bluuebunny/crossref_metadata_2025_split huggingface dataset:
PRYNT: a tool for prioritization of disease candidates from proteomics data using a combination of shortest-path and random walk algorithms
Authors: Boizard Franck , Buffin-Meyer Bénédicte , Aligon Julien , Teste Olivier , Schanstra Joost P. , Klein Julie 
Published: March 2021

AbstractThe urinary proteome is a promising pool of biomarkers of kidney disease. However, the protein changes observed in urine only partially reflect the deregulated mechanisms within kidney tissue. In order to improve on the mechanistic insight based on the urinary protein changes, we developed a new prioritization strategy called PRYNT (PRioritization bY protein NeTwork) that employs a combination of two closeness-based algorithms, shortest-path and random walk, and a contextualized protein–protein interaction (PPI) network, mainly based on clique consolidation of STRING network. To assess the performance of our approach, we evaluated both precision and specificity of PRYNT in prioritizing kidney disease candidates. Using four urinary proteome datasets, PRYNT prioritization performed better than other prioritization methods and tools available in the literature. Moreover, PRYNT performed to a similar, but complementary, extent compared to the upstream regulator analysis from the commercial Ingenuity Pathway Analysis software. In conclusion, PRYNT appears to be a valuable freely accessible tool to predict key proteins indirectly from urinary proteome data. In the future, PRYNT approach could be applied to other biofluids, molecular traits and diseases. The source code is freely available on GitHub at: https://github.com/Boizard/PRYNT and has been integrated as an interactive web apps to improved accessibility (https://github.com/Boizard/PRYNT/tree/master/AppPRYNT).
Epidermal and fibroblast growth factors incorporated polyvinyl alcohol electrospun nanofibers as biological dressing scaffold
Authors: Asiri Amnah , Saidin Syafiqah , Sani Mohd Helmi , Al-Ashwal Rania Hussien 
Published: March 2021

AbstractIn this study, single, mix, multilayer Polyvinyl alcohol (PVA) electrospun nanofibers with epidermal growth factor (EGF) and fibroblast growth factor (FGF) were fabricated and characterized as a biological wound dressing scaffolds. The biological activities of the synthesized scaffolds have been verified by in vitro and in vivo studies. The chemical composition finding showed that the identified functional units within the produced nanofibers (O–H and N–H bonds) are attributed to both growth factors (GFs) in the PVA nanofiber membranes. Electrospun nanofibers' morphological features showed long protrusion and smooth morphology without beads and sprayed with an average range of 198–286 nm fiber diameter. The fiber diameters decrement and the improvement in wettability and surface roughness were recorded after GFs incorporated within the PVA Nanofibers, which indicated potential good adoption as biological dressing scaffolds due to the identified mechanical properties (Young’s modulus) in between 18 and 20 MPa. The MTT assay indicated that the growth factor release from the PVA nanofibers has stimulated cell proliferation and promoted cell viability. In the cell attachment study, the GFs incorporated PVA nanofibers stimulated cell proliferation and adhered better than the PVA control sample and presented no cytotoxic effect. The in vivo studies showed that compared to the control and single PVA-GFs nanofiber, the mix and multilayer scaffolds gave a much more wound reduction at day 7 with better wound repair at day 14–21, which indicated to enhancing tissue regeneration, thus, could be a projected as a suitable burn wound dressing scaffold.
Development of a two-step nucleic acid amplification test for accurate diagnosis of the Mycobacterium tuberculosis complex
Authors: Lin Chien-Ru , Wang Hsin-Yao , Lin Ting-Wei , Lu Jang-Jih , Hsieh Jason Chia-Hsun , Wu Min-Hsien 
Published: March 2021

AbstractThe Mycobacterium tuberculosis complex (MTBC) remains one of the top 10 leading causes of death globally. The early diagnosis of MTBC can reduce mortality and mitigate disease transmission. However, current nucleic acid amplification diagnostic test methods are generally time-consuming and show suboptimal diagnostic performance, especially in extrapulmonary MTBC samples or acid-fast stain (AFS)-negative cases. Thus, development of an accurate assay for the diagnosis of MTBC is necessary, particularly under the above mentioned conditions. In this study, a single-tube nested real-time PCR assay (N-RTP) was developed and compared with a newly in-house-developed high-sensitivity real-time PCR assay (HS-RTP) using 134 clinical specimens (including 73 pulmonary and 61 extrapulmonary specimens). The amplification efficiency of HS-RTP and N-RTP was 99.8% and 100.7%, respectively. The sensitivity and specificity of HS-RTP and N-RTP for the diagnosis of MTBC in these specimens were 97.5% (77/79) versus 94.9% (75/79) and 80.0% (44/55) versus 89.1% (49/55), respectively. The sensitivity and specificity of HS-RTP and N-RTP for the diagnosis of MTBC in pulmonary specimens were 96.3% (52/54) versus 96.3% (52/54) and 73.7.0% (14/19) versus 89.5% (17/19), respectively; in extrapulmonary specimens, the sensitivity and specificity of HS-RTP and N-RTP were 100% (25/25) versus 92% (23/25) and 83.3% (30/36) versus 88.9% (32/36), respectively. Among the AFS-negative cases, the sensitivity and specificity of HS-RTP and N-RTP were 97.0% (32/33) versus 90.9% (30/33) and 88.0% (44/50) versus 92.0% (46/50), respectively. Overall, the sensitivity of HS-RTP was higher than that of N-RTP, and the performance was not compromised in extrapulmonary specimens and under AFS-negative conditions. In contrast, the specificity of the N-RTP assay was higher than that of the HS-RTP assay in all types of specimens. In conclusion, the HS-RTP assay would be useful for screening patients suspected of exhibiting an MTBC infection due to its higher sensitivity, while the N-RTP assay could be used for confirmation because of its higher specificity. Our results provide a two-step method (screen to confirm) that simultaneously achieves high sensitivity and specificity in the diagnosis of MTBC.
Apelin promotes blood and lymph vessel formation and the growth of melanoma lung metastasis
Authors: Berta Judit , Török Szilvia , Tárnoki-Zách Júlia , Drozdovszky Orsolya , Tóvári József , Paku Sándor , Kovács Ildikó , Czirók András , Masri Bernard , Megyesfalvi Zsolt , Oskolás Henriett , Malm Johan , Ingvar Christian , Markó-Varga György , Döme Balázs , László Viktória 
Published: March 2021

AbstractApelin, a ligand of the APJ receptor, is overexpressed in several human cancers and plays an important role in tumor angiogenesis and growth in various experimental systems. We investigated the role of apelin signaling in the malignant behavior of cutaneous melanoma. Murine B16 and human A375 melanoma cell lines were stably transfected with apelin encoding or control vectors. Apelin overexpression significantly increased melanoma cell migration and invasion in vitro, but it had no impact on its proliferation. In our in vivo experiments, apelin significantly increased the number and size of lung metastases of murine melanoma cells. Melanoma cell proliferation rates and lymph and blood microvessel densities were significantly higher in the apelin-overexpressing pulmonary metastases. APJ inhibition by the competitive APJ antagonist MM54 significantly attenuated the in vivo pro-tumorigenic effects of apelin. Additionally, we detected significantly elevated circulating apelin and VEGF levels in patients with melanoma compared to healthy controls. Our results show that apelin promotes blood and lymphatic vascularization and the growth of pulmonary metastases of skin melanoma. Further studies are warranted to validate apelin signaling as a new potential therapeutic target in this malignancy.
A two-stream convolutional neural network for microRNA transcription start site feature integration and identification
Authors: Cha Mingyu , Zheng Hansi , Talukder Amlan , Barham Clayton , Li Xiaoman , Hu Haiyan 
Published: March 2021

AbstractMicroRNAs (miRNAs) play important roles in post-transcriptional gene regulation and phenotype development. Understanding the regulation of miRNA genes is critical to understand gene regulation. One of the challenges to study miRNA gene regulation is the lack of condition-specific annotation of miRNA transcription start sites (TSSs). Unlike protein-coding genes, miRNA TSSs can be tens of thousands of nucleotides away from the precursor miRNAs and they are hard to be detected by conventional RNA-Seq experiments. A number of studies have been attempted to computationally predict miRNA TSSs. However, high-resolution condition-specific miRNA TSS prediction remains a challenging problem. Recently, deep learning models have been successfully applied to various bioinformatics problems but have not been effectively created for condition-specific miRNA TSS prediction. Here we created a two-stream deep learning model called D-miRT for computational prediction of condition-specific miRNA TSSs (http://hulab.ucf.edu/research/projects/DmiRT/). D-miRT is a natural fit for the integration of low-resolution epigenetic features (DNase-Seq and histone modification data) and high-resolution sequence features. Compared with alternative computational models on different sets of training data, D-miRT outperformed all baseline models and demonstrated high accuracy for condition-specific miRNA TSS prediction tasks. Comparing with the most recent approaches on cell-specific miRNA TSS identification using cell lines that were unseen to the model training processes, D-miRT also showed superior performance.
Cycling hypoxia selects for constitutive HIF stabilization
Authors: Pressley Mariyah , Gallaher Jill A. , Brown Joel S. , Tomaszewski Michal R. , Borad Punit , Damaghi Mehdi , Gillies Robert J. , Whelan Christopher J. 
Published: March 2021

AbstractTumors experience temporal and spatial fluctuations in oxygenation. Hypoxia inducible transcription factors (HIF-α) respond to low levels of oxygen and induce re-supply oxygen. HIF-α stabilization is typically facultative, induced by hypoxia and reduced by normoxia. In some cancers, HIF-α stabilization becomes constitutive under normoxia. We develop a mathematical model that predicts how fluctuating oxygenation affects HIF-α stabilization and impacts net cell proliferation by balancing the base growth rate, the proliferative cost of HIF-α expression, and the mortality from not expressing HIF-α during hypoxia. We compare optimal net cell proliferation rate between facultative and constitutive HIF-α regulation in environments with different oxygen profiles. We find that that facultative HIF-α regulation promotes greater net cell proliferation than constitutive regulation with stochastic or slow periodicity in oxygenation. However, cell fitness is nearly identical for both HIF-α regulation strategies under rapid periodic oxygenation fluctuations. The model thus indicates that cells constitutively expressing HIF-α may be at a selective advantage when the cost of expression is low. In cancer, this condition is known aspseudohypoxiaor the “Warburg Effect”. We conclude that rapid and regular cycling of oxygenation levels selects for pseudohypoxia, and that this is consistent with the ecological theory of optimal defense.
Streptococcus mutans induces IgA nephropathy-like glomerulonephritis in rats with severe dental caries
Authors: Naka Shuhei , Wato Kaoruko , Misaki Taro , Ito Seigo , Matsuoka Daiki , Nagasawa Yasuyuki , Nomura Ryota , Matsumoto-Nakano Michiyo , Nakano Kazuhiko 
Published: March 2021

AbstractThe mechanisms underlying immunoglobulin A nephropathy (IgAN), the most common chronic form of primary glomerulonephritis, remain poorly understood. Streptococcus mutans, a Gram-positive facultatively anaerobic oral bacterium, is a common cause of dental caries. In previous studies, S. mutans isolates that express Cnm protein on their cell surface were frequently detected in IgAN patients. In the present study, inoculation of Cnm-positive S. mutans in the oral cavities of 2-week-old specific-pathogen free Sprague–Dawley rats fed a high-sucrose diet for 32 weeks produced severe dental caries in all rats. Immunohistochemical analyses of the kidneys using IgA- and complement C3-specific antibodies revealed positive staining in the mesangial region. Scanning electron microscopy revealed a wide distribution of electron dense deposits in the mesangial region and periodic acid-Schiff staining demonstrated prominent proliferation of mesangial cells and mesangial matrix. These results suggest that IgAN-like glomerulonephritis was induced in rats with severe dental caries by Cnm-positive S. mutans.
Philadelphia chromosome-negative B-cell acute lymphoblastic leukaemia with kinase fusions in Taiwan
Authors: Hsu Yin-Chen , Yu Chih-Hsiang , Chen Yan-Ming , Roberts Kathryn G. , Ni Yu-Ling , Lin Kai-Hsin , Jou Shiann-Tarng , Lu Meng-Yao , Chen Shu-Huey , Wu Kang-Hsi , Chang Hsiu-Hao , Lin Dong-Tsamn , Lin Shu-Wha , Lin Ze-Shiang , Chiu Wei-Tzu , Chang Chia-Ching , Ho Bing-Ching , Mullighan Charles G. , Yu Sung-Liang , Yang Yung-Li 
Published: March 2021

AbstractPhiladelphia chromosome-like (Ph-like) acute lymphoblastic leukaemia (ALL), a high-risk subtype characterised by genomic alterations that activate cytokine receptor and kinase signalling, is associated with inferior outcomes in most childhood ALL clinical trials. Half of the patients with Ph-like ALL have kinase rearrangements or fusions. We examined the frequency and spectrum of these fusions using a retrospective cohort of 212 newly diagnosed patients with childhood B-cell ALL. Samples without known chromosomal alterations were subject to multiplex reverse transcription polymerase chain reaction to identify known Ph-like kinase fusions. Immunoglobulin heavy chain locus (IGH) capture and kinase capture were applied to samples without known kinase fusions. We detected known kinase fusions in five of 212 patients, comprising EBF1-PDGFRB, ETV6-ABL1, ZC3HAV1-ABL2, EPOR-IGH, and CNTRL-ABL1. Two patients with P2RY8-CRLF2 were identified. Patients with non-Ph kinase fusions had inferior 5-year event-free survival and overall survival compared with patients with other common genetic alterations. The prevalence of non-Ph kinase fusions in our Taiwanese cohort was lower than that reported in Caucasian populations. Future clinical trials with tyrosine kinase inhibitors may be indicated in Taiwan because of the inferior outcomes for B-cell ALL with kinase fusions.
High Jc and low anisotropy of hydrogen doped NdFeAsO superconducting thin film
Authors: Iida Kazumasa , Hänisch Jens , Kondo Keisuke , Chen Mingyu , Hatano Takafumi , Wang Chao , Saito Hikaru , Hata Satoshi , Ikuta Hiroshi 
Published: March 2021

AbstractThe recent realisations of hydrogen doped LnFeAsO (Ln = Nd and Sm) superconducting epitaxial thin films call for further investigation of their structural and electrical transport properties. Here, we report on the microstructure of a NdFeAs(O,H) epitaxial thin film and its temperature, field, and orientation dependencies of the resistivity and the critical current density Jc. The superconducting transition temperature Tc is comparable to NdFeAs(O,F). Transmission electron microscopy investigation supported that hydrogen is homogenously substituted for oxygen. A high self-field Jc of over 10 MA/cm2 was recorded at 5 K, which is likely to be caused by a short London penetration depth. The anisotropic Ginzburg–Landau scaling for the angle dependence of Jc yielded temperature-dependent scaling parameters γJ that decreased from 1.6 at 30 K to 1.3 at 5 K. This is opposite to the behaviour of NdFeAs(O,F). Additionally, γJ of NdFeAs(O,H) is smaller than that of NdFeAs(O,F). Our results indicate that heavily electron doping by means of hydrogen substitution for oxygen in LnFeAsO is highly beneficial for achieving high Jc with low anisotropy without compromising Tc, which is favourable for high-field magnet applications.
Solution structure of multi-domain protein ER-60 studied by aggregation-free SAXS and coarse-grained-MD simulation
Authors: Okuda Aya , Shimizu Masahiro , Morishima Ken , Inoue Rintaro , Sato Nobuhiro , Urade Reiko , Sugiyama Masaaki 
Published: March 2021

AbstractMulti-domain proteins (MDPs) show a variety of domain conformations under physiological conditions, regulating their functions through such conformational changes. One of the typical MDPs, ER-60 which is a protein folding enzyme, has a U-shape with four domains and is thought to have different domain conformations in solution depending on the redox state at the active centres of the edge domains. In this work, an aggregation-free small-angle X-ray scattering revealed that the structures of oxidized and reduced ER-60 in solution are different from each other and are also different from those in the crystal. Furthermore, structural modelling with coarse-grained molecular dynamics simulation indicated that the distance between the two edge domains of oxidized ER-60 is longer than that of reduced ER-60. In addition, one of the edge domains has a more flexible conformation than the other.
Burkholderia cenocepacia transcriptome during the early contacts with giant plasma membrane vesicles derived from live bronchial epithelial cells
Authors: Pimenta Andreia I. , Bernardes Nuno , Alves Marta M. , Mil-Homens Dalila , Fialho Arsenio M. 
Published: March 2021

AbstractBurkholderia cenocepacia is known for its capacity of adherence and interaction with the host, causing severe opportunistic lung infections in cystic fibrosis patients. In this work we produced Giant Plasma Membrane Vesicles (GPMVs) from a bronchial epithelial cell line and validated their use as a cell-like alternative to investigate the steps involved in the adhesion process of B. cenocepacia. RNA-sequencing was performed and the analysis of the B. cenocepacia K56-2 transcriptome after the first contacts with the surface of host cells allowed the recognition of genes implicated in bacterial adaptation and virulence-associated functions. The sensing of host membranes led to a transcriptional shift that caused a cascade of metabolic and physiological adaptations to the host specific environment. Many of the differentially expressed genes encode proteins related with central metabolic pathways, transport systems, cellular processes, and virulence traits. The understanding of the changes in gene expression that occur in the early steps of infection can uncover new proteins implicated in B. cenocepacia-host cell adhesion, against which new blocking agents could be designed to control the progression of the infectious process.
Development of a drug screening system using three-dimensional cardiac tissues containing multiple cell types
Authors: Takeda Maki , Miyagawa Shigeru , Ito Emiko , Harada Akima , Mochizuki-Oda Noriko , Matsusaki Michiya , Akashi Mitsuru , Sawa Yoshiki 
Published: March 2021

AbstractWe hypothesized that an appropriate ratio of cardiomyocytes, fibroblasts, endothelial cells, and extracellular matrix (ECM) factors would be required for the development of three-dimensional cardiac tissues (3D-CTs) as drug screening systems. To verify this hypothesis, ECM-coated human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), ECM-coated cardiac fibroblasts (CFs), and uncoated cardiac endothelial cells (CEs) were mixed in the following ratios: 10:0:0 (10CT), 7:2:1 (7CT), 5:4:1 (5CT), and 2:7:1 (2CT). The expression of cardiac-, fibroblasts-, and endothelial-specific markers was assessed by FACS, qPCR, and immunostaining while that of ECM-, cell adhesion-, and ion channel-related genes was examined by qPCR. Finally, the contractile properties of the tissues were evaluated in the absence or presence of E-4031 and isoproterenol. The expression of ECM- and adhesion-related genes significantly increased, while that of ion channel-related genes significantly decreased with the CF proportion. Notably, 7CT showed the greatest contractility of all 3D-CTs. When exposed to E-4031 (hERG K channel blocker), 7CT and 5CT showed significantly decreased contractility and increased QT prolongation. Moreover, 10CT and 7CT exhibited a stronger response to isoproterenol than did the other 3D-CTs. Finally, 7CT showed the highest drug sensitivity among all 3D-CTs. In conclusion, 3D-CTs with an appropriate amount of fibroblasts/endothelial cells (7CT in this study) are suitable drug screening systems, e.g. for the detection of drug-induced arrhythmia.
Hepatoprotective effect of Thymus vulgaris extract on sodium nitrite-induced changes in oxidative stress, antioxidant and inflammatory marker expression
Authors: Soliman Mohamed Mohamed , Aldhahrani Adil , Metwally Mohammed M. M. 
Published: March 2021

AbstractThe herb thyme (Thymus vulgaris) has multiple therapeutic uses. In this study, we explored how T. vulgaris leaf extract protects liver cells against sodium nitrite-(NaNO2) induced oxidative stress. Mice were divided into four groups; each group received one of the following treatments orally: saline; T. vulgaris extract alone; NaNO2 alone; or T. vulgaris extract + NaNO2. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), reduced glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), IL-1β, IL-6, TNF-α, and total proteins were measured in serum using standard methods. TNF-α, hemooxygenase-1 (HO-1), thioredoxin, SOD, and GSH synthase, all of which are linked to oxidative stress, were measured using quantitative real-time PCR (qRT-PCR). In mice treated with T. vulgaris extract, the effect of NaNO2 on ALT and AST levels and total proteins was reduced, and its effect on antioxidant levels was reversed. Normally, NaNO2 causes hepatocyte congestion and severe hepatic central vein congestion. Tissues in the mice treated with T. vulgaris were restored to normal conditions. Our results demonstrate that NaNO2-induced hepatic injury is significantly reduced by pretreatment with T. vulgaris extract, which protects against hepatic oxidative stress and its associated genes at the biochemical, molecular, and cellular levels.
Association of early failure of arteriovenous fistula with mortality in hemodialysis patients
Authors: Yap Yit-Sheung , Chi Wen-Che , Lin Cheng-Hao , Liu Yi-Chun , Wu Yi-Wen 
Published: March 2021

AbstractArteriovenous fistula (AVF) is prone to early dysfunction and relates to poor outcome. However, little is known about the role of early AVF dysfunction as an independent risk factor for death in hemodialysis patients. A retrospective cohort study was performed using data of patients who underwent initial AVF surgery at a single institution. Demographic, clinical, biochemistry and AVF parameters were extracted from the electronic records, and the association between these variables and mortality was analyzed by Cox proportional hazards model. A total of 501 patients on hemodialysis (63.4 ± 12.7 years, 57.3% male) were included, and the median observation period was 3.66 years. In multivariate analysis, early failure of AVF (hazard ratio (95% confidence interval): 1.54 (1.06–2.24); p = 0.023) was associated with overall mortality but not cardiovascular mortality. Other identified predictors of overall mortality included older age, peripheral artery disease (PAD), cardiomegaly, higher white blood cell (WBC) count and corrected calcium level, and lower total cholesterol level, while predictors of cardiovascular mortality included older age, coronary artery disease (CAD), PAD and lower hemoglobin level. In conclusion, patients with early AVF failure were associated with increased risk of overall mortality.