bluuebunny/crossref_metadata_2025_split huggingface dataset:
Learning Curves for Two Fiberscopes in Simulated Difficult Airway Scenario With Cumulative Sum Method
Authors: Altun Demet , Ozkan-Seyhan Tulay , Camci Emre , Sivrikoz Nukhet , Orhan-Sungur Mukadder 
Published: March 2019

Introduction
The aims of this randomized prospective mannequin study were to determine the amount of attempts required for successful intubation using different fiberscopes (Bonfils and SensaScope) by inexperienced anesthesiologists in a difficult airway scenario and to build the associated learning curves.

Methods
Difficult airway simulation was achieved with tongue edema in mannequin. After approval of volunteers, we asked 15 anesthesiology residents without any experience with fiberscopes to intubate with each device in a random order. Intubation success (endotracheal intubation within 120 seconds), the degree of difficulty of intubation, and reality of simulation using a 10-point scale were recorded. Learning curves were generated with cumulative sum method.

Results
With Bonfils, 13 volunteers were able to pass lower decision boundary with a median number of 26 [95% confidence interval (CI) = 21.4–25.9] attempts, whereas in SensaScope, the same outcome was observed in 10 residents with a median number of attempts of 26 (95% CI = 23.5–32.5). Total success rate was found significantly higher with Bonfils compared with SensaScope (550/600 vs 512/600, respectively, P < 0.001). Intubation with Bonfils was considered as less difficult compared with SensaScope [median = 4 (95% CI = 3.32–4.42) and 6 (95% CI = 4.96–6.64), P = 0.01, respectively]. The reality of the simulation was rated as a median of 5 (95% CI = 4.37–5.8).

Conclusions
Although a similar number of attempts were required to reach predetermined competency for both fiberscopes, only 10 of residents were able to obtain the targeted success using SensaScope as compared with 13 with Bonfils. Inexperienced residents found intubation via Bonfils less difficult than SensaScope. High individual variability in obtaining competency observed in this study with cumulative sum analysis underlines the importance of defining success a priori to simulation, the need for follow-up of individual progress, and the need to offer adequate trials to achieve competency. Therefore, learning opportunities should be adapted accordingly.
Lifetime changes in CD4 count, viral load suppression and adherence among adolescents living with HIV in urban Peru
Authors: Rodriguez Carly A , Kolevic Lenka , Ramos Alicia , Wong Milagros , Munoz Maribel , Patel Kunjal , Franke Molly F 
Published: March 2019

AbstractIntroductionViral load suppression and adherence to combined antiretroviral therapy (cART) have been shown to be lower in adolescents than in other age groups; however, this relationship has not been documented longitudinally from childhood to adolescence and has rarely been examined outside of high-resource settings and sub-Saharan Africa. To address this knowledge gap, we quantified longitudinal changes in CD4 cell count, viral load suppression, and cART adherence in adolescents living with HIV in urban, Peru.MethodsWe conducted a retrospective chart review among adolescents ages 10-18 years on cART and receiving care at a large, public sector pediatric hospital as of December 2015. We abstracted clinical notes indicating nonadherence and viral load and CD4 counts from childhood to adolescence. We modeled the association between age and each outcome with restricted cubic splines accounting for multiple observations per person, and graphed study outcomes by age.ResultsA median of 7.7 years (25th percentile=4.9, 75th percentile=10.2) of follow up were observed for 128 adolescents. Nearly 70% of patients had at least one nonadherence note and the proportion with nonadherence increased log-linearly with age (p<0.0001). The peak proportion with viral load suppression was 84% (95% CI: 79, 88) at age 13, which dropped to 67% (95% CI: 47, 83) by age 18. Mean CD4 count decreased at age 13, dropping from 723 cells/mm3 (95% CI: 666, 784) to 429 cells/mm3 (95% CI: 356, 517) by age 18.ConclusionThis is the first report from Latin America to examine longitudinal changes in HIV outcomes from childhood into adolescence. Consistent with the limited evidence from other settings, decreases in viral load suppression and mean CD4 count occurred in early adolescence in tandem with increases in nonadherence. Adolescent-friendly cART adherence support interventions to target this critical period are urgently needed.
Patterns and predictors ofStaphylococcus aureuscarriage during the first year of life; a longitudinal study
Authors: Reiss-Mandel Aylana , Rubin Carmit , Maayan-Mezger Ayala , Novikov Ilya , Jaber Hanaa , Dolitzky Mordechay , Freedman Laurence , Rahav Galia , Regev-Yochay Gili 
Published: March 2019

AbstractObjectives’To determine the patterns ofS. aureuscarriage in the first year of life, its determinants and dynamics of transmission between mothers and infants.MethodsProspective longitudinal cohort study ofS. aureuscarriage among mothers and their infants. Monthly screenings from pregnancy/birth through the first year of the infant’s life. Medical and lifestyle data was collected. InfantS. aureuscarriage was detected by rectal and nasal swabs and maternal carriage by nasal swabs. Multivariate analysis and an NLMixed model were used to determine predictors of carriage andS. aureuspersistence.Results130S. aureuscarrier women and their 132 infants were included in the study. 93% of the infants acquiredS. aureussometime during the first year of life, 64% of them acquired the maternal strain, mostly (66%) during the first month of life. 70 women (52.50%) and 17 infants (14%) carriedS. aureuspersistently. Early acquisition ofS. aureuscarriage was associated with longer duration of initial carriage and was the most significant predictor ofS. aureuspersistence, while day-care center attendance was negatively associated with persistent carriage.ConclusionsEarly acquisition ofS. aureus, mostly from the mother, is an important determinant of carriage persistence in infancy.
Measures of states of consciousness during attentional and cognitive load
Authors: Nilsen André S. , Juel Bjørn E. , Storm Johan F. 
Published: March 2019

AbstractBackgroundDeveloping and testing methods for reliably assessing states of consciousness in humans is important for both basic research and clinical purposes. Several potential measures, partly grounded in theoretical developments, have been proposed, and some of them seem to reliably distinguish between conscious and unconscious brain states. However, the degrees to which these measures may also be affected by changes in brain activity or conditions that can occur within conscious brain states have rarely been tested. In this study we test whether several of these measures are modulated by attentional load and related use of cognitive resources.MethodsWe recorded EEG from 12 participants while they passively received three types of stimuli: (1) transcranial magnetic stimulation (TMS) pulses (for measuring perturbational complexity), (2) auditory stimuli (for detection of auditory pattern deviants), or (3) audible clicks from a clock (spontaneous EEG, for measures of signal diversity and functional connectivity). We investigated whether the measures significantly differed between the passive condition and a attentional and cognitively demanding working memory task.ResultsOur results showed that in the attention-based auditory P3b ERP measure (global auditory pattern deviant) was significantly affected by increased attentional and cognitive load, while the various measures based on spontaneous and perturbed EEG were not affected.ConclusionMeasures of conscious state based on complexity, diversity, and effective connectivity, are not affected by attentional and cognitive load, suggesting that these measures can be used to test both for the presence and absence of consciousness.
Structure-guided enhancement of selectivity of chemical probe inhibitors targeting bacterial seryl-tRNA synthetase
Authors: Cain Ricky , Salimraj Ramya , Punekar Avinash S. , Bellini Dom , Fishwick Colin W. G. , Czaplewski Lloyd , Scott David J. , Harris Gemma , Dowson Christopher G. , Lloyd Adrian J. , Roper David I. 
Published: March 2019

AbstractAminoacyl-tRNA synthetases are ubiquitous and essential enzymes for protein synthesis and also a variety of other metabolic processes, especially in bacterial species. Bacterial aminoacyl-tRNA synthetases represent attractive and validated targets for antimicrobial drug discovery if issues of prokaryotic versus eukaryotic selectivity and antibiotic resistance generation can be addressed. We have determined high resolution X-ray crystal structures of the Escherichia coli and Staphylococcus aureus seryl-tRNA synthetases in complex with aminoacyl adenylate analogues and applied a structure-based drug discovery approach to explore and identify a series of small molecule inhibitors that selectively inhibit bacterial seryl-tRNA synthetases with greater than two orders of magnitude compared to their human homologue, demonstrating a route to selective chemical inhibition of these bacterial targets.
Effective Clustering for Single Cell Sequencing Cancer Data
Authors: Ciccolella Simone , Patterson Murray , Bonizzoni Paola , Vedova Gianluca Della 
Published: March 2019

AbstractSingle cell sequencing (SCS) technologies provide a level of resolution that makes it indispensable for inferring from a sequenced tumor, evolutionary trees or phylogenies representing an accumulation of cancerous mutations. A drawback of SCS is elevated false negative and missing value rates, resulting in a large space of possible solutions, which in turn makes it difficult, sometimes infeasible using current approaches and tools. One possible solution is to reduce the size of an SCS instance — usually represented as a matrix of presence, absence, and uncertainty of the mutations found in the different sequenced cells — and to infer the tree from this reduced-size instance. In this work, we present a new clustering procedure aimed at clustering suchcategoricalvector, or matrix data — here representing SCS instances, calledcelluloid. We show that celluloid clusters mutations with high precision: never pairing too many mutations that are unrelated in the ground truth, but also obtains accurate results in terms of the phylogeny inferred downstream from the reduced instance produced by this method. We demonstrate the usefulness of a clustering step by applying the entire pipeline (clustering + inference method) to a real dataset, showing a significant reduction in the runtime, raising considerably the upper bound on the size of SCS instances which can be solved in practice. Our approach, celluloid:clustering single cell sequencing data around centroidsis available athttps://github.com/AlgoLab/celluloid/under an MIT license, as well as on thePython Package Index(PyPI) athttps://pypi.org/project/celluloid-clust/
Honey bee (Apis mellifera) larval pheromones regulate gene expression related to foraging task specialization
Authors: Ma R , Rangel J , Grozinger CM 
Published: March 2019

AbstractBackgroundForaging behavior in honey bees (Apis mellifera) is a complex phenotype which is regulated by physiological state and social signals. How these factors are integrated at the molecular level to modulate foraging behavior has not been well-characterized. The transition of worker bees from nursing to foraging behavior is mediated by large-scale changes in brain gene expression, which are influenced by pheromones produced by the queen and larvae. Larval pheromones can also stimulate foragers to leave the colony to collect pollen, but the mechanisms underpinning this rapid behavioral plasticity are unknown. Furthermore, the mechanisms through which foragers specialize on collecting nectar or pollen, and how larval pheromones impact these different behavioral states, remains to be determined. Here, we investigated the patterns of gene expression related to rapid behavioral plasticity and task allocation among honey bee foragers exposed to two larval pheromones, brood pheromone (BP) and (E)-beta-ocimene (EBO).ResultsWe hypothesized that both pheromones would alter expression of genes in the brain related to foraging and would differentially impact expression of genes in the brains of pollen compared to nectar foragers. Combining data reduction, clustering, and network analysis methods, we found that foraging preference (nectar vs. pollen) and pheromone exposure are each associated with specific brain gene expression profiles. Furthermore, pheromone exposure has a strong transcriptional effect on genes that are preferentially expressed in nectar foragers. Representation factor analysis between our study and previous landmark honey bee transcriptome studies revealed significant overlaps for both pheromone communication and foraging task specialization.ConclusionsSocial signals (i.e. pheromones) may invoke foraging-related genes to upregulate pollen foraging at both long and short time scales. These results provide new insights into how social signals integrate with task specialization at the molecular level and highlights the important role that brain gene expression plays in behavioral plasticity across time scales.
CDC6 regulates both G2/M transition and metaphase-to-anaphase transition during the first meiosis of mouse oocytes
Authors: Yi Zi-Yun , Meng Tie-Gang , Ma Xue-Shan , Li Jian , Zhang Chun-Hui , Ouyang Ying-Chun , Schatten Heide , Qiao Jie , Sun Qing-Yuan , Qian Wei-Ping 
Published: March 2019

AbstractCell division cycle protein CDC6 is essential for the initiation of DNA replication. CDC6 was recently shown to inhibit the microtubule-organizing activity of the centrosome. Here, we show that CDC6 is localized to the spindle from Pro-MI to MII stages of oocytes, and it plays important roles at two critical steps of oocyte meiotic maturation. CDC6 depletion facilitated the G2/M transition (GV breakdown, GVBD) through regulation of Cdh1 and cyclin B1 expression and CDK1 phosphorylation in a GVBD-inhibiting culture system containing milrinone. Furthermore, GVBD was significantly decreased after knockdown of cyclin B1 in CDC6-depleted oocytes, indicating that the effect of CDC6 loss on GVBD stimulation was mediated, at least in part, by raising cyclin B1. Knockdown of CDC6 also caused abnormal localization of γ-tubulin, resulting in defective spindles, misaligned chromosomes, cyclin B1 accumulation and spindle assembly checkpoint (SAC) activation, leading to significant Pro-MI/MI arrest and PB1 extrusion failure. These phenotypes were also confirmed by time-lapse live cell imaging analysis. The results indicate that CDC6 is indispensable for maintaining G2 arrest of meiosis and functions in G2/M checkpoint regulation in mouse oocytes. Moreover, CDC6 is also a key player regulating meiotic spindle assembly and metaphase-to-anaphase transition in meiotic oocytes.Summary statementWe show that CDC6 is indispensable for maintaining G2 arrest of mouse oocytes. Moreover, CDC6 is also a key player regulating meiotic spindle assembly and metaphase-to-anaphase transition in meiotic oocytes.
Random birth order and bursty Notch ligand expression drive the stochastic AC/VU cell fate decision inC. elegans
Authors: Kienle Simone , Gritti Nicola , Kroll Jason R. , Kriselj Ana , Goos Yvonne , van Zon Jeroen S. 
Published: March 2019

AbstractCells in developing organisms must robustly assume the correct fate in order to fulfill their specific function. At the same time, cells are strongly affected by molecular fluctuations, i.e. ‘noise’, leading to inherent variability in individual cells. During development, some cells are thought to exploit such molecular noise to drive stochastic cell fate decisions, with cells randomly picking one cell fate out of several possible ones. Yet, how molecular noise drives such decisions is an open question. We address this question using a novel quantitative approach to study one of the best-understood stochastic cell fate decisions: the AC/VU decision inC. elegansgonad development. Here, two initially equivalent cells, Z1.ppp and Z4.aaa, interact, so that one cell becomes the anchor cell (AC) and the other a ventral uterine precursor cell (VU). It is thought that the symmetry is broken when small molecular fluctuations are amplified into cell fate by positive feedback loops in the Notch signaling pathway. To identify the noise sources that drive the AC/VU decision, we used a novel time-lapse microscopy approach to follow expression dynamics in live animals and single molecule FISH to quantify gene expression with single mRNA resolution. We found not only that random Z1.ppp/Z4.aaa birth order biased the decision outcome, with the first-born cell typically assuming VU fate, but that the strength of this bias and the speed of the decision decreased as the two cells were born closer together in time. Moreover, we find that the Notch ligandlag-2/Deltaexhibited strongly stochastic expression already in the two mother cells, Z1.pp/Z4.aa. Combining experiments with mathematical models, we showed that the resulting asymmetry inlag-2/Deltalevels inherited by the daughter cells, Z1.ppp/Z4.aaa, stochastic symmetry breaking when both cells are born at similar times. Together, our results suggest that two independent noise sources, birth order and stochasticlag-2/Deltaexpression, are exploited to amplify noise into cell fate in a manner that ensures a robust decision.
Polyphosphate initiates tau aggregation through intra- and intermolecular scaffolding
Authors: Wickramasinghe S. P. , Lempart J. , Merens H. E. , Murphy J. , Jakob U. , Rhoades E. 
Published: March 2019

AbstractThe aggregation and deposition of tau is a hallmark of a class of neurodegenerative diseases called tauopathies. Despite intensive study, cellular and molecular factors that trigger tau aggregation are not well understood. Here we provide evidence for two mechanisms relevant to the initiation of tau aggregation in the presence of cytoplasmic polyphosphates (polyP): changes in the conformational ensemble of monomer tau and noncovalent cross-linking of multiple tau monomers. We identified conformational changes throughout full-length tau, most notably diminishment of long-range interactions between the termini coupled with compaction of the microtubule binding and proline rich regions. We found that while the proline rich and microtubule binding regions both contain polyP binding sites, the proline rich region is a requisite for compaction of the microtubule binding region upon binding. Additionally, both the magnitude of the conformational change and the aggregation of tau are dependent on the chain length of the polyP polymer. Longer polyP chains are more effective at intermolecular, noncovalent cross-linking of tau. These observations provide an understanding of the initial steps of tau aggregation through interaction with a physiologically relevant aggregation inducer.
VHLSynthetic Lethality Signatures Uncovered by Genotype-specific CRISPR-Cas9 Screens
Authors: Sun Ning , Petiwala Sakina , Lu Charles , Hutti Jessica E , Hu Min , Hu Mufeng , Domanus Marc H , Mitra Diya , Addo Sadiya N , Miller Christopher P , Chung Namjin 
Published: March 2019

AbstractBackgroundGenome-wide CRISPR-Cas9 essentiality screening represents a powerful approach to identify genetic vulnerabilities in cancer cells. Here, we applied this technology and designed a strategy to identify target genes that are synthetic lethal (SL) withvon Hippel-Lindau(VHL) tumor suppressor gene. Inactivation ofVHLhas been frequently found in clear cell renal cell carcinoma (ccRCC). Its SL partners serve as potential drug targets for the development of targeted cancer therapies.ResultsWe performed parallel genome-wide CRISPR screens in two pairs of isogenic ccRCC cell lines that differ only in theVHLstatus. Comparative analyses of screening results not only confirmed a well-known role for mTOR signaling in renal carcinoma, but also identified DNA damage response and selenocysteine biosynthesis pathways as major SL targets inVHL-inactivated cancer cells. Follow-up studies provided cellular and mechanistic insights into SL interactions of these pathway genes with theVHLgene.ConclusionsUsing isogenic CRISPR screening approach, we uncovered novel biological processes that are SL withVHL, which can be exploited for drug development for ccRCC. Our CRISPR and RNA-seq datasets provide a rich resource for future investigation of the function of the VHL tumor suppressor protein. Our work demonstrates the efficiency of CRISPR-based synthetic lethality screening in human isogenic cell pairs. Similar strategies could be employed to unveil SL partners with other oncogenic drivers.
Mutualistic interactions with phoretic mites Poecilochirus carabi expand the realised thermal niche of the burying beetle Nicrophorus vespilloides
Authors: Sun Syuan-Jyun , Kilner Rebecca M. 
Published: March 2019

AbstractMutualisms are so ubiquitous, and play such a key role in major biological processes, that it is important to understand how they will function in a changing world. Here we test whether mutualisms can help populations to persist in challenging new environments, by focusing on the protective mutualism between burying beetles Nicrophorus vespilloides and their phoretic mites (Poecilochirus carabi). Our experiments identify the burying beetle’s fundamental thermal niche and show that it is restricted by competition with blowfly larvae at higher and lower temperatures (within the natural range). We further demonstrate that mites expand the burying beetle’s realised thermal niche, by reducing competition with blowflies at lower and higher temperatures, thereby enabling beetles to produce more offspring across a wider thermal range. We conclude that mutualisms can play an important role in promoting survival under novel and adverse conditions, particularly when these conditions enhance the performance of a common enemy.
Cataloguing practices at university libraries
Authors: Çakmak Tolga 
Published: March 2019

Purpose
This study aims to analyse current practices and cooperation between the Turkish university libraries related to cataloguing processes and present cataloguing librarians’ evaluations about clarity and comprehensiveness of the given information in library catalogues.

Design/methodology/approach
In line with the literature review, a Web-based questionnaire was developed concerning the cataloguing practices implemented at university libraries in Turkey. The questionnaire was submitted to 316 cataloguing librarians. In all, 104 cataloguing librarians from 61 different libraries responded to the survey. The collected data were analysed through descriptive statistics. The responses given to some open-ended questions were assessed with respective expressions presented verbatim in the study and some of them visualised via VOSViewer software.

Findings
The findings reflect that analysed university libraries implement different cataloguing processes. It is seen that some libraries use the necessary systems and services related to cataloguing and classification while others use individual solutions without using such systems and services. Findings reveal that there is cooperation between the analysed libraries about sharing catalogue records. In this regard, it is understood that cataloguing librarians mostly prefer transferring catalogue records from the catalogues of university libraries they trusted. Findings also indicate that analysed librarians think that the descriptive information provided via Online Public Access Catalogues are in moderate level in terms of clarity and comprehensibility.

Originality/value
The study contributes to the existing literature of a limited number of relevant studies by establishing the baseline pertaining to cataloguing processes undertaken at university libraries in Turkey.