bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aptima Human Papillomavirus E6/E7 mRNA Test Results Strongly Associated With Risk for High-Grade Cervical Lesions in Follow-Up Biopsies
Authors: Ge Yimin , Christensen Paul , Luna Eric , Armylagos Donna , Xu Jiaqiong , Schwartz Mary R. , Mody Dina R. 
Published: March 2018

Objective
Human papillomavirus (HPV) tests and genotyping (GT) have been used in clinical risk assessment. The purpose of this study was to analyze the performance of 2 common HPV testing platforms in risk evaluation for high-grade cervical lesions.

Materials and Methods
Between January 1, 2015, and December 31, 2016, a total of 4,562 Pap tests with follow-up biopsies in our laboratory database were analyzed along with HPV tests performed on Cobas (CHPV, n = 3,959) or Aptima (AHPV, n = 603) platforms.

Results
The sensitivity for biopsy-confirmed HSIL or worse lesions was 97% for both CHPV and AHPV (p = .75). AHPV showed significantly lower positive rates than CHPV in benign (56% vs 86%) or LSIL (66% vs 90%) biopsies, resulting in significantly higher specificity for HSIL or worse than CHPV (38% vs 12%, p < .001). AHPV demonstrated significantly higher positive predictive value for HSIL or worse (24% vs 16%, p < .001) and overall accuracy (48% vs 24%, p < .001) than CHPV. AHPV GT also had significantly higher specificity for biopsy-confirmed HSIL or worse than CHPV (88% vs 72%, p < .001) with comparable sensitivity (50% vs 51%, p = .75). Women with HPV 16 on AHPV were significantly more likely to have HSIL or worse on biopsies than those with HPV 16 on CHPV (likelihood ratio = 4.3 vs 2.0, p = .004).

Conclusions
Although both AHPV and CHPV were highly sensitive for biopsy-confirmed HSIL or worse lesions, AHPV and GT demonstrated significantly higher specificity and positive predictive value than CHPV. The difference is probably related to E6/E7 overexpression after viral DNA integration in high-grade lesions. The significantly higher specificity and overall accuracy of AHPV and GT for HSIL or worse lesions may be useful in clinical risk management.
MicroRNAs in endothelial cell homeostasis and vascular disease
Authors: Fernández-Hernando Carlos , Suárez Yajaira 
Published: March 2018

Purpose of review
Since the first discovery of microRNAs (miRNAs) in 1993, the involvement of miRNAs in different aspects of vascular disease has emerged as an important research field. In this review, we summarize the fundamental roles of miRNAs in controlling endothelial cell functions and their implication with several aspects of vascular dysfunction.

Recent findings
MiRNAs have been found to be critical modulators of endothelial homeostasis. The dysregulation of miRNAs has been linked to endothelial dysfunction and the development and progression of vascular disease which and open new opportunities of using miRNAs as potential therapeutic targets for vascular disease.

Summary
Further determination of miRNA regulatory circuits and defining miRNAs-specific target genes remains key to future miRNA-based therapeutic applications toward vascular disease prevention. Many new and unanticipated roles of miRNAs in the control of endothelial functions will assist clinicians and researchers in developing potential therapeutic applications.
Qualitative Content Analysis of Coworkers’ Safety Reports of Unprofessional Behavior by Physicians and Advanced Practice Professionals
Authors: Martinez William , Pichert James W. , Hickson Gerald B. , Braddy Casey H. , Brown Amy J. , Catron Thomas F. , Moore Ilene N. , Stampfle Morgan R. , Webb Lynn E. , Cooper William O. 
Published: March 2018

Objectives
The aims of the study were to develop a valid and reliable taxonomy of coworker reports of alleged unprofessional behavior by physicians and advanced practice professionals and determine the prevalence of reports describing particular types of unprofessional conduct.

Methods
We conducted qualitative content analysis of coworker reports of alleged unprofessional behavior by physicians and advanced practice professionals to create a standardized taxonomy. We conducted a focus group of experts in medical professionalism to assess the taxonomy’s face validity. We randomly selected 120 reports (20%) of the 590 total reports submitted through the medical center’s safety event reporting system between June 2015 and September 2016 to measure interrater reliability of taxonomy codes and estimate the prevalence of reports describing particular types of conduct.

Results
The initial taxonomy contained 22 codes organized into the following four domains: competent medical care, clear and respectful communication, integrity, and responsibility. All 10 experts agreed that the four domains reflected essential elements of medical professionalism. Interrater reliabilities for all codes and domains had a κ value greater than the 0.60 threshold for good reliability. Most reports (60%, 95% confidence interval = 51%–69%) described disrespectful or offensive communication. Nine codes had a prevalence of less than 1% and were folded into their respective domains resulting in a final taxonomy composed of 13 codes.

Conclusions
The final taxonomy represents a useful tool with demonstrated validity and reliability, opening the door for reliable analysis and systems to promote accountability and behavior change. Given the safety implications of unprofessional behavior, understanding the typology of coworker observations of unprofessional behavior may inform organization strategies to address this threat to patient safety.
A Prospective Cohort Study of Fertility Desire, Unprotected Sex, and Detectable Viral Load in HIV-Positive Female Sex Workers in Mombasa, Kenya
Authors: Wilson Kate S. , Wanje George , Masese Linnet , Simoni Jane M. , Shafi Juma , Adala Lucy , Overbaugh Julie , Jaoko Walter , Richardson Barbra A. , McClelland Raymond S. 
Published: March 2018

Background:Little is known about fertility desire in HIV-positive female sex workers. Fertility desire could increase HIV transmission risk if it was associated with condomless sex or lower adherence to antiretroviral therapy.Methods:A prospective cohort study was conducted among 255 HIV-positive female sex workers in Mombasa, Kenya. Using generalized estimating equations, fertility desire was evaluated as a risk factor for semen detection in vaginal secretions by prostate-specific antigen (PSA) test, a biomarker of condomless sex, detectable plasma viral load (VL), and HIV transmission potential, defined as visits with positive PSA and detectable VL.Results:The effect of fertility desire on PSA detection varied significantly by nonbarrier contraception use (P-interaction < 0.01). At visits when women reported not using nonbarrier contraception, fertility desire was associated with higher risk of semen detection [82/385, 21.3% vs. 158/1007, 15.7%; adjusted relative risk (aRR) 1.58, 95% confidence interval (CI): 1.12 to 2.23]. However, when women used nonbarrier contraception, fertility desire was associated with lower risk of PSA detection (10/77, 13.0% vs. 121/536, 22.6%; aRR 0.58, 95% CI: 0.35 to 0.94). Fertility desire was not associated with detectable VL (31/219, 14.2% vs. 128/776, 16.5%; aRR 0.82, 95% CI: 0.46 to 1.45) or higher absolute risk of transmission potential (10/218, 4.6% vs. 21/769, 2.7%; adjusted risk difference = 0.011, 95% CI −0.031 to 0.050).Conclusions:Fertility desire was associated with higher risk of biological evidence of semen exposure when women were not using nonbarrier contraceptives. Low HIV transmission potential regardless of fertility desire suggests that the combination of condoms and antiretroviral therapy adherence was effective.
Reduction of Artifacts Caused by Deep Brain Stimulating Electrodes in Cranial Computed Tomography Imaging by Means of Virtual Monoenergetic Images, Metal Artifact Reduction Algorithms, and Their Combination
Authors: Große Hokamp Nils , Hellerbach Alexandra , Gierich Andreas , Jordan David W. , Visser-Vandewalle Veerle , Maintz David , Haneder Stefan 
Published: March 2018

Objectives
The aim of this study was to evaluate the reduction of artifacts from deep brain stimulation electrodes (DBS) using an iterative metal artifact reduction algorithm (O-MAR), virtual monoenergetic images (VMI), and both in combination in postoperative spectral detector computed tomography using a dual-layer detector (spectral detector computed tomography [SDCT]) of the head.

Material and Methods
Nonanthropomorphic phantoms with different DBS leads were examined on SDCT; in 1 phantom periprocedural bleeding was simulated. A total of 20 patients who underwent SDCT after DBS implantation between October 2016 and April 2017 were included in this institutional review board–approved retrospective study. Images were reconstructed using standard-of-care iterative reconstruction (CI) and VMI, each with and without O-MAR processing (IR and MAR). Artifacts were quantified by determining the percentage integrity uniformity in an annular region of 1.4 cm2 around the DBS lead; a percentage integrity uniformity of 100% indicates the absence of artifacts. In phantoms, conspicuity of blood was determined on a binary scale, whereas in patients, image quality, DBS lead assessment, and extent of artifact reduction were assessed on Likert scales by 2 radiologists. Statistical significance was assessed using analysis of variance and Wilcoxon tests; sensitivity and specificity were calculated.

Results
The O-MAR processing significantly decreased artifacts in phantom and patients (P ≤ 0.05), whereas VMI did not reduce artifact burden compared with corresponding CI (P > 0.05): for example, CI-IR/MAR and 200 keV-IR/MAR for patients: 76.3%/90.7% and 75.9%/91.2%, respectively. Qualitatively, overall image quality was not improved (P > 0.05) and MAR improved DBS assessment (CI-IR/MAR: 2 [1–3]/3 [2–4]; P ≤ 0.05) and reduced artifacts significantly (P ≤ 0.05). The O-MAR processing increased sensitivity for bleeding by 160%. In some cases, new artifacts were induced through O-MAR processing, none of which impaired diagnostic image assessment.

Discussion
The investigated O-MAR algorithm reduces artifacts from DBS electrodes and should be used in the assessment of postoperative patients; however, combination with VMI does not provide an additional benefit.
Involvement of TLR4 and PPAR-α Receptors in Host Response and NLRP3 Inflammasome Activation, Against Pulmonary Infection With Pseudomonas Aeruginosa
Authors: Gugliandolo Enrico , Fusco Roberta , Ginestra Giovanna , D’amico Ramona , Bisignano Carlo , Mandalari Giuseppina , Cuzzocrea Salvatore , Di Paola Rosanna 
Published: March 2018

ABSTRACT

Background:
Colonization with Pseudomonas aeruginosa (PA), the most common pathogen isolated mainly in patients with cystic fibrosis, is particularly difficult to eradicate and is associated with acceleration of decline in lung function and with poorer prognosis. PA LPS is recognized by Toll-like receptors-4 (TLR4) and has been shown to induce lung inflammation in vivo. In addition, regulation of this process is essential for proper pathogen clearance and to prevent excessive inflammatory response resulting in tissue damage. One potential regulator of these process is the peroxisome proliferator-activated receptors (PPARs), and in particular PPARα. Thus, the purpose of the present study was to evaluate the effects of the absence of TLR4 and PPARα receptors in the pulmonary innate immunity response to PA and in the consequent inflammatory response and in the activation of the macromolecular complex of the NLRP3 inflammosome.

Methods:
To evaluate the involvement of TLR4 and PPARα in a PA infection, we used TLR4 KO and PPARα KO mice that received an intratracheal (i.t.) administration of 50 μL of PA strain (106 CFU), thus evaluating if these mice were profoundly susceptible to PA compared with WT mice.

Results:
The results of the present study showed that administration of PA worsened the pathophysiology of PA lung disease in TLR4 and PPARα KO mice compared with WT mice.

Conclusions:
The present study demonstrated that TLR4 and PPARα receptors would mediate the earliest control of bacterial replication as well as proinflammatory responses to PA infections, and in particular that PPARα receptors are needed to prevent an excessive inflammatory response, as in the control of the inflammasome complex NLP3 activation.
Acidic microenvironment shaped by lactate accumulation promotes pluripotency through multiple mechanisms
Authors: Guo Wen-Ting , Wang Shao-Hua , Zhang Xiao-Shan , Shi Ming , Hao Jing , Wang Xi-Wen , Gu Kai-Li , Duan Fei-Fei , Yan Ying , Yang Xi , Zhang Chao , Liao Le-Qi , Wang Yangming 
Published: March 2018

AbstractEnhanced glycolysis is a distinct feature associated with numerous stem cells and cancer cells. However, little is known about its regulatory roles in gene expression and cell fate determination. Here we show that acidic environment shaped by lactate accumulation promotes the self-renewal and pluripotency of both mouse and human embryonic stem cells (ESCs). Mechanistically, acidic pH reduces the tri-methylation of H3K27 globally at transcriptional start sites to partially prevent ESC differentiation. In addition, acidic pH stabilizes a large number of mRNAs including pluripotency genes. Furthermore, we found that AGO1 protein is downregulated at acidic conditions, leading to the de-repression of a subset of microRNA targets in low-pH treated ESCs. Altogether, our study provides insights into mechanisms whereby acidic microenvironment produced by enhanced glycolysis regulates gene expression to determine cell fate and has broad implications in the fields of regenerative medicine and cancer biology.
Cohesiveness in microbial community coalescence
Authors: Lu Nanxi , Sanchez-Gorostiaga Alicia , Tikhonov Mikhail , Sanchez Alvaro 
Published: March 2018

AbstractMicrobial invasions exhibit many unique properties; notably, entire microbial communities often invade one another, a phenomenon known as community coalescence. In spite of the potential importance of this process for the dynamics and stability of microbiome assembly, our understanding of it is still very limited. Recent theoretical and empirical work has proposed that large microbial communities may exhibit an emergent cohesiveness, as a result of collective consumer-resource interactions and metabolic feedbacks between microbial growth and the environment. A fundamental prediction of this proposal is the presence of ecological co-selection during community coalescence, where the invasion success of a given taxon is determined by its community members. To establish the generality of this prediction in experimental microbiomes, we have performed over one hundred invasion and coalescence experiments with environmental communities of different origins that had spontaneously and stably assembled in two different synthetic aerobic environments. We show that the dominant species of the coalesced communities can both recruit their community members (top-down co-selection) and be recruited by them (bottom-up co-selection) into the coalesced communities. Our results provide direct evidence that collective invasions generically produce ecological co-selection of interacting species, emphasizing the importance of community-level interactions during microbial community assembly.
Using supervised learning methods for gene selection in RNA-Seq case-control studies
Authors: Wenric Stephane , Shemirani Ruhollah 
Published: March 2018

AbstractWhole transcriptome studies typically yield large amounts of data, with expression values for all genes or transcripts of the genome. The search for genes of interest in a particular study setting can thus be a daunting task, usually relying on automated computational methods. Moreover, most biological questions imply that such a search should be performed in a multivariate setting, to take into account the inter-genes relationships.Differential expression analysis commonly yields large lists of genes deemed significant, even after adjustment for multiple testing, making the subsequent study possibilities extensive.Here, we explore the use of supervised learning methods to rank large ensembles of genes defined by their expression values measured with RNA-Seq in a typical 2 classes sample set. First, we use one of the variable importance measures generated by the random forests classification algorithm as a metric to rank genes. Second, we define the EPS (extreme pseudo-samples) pipeline, making use of VAEs (Variational Autoencoders) and regressors to extract a ranking of genes while leveraging the feature space of both virtual and comparable samples.We show that, on 12 cancer RNA-Seq data sets ranging from 323 to 1210 samples, using either a random forests based gene selection method or the EPS pipeline outperforms differential expression analysis for 9 and 8 out of the 12 datasets respectively, in terms of identifying subsets of genes associated with survival.These results demonstrate the potential of supervised learning-based gene selection methods in RNA-Seq studies and highlight the need to use such multivariate gene selection methods alongside the widely used differential expression analysis.
Structural plasticity of CENP-A regulated by H4 influences cellular levels and kinetochore assembly
Authors: Malik Nikita , Dantu Sarath Chandra , Kombrabail Mamta , Ghosh Santanu Kumar , Krishnamoorthy Guruswamy , Kumar Ashutosh 
Published: March 2018

AbstractThe Histone variant CENP-ACse4 is a core component of the specialized nucleosome at the centromere in budding yeast. The level of Cse4 in cells is tightly regulated, primarily by ubiquitin-mediated proteolysis. However, the structural transitions in Cse4 that regulate centromere localization and interaction with regulatory components are poorly understood. Using time resolved fluorescence, NMR and molecular dynamics we show for the first time that soluble Cse4 can exist in a ‘closed’ conformation, inaccessible to various regulatory components. We further determined that binding of its obligate partner H4, alters the inter-domain interaction within Cse4, ensuring an ‘open’ state that will lend itself to proteolysis. This dynamic model allows kinetochore formation only in presence of H4, as the N-terminus, which is required for interaction with centromeric components will be unavailable in absence of H4. The specific requirement of H4 binding for the conformational regulation of Cse4 suggests a unique structure-based regulatory mechanism for Cse4 localization and prevention of premature kinetochore assembly.
Mutant Plasticity Related Gene 1 (PRG1) acts as a potential modifier in SCN1A related epilepsy
Authors: Knierim Ellen , Vogt Johannes , Kintscher Michael , Ponomarenko Alexey , Baumgart Jan , Beed Prateep , Korotkova Tatiana , Trimbuch Thorsten , Panzer Axel , Stephani Ulrich , Escayg Andrew , Lerche Holger , Nitsch Robert , Schmitz Dietmar , Schuelke Markus 
Published: March 2018

ABSTRACTPlasticity related gene 1 encodes a cerebral neuron-specific synaptic transmembrane protein that modulates hippocampal excitatory transmission on glutamatergic neurons. In mice, homozygous Prg1-deficiency results in juvenile epilepsy. Screening a cohort of 18 patients with infantile spasms (West syndrome), we identified one patient with a heterozygous mutation in the highly conserved third extracellular phosphatase domain (p.T299S). The functional relevance of this mutation was verified by in-utero electroporation of a mutant Prg1 construct into neurons of Prg1-knockout embryos, and the subsequent inability of hippocampal neurons to rescue the knockout phenotype on the single cell level. Whole exome sequencing revealed the index patient to additionally harbor a novel heterozygous SCN1A variant (p.N541S) that was inherited from her healthy mother. Only the affected child carried both heterozygous PRG1 and SCN1A mutations. The aggravating effect of Prg1-haploinsufficiency on the epileptic phenotype was verified using the kainate-model of epilepsy. Double heterozygous Prg1-/+|Scn1awt/p.R1648Hmice exhibited higher seizure susceptibility than either wildtype, Prg1-/+, or Scn1awt/p.R1648H littermates. Our study provides evidence that PRG1-mutations have a potential modifying influence on SCN1A-related epilepsy in humans.
Long-read DNA metabarcoding of ribosomal rRNA in the analysis of fungi from aquatic environments
Authors: Heeger Felix , Bourne Elizabeth C. , Baschien Christiane , Yurkov Andrey , Bunk Boyke , Spröer Cathrin , Overmann Jörg , Mazzoni Camila J. , Monaghan Michael T. 
Published: March 2018

ABSTRACTDNA metabarcoding is now widely used to study prokaryotic and eukaryotic microbial diversity. Technological constraints have limited most studies to marker lengths ofca.300-600 bp. Longer sequencing reads of several 5 thousand bp are now possible with third-generation sequencing. The increased marker lengths provide greater taxonomic resolution and enable the use of phylogenetic methods of classifcation, but longer reads may be subject to higher rates of sequencing error and chimera formation. In addition, most well-established bioinformatics tools for DNA metabarcoding were originally 10 designed for short reads and are therefore not suitable. Here we used Pacifc Biosciences circular consensus sequencing (CCS) to DNA-metabarcode environmental samples using aca.4,500 bp marker that included most of the eukaryote ribosomal SSU and LSU rRNA genes and the ITS spacer region. We developed a long-read analysis pipeline that reduced error rates to levels 15 comparable to short-read platforms. Validation using fungal isolates and a mock community indicated that our pipeline detected 98% of chimerasde novoi.e., even in the absence of reference sequences. We recovered 947 OTUs from water and sediment samples in a natural lake, 848 of which could be classifed to phylum, 486 to family, 397 to genus and 330 to species. By 20 allowing for the simultaneous use of three global databases (Unite, SILVA, RDP LSU), long-read DNA metabarcoding provided better taxonomic resolution than any single marker. We foresee the use of long reads enabling the cross-validation of reference sequences and the synthesis of ribosomal rRNA gene databases. The universal nature of the rRNA operon and our recovery of >100 25 non-fungal OTUs indicate that long-read DNA metabarcoding holds promise for the study of eukaryotic diversity more broadly.