bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro testing of a funnel-tip catheter model to decrease clot migration and to evaluate clot effects in mechanical thrombectomy
Authors: Payne Emily S. , Krost-Reuhl Samantha , Heimann Axel , Kempski Oliver , Keric Naureen , Masomi-Bornwasser Julia , Gerber Tiemo , Seidmann Larissa , Leithner Doris , Kloeckner Roman , Hahn Felix , Müller Lukas , Auer Timo A. , Kirschner Stefanie , Brockmann Marc A. , Tanyildizi Yasemin 
Published: February 2021

Abstract
Clot-retrieval failure and embolism in new territories (ENT) are complications reducing the efficacy of mechanical thrombectomy (MT). Reasons for these problems are clot abruption during stent retriever retraction into the cylindrical tip of a standard distal access catheter (DAC), and antegrade blood flow during retrieval. To overcome these complications, a funnel-shaped tip catheter model was developed and tested. Using an experimental in vitro setup, this study compared the efficacy of a funnel-shaped tip with a standard cylindrical tip in combination with different clot compositions. Mechanical thrombectomy was performed 80 times for each tip, using two stent retrievers (Trevo XP ProVue 3/20 mm and 4/20 mm) and four different clot types (mechanical vs. static preparation, 0-24h vs. 72h clot aging times). Significantly higher first-pass recanalization rates were observed for the funnel-shaped tip, which reached 70.0% vs. 30.0% for the standard tip (absolute difference, 32; relative difference 20.0%, P < 0.05), regardless of the clot type and stent retriever. Recanalization could be increased using fibrin-rich mechanical clots vs. clots prepared under static conditions, as well as 0-24h vs. 72h aged clots, respectively. The extended in vitro-experiments verified the usability of the recently patented funnel-shaped DAC, hereby implementing next-level in vivo-experiments.
The role of IL-1 in adipose browning and muscle wasting in CKD-associated cachexia
Authors: Cheung Wai W , Zheng Ronghao , Hao Sheng , Wang Zhen , Gonzalez Alex , Zhou Ping , Hoffman Hal M , Mak Robert H 
Published: February 2021

Abstract
Cytokines such as IL-6, TNF-α and IL-1β trigger inflammatory cascades which may play a role in the pathogenesis of chronic kidney disease (CKD)-associated cachexia. CKD was induced by 5/6 nephrectomy in mice. We studied energy homeostasis in Il1β −/−/CKD, Il6−/−/CKD and Tnfα −/−/CKD mice and compared with wild type (WT)/CKD controls. Parameters of cachexia phenotype were completely normalized in Il1β −/−/CKD mice but were only partially rescued in Il6−/−/CKD and Tnfα −/−/CKD mice. We tested the effects of anakinra, an IL-1 receptor antagonist, on CKD-associated cachexia. WT/CKD mice were treated with anakinra (2.5 mg.kg.day, IP) or saline for 6 weeks and compared with WT/sham controls. Anakinra normalized food intake and weight gain, fat and lean mass content, metabolic rate and muscle function, and also attenuated molecular perturbations of energy homeostasis in adipose tissue and muscle in WT/CKD mice. Anakinra attenuated browning of white adipose tissue in WT/CKD mice. Moreover, anakinra normalized gastrocnemius weight and fiber size as well as attenuated muscle fat infiltration in WT/CKD mice. This was accompanied by correcting the increased muscle wasting signaling pathways while promoting the decreased myogenesis process in gastrocnemius of WT/CKD mice. We performed qPCR analysis for the top 20 differentially expressed muscle genes previously identified via RNAseq analysis in WT/CKD mice versus controls. Importantly, 17 differentially expressed muscle genes were attenuated in anakinra treated WT/CKD mice. In conclusion, IL-1 receptor antagonism may represent a novel targeted treatment for adipose tissue browning and muscle wasting in CKD.
Association between myocardial mechanical dispersion and ventricular arrhythmogenicity in Chagas cardiomyopathy.
Authors: de Azevedo Alda Cristina Alves , Barros Marcio Vinicius Lins , Klaboe Lars Gunnar , Edvardsen Thor , Costa Henrique Silveira , Paixao Gabriela Miana de Mattos , Junior Omar Ribeiro Santos , Nunes Maria do Carmo Pereira , Rocha Manoel Otavio da Costa 
Published: February 2021

Abstract
Endemic Chagas diseaseis a major health concernin LatinAmerica. Ventricular arrhythmias (VA) is a hallmark of Chagas cardiomyopathy (ChC) associated with worse prognosis. To verify if there is an association between myocardial mechanical dispersion and ventricular arrhythmogenicity in CCM. This is a cross-sectional study involving 77 patients with CCM. Global longitudinal strain (GLS) and MD were evaluated by echocardiogram, derived from the speckle tracking technique. Myocardial MD was measured from the onset of the Q / R wave on electrocardiogram to the peak longitudinal strain in 16 segments of the left ventricle. Frequency and complexity of ventricular extrasystoles (VES) were assessed by dynamic electrocardiography. The density and complexity of VES and the presence of non-sustained ventricular tachycardias (NSVTs) increase as MD increases. In logistic regression, MD was the only variable associated with the presence of VES in pairs and bigeminy. In the univariate analysis, both MD and GLS were associated with the presence of NSVT (both, p < 0.01), and MD was independently associated with NSVT (OR 1.04, 95% CI: 1.004–1.201, p = 0.031). In Chagas cardiomyopathy, MD is associated with a higher density and complexity of ventricular extrasystoles, including NSVT.
Geochemical Characteristics of the Late Cretaceous Lower Zhoutian Formation in the Jitai Basin, Southeast China: Implications for palaeoenvironment and provenance
Authors: Yan Kai , Wang Chun-Lian , Mischke Steffen , Wang Jiu-Yi , Shen Li-Jian , Yu Xiao-Can , Meng Ling-Yang 
Published: February 2021

Abstract
Major, trace and rare earth element geochemistry of the late Cretaceous lower Zhoutian Formation from the Jitai Basin of Southeast China were measured by inductively coupled plasma mass spectromentry (ICP-MS) analysis. The paleoclimate, paleo-environment and provenance of lower Zhoutian Formation in the Jitai Basin are analyzed in detail with these data.According to the research, the range of Sr/Cu values is wide, which indicates the changeable palaeoclimate, the curves of FeO/MnO and Al2O3/MgO are negatively correlated with the Sr/Cu curves. These changes indicate that the palaeoclimate of the late Cretaceous lower Zhoutian Formation in the Jitai Basin was divided into two parts. The lower part experienced two cooling events; the upper part was dominated by warm humid climate.The changes of B/Ga and Sr/Ba curves are similar to Sr/Cu curves. According to these values, the salinity of the late Cretaceous lower Zhoutian Formation in the Jitai Basin was consistent with palaeoclimate. The salinity of lower part changed from salt water to fresh/brackish water. The upper part was mainly fresh/brackish water, and there were many changes from fresh/brackish water to salt water. The values of Ni/Co, V/Cr, V/(V + Ni) and Ce/Ce* are relatively stable, indicating a long-term oxidation environment. The diagrams of La-Th-Sc, Th-Sc-Zr/10, La/Th-Hf and sandstone-siltstone background function show that the provenance in lower Zhoutian Formation mainly is a mixture of upper crust felsic sediments and old components.
Human Exposure Assessment to Potentially Toxic Elements (PTEs) from Tofu Consumption
Authors: Paz Soraya , Rubio Carmen , Gutiérrez Ángel J. , González-Weller Dailos , Hardisson Arturo 
Published: February 2021

Abstract
Potentially toxic elements (PTEs) (V, B, Ba, Li, Sr, Cr, Ni, Al, Pb, Cd) were determined in 130 samples of different tofu types (natural, flavoured, smoked and fresh made) by ICP-OES (inductively coupled plasma optical emission spectrometry). Al was the most notable element found with the highest concentration (6.71 mg/kg ww) found in flavoured tofu. Ni level (0.38 mg/kg) stands out in smoked tofu. European tofu has higher PTEs levels than Chinese tofu. Organic produced tofu has higher PTEs concentrations than conventional produced tofu. 200 g/day of smoked tofu confers a contribution percentage of 39.6% of its TDI (tolerable daily intake). In addition, 200 g/day of flavoured tofu would mean a high Pb contribution with a 23.2% of the BMDL (benchmark dose level) set in 0.63 µg/kg bw/day to the development of nephrotoxicity. Mean consumption would not pose a risk to adults’ health. Considering the obtained results, it would be advisable to establish limits for certain metals such as Pb, Al and Ni in this type of product. Furthermore, it is recommendable to set consumer guidelines to some tofu types in order to avoid excessive intake of PTEs.
Identification and molecular analysis of 17 novel hydroxymethylbilane synthase mutations in 69 Chinese patients with acute intermittent porphyria
Authors: xiang Hu yuan , hao Li wei , lin Kang ning , yan Ma li , qing Teng , ling Mo gui , hong Wu jia , yang Wang xin , jie Bi ren , yun Zhang song 
Published: February 2021

Abstract
BACKGROUND: Acute intermittent porphyria (AIP) is an autosomal dominant hereditary disease caused by mutations to the hydroxymethylbilane synthase (HMBS) gene in the heme biosynthesis pathway. AIP is a rare disease that is thought to display incomplete penetrance. Studies on the characteristics of HMBS mutations in people from Britain, France, Russia, and Sweden have been performed. RESULT: In this study, a total of 45 different gene mutations were found, 17 of which were novel mutations that have not been previously reported. The 45 HMBS mutations included 19 missense, 11 splicing, and 4 nonsense mutations; 9 small deletions, 1 repeat insertion, and 1 complex deletion-insertion mutation. One mutation (c.673C>T) was found in the gene sequence of 8 unrelated patients, making it the most common mutation, and another mutation (c.517C>T) was found in 7 unrelated patients, making it the next most common mutation found in this study. To study the expression level of mutant HMBSs, Western blot and immunofluorescence staining were performed with four novel mutants (c.653G>A, c.597dupC, c.673_674del, c.1045_1046delAA), and the crystal structure changes were compared through homologous modeling to indicate the possible pathogenic mechanism.CONCLUSIONS: In this study, the characteristics of HMBS gene mutation in Chinese were studied, which laid a foundation for further research in the future.
Design, Synthesis and Biological Evaluation of Pyrimidine Analogues as&nbsp;SecA Inhibitors
Authors: BAMBA FANTE , Jin Jinshan , Chaudhary Arpana S. , Tai Phang C. , Wang Binghe 
Published: February 2021

Abstract
SecA, a key component of the bacterial Sec-dependent secretion pathway, is an attractive target for the development of new antimicrobial agents. We have previously reported pyrimidine analogs as SecA inhibitors. Herein, we report an extension of the earlier work in the synthesis and evaluation of a series of 15 5-cyanothiouracil derivatives as SecA inhibitors. All the compounds have been evaluated for their inhibition of SecA ATPase (EcSecAN68) and for their antimicrobial activity against Escherichia coli NR698 (a leaky mutant) and Bacillus anthracis Sterne. Twelve compounds showed IC50 of less than 6.3 µM when tested against EcSecAN68. In antimicrobial studies against E. coli NR698, six compounds showed MIC of less than 12.5 µM with three being less than 6.3 µM. Against B. anthracis Sterne, three compounds showed MIC of less than 6.3 µM.
Gosha-jinki-Gan (GJG) shows anti-aging effects through suppression of TNF-α production by Chikusetsusaponin V
Authors: Hagihara Keisuke , Nunomura Kazuto , Lin Bangzhong , Fumimoto Megumi , Watanabe Junko , Mizuhara Yasuharu 
Published: February 2021

Abstract
Frailty develops due to multiple factors, such as sarcopenia, chronic pain, and dementia. Go-sha-jinki-Gan (GJG) is a traditional Japanese herbal medicine used for age-related symptoms. We have reported that GJG improved sarcopenia, chronic pain, and central nervous system function through suppression of TNF-α production. In the present study, GJG was found to reduce the production of TNF-α in the soleus muscle of senescence-accelerated mice at 12 weeks and 36 weeks. GJG did not change the differentiation of C2C12 cells with 2% horse serum. GJG significantly decreased the expression of MAFbx induced by TNF-α in C2C12 cells on real-time PCR. TNF-α significantly decreased the expression of PGC-1α and negated the enhancing effect of GJG for the expression of PGC-1α on digital PCR. Examining 20 chemical compounds derived from GJG, cinnamaldehyde from cinnamon bark and Chikusetsusaponin V (CsV) from Achyrantes Root dose-dependently decreased the production of TNF-⍺ in RAW264.7 cells stimulated by LPS. CsV inhibited the nuclear translocation of NF-κB p65 in RAW264.7 cells. CsV showed low permeability using Caco-2 cells. However, the plasma concentration of CsV was detected from 30 minutes to 6 h and peaked at 1 h in the CD1 (ICR) mice after a single dose of GJG. In 8-week-old SAMP8 mice fed 4% (w/w) GJG from one week to four weeks, the plasma CsV concentration ranged from 0.0500 to 10.0 ng/mL. The evidence that CsV plays an important role in various anti-aging effects of GJG via suppression of TNF-⍺ expression is presented.
Pan-Cancer analysis of clinical significance and associated molecular features of glycolysis
Authors: Liu Yi-chen , Lin Peng , Zhao Yu-jia , Wu Lin-yong , Wu Yu-quan , Peng Jin-bo , Yang Hong , He Yun 
Published: February 2021

Abstract
Background Tumor glycolysis acts as a major promoter of carcinogenesis and cancer progression. Given its complex mechanisms and interactions, a comprehensive analysis to reveal its clinical significance and molecular features is urgent. Materials and Methods Based on a well-established glycolysis gene expression signature, we quantified 8633 patients across different cancer types from The Cancer Genome Atlas (TCGA) and evaluated their prognostic associations. High tumor glycolytic activity correlated with inferior overall survival in pan-cancer patients (hazard ratio: 1.70, 95% confidence interval: 1.20–2.40, P = 0.003). The prognostic value of glycolysis was stable regardless of clinical parameters and correlated with molecular subtypes. The prognostic significance of glycolysis was validated using another three independent datasets. In addition, genome, transcriptome, and proteome profiles were utilized to characterize distinctive molecular features associated with glycolysis.Results Mechanistically, glycolysis fulfilled the fundamental needs of tumor proliferation in multiple ways. Exploration of the relationships between glycolysis and tumor infiltrating immune cells showed that glycolysis enabled immune evasion of tumor cells. Mammalian target of rapamycin inhibitors and dopamine receptor antagonists represent classes of compounds that can effectively reverse the glycolytic status of cancers.Conclusion Our study provides an in-depth molecular understanding of tumor glycolysis and may have practical implications for clinical cancer therapy.
Mineralogical, Physico-chemical and Geochemical Characterization of Three Kaolinitic Clays (Ne Algeria): Comparative Study
Authors: boukoffa mechati , Lamouri Bachir , Bouabsa Lakhdar , Fagel Nathalie 
Published: February 2021

Abstract
Forteen clay samples collected from three kaolin deposits (Tamazert, Hadj Ali and Chekfa; NE Algeria) are characterized by several techniques in order to compares them to somes kaolins used in industry especially that used in ceramics. All the samples were investigated by X-ray diffraction, Infrared absorption spectroscopy, thermal analysis (TG), plasticity, environmental scanning electron microscopy and chemical major elements analysis. The bulk mineralogical composition of all clays samples is dominated by kaolinite (21-75%), illite/ muscovite (33-76%) and quartz (7-21%). K-feldspar and plagioclase are only present in Chekfa and Hadj Ali clays with small amounts. Clay fraction (< 2µm) dominated by kaolinite and illite (98%). Chlorite and smectite are present in some samples of Chekfa and Hadj Ali clays with insignificant amount (˂1%). The particles-size distribution of all samples showed the abundance of sandy silt fraction (28-63%) and silty sand (39-64%) with moderate clayey fraction (2-7%). The chemical composition showed variable amounts of SiO2 (59-68%), Al2O3 (18-39%), Fe2O3 (.26-1.38%) and TiO2 (0.34-0.69%) in accordance with the free quartz in all studied samples. Plasticity-index (7.5-7.9%), Specific surface (28-47m2) and Cation exchange (5-11meq/100g) values are moderate in all samples. Given these properties, these clays may be suitable in bricks and ceramic product.
Microvascular Comparison in Younger and Older Patients With Retinal Vein Occlusion Analyzed by OCT&nbsp;Angiography
Authors: Ye Panpan , Zhu Tiepei , Zheng Fang , Zhou Min , Fang Xiaoyun , Yao Ke 
Published: February 2021

Abstract
Background: To compare changes in retinal microvasculature of young and elderly patients with retinal vein occlusion (RVO) after anti-VEGF treatment.Methods: RVO patients who underwent anti-VEGF treatment were retrospectively reviewed and categorized into two groups based on age. The OCT angiography images were obtained during each visit. Best corrected visual acuity (BCVA), vessel density (VD) and foveal avascular zone (FAZ) were measured and compared between the two groups. Vision improvements and retinal microvasculature changes were also correlated.Results: Twenty patients with 20 eyes were enrolled in the younger group and 46 patients with 46 eyes were enrolled in the older group. Younger patients demonstrated better BCVA, higher VD and smaller FAZ than older patients at 12 months after the first anti-VEGF treatment. The improvement of VD was observed only in the younger group. A positive correlation between vision improvement and VD increase was noted.Conclusion: Young patients with RVO can achieve rapid rehabilitation of deep retinal vasculature which lead to a better visual outcome.
Individualized Surgery Combined with Radiotherapy and Triamcinolone Acetonide Injection for the treatment of Auricular Keloids
Authors: Sun Qiang , Yu Er-te , Zhou You , Tong Shuang , Zhou Kai-jian , Guo Shu 
Published: February 2021

Abstract
Background: Although multiple methods have been proposed to treat auricular keloids, low curative effects and high recurrence rates are currently major clinical problems. Thereinto, surgery combined with radiotherapy and triamcinolone acetonide injection is considered to be the proper choice for comprehensive treatment of auricular keloids.Objective: This study aimed to evaluate the therapeutic effect of individualized surgery combined with radiotherapy for the treatment of auricular keloids. Methods: From February 2014 to February 2017, a total of 67 patients with 113 auricular keloids were enrolled in this study. According to the specific conditions of the lesions, the local tissue and the patient's wishes, different surgical methods were selected for scar excision and repair of the defect. Within 24 hours after the keloid was excised, 5 Mev electron beam irradiation by the linear accelerator was used for radiotherapy with a total dose of 20 Gy at interval of 1 day for 10 consecutive times. Triamcinolone acetonide was injected immediately after 1, 2, and 3 months after surgery.Results: A total of 113 keloids were received treatment. The follow-up period was 24 months. Fourteen keloids (12.39%) showed subjective recurrence with a success rate of 87.61%. The VSS scores were as follows: 82 keloids (72.57%) scored less than 5 points (good result), 21 keloids (18.58%) scored 6 to 10 points (fair result), and only 10 keloids (8.85%) scored more than 10 points (bad result). The effective rate was 91.15%.Conclusions: Individualized surgery combined with early postoperative radiotherapy and triamcinolone acetonide injection is an ideal treatment method to ensure good auricular appearance, low incidences of complications and recurrence based on effective treatment of auricular keloids.
Computational pharmacogenomic screen identifies drugs that phenocopy dipyridamole and potentiate anti-breast cancer activity of statins
Authors: Leeuwen Jenna van , alawi Wail Ba , Branchard Emily , Longo Joseph , Silvester Jennifer , Cescon David , Haibe-Kains Benjamin , Penn Linda , Gendoo Deena 
Published: February 2021

Abstract
Statins are a family of FDA-approved cholesterol-lowering drugs that inhibit the rate-limiting enzyme of the metabolic mevalonate pathway, which have been shown to have anti-cancer activity. As therapeutic efficacy increases when drugs are used in combination, we sought to identify agents, like dipyridamole, that potentiate statin-induced tumor cell death. As an antiplatelet agent dipyridamole will not be suitable for all cancer patients. Thus, we developed an integrative pharmacogenomics pipeline to identify agents that were similar to dipyridamole at the level of drug structure, in vitro sensitivity and molecular perturbation. To enrich for compounds expected to target the mevalonate pathway, we took a pathway-centric approach towards computational selection, which we called mevalonate drug network fusion (MVA-DNF). We validated two of the top ranked compounds, nelfinavir and honokiol and demonstrated that, like dipyridamole, they synergize with fluvastatin to potentiate tumour cell death by blocking the restorative feedback loop. This is achieved by inhibiting activation of the key transcription factor that induces mevalonate pathway gene transcription, sterol regulatory element-binding protein 2 (SREBP2). Mechanistically, the synergistic response of fluvastatin-nelfinavir and fluvastatin-honokiol was associated with similar transcriptomic and proteomic pathways, indicating a similar mechanism of action between nelfinavir and honokiol when combined with fluvastatin. Further analysis identified the canonical epithelial-mesenchymal transition (EMT) gene, E-cadherin as a biomarker of these synergistic responses across a large panel of breast cancer cell lines. Thus, our computational pharmacogenomic approach can identify novel compounds that phenocopy a compound of interest in a pathway-specific manner.