bluuebunny/crossref_metadata_2025_split huggingface dataset:
Romina: A powerful strawberry with in vitro efficacy against uterine leiomyoma cells
Authors: Giampieri Francesca , Islam Md Soriful , Greco Stefania , Gasparrini Massimiliano , Forbes Hernandez Tamara Y. , Delli Carpini Giovanni , Giannubilo Stefano Raffaele , Ciavattini Andrea , Mezzetti Bruno , Mazzoni Luca , Capocasa Franco , Castellucci Mario , Battino Maurizio , Ciarmela Pasquapina 
Published: October 2018

AbstractUterine leiom yomas are benign tumors highly prevalent in reproductive women. In thecurrent study, initially, we aimed to screen five different strawberry cultivars (Alba, Clery, Portola, Tecla, and Romina) to identify efficient cultivars in terms of phytochemical characterization and biological properties by measuring phenolic and anthocyanin content as well as antioxidant capacity, and by measuring apoptotic rate and reactive oxygen species (ROS) production in uterine leiomyoma cells. Next, we focused on the most efficient ones, cultivar Alba (A) and Romina (R) as well as Romina anthocyanin (RA) fraction for their ability to regulate oxidative phosphorylation (oxygen consumption rate [OCR]) glycolysis (extracellular acidification rate [ECAR]), and also fibrosis. Leiomyoma and myometrial cells were treated with a methanolic extract of A and R (250 μg/ml) or with RA (50 μg/ml) for 48 hr to measure OCR and ECAR, as well as gene expression associated with fibrosis. In the leiomyoma cells, RA was more effective in inducing apoptosis and increasing intracellular ROS levels, followed by R and A. In myometrial cells, all strawberry treatments increased the cellular viability and decreased ROS concentrations. Leiomyoma cells showed also a significant decrease in ECAR, especially after RA treatment, while OCR was slightly increased in both myometrial and leiomyoma cells. R and RA treatment significantly decreased collagen 1A1, fibronectin, versican, and activin A messenger RNA expression in leiomyoma cells. In conclusion, this study suggests that Romina, or its anthocyanin fraction, can be developed as a therapeutic and/or preventive agent for uterine leiomyomas, confirming the healthy effects exerted by these fruits and their bioactive compounds.
EA15, MIR22, LINC00472 as diagnostic markers for diabetic kidney disease
Authors: Wang Yan‐Zhe , Zhu Ding‐Yu , Xie Xin‐Miao , Ding Miao , Wang Yong‐Lan , Sun Lin‐Lin , Zhang Nan , Shen E. , Wang Xiao‐Xia 
Published: October 2018

AbstractThis study aimed to investigate the molecular mechanisms of diabetic kidney disease (DKD) and to explore new potential therapeutic strategies and biomarkers for DKD. First we analyzed the differentially expressed changes between patients with DKD and the control group using the chip data in Gene Expression Omnibus (GEO) database. Then the gene chip was subjected to be annotated again, so as to screen long noncoding RNAs (lncRNAs) and study expression differences of these lncRNAs in DKD and controlled samples. At last, the function of the differential lncRNAs was analyzed. A total of 252 lncRNAs were identified, and 14 were differentially expressed. In addition, there were 1,629 differentially expressed messenger RNAs (mRNAs) genes, and proliferation and apoptosis adapter protein 15 (PEA15),
MIR22, and long intergenic nonprotein coding RNA 472 (
LINC00472) were significantly differentially expressed in DKD samples. Through functional analysis of the encoding genes coexpressed by the three lncRNAs, we found these genes were mainly enriched in type 1 diabetes and autoimmune thyroid disease pathways, whereas in Gene Ontology (GO) function classification, they were also mainly enriched in the immune response, type I interferon signaling pathways, interferon‐γ mediated signaling pathways, and so forth. To summary, we identified
EA15,
MIR22, and
LINC00472 may serve as the potential diagnostic markers of DKD.
Long noncoding RNA gastric cancer‐associated transcript 3 plays oncogenic roles in glioma through sponging miR‐3127‐5p
Authors: Pan Bailin , Zhao Ming , Xu Longbiao 
Published: October 2018

AbstractEvidence is emerging that long noncoding RNAs (lncRNAs) play vital roles in tumorigenesis. LncRNA gastric cancer‐associated transcript 3 (GACAT3) is reported to participate in the development of breast cancer, colorectal cancer, nonsmall cell lung cancer, and gastric cancer. However, whether it is implicated in glioma has not been elucidated. Here, we found that GACAT3 level was aberrantly elevated in glioma tissues and cell lines. Higher GACAT3 expression predicted lower survival rate. Knockdown of GACAT3 suppressed the proliferation, colony formation, migration, and invasion but promoting apoptosis in glioma cells. Next, we determined that GACAT3 contributes to glioma progression through inhibiting microRNA (miR)‐3127‐5p. Subsequently, ELAVL1 was identified as a direct target of miR‐3127‐5p by bioinformatics analysis and luciferase reporter assay. Moreover, we confirmed that GACAT3 promoted ELAVL1 expression through sponging miR‐3127‐5p, leading to glioma progression. Taken together, our study elucidated that GACAT3/miR‐3127‐5p/ELAVL1 signaling regulates glioma development and might be a promising therapeutic target.
Lipopolysaccharide‐induced proliferation and glycolysis in airway smooth muscle cells via activation of Drp1
Authors: Zhang Lixin , Ma Cui , Wang Xiaoying , He Siyu , Li Qian , Zhou Yutian , Liu Ying , Zhang Min , Yu Xiufeng , Zhao Xijuan , Li Fei , Zhu Da‐ling 
Published: October 2018

AbstractAbnormal airway smooth muscle cells (ASMCs) proliferation is an important pathological process in airway remodeling contributes to increased mortality in asthma. Mitochondrial dynamics and metabolism have a central role in the maintenance of the cell function. In this study, lipopolysaccharide (LPS)‐induced ASMCs proliferative model was used to investigate the effect of mitochondria on the proliferation of ASMCs and the possible mechanism. We used cell and molecular biology to determine the effect of dynamin‐related protein 1 (Drp1) on LPS‐mediated ASMCs cell cycle progression and glycolysis. The major findings of the current study are as follows: LPS promoted an increased mitochondrial fission and phosphorylation of Drp1 at Ser616 (p‐Drp1 Ser616). LPS‐induced ASMCs proliferation and cell cycle progression, which was significantly inhibited application of Drp1 RNA interfering. Glycolysis inhibitor 2‐deoxyglucose (2‐DG) depressed ASMCs proliferative process induced by LPS stimulation. LPS caused mitochondrial metabolism disorders and aerobic glycolysis in a dependent on Drp1 activation. These results indicated that Drp1 may function as a key factor in asthma airway remodeling by mediating ASMC proliferation and cell cycle acceleration through an effect on mitochondrial metabolic disturbance.
Retracted: Resistin effects on pancreatic cancer progression and chemoresistance are mediated through its receptors CAP1 and TLR4
Authors: Zhang Min , Yan Li , Wang Gui‐Jie , Jin Ronghui 
Published: October 2018

AbstractResistin, secreted by macrophages in tumor microenvironment, has never been investigated in pancreatic cancer models, despite a vibrant tumor microenvironment around pancreatic tumors. We evaluated serum resistin levels in healthy individuals versus pancreatic cancer patients representing different tumor grades. In vitro mechanistic analysis involved MiaPaCa‐2 and SW1990 cells. Resistin signaling depends on binding of resistin to its cognitive receptors. Therefore, we silenced adenylyl cyclase‐associated protein 1 (CAP1) and toll‐like receptor 4 (TLR4), its two known receptors, individually as well as in combination, by short hairpin RNA (shRNA). Effect of resistin on cell proliferation, migration, invasion, cell cycle, and sensitivity to gemcitabine was studied without or with silencing of resistin receptors CAP1 and/or TLR4. The results were also confirmed in vivo in mice xenografted with MiaPaCa‐2 cells without or with receptor silencing. We report high resistin levels in pancreatic cancer patients which correlate positively with tumor grades. We observed a marked reduction in the resistin‐induced proliferation, migration, invasion, and cell cycle of pancreatic cancer cells MiaPaCa‐2 and SW1990 when the receptors were silenced. The results were confirmed in vivo wherein resistin effects were significantly attenuated in MiaPaCa‐2 xenografts with silenced receptors. The combined silencing of CAP1 and TLR4 was found to be most effective in vitro and in vivo. We found activation of STAT3 by resistin in vivo and in vitro which was dependent on the presence of CAP1 and TLR4. Further, resistin was found to induce resistance to gemcitabine through its receptors. Our results describe novel functional roles of resistin with implications toward a better understanding of pancreatic tumor microenvironment.
Fusion of quantitative imaging features and serum biomarkers to improve performance of computer‐aided diagnosis scheme for lung cancer: A preliminary study
Authors: Gong Jing , Liu Ji‐yu , Jiang Yao‐jun , Sun Xi‐wen , Zheng Bin , Nie Sheng‐dong 
Published: October 2018

ObjectivesTo develop and test a new multifeature‐based computer‐aided diagnosis (CADx) scheme of lung cancer by fusing quantitative imaging (QI) features and serum biomarkers to improve CADx performance in classifying between malignant and benign pulmonary nodules.MethodsFirst, a dataset involving 173 patients was retrospectively assembled, which includes computed tomography (CT) images and five serum biomarkers extracted from blood samples. Second, a CADx scheme using a four‐step–based semiautomatic segmentation method was applied to segment the targeted lung nodules, and compute 78 QI features from each segmented nodule from CT images. Third, two support vector machine (SVM) classifiers were built using QI features and serum biomarkers, respectively. SVM classifiers were trained and tested using the overall dataset with a Relief feature selection method, a synthetic minority oversampling technique and a leave‐one‐case‐out validation method. Finally, to further improve CADx performance, an information‐fusion method was used to combine the prediction scores generated by two SVM classifiers.ResultsAreas under receiver operating characteristic curves (AUC) generated by QI feature and serum biomarker‐based SVMs were 0.81 ± 0.03 and 0.69 ± 0.05, respectively. Using an optimal weighted fusion method to combine prediction scores generated by two SVMs, AUC value significantly increased to 0.85 ± 0.03 (P < 0.05).ConclusionsThis study demonstrates (a) higher CADx performance by using QI features than using the serum biomarkers and (b) feasibility of further improving CADx performance by fusion of QI features and serum biomarkers, which indicates that QI features and serum biomarkers contain the complementary classification information.
CSBFinder: discovery of colinear syntenic blocks across thousands of prokaryotic genomes
Authors: Svetlitsky Dina , Dagan Tal , Chalifa-Caspi Vered , Ziv-Ukelson Michal 
Published: October 2018

Abstract

Motivation
Identification of conserved syntenic blocks across microbial genomes is important for several problems in comparative genomics such as gene annotation, study of genome organization and evolution and prediction of gene interactions. Current tools for syntenic block discovery do not scale up to the large quantity of prokaryotic genomes available today.

Results
We present a novel methodology for the discovery, ranking and taxonomic distribution analysis of colinear syntenic blocks (CSBs)—groups of genes that are consistently located close to each other, in the same order, across a wide range of taxa. We present an efficient algorithm that identifies CSBs in large genomic datasets. The algorithm is implemented and incorporated in a novel tool with a graphical user interface, denoted CSBFinder, that ranks the discovered CSBs according to a probabilistic score and clusters them to families according to their gene content similarity. We apply CSBFinder to data mine 1487 prokaryotic genomes including chromosomes and plasmids. For post-processing analysis, we generate heatmaps for visualizing the distribution of CSB family members across various taxa. We exemplify the utility of CSBFinder in operon prediction, in deciphering unknown gene function and in taxonomic analysis of colinear syntenic blocks.

Availability and implementation
CSBFinder software and code are publicly available at https://github.com/dinasv/CSBFinder.

Supplementary information
Supplementary data are available at Bioinformatics online.
Multitasking in Nursing Homes: Differences Between For-Profit and Nonprofit Quality Outcomes
Authors: Gaudet Hefele Jennifer , Wang Xiao (Joyce) , Bishop Christine E , Barooah Adrita 
Published: October 2018

Abstract

Background and Objectives
Nursing homes (NHs) in the United States face increasing pressures to admit Medicare postacute patients, given higher payments relative to Medicaid. Changes in the proportion of residents who are postacute may initiate shifts in care practices, resource allocations, and priorities. Our study sought to determine whether increases in Medicare short-stay census have an impact on quality of care for long-stay residents.

Research Design and Methods
This study used panel data (2005–2010) from publicly-available sources (Nursing Home Compare, Area Health Resource File, LTCFocus.org) to examine the relationship between a 1-year change in NH Medicare census and 14 measures of long-stay quality among NHs that experienced a meaningful increase in Medicare census during the study period (N = 7,932). We conducted analyses on the overall sample and stratified by for- and nonprofit ownership.

Results
Of the 14 long-stay quality measures examined, only one was shown to have a significant association with Medicare census: increased Medicare census was associated with improved performance on the proportion of residents with pressure ulcers. Stratified analyses showed increased Medicare census was associated with a significant decline in performance on 3 of 14 long-stay quality measures among nonprofit, but not for-profit, facilities.

Discussion and Implications
Our findings suggest that most NHs that experience an increase in Medicare census maintain long-stay quality. However, this may be more difficult to do for some, particularly nonprofits. As pressure to focus on postacute care mount in the current payment innovation environment, our findings suggest that most NHs will be able to maintain stable quality.
Alterations in the amplitude and burst distribution of sensorimotor beta oscillations impair reward-dependent motor learning in anxiety
Authors: Sporn Sebastian , Hein Thomas P. , Ruiz María Herrojo 
Published: October 2018

AbstractAnxiety results in sub-optimal motor performance and learning; yet, the precise mechanisms through which these modifications occur remain unknown. Using a reward-based motor sequence learning paradigm, we show that concurrent and prior anxiety states impair learning by biasing estimates about the hidden performance goal and the stability of such estimates over time (volatility). In an electroencephalography study, three groups of participants completed our motor task, which had separate phases for motor exploration (baseline) and reward-based learning. Anxiety was manipulated either during the initial baseline exploration phase or while learning. We show that anxiety induced at baseline reduced motor variability, undermining subsequent reward-based learning. Mechanistically, however, the most direct consequence of state anxiety was an underestimation of the hidden performance goal and a higher tendency to believe that the goal was unstable over time. Further, anxiety decreased uncertainty about volatility, which attenuated the update of beliefs about this quantity. Changes in the amplitude and burst distribution of sensorimotor and prefrontal beta oscillations were observed at baseline, which were primarily explained by the anxiety induction. These changes extended to the subsequent learning phase, where phasic increases in beta power and in the rate of long (> 500 ms) oscillation bursts following reward feedback were linked to smaller updates in predictions about volatility, with a higher anxiety-related increase explaining the biased volatility estimates. These data suggest that state anxiety alters the dynamics of beta oscillations during general performance, yet more prominently during reward processing, thereby impairing proper updating of motor predictions when learning in unstable environments.
BitMapperBS: a fast and accurate read aligner for whole-genome bisulfite sequencing
Authors: Cheng Haoyu , Xu Yun 
Published: October 2018

AbstractAs a gold-standard technique for DNA methylation analysis, whole-genome bisulfite sequencing (WGBS) helps researchers to study the genome-wide DNA methylation at single-base resolution. However, aligning WGBS reads to the large reference genome is a major computational bottleneck in DNA methylation analysis projects. Although several WGBS aligners have been developed in recent years, it is difficult for them to efficiently process the ever-increasing bisulfite sequencing data. Here we propose BitMapperBS, an ultrafast and memory-efficient aligner that is designed for WGBS reads. To improve the performance of BitMapperBS, we propose various strategies specifically for the challenges that are unique to the WGBS aligners, which are ignored in most existing methods. Our experiments on real and simulated datasets show that BitMapperBS is one order of magnitude faster than the state-of-the-art WGBS aligners, while achieves similar or better sensitivity and precision. BitMapperBS is freely available at https://github.com/chhylp123/BitMapperBS.
Rapid covalent-probe discovery by electrophile fragment screening
Authors: Resnick Efrat , Bradley Anthony , Gan Jinrui , Douangamath Alice , Krojer Tobias , Sethi Ritika , Aimon Anthony , Amitai Gabriel , Belini Dom , Bennett James , Fairhead Michael , Fedorov Oleg , Geurink Paul P. , Guo Jingxu , Plotnikov Alexander , Reznik Nava , Ruda Gian Filippo , Saez Laura Diaz , Straub Verena M. , Szommer Tamas , Velupillai Srikannathasan , Zaidman Daniel , Coker Alun R. , Dowson Christopher G. , Barr Haim , Huber Killian V.M. , Brennan Paul E. , Ovaa Huib , Delft Frank von , London Nir 
Published: October 2018

AbstractCovalent probes can display unmatched potency, selectivity and duration of action, however, their discovery is challenging. In principle, fragments that can irreversibly bind their target can overcome the low affinity that limits reversible fragment screening. Such electrophilic fragments were considered non-selective and were rarely screened. We hypothesized that mild electrophiles might overcome the selectivity challenge, and constructed a library of 993 mildly electrophilic fragments. We characterized this library by a new high-throughput thiol-reactivity assay and screened them against ten cysteine-containing proteins. Highly reactive and promiscuous fragments were rare and could be easily eliminated. By contrast, we found selective hits for most targets. Combination with high-throughput crystallography allowed rapid progression to potent and selective probes for two enzymes, the deubiquitinase OTUB2, and the pyrophosphatase NUDT7. No inhibitors were previously known for either. This study highlights the potential of electrophile fragment screening as a practical and efficient tool for covalent ligand discovery.
Dual prognostic role for 2-oxoglutarate oxygenases in ten diverse cancer types: Implications for cell cycle regulation and cell adhesion maintenance
Authors: Chang Wai Hoong , Forde Donall , Lai Alvina G. 
Published: October 2018

AbstractObjectivesTumor hypoxia is associated with metastasis and resistance to chemotherapy and radiotherapy. Genes involved in oxygen-sensing are clinically relevant and have significant implications on prognosis.MethodsWe identified of two signatures, signature 1 (good prognosis) and signature 2 (adverse prognosis), each consisting of 5 genes using three pancreatic cancer cohorts (n=681). We validated the signatures’ performance in predicting survival in ten cancers using Cox regression and receiver operating characteristic (ROC) analyses.ResultsSignature 1 and signature 2 were associated with good and poor overall survival respectively. Prognosis of signature 1 in 8 cohorts representing 6 cancers (n=2,627): bladder (hazard ratio [HR]=0.68, P=0.039), papillary renal cell (HR=0.35, P=0.013), liver (HR=0.64, P=0.033 and HR=0.49, P=0.025), lung (HR=0.66, P=0.014) and pancreatic (HR=0.42, P<0.001 and HR=0.64, P=0.04) and endometrial (HR=0.40, P<0.001). Prognosis of signature 2 in 12 cohorts representing 9 cancers (n=4,134): bladder (HR=1.46, P=0.039), cervical (HR=1.97, P=0.035), head and neck (HR=1.39, P=0.038), renal clear cell (HR=1.47, P=0.012), papillary renal cell (HR=3.89, P=0.0015), liver (HR=5.10, P<0.0001 and HR=2.26, P<0.001), lung (HR=1.54, P=0.011), pancreatic (HR=2.09, P=0.002, HR=1.46, P=0.018, and HR=1.99, P<0.0001) and stomach (HR=1.78, P=0.004). Multivariate Cox regression confirmed independent clinical relevance of signatures in these cancers. ROC analyses confirmed superior performance of signatures to current tumor staging benchmarks. KDM8 is a potential tumor suppressor downregulated in liver and pancreatic cancers and is an independent prognostic factor. KDM8 expression negatively correlated with cell cycle regulators. Low KDM8 in tumors was associated with loss of cell adhesion phenotype through HNF4A signaling.ConclusionsPan-cancer signatures of oxygen-sensing genes used for risk assessment in 10 cancers (n=6,761) could guide individualized treatment plans.
Asi1 regulates the distribution of proteins at the inner nuclear membrane inSaccharomyces cerevisiae
Authors: Smoyer Christine J. , Smith Sarah E. , McCroskey Scott , Unruh Jay R. , Jaspersen Sue L. 
Published: October 2018

AbstractInner nuclear membrane (INM) protein composition regulates nuclear function, affecting processes such as gene expression, chromosome organization, nuclear shape and stability. Mechanisms that drive changes in the INM proteome are poorly understood in part because it is difficult to definitively assay INM composition rigorously and systematically. Using a split-GFP complementation system to detect INM access, we examined the distribution of all C-terminally taggedSaccharomyces cerevisiaemembrane proteins in wild-type cells and in mutants affecting protein quality control pathways, such as INM-associated degradation (INMAD), ER-associated degradation (ERAD) and vacuolar proteolysis. Deletion of the E3 ligase Asi1 had the most pronounced effect on the INM compared to mutants in vacuolar or ER-associated degradation pathways, consistent with a role for Asi1 in the INMAD pathway. Our data suggests that Asi1 not only removes mis-targeted proteins at the INM, but it also controls the levels and distribution of native INM components, such as the membrane nucleoporin Pom33. Interestingly, loss of Asi1 does not affect Pom33 protein levels but instead alters Pom33 distribution in the NE through Pom33 ubiquitination, which drives INM redistribution. Taken together, our data demonstrate that the Asi1 E3 ligase has a novel function in INM protein regulation in addition to protein turnover.