tube morphology. There exist two intermediate bands in the band gap of BNNTs, which could be distinguishably assigned to structural defects and chemical impurities

    Prediction of Deleterious Non-Synonymous SNPs Based on Protein Interaction Network and Hybrid Properties

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    Non-synonymous SNPs (nsSNPs), also known as Single Amino acid Polymorphisms (SAPs) account for the majority of human inherited diseases. It is important to distinguish the deleterious SAPs from neutral ones. Most traditional computational methods to classify SAPs are based on sequential or structural features. However, these features cannot fully explain the association between a SAP and the observed pathophysiological phenotype. We believe the better rationale for deleterious SAP prediction should be: If a SAP lies in the protein with important functions and it can change the protein sequence and structure severely, it is more likely related to disease. So we established a method to predict deleterious SAPs based on both protein interaction network and traditional hybrid properties. Each SAP is represented by 472 features that include sequential features, structural features and network features. Maximum Relevance Minimum Redundancy (mRMR) method and Incremental Feature Selection (IFS) were applied to obtain the optimal feature set and the prediction model was Nearest Neighbor Algorithm (NNA). In jackknife cross-validation, 83.27% of SAPs were correctly predicted when the optimized 263 features were used. The optimized predictor with 263 features was also tested in an independent dataset and the accuracy was still 80.00%. In contrast, SIFT, a widely used predictor of deleterious SAPs based on sequential features, has a prediction accuracy of 71.05% on the same dataset. In our study, network features were found to be most important for accurate prediction and can significantly improve the prediction performance. Our results suggest that the protein interaction context could provide important clues to help better illustrate SAP's functional association. This research will facilitate the post genome-wide association studies

    The Association Between Post-stroke Depression, Aphasia, and Physical Independence in Stroke Patients at 3-Month Follow-Up

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    Objective: Few studies have examined the association between post-stroke depression (PSD), aphasia, and physical independence in Chinese patients. This study investigated the above association in stroke patients in China at 3-month follow-up.Methods: Altogether 270 patients within 14 days after ischemic stroke were recruited and followed up at 3 months. PSD, aphasia, and physical functional status were measured using the Stroke Aphasia Depression Questionnaire (SADQ), Western Aphasia Battery (WAB), and modified Rankin Scale (mRS), respectively. Patients with mRS total score &gt;2 were considered as having “physical dependence.”Results: Out of 248 patients at 3-month follow up, 119 (48%) were rated as having physical dependence. Multiple logistic regression analyses revealed that female (p = 0.04; OR = 2.2; 95% CI: 1.0–5.1), more severe stroke at admission (p &lt; 0.01; OR = 1.4; 95% CI: 1.3–1.5), and more severe PSD at 3 months (p = 0.01; OR = 1.05; 95% CI: 1.01–1.1) were independently associated with physical dependence at 3 months.Conclusions: Greater PSD and stroke severity were independently associated with physical dependence at 3 months after stroke. Aphasia was also associated with physical dependence but the relationship was not significant. Early and effective depression screening, treatment and stroke rehabilitation appear to be important to improve the physical outcome and reduce the burden of stroke survivors

    Mechanically activated catalyst mixing for high-yield boron nitride nanotube growth

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    Boron nitride nanotubes (BNNTs) have many fascinating properties and a wide range of applications. An improved ball milling method has been developed for high-yield BNNT synthesis, in which metal nitrate, such as Fe(NO(3))(3), and amorphous boron powder are milled together to prepare a more effective precursor. The heating of the precursor in nitrogen-containing gas produces a high density of BNNTs with controlled structures. The chemical bonding and structure of the synthesized BNNTs are precisely probed by near-edge X-ray absorption fine structure spectroscopy. The higher efficiency of the precursor containing milling-activated catalyst is revealed by thermogravimetric analyses. Detailed X-ray diffraction and X-ray photoelectron spectroscopy investigations disclose that during ball milling the Fe(NO(3))(3) decomposes to Fe which greatly accelerates the nitriding reaction and therefore increases the yield of BNNTs. This improved synthesis method brings the large-scale production and application of BNNTs one step closer

    Heterodimers of photoreceptor-specific nuclear receptor (PNR/NR2E3) and peroxisome proliferator-activated receptor (PPARγ) are disrupted by retinal disease-associated mutations

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    Photoreceptor-specific nuclear receptor (PNR/NR2E3) and Tailless homolog (TLX/NR2E1) are human orthologs of the NR2E group, a subgroup of phylogenetically related members of the Nuclear Receptor (NR) superfamily of transcription factors. We assessed the ability of these NRs to form heterodimers with other members of the human NRs representing all major subgroups. The TLX ligand binding domain (LBD) did not appear to form homodimers or interact directly with any other NR tested. The PNR LBD was able to form homodimers, but also exhibited robust interactions with the LBDs of PPARγ/NR1C3 and TRβ/NR1A2. The binding of PNR to PPARγ was specific for this paralog, as no interaction was observed with the LBDs of PPARαNR1C1 or PPARδNR1C2. In support of these findings, PPARγ and PNR were found to be co-expressed in human retinal tissue extracts and could be co-immunoprecipitated as a native complex. Selected sequence variants in the PNR LBD associated with human retinopathies, or a mutation in the dimerization region of PPARγ LBD associated with familial partial lipodystrophy type 3, were found to disrupt PNR/PPARγ complex formation. Wild type PNR, but not a PNR309G mutant, was able to repress PPARγ-mediated transcription in reporter assays. In summary our results reveal novel heterodimer interactions in the NR superfamily, suggesting previously unknown functional interactions of PNR with PPARγ and TRβ that have potential importance in retinal development and disease
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