bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lower emergency general surgery (EGS) mortality among hospitals with higher-quality trauma care
Authors: Scott John W. , Tsai Thomas C. , Neiman Pooja U. , Jurkovich Gregory J. , Utter Garth H. , Haider Adil H. , Salim Ali , Havens Joaquim M. 
Published: December 2017

BACKGROUND
Patients undergoing emergency general surgery (EGS) procedures are up to eight times more likely to die than patients undergoing the same procedures electively. This excess mortality is often attributed to nonmodifiable patient factors including comorbidities and physiologic derangements at presentation, leaving few targets for quality improvement. Although the hospital-level traits that contribute to EGS outcomes are not well understood, we hypothesized that facilities with lower trauma mortality would have lower EGS mortality.

METHODS
Using the Nationwide Inpatient Sample (2008–2011), we calculated hospital-level risk-adjusted trauma mortality rates for hospitals with more than 400 trauma admissions. We then calculated hospital-level risk-adjusted EGS mortality rates for hospitals with more than 200 urgent/emergent admissions for seven core EGS procedures (laparotomy, large bowel resection, small bowel resection, lysis of adhesions, operative intervention for ulcer disease, cholecystectomy, and appendectomy). We used univariable and multivariable techniques to assess for associations between hospital-level risk-adjusted EGS mortality and hospital characteristics, patient-mix traits, EGS volume, and trauma mortality quartile.

RESULTS
Data from 303 hospitals, representing 153,544 admissions, revealed a median hospital-level EGS mortality rate of 1.21% (interquartile range, 0.86%–1.71%). After adjusting for hospital traits, hospital-level EGS mortality was significantly associated with trauma mortality quartile as well as patients’ community income-level and race/ethnicity (p < 0.05 for all). Mean risk-adjusted EGS mortality was 1.09% (95% confidence interval, 0.94–1.25%) at hospitals in the lowest quartile for risk-adjusted trauma mortality, and 1.64% (95% confidence interval, 1.48–1.80%) at hospitals in the highest quartile of trauma mortality (p < 0.01). Sensitivity analyses limited to (1) high-mortality procedures and (2) high-volume facilities; both found similar trends (p < 0.01).

CONCLUSIONS
Patients at hospitals with lower risk-adjusted trauma mortality have a nearly 33% lower risk of mortality after admission for EGS procedures. The structures and processes that improve trauma mortality may also improve EGS mortality. Emergency general surgery–specific systems measures and process measures are needed to better understand drivers of variation in quality of EGS outcomes.

LEVEL OF EVIDENCE
Epidemiological, level III; Care management, level IV.
Reconciling persistent and dynamic hypotheses of working memory coding in prefrontal cortex
Authors: Cavanagh SE , Towers JP , Wallis JD , Hunt LT , Kennerley SW 
Published: December 2017

AbstractCompeting accounts propose that working memory (WM) is subserved either by persistent activity in single neurons or by dynamic (time-varying) activity across a neural population. Here we compare these hypotheses across four regions of prefrontal cortex (PFC) in a spatial WM task, where an intervening distractor indicated the reward available for a correct saccade. WM representations were strongest in ventrolateral PFC (VLPFC) neurons with higher intrinsic temporal stability (time-constant). At the population-level, although a stable mnemonic state was reached during the delay, this tuning geometry was reversed relative to cue-period selectivity, and was disrupted by the distractor. Single-neuron analysis revealed many neurons switched to coding reward, rather than maintaining task-relevant spatial selectivity until saccade. These results imply WM is fulfilled by dynamic, population-level activity within high time-constant neurons. Rather than persistent activity supporting stable mnemonic representations that bridge distraction, PFC neurons may stabilise a dynamic population-level process that supports WM.
Alterations in Cell Motility, Proliferation, and Metabolism in Novel Models of Acquired Temozolomide Resistant Glioblastoma
Authors: Tiek DM , Rone JD , Graham GT , Pannkuk EL , Haddad BR , Riggins RB 
Published: December 2017

AbstractGlioblastoma (GBM) is an aggressive and incurable tumor of the brain with limited treatment options. Current first-line standard of care is the DNA alkylating agent temozolomide (TMZ), but this treatment strategy adds only ~4 months to median survival due to the rapid development of resistance. While some mechanisms of TMZ resistance have been identified, they are not fully understood. There are few effective strategies to manage therapy resistant GBM, and we lack diverse preclinical models of acquired TMZ resistance in which to test therapeutic strategies on TMZ resistant GBM. In this study, we create and characterize two new GBM cell lines resistant to TMZ, based on the 8MGBA and 42MGBA cell lines. Analysis of the TMZ resistant (TMZres) variants in conjunction with their parental, sensitive cell lines shows that acquisition of TMZ resistance is accompanied by broad phenotypic changes, including increased proliferation, migration, chromosomal aberrations and secretion of cytosolic lipids. Importantly, each TMZ resistant model captures a different facet of the “go” (8MGBA-TMZres) or “grow” (42MGBA-TMZres) hypothesis of GBM behavior. These model systems will be important additions to the available tools for investigators seeking to define molecular mechanisms of acquired TMZ resistance.
An accumulation-of-evidence task using visual pulses for mice navigating in virtual reality
Authors: Pinto Lucas , Koay Sue Ann , Engelhard Ben , Yoon Alice M. , Deverett Ben , Thiberge Stephan Y. , Witten Ilana B. , Tank David W. , Brody Carlos D. 
Published: December 2017

ABSTRACTThe gradual accumulation of sensory evidence is a crucial component of perceptual decision making, but its neural mechanisms are still poorly understood. Given the wide availability of genetic and optical tools for mice, they can be useful model organisms for the study of these phenomena; however, behavioral tools are largely lacking. Here, we describe a new evidence-accumulation task for head-fixed mice navigating in a virtual reality environment. As they navigate down the stem of a virtual T-maze, they see brief pulses of visual evidence on either side, and retrieve a reward on the arm with the highest number of pulses. The pulses occur randomly with Poisson statistics, yielding a diverse yet well-controlled stimulus set, making the data conducive to a variety of computational approaches. A large number of mice of different genotypes were able to learn and consistently perform the task, at levels similar to rats in analogous tasks. They are sensitive to side differences of a single pulse, and their memory of the cues is stable over time. Moreover, using non-parametric as well as modeling approaches, we show that the mice indeed accumulate evidence: they use multiple pulses of evidence from throughout the cue region of the maze to make their decision, albeit with a small overweighting of earlier cues, and their performance is affected by the magnitude but not the duration of evidence. Additionally, analysis of the mice's running patterns revealed that trajectories are fairly stereotyped yet modulated by the amount of sensory evidence, suggesting that the navigational component of this task may provide a continuous readout correlated to the underlying cognitive variables. Our task, which can be readily integrated with state-of-the-art techniques, is thus a valuable tool to study the circuit mechanisms and dynamics underlying perceptual decision making, particularly under more complex behavioral contexts.
Isolation of nucleic acids from low biomass samples: detection and removal of sRNA contaminants
Authors: Heintz-Buschart Anna , Yusuf Dilmurat , Kaysen Anne , Etheridge Alton , Fritz Joëlle V. , May Patrick , de Beaufort Carine , Upadhyaya Bimal B. , Ghosal Anubrata , Galas David J. , Wilmes Paul 
Published: December 2017

ABSTRACTBackgroundSequencing-based analyses of low-biomass samples are known to be prone to misinterpretation due to the potential presence of contaminating molecules derived from laboratory reagents and environments. Due to its inherent instability, contamination with RNA is usually considered to be unlikely.ResultsHere we report the presence of small RNA (sRNA) contaminants in widely used microRNA extraction kits and means for their depletion. Sequencing of sRNAs extracted from human plasma samples was performed and significant levels of non-human (exogenous) sequences were detected. The source of the most abundant of these sequences could be traced to the microRNA extraction columns by qPCR-based analysis of laboratory reagents. The presence of artefactual sequences originating from the confirmed contaminants were furthermore replicated in a range of published datasets. To avoid artefacts in future experiments, several protocols for the removal of the contaminants were elaborated, minimal amounts of starting material for artefact-free analyses were defined, and the reduction of contaminant levels for identification of bona fide sequences using ‘ultraclean’ extraction kits was confirmed.ConclusionThis is the first report of the presence of RNA molecules as contaminants in laboratory reagents. The described protocols should be applied in the future to avoid confounding sRNA studies.
Leishmania naiffi and Leishmania guyanensis reference genomes highlight genome structure and gene evolution in the Viannia subgenus
Authors: Coughlan Simone , Taylor Ali Shirley , Feane Eoghan , Sanders Mandy , Schonian Gabriele , Cotton James A. , Downing Tim 
Published: December 2017

AbstractThe unicellular protozoan parasite Leishmania causes the neglected tropical disease leishmaniasis, affecting 12 million people in 98 countries. In South America where the Viannia subgenus predominates, so far only L. (Viannia) braziliensis and L. (V.) panamensis have been sequenced, assembled and annotated as reference genomes. Addressing this deficit in molecular information can inform species typing, epidemiological monitoring and clinical treatment. Here, L. (V.) naiffi and L. (V.) guyanensis genomic DNA was sequenced to assemble these two genomes as draft references from short sequence reads. The methods used were tested using short sequence reads for L. braziliensis M2904 against its published reference as a comparison. This assembly and annotation pipeline identified 70 additional genes not annotated on the original M2904 reference. Phylogenetic and evolutionary comparisons of L. guyanensis and L. naiffi with ten other Viannia genomes revealed four traits common to all Viannia: aneuploidy, 22 orthologous groups of genes absent in other Leishmania subgenera, elevated TATE transposon copies, and a high NADH-dependent fumarate reductase gene copy number. Within the Viannia, there were limited structural changes in genome architecture specific to individual species: a 45 Kb amplification on chromosome 34 was present in all bar L. lainsoni, L. naiffi had a higher copy number of the virulence factor leishmanolysin, and laboratory isolate L. shawi M8408 had a possible minichromosome derived from the 3’ end of chromosome 34. This combination of genome assembly, phylogenetics and comparative analysis across an extended panel of diverse Viannia has uncovered new insights into the origin and evolution of this subgenus and can help improve diagnostics for leishmaniasis surveillance.
Prevalence and patterns of higher-order interactions
Authors: Tekin Elif , White Cynthia , Kang Tina Manzhu , Singh Nina , Cruz-Loya Mauricio , Damoiseaux Robert , Savage Van M. , Yeh Pamela J. 
Published: December 2017

AbstractInteractions and emergent processes are essential for research on complex systems involving many components. Most studies focus solely on pairwise interactions and ignore higher-order interactions among three or more components. To gain deeper insights into higher-order interactions and complex environments, we study antibiotic combinations applied to pathogenicEscherichia coliand obtain unprecedented amounts of detailed data (251 two-drug combinations, 1512 three-drug combinations, 5670 four-drug combinations, and 13608 five-drug combinations). Directly opposite to previous assumptions and reports, we find higher-order interactions increase in frequency with the number of drugs in the bacteria’s environment. Furthermore, we observe a shift towards net synergy (effect greater than expected based on independent individual effects) and towards emergent antagonism (effect less than expected based on lower-order interaction effects). These findings have implications for the potential efficacy of drug combinations and are crucial for better navigating problems associated with the combinatorial complexity of multi-component systems.
Drivers of antimicrobial resistance amongst intestinalEscherichia coliisolated from children in South Asia and sub-Saharan Africa
Authors: Ingle Danielle J. , Levine Myron M. , Kotloff Karen L. , Holt Kathryn E. , Robins-Browne Roy M. 
Published: December 2017

AbstractAntimicrobial resistance (AMR) dynamics are poorly understood in developing countries, where data on the prevalence of AMR in enteric bacteria are sparse, particularly among children and in the community setting. Here we use a combination of phenotyping, genomics and antimicrobial usage data to investigate patterns of AMR amongst atypical enteropathogenicE. coli(aEPEC) strains isolated from children <5 years old in seven countries (four in sub-Saharan Africa and three in South Asia) over a three-year period. We detected very high rates of AMR, with 65% of isolates displaying resistance to ≥3 drug classes; the rates of AMR were the same amongst strains associated with diarrhea and strains that were carried asymptomatically. Whole genome sequencing identified a diversity of genetic mechanisms for AMR, which could explain >95% of observed phenotypic resistance. Analysis of AMR gene co-occurrence revealed clusters of acquired AMR genes that were frequently co-located on small plasmids and transposons, providing opportunities for acquisition of multidrug resistance in a single step. We used discriminant analysis to investigate potential drivers of AMR within the bacterial population, and found that genetic determinants of AMR were associated with geographical location of isolation but not with phylogenetic lineage of theE. colistrain or disease status of the human host. Comparison with antimicrobial usage data showed that the prevalence of resistance to newer drugs (fluoroquinolones and third-generation cephalosporins) was correlated with usage, which was generally higher in South Asia than Africa. In particular, fluoroquinolone resistance-associated mutations ingyrAwere significantly associated with use of these drugs for treatment of diarrheic children. Notably resistance to older drugs such as trimethoprim, chloramphenicol and ampicillin, which are conferred by acquired AMR genes that were frequently clustered together in mobile genetic elements, were common in all locations despite differences in usage; this suggests that reversion to sensitivity is unlikely to occur even if these drugs are removed from circulation. This study provides much-needed insights into the frequencies of AMR in intestinalE. coliin community-based children in developing countries and to antimicrobial usage for diarrhea where the burden of infections is greatest.
Tracking temporal hazard in the human electroencephalogram using a forward encoding model
Authors: Herbst Sophie K. , Fiedler Lorenz , Obleser Jonas 
Published: December 2017

AbstractHuman observers automatically extract temporal contingencies from the environment and predict the onset of future events. Temporal predictions are modelled by the hazard function, which describes the instantaneous probability for an event to occur given it has not occurred yet. Here, we tackle the question of whether and how the human brain tracks continuous temporal hazard on a moment-to-moment basis, and how flexibly it adjusts to strictly implicit variations in the hazard function. We applied an encoding-model approach to human electroencephalographic (EEG) data recorded during a pitch-discrimination task, in which we implicitly manipulated temporal predictability of the target tones by varying the interval between cue and target tone (the foreperiod). Critically, temporal predictability was either solely driven by the passage of time (resulting in a monotonic hazard function), or was modulated to increase at intermediate foreperiods (resulting in a modulated hazard function with a peak at the intermediate foreperiod). Forward encoding models trained to predict the recorded EEG signal from different temporal hazard functions were able to distinguish between experimental conditions, showing that implicit variations of temporal hazard bear tractable signatures in the human electroencephalogram. Notably, this tracking signal was reconstructed best from the supplementary motor area (SMA), underlining this area’s link to cognitive processing of time. Our results underline the relevance of temporal hazard to cognitive processing, and show that the predictive accuracy of the encoding-model approach can be utilised to track abstract time-resolved stimuli.Significance StatementExtracting temporal predictions from sensory input allows to process future input more efficiently and to prepare responses in time. In mathematical terms, temporal predictions can be described by the hazard function, modelling the probability of an event to occur over time. Here, we show that the human EEG tracks temporal hazard in an implicit foreperiod paradigm. Forward encoding models trained to predict the recorded EEG signal from different temporal-hazard functions were able to distinguish between experimental conditions that differed in their build-up of hazard over time. These neural signatures of tracking temporal hazard converge with the extant literature on temporal processing and provide new evidence that the supplementary motor area tracks hazard under strictly implicit timing conditions.
Glucocorticoid receptor-mediated amygdalar metaplasticity underlies adaptive modulation of fear memory by stress
Authors: Inoue Ran , Abdou Kareem , Hayashi-Tanaka Ayumi , Muramatsu Shin-ichi , Mino Kaori , Inokuchi Kaoru , Mori Hisashi 
Published: December 2017

AbstractGlucocorticoid receptor (GR) is crucial for signaling mediated by stress-induced high levels of glucocorticoids. The lateral nucleus of the amygdala (LA) is a key structure underlying auditory-cued fear conditioning. Here, we demonstrate that genetic disruption of GR in the LA (LAGRKO) resulted in an auditory-cued fear memory deficit for strengthened conditioning. Furthermore, the suppressive effect of a single restraint stress (RS) prior to conditioning on auditory-cued fear memory in floxed GR (control) mice was abolished in LAGRKO mice. Optogenetic induction of long-term depression (LTD) at auditory inputs to the LA reduced auditory-cued fear memory in RS-exposed LAGRKO mice, and in contrast, optogenetic induction of long-term potentiation (LTP) increased auditory-cued fear memory in RS-exposed floxed GR mice. These findings suggest that prior stress suppresses fear conditioning-induced LTP at auditory inputs to the LA in a GR-dependent manner, thereby protecting animals from encoding excessive cued fear memory under stress conditions.
Simultaneous Estimation of Population Receptive Field and Hemodynamic Parameters from Single Point BOLD Responses using Metropolis-Hastings Sampling
Authors: Adaszewski Stanisław , Slater David , Melie-Garcia Lester , Draganski Bogdan , Bogorodzki Piotr 
Published: December 2017

AbstractWe introduce a new approach to Bayesian pRF model estimation using Markov Chain Monte Carlo (MCMC) sampling for simultaneous estimation of pRF and hemodynamic parameters. To obtain high performance on commonly accessible hardware we present a novel heuristic consisting of interpolation between precomputed responses for predetermined stimuli and a large cross-section of receptive field parameters. We investigate the validity of the proposed approach with respect to MCMC convergence, tuning and biases. We compare different combinations of pRF - Compressive Spatial Summation (CSS), Dumoulin-Wandell (DW) and hemodynamic (5-parameter and 3-parameter Balloon-Windkessel) models within our framework with and without the usage of the new heuristic. We evaluate estimation consistency and log probability across models. We perform as well a comparison of one model with and without lookup table within the RStan framework using its No-U-Turn Sampler. We present accelerated computation of whole-ROI parameters for one subject. Finally, we discuss risks and limitations associated with the usage of the new heuristic as well as the means of resolving them. We found that the new algorithm is a valid sampling approach to joint pRF/hemodynamic parameter estimation and that it exhibits very high performance.
Behavioral context determines network state and variability dynamics in monkey motor cortex
Authors: Riehle Alexa , Brochier Thomas , Nawrot Martin Paul , Grün Sonja 
Published: December 2017

AbstractVariability of spiking activity is ubiquitous throughout the brain but little is known about its contextual dependence. Trial-to-trial spike count variability, estimated by the Fano Factor (FF), and within-trial spike time irregularity, quantified by the local coefficient of variation (CV2), reflect variability on long and short time scales, respectively. We co-analyzed FF and CV2 in monkey motor cortex comparing two behavioral contexts, movement preparation (wait) and execution (movement). We find that FF significantly decreases from wait to movement, while CV2 increases. The more regular firing (low CV2) during wait is related to an increased power of local field potential beta oscillations and phase locking of spikes to these oscillations. In renewal processes, a widely used model for spiking activity under stationary input conditions, both measures are related as FF≈CV2. This expectation was met during movement, but not during wait where FF≫CV22. We conclude that during movement preparation, ongoing brain processes result in changing network states and thus in high trial-to-trial variability (high FF). During movement execution, the network is recruited for performing the stereotyped motor task, resulting in reliable single neuron output. We discuss our results in the light of recent computational models that generate non-stationary network conditions.