bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive evaluation of physicochemical properties and antioxidant activity of B. subtilis‐fermented polished adlay subjected to different drying methods
Authors: Wen Anyan , Qin Likang , Zeng Haiying , Zhu Yi 
Published: March 2020

AbstractThe physicochemical properties and antioxidant activity of B. subtilis‐fermented polished adlay (BPA) subjected to different drying methods (hot‐air drying, HAD; infrared‐radiation drying, IRD; vacuum drying, VD; microwave‐vacuum drying, MVD; and freeze‐vacuum drying, FVD) were evaluated in this study. Results showed FVD was ideal for maintaining the natural appearance and higher contents of proximate compositions, free fatty acids, tetramethylpyrazine (6.91 mg/g DW), coixol (0.62 mg/g DW), coixenolide (4.21% DW), coixan (35.10% DW), and triterpenoids (17.41 mg/g DW). The higher contents of total phenolics and flavonoids, stronger antioxidant activity, and higher color differences were observed in HAD and IRD samples. MVD displayed the shorter drying time, higher γ‐aminobutyric acid content, and higher retention ratios of tetramethylpyrazine (75.54%), coixol (87.10%), coixenolide (98.57%), and coixan (99.11%). Pearson's correlation coefficient exhibited that the positive correlation between the contents of phenolics and flavonoids and the antioxidant activities of all dried BPA samples was observed (R2 > 0.881, p < .05). Principal component analysis showed that the top three categories of comprehensive quality were FVD‐, MVD‐, and VD‐treated BPA samples. In conclusion, MVD should be a potential preservation method to obtain high‐quality dried BPA for short drying time and high comprehensive quality.
Variant WWTR1 gene fusions in epithelioid hemangioendothelioma—A genetic subset associated with cardiac involvement
Authors: Suurmeijer Albert J. H. , Dickson Brendan C. , Swanson David , Sung Yun S. , Zhang Lei , Antonescu Cristina R. 
Published: March 2020

AbstractThe genetic hallmark of epithelioid hemangioendothelioma (EHE) is a recurrent WWTR1‐CAMTA1 fusion, which is present in most cases bearing a conventional histology. A subset of cases is characterized by a distinct morphology and harbors instead of YAP1‐TFE3 fusion. Nevertheless, isolated cases lack these canonical fusions and remain difficult to classify. Triggered by an index case of a left atrial mass in a 76‐year‐old female with morphologic features typical of EHE, but which showed a WWTR1‐MAML2 fusion by targeted RNA sequencing, we searched our files for similar cases displaying alternative WWTR1 fusions. A total of 6 EHE cases were identified with variant WWTR1 fusions, four of them presenting within the heart. There were three females and three males, with a wide age range at diagnosis (21‐76 years, mean 62, median 69). The four cardiac cases occurred in older adults (mean age of 72, equal gender distribution); three involved the left atrium and one the right ventricle. One case presented in the vertebral bone and one in pelvic soft tissue. Microscopically, all tumors had morphologic features within the spectrum of classic EHE; two of the cases appeared overtly malignant. All cases were tested by FISH and four were investigated by targeted RNA sequencing. Two tumors harbored WWTR1‐MAML2 fusions, one WWTR1‐ACTL6A, and in three cases, no WWTR1 partner was identified. Of the four patients with follow‐up, two died of disease, one was alive with lung metastases, and the only patient free of disease was s/p resection of a T11 vertebral mass. Our findings report on additional genetic variants involving WWTR1 rearrangements, with WWTR1‐MAML2 being a recurrent event, in a small subset of EHE, which appears to have predilection for the heart.
Glutamate transporter 1‐expressing glia in the rat substantia nigra—Morphometric analysis and relationships to synapses
Authors: Kessler Jean‐Pierre , Salin Pascal , Kerkerian‐Le Goff Lydia 
Published: March 2020

AbstractGlial cells have a major role in protecting neurons against various forms of stress. Especially, astrocytes mediate the bulk of glutamate clearance in the brain via specific membrane transporters (GLAST and GLT1), thereby preventing the occurrence of excitotoxic events. Although glutamate‐mediated mechanisms are thought to contribute to nigral dopaminergic neuron degeneration in Parkinson's disease, detailed information on the organization of glia in the substantia nigra is still lacking. The present study was performed to provide quantitative information on the organization of astroglia and on the relationships between astrocytes and excitatory synapses in the rat substantia nigra. Using immunolabeling of GLT1 and confocal imaging, we found that the substantia nigra was filled with a dense meshwork of immunoreactive astrocyte processes. Stereological analysis performed on electron microscope images revealed that the density of immunoreactive astrocyte plasma membranes was substantial, close to 1 μm2/μm3, in the substantia nigra neuropil, both in the pars compacta and the pars reticulata. Excitatory synapses had on average two thirds of their perimeters free from glia, a disposition that may favor transmitter spillover. The density of glutamatergic synapses, as quantified on confocal images by the simultaneous detection of bassoon and of vesicular glutamate transporter 1 or 2, was very low (0.01 and 0.025 per μm3 in the reticulata and compacta subdivisions, respectively). Thus the ratio of GLT1‐expressing glial membrane surface to glutamatergic synapses was very high (40–100 μm2), suggesting an efficient regulation of extracellular glutamate concentrations.
Hepatitis B Virus–Telomerase Reverse Transcriptase Promoter Integration Harnesses Host ELF4, Resulting in Telomerase Reverse Transcriptase Gene Transcription in Hepatocellular Carcinoma
Authors: Sze Karen Man‐Fong , Ho Daniel Wai‐Hung , Chiu Yung‐Tuen , Tsui Yu‐Man , Chan Lo‐Kong , Lee Joyce Man‐Fong , Chok Kenneth Siu‐Ho , Chan Albert Chi‐Yan , Tang Chung‐Ngai , Tang Victor Wai‐Lun , Lo Irene Lai‐Oi , Yau Derek Tsz‐Wai , Cheung Tan‐To , Ng Irene Oi‐Lin 
Published: March 2020

Background and Aims
Hepatitis B virus (HBV) integrations are common in hepatocellular carcinoma (HCC). In particular, alterations of the telomerase reverse transcriptase (TERT) gene by HBV integrations are frequent; however, the molecular mechanism and functional consequence underlying TERT HBV integration are unclear.

Approach and Results
We adopted a targeted sequencing strategy to survey HBV integrations in human HBV‐associated HCCs (n = 95). HBV integration at the TERT promoter was frequent (35.8%, n = 34/95) in HCC tumors and was associated with increased TERT mRNA expression and more aggressive tumor behavior. To investigate the functional importance of various integrated HBV components, we employed different luciferase reporter constructs and found that HBV enhancer I (EnhI) was the key viral component leading to TERT activation on integration at the TERT promoter. In addition, the orientation of the HBV integration at the TERT promoter further modulated the degree of TERT transcription activation in HCC cell lines and patients’ HCCs. Furthermore, we performed array‐based small interfering RNA library functional screening to interrogate the potential major transcription factors that physically interacted with HBV and investigated the cis‐activation of host TERT gene transcription on viral integration. We identified a molecular mechanism of TERT activation through the E74 like ETS transcription factor 4 (ELF4), which normally could drive HBV gene transcription. ELF4 bound to the chimeric HBV EnhI at the TERT promoter, resulting in telomerase activation. Stable knockdown of ELF4 significantly reduced the TERT expression and sphere‐forming ability in HCC cells.

Conclusions
Our results reveal a cis‐activating mechanism harnessing host ELF4 and HBV integrated at the TERT promoter and uncover how TERT HBV‐integrated HCCs may achieve TERT activation in hepatocarcinogenesis.
Travel times for snowmelt‐dominated headwater catchments: Influences of wetlands and forest harvesting, and linkages to stream water quality
Authors: Leach Jason A. , Buttle James M. , Webster Kara L. , Hazlett Paul W. , Jeffries Dean S. 
Published: March 2020

AbstractThe time it takes water to travel through a catchment, from when it enters as rain and snow to when it leaves as streamflow, may influence stream water quality and catchment sensitivity to environmental change. Most studies that estimate travel times do so for only a few, often rain‐dominated, catchments in a region and use relatively short data records (<10 years). A better understanding of how catchment travel times vary across a landscape may help diagnose inter‐catchment differences in water quality and response to environmental change. We used comprehensive and long‐term observations from the Turkey Lakes Watershed Study in central Ontario to estimate water travel times for 12 snowmelt‐dominated headwater catchments, three of which were impacted by forest harvesting. Chloride, a commonly used water tracer, was measured in streams, rain, snowfall and as dry atmospheric deposition over a 31 year period. These data were used with a lumped convolution integral approach to estimate mean water travel times. We explored relationships between travel times and catchment characteristics such as catchment area, slope angle, flowpath length, runoff ratio and wetland coverage, as well as the impact of harvesting. Travel time estimates were then used to compare differences in stream water quality between catchments. Our results show that mean travel times can be variable for small geographic areas and are related to catchment characteristics, in particular flowpath length and wetland cover. In addition, forest harvesting appeared to decrease mean travel times. Estimated mean travel times had complex relationships with water quality patterns. Results suggest that biogeochemical processes, particularly those present in wetlands, may have a greater influence on water quality than catchment travel times.
Circulating levels of C1q/TNF‐α‐related protein 6 (CTRP6) in polycystic ovary syndrome
Authors: Sadeghi Asie , Fadaei Reza , Moradi Nariman , Fouani Fatima Z. , Roozbehkia Maryam , Zandieh Zahra , Ansaripour Soheila , Vatannejad Akram , Doustimotlagh Amir H. 
Published: March 2020

AbstractPolycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting females of reproductive age. It has been associated with cardiometabolic disorders including diabetes mellitus and cardiovascular disorders, and increases the risk of developing fecundity pathologies including recurrent pregnancy loss (RPL) and infertility. C1q/tumor necrosis factor‐α‐related protein‐6 (CTRP6) is a novel adipokine involved in glucose and lipid metabolism, host inflammation, and organogenesis. In the present study, we aimed to determine the association of serum CTRP6 levels with some components of metabolic syndrome in PCOS patients (infertile PCOS [inf‐PCOS] and PCOS‐RPL). This case–control study included 120 PCOS patients (60 inf‐PCOS and 60 PCOS‐RPL) and 60 healthy controls. Serum high‐sensitivity C‐reactive protein (hs‐CRP) and homocysteine were measured using commercial kits, while adiponectin and CTRP6 levels were assessed using ELISA technique. Inf‐PCOS and PCOS‐RPL individuals had higher levels of serum CTRP6 than controls (546.15 ± 125.02 ng/ml and 534.04 ± 144.19 ng/ml vs. 440.16 ± 159.24 ng/ml; both p < .001). Moreover, serum adiponectin levels were significantly reduced, while fasting insulin, homeostasis model assessment of insulin resistance, free testosterone, and hs‐CRP levels were significantly elevated in PCOS group, when compared with controls. Furthermore, serum CTRP6 positively associated with body mass index in all subjects. It showed an inverse correlation with adiponectin in PCOS group and subgroups. However, it had a direct association with hs‐CRP in PCOS group and inf‐PCOS subgroup, but not PCOS‐RPL subgroup. These findings unravel a probable role of CTRP6 in PCOS pathogenesis, which poses a possibility to be a good diagnostic target. However, further investigation is needed.
Exosome‐based targeted RNA delivery for immune tolerance induction in skin transplantation
Authors: Li Chunmin , Guo Fengjie , Wang Xueli , Liu Dongxu , Wu Bolun , Wang Fenghua , Chen Wen 
Published: March 2020

AbstractExosomes have been widely applied to the delivery of RNA and small molecules currently. However, the low targeting and specificity greatly limited the effect of exosome delivery. Here we designed an exosome that can perform the targeted delivery of two different types of RNA. Based on the mesenchymal stem cells (MSCs) derived exosomes, the RNA delivery system of targeted dendritic cells (DC‐Exosome) was constructed, using the layer by layer self‐assembly. DC‐Exosomes can specifically bind to DCs, while guiding the endocytosis of chimeras and exosome. Then aptamer/siRNA chimera was cut into mTOR siRNA by Dicer, and microRNA was released from exosome under lysosomal digestion. SIGN aptamer performed the rapid induction of immune tolerance, and later mTOR siRNA was formed to inhibit mTOR pathway and suppress immune responses. Exosomes could maintain long time‐stability after PEG‐PEI polyplexes modification and promote HLA‐G expression in DCs continuously. Animal experiments showed that DC‐Exosomes could induce immune tolerance at 3, 7, and 14 days after skin transplantation. Compared with the microRNA‐Exosome group, the number of CD11c+ DCs in DC‐Exosome group decreased, while the proportion of HLA‐G+ DCs increased remarkably. In conclusion, we constructed a new exosome‐based targeted delivery system which could effectively induce the immune tolerance in transplantation.
Systems toxicology assessment revealed the impact of graphene‐based materials on cell cycle regulators
Authors: Farahani Masoumeh , Rezaei‐Tavirani Mostafa , Zali Hakimeh , Hatamie Shadie , Ghasemi Nazanin 
Published: March 2020

AbstractUnderstanding the cellular and molecular toxicity of graphene and its derivatives is essential for their biomedical applications. Herein, gene expression profile of graphene‐exposed cells was retrieved from the Gene expression omnibus database. Differentially expressed genes and their functional roles were then investigated through the pathway, protein–protein interaction (PPI) network, and module analysis. High degree (hub) and high betweenness centrality (bottleneck) nodes were subsequently identified. The functional analysis of central genes indicated that these graphene–gene interactions could be of great value for further investigation. Accordingly, we also followed the expression of five hub–bottleneck genes in graphene‐treated murine peritoneal macrophages and human breast cancer cell line by real‐time PCR. The five hub–bottleneck genes related to graphene cytotoxicity; CDK1, CCNB1, PLK1, TOP2A, and CCNA2 were identified through network analysis, which were highly correlated with regulation of cell cycle processes. The module analysis indicated the cell cycle pathway to be the predominant one. Gene expression evaluation showed downregulation of these genes in the macrophages and cancer cells treated with graphene. These results provided some new intuitions concerning the graphene–cell interactions and unveiled targeting critical cell cycle regulators. The present study indicated some toxic effects of graphene‐based materials through systems toxicology assessment. Integrating gene expression and PPI network may help explaining biological responses of graphene and lead to beneficial impacts in nanomedicine.
Mechanical and degradation properties of poly(methyl methacrylate) cement/borate bioactive glass composites
Authors: Cole Kimberly A. , Funk Grahmm A. , Rahaman Mohamed N. , McIff Terence E. 
Published: March 2020

AbstractBone cement is used extensively in orthopedics to anchor prostheses to bone and fill voids. Incorporating bioactive glass into poly(methyl methacrylate) (PMMA)‐based bone cement could potentially improve its effectiveness for these tasks. This study characterizes the mechanical and degradation properties of composites containing PMMA‐based bone cement and particles of borate bioactive glass designated as 13‐93B3. Glass particles of size 5, 33, and 100 μm were mixed with PMMA bone cement to create composites containing 20, 30, and 40 wt % glass. Composites and a bone cement control were soaked in phosphate‐buffered saline. Compressive strength, Young's modulus, weight loss, water uptake, solution pH, and ionic concentrations were measured over 21 days. The compressive strengths of composites decreased over 21 days. Average Young's moduli of the composites remained below 3 GPa. Weight loss and water uptake of specimens did not exceed 2 and 6%, respectively. Boron concentrations and pH of all solutions increased over time, with higher glass weight fractions leading to higher pH values. Results demonstrated that the composite can sustain glass degradation and ionic release without compromising short‐term mechanical strength.
Comparison of two pore sizes of LAE442 scaffolds and their effect on degradation and osseointegration behavior in the rabbit model
Authors: Augustin Julia , Feichtner Franziska , Waselau Anja‐Christina , Julmi Stefan , Klose Christian , Wriggers Peter , Maier Hans Jürgen , Meyer‐Lindenberg Andrea 
Published: March 2020

AbstractThe magnesium alloy LAE442 emerged as a possible bioresorbable bone substitute over a decade ago. In the present study, using the investment casting process, scaffolds of the Magnesium (Mg) alloy LAE442 with two different and defined pore sizes, which had on average a diameter of 400 μm (p400) and 500 μm (p500), were investigated to evaluate degradation and osseointegration in comparison to a ß‐TCP control group. Open‐pored scaffolds were implanted in both greater trochanter of rabbits. Ten scaffolds per time group (6, 12, 24, and 36 weeks) and type were analyzed by clinical, radiographic and μ‐CT examinations (2D and 3D). None of the scaffolds caused adverse reactions. LAE442 p400 and p500 developed moderate gas accumulation due to the Mg associated in vivo corrosion, which decreased from week 20 for both pore sizes. After 36 weeks, p400 and p500 showed volume decreases of 15.9 and 11.1%, respectively, with homogeneous degradation, whereas ß‐TCP lost 74.6% of its initial volume. Compared to p400, osseointegration for p500 was significantly better at week 2 postsurgery due to more frequent bone‐scaffold contacts, higher number of trabeculae and higher bone volume in the surrounding area. No further significant differences between the two pore sizes became apparent. However, p500 was close to the values of ß‐TCP in terms of bone volume and trabecular number in the scaffold environment, suggesting better osseointegration for the larger pore size.
Predictive and prognostic values of preoperative platelet parameters in patients with gynecological tumors
Authors: Yang Wei , Chen Ying‐ying , Bi Chen , Shu Kuang‐yi , Ye Man‐li , Li Fan‐fan , Chen Jie , Wang Xiao‐ou , Chen Xiao‐jian , Jiang Ming‐hua 
Published: March 2020

AbstractBackgroundPlatelets play a role in tumor cell growth, metastasis, and angiogenesis, and the present study aimed to evaluate diagnostic and prognostic values of platelet parameters in patients with gynecological tumors.MethodsA total of 1062 women were included. Differences of platelet parameters (platelet count [PLT], plateletcrit [PCT], mean platelet volume [MPV], platelet‐large cell rate [P‐LCR], and platelet distribution width [PDW]) between different categories were analyzed by nonparametric test. The optimal cutoff value was calculated with receiver operating characteristic analysis. Overall survivals were analyzed with Kaplan‐Meier method and log‐rank tests for univariate analysis.ResultsPlatelet count and PCT were significantly increased, and MPV and P‐LCR were significantly reduced in malign and benign gynecological tumor groups compared with the controls (P < .001); PDW had no significant differences. There were no significant differences in PLT, PCT, MPV, P‐LCR, and PDW between different tumor locations and pathologic types. The optimal cutoff values of PLT, PCT, MPV and P‐LCR were 274, 0.26, 10.08, and 24.8 (AUC: 0.661, 0.643, 0.593, 0.562), and PCT had preferable sensibility and specificity (50.84% and 70.42%) in predicting the presence of gynecological tumors. According to survival analysis, increased PLT (≥274 × 109/L) and PCT (≥0.26), and induced MPV (<10.08 fL) and P‐LCR (<24.8%) were associated with shorter overall survival.ConclusionsPlatelet count, PCT, MPV, and P‐LCR can be used as preferable auxiliary parameters for predicting the presence of gynecological tumors. Increased PLT and PCT, or decreased MPV and P‐LCR indicated a heavier tumor burden and shorter overall survival.
Facile green synthesis approach for the production of chromium oxide nanoparticles and their different in vitro biological activities
Authors: Iqbal Javed , Abbasi Banzeer Ahsan , Munir Akhtar , Uddin Siraj , Kanwal Sobia , Mahmood Tariq 
Published: March 2020

AbstractGreen synthesis of nanoparticles using plants has become a promising substitute for the conventional chemical synthesis methods. In the present study, our aim was to synthesize chromium oxide nanoparticles (Cr2O3NPs) through a facile, low‐cost, eco‐friendly route using leaf extract of Rhamnus virgata (RV). The formation of Cr2O3NPs was confirmed and characterized by spectroscopic profile of UV–Vis, EDX, FTIR, and XRD analyses. The UV‐visible spectroscopy has confirmed the formation of Cr2O3NPs by the change of color owing to surface plasmon resonance. The bioactive functional groups present in the leaf extract of RV involved in reduction and stabilization of Cr2O3NPs were determined by FTIR analysis. Based on XRD analysis, crystalline nature of Cr2O3NPs was determined. The morphological shape and elemental composition of Cr2O3NPs were investigated using SEM and EDX analyses, respectively. With growing applications of Cr2O3NPs in biological perspectives, Cr2O3NPs were evaluated for diverse biopotentials. Cr2O3NPs were further investigated for its cytotoxicity potentials against HepG2 and HUH‐7 cancer cell lines (IC50: 39.66 and 45.87 μg/ml), respectively. Cytotoxicity potential of Cr2O3NPs was confirmed against promastigotes (IC50: 33.24 μg/ml) and amastigotes (IC50: 44.31 μg/ml) using Leishmania tropica (KMH23). The Cr2O3NPs were further evaluated for antioxidants, biostatic, alpha‐amylase, and protein kinase inhibition properties. Biocompatibility assay was investigated against human macrophages which confirmed the nontoxic nature of Cr2O3NPs. Overall, the synthesized Cr2O3NPs are biocompatible and nontoxic and proved to possess significant biopotentials. In future, different in vivo studies are needed to fully investigate the cytotoxicity and mechanism of action associated with these Cr2O3NPs.