bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concomitant chest trauma and traumatic brain injury, biomarkers correlate with worse outcomes
Authors: Crawford Angela M. , Yang Shiming , Hu Peter , Li Yao , Lozanova Petya , Scalea Thomas M. , Stein Deborah M. 
Published: March 2019

BACKGROUND
Clinical data are lacking on the influence of chest trauma on the secondary injury process after traumatic brain injury (TBI), with some data suggesting that multiple trauma may worsens brain injury. Blunt chest trauma and TBI represent the two major single injury entities with the highest risk of complications and are potential biomarker targets.

METHODS
Trauma patients with severe TBI were enrolled. Serum biomarker levels were obtained every 6 hours for 72 hours. Baseline, 6 hours and 24 hours CT head scans were evaluated. Neurologic worsening was defined as increased contusions, ischemia, compression of basal cisterns, and/or midline shift. The TBI patients with chest injury (Abbreviated Injury Scale chest score ≥1) and those without chest injury were compared. Wilcoxon rank sum test, univariate logistic regression and receiver operating characteristic were reported.

RESULTS
Fifty-seven patients. Mean age of 40.5 years. Median motor Glasgow Coma Scale score at admission and 24 hours was 3 (interquartile range, 1–5) and 5 (interquartile range, 3–5). Of the patients enrolled, 12.2% patients underwent craniotomy within 6 hours from the time of admission and 22.8% within 12 hours. Patients with chest trauma, 24.5% had a chest Abbreviated Injury Scale score of 3 or greater, and 73.6% sustained blunt chest trauma. Stratifying TBI patients with and without chest injury revealed higher mean levels of IL-4, IL-5, IL-8, and IL-10 and lower mean IFN-γ and IL-7 levels in patient with chest injury. IL-7 levels adjusted for chest injury predicted neurological worsening with area under the receiver operating characteristic of 0.59 (p value = 0.011). The TBI and chest trauma patients' IL-4 and neuron-specific enolase levels were predictive of mortality (area under the receiver operating characteristic of 0.67 and 0.63, p = 0.0001, 0.003), respectively.

CONCLUSION
Utilizing biomarkers for early identification of patients with TBI and chest trauma has the capability of modifying adverse factors affecting morbidity and mortality in this subset of TBI patients.

LEVEL OF EVIDENCE
Level III.
Transplant Recipients and Anal Neoplasia Study: Design, Methods, and Participant Characteristics of a Prevalence Study
Authors: Rosales Brenda Maria , Langton-Lockton Julian , Cornall Alyssa M. , Roberts Jennifer M. , Hillman Richard J. , Webster Angela Claire 
Published: March 2019

Abstract
Kidney recipients have anal cancer rates 3 times higher than the general population in Australia and New Zealand. High-risk human papillomavirus (HPV) genotypes are implicated in the majority of anal cancers. Establishing the epidemiology of anal HPV infection and precursors of anal cancer in transplant recipient populations is 1 consideration in any potential screening program. The Transplant and Anal Neoplasia Study is a cross-sectional study of the prevalence of anal cytological abnormalities and HPV deoxyribonucleic acid in kidney transplant recipients, as well as evaluating the acceptability of an anal cancer screening intervention. The study aims to recruit 100 kidney transplant recipients, older than 18 years, in Australia. Transplant recipients attending for a protocol biopsy at 3 and 12 months and annually posttransplant are approached to participate. Participants undergo an anal swab, which is then analyzed using liquid-based cytological examination and tested for the detection of 37 anogenital HPV deoxyribonucleic acid genotypes. Participants also complete a demographic and behavioral questionnaire that covers sexual behavior, history of anal symptoms, and possible anal cancer risk factors. Associations will be tested using multiple regression analysis. Recruitment for the study began in 2015 and is ongoing. To date, 96 (77%) of 125 kidney transplant recipients approached have consented to the study. The mean age is 48 (median, 47 y; range, 20–76 y), 59% are male, and Northwest European (58%) represented the largest ethnic group. No participants self-identified as Aboriginal or Torres Strait Islander. High consent rates and positive qualitative results suggest that a larger screening program may be well received by kidney transplant recipients, with increased resources and some modification to the timing of approach. Further results of the study will inform the possible implementation of a larger screening trial for prevention of anal cancers in kidney and other solid organ transplant recipients.
Sodium nitroprusside prevents the detrimental effects of glucose on the neurovascular unit and behaviour in zebrafish
Authors: Chhabria K. , Vouros A. , Gray C. , MacDonald R.B. , Jiang Z. , Wilkinson R.N. , Plant K , Vasilaki E. , Howarth C. , Chico T.J.A. 
Published: March 2019

AbstractDiabetes is associated with dysfunction of the neurovascular unit, although the mechanisms of this are incompletely understood, and currently no treatment exists to prevent these negative effects. We previously found that the NO donor sodium nitroprusside (SNP) prevents the detrimental effect of glucose on neurovascular coupling in zebrafish. We therefore sought to establish the wider effects of glucose exposure on both the neurovascular unit and on behaviour in zebrafish and the ability of SNP to prevent these.We incubated 4 days post fertilisation (dpf) zebrafish embryos in 20mM glucose or mannitol for five days until 9dpf, with or without 0.1mM SNP co-treatment for 24h (8-9dpf), and quantified vascular nitric oxide reactivity, vascular mural cell number, expression of aklf2areporter, glial fibrillary acidic protein (GFAP) and TRPV4, as well as spontaneous neuronal activation at 9dpf, all in the optic tectum. We also assessed the effect on light/dark preference and locomotory characteristics during free-swimming studies.We find that glucose exposure significantly reduced nitric oxide reactivity,klf2areporter expression, vascular mural cell number and TRPV4 expression, while significantly increasing spontaneous neuronal activation and GFAP expression (all in the optic tectum). Furthermore, when we examined larval behaviour we found glucose exposure significantly altered light/dark preference and high and low speed locomotion while in light. Co-treatment with SNP reversed all these molecular and behavioural effects of glucose exposure.Our findings comprehensively describe the negative effects of glucose exposure on the vascular anatomy, molecular phenotype, and function of the optic tectum and on whole organism behaviour. We also show that SNP or other NO donors may represent a therapeutic strategy to ameliorate the complications of diabetes on the neurovascular unit.
Comparative analysis of novel MGISEQ-2000 sequencing platform vs Illumina HiSeq 2500 for whole-genome sequencing
Authors: Korostin Dmitriy , Kulemin Nikolay , Naumov Vladimir , Belova Vera , Kwon Dmitriy , Gorbachev Alexey 
Published: March 2019

AbstractBackgroundMGISEQ-2000 developed by MGI Tech Co. Ltd. (a subsidiary of the BGI Group) is a new competitor of such next-generation sequencing platforms as NovaSeq and HiSeq (Illumina). Its sequencing principle is based on the DNB and cPAS technologies, which were also used in the previous version of the BGISEQ-500 device. However, the reagents for MGISEQ-2000 have been refined and the platform utilizes updated software. The cPAS method is an advanced technology based on cPAL previously created by Complete Genomics.ResultIn this paper, the authors compare the results of the whole-genome sequencing of a DNA sample from a Russian female donor performed on MGISEQ-2000 and Illumina HiSeq 2500 (both PE150). Two platforms were compared in terms of sequencing quality, number of errors and performance. Additionally, we performed variant calling using four different software packages: Samtools mpileaup, Strelka2, Sentieon, and GATK. The accuracy of single nucleotide polymorphism (SNP) detection was similar in the data generated by MGISEQ-2000 and HiSeq 2500, which was used as a reference. At the same time, a separate indel analysis of the overall error rate revealed similar FPR values and lower sensitivity.Conclusionsit may be concluded with confidence that the data generated by the analyzed sequencing systems is characterized by comparable magnitudes of error and that MGISEQ-2000 can be used for a wide range of research tasks on par with HiSeq 2500.
Pattern separation is the key driver of expectation-modulated memory
Authors: Frank Darya , Montaldi Daniela 
Published: March 2019

AbstractThe hippocampus uses pattern separation and pattern completion in a continuous manner to successfully encode and retrieve memories1,2. However, whether and how cognitive factors might modulate the dynamics between these types of computation is not well understood. Here we examine the role of expectation in shifting the hippocampus to perform pattern separation. Expectation can be built up through multiple contextual exposures leading to prediction (as in a learnt contingency) or through logical deduction based on a previous mnemonic response. Participants first learned a contingency between a cue and an object’s category (man-made or natural). Then, at encoding, one third of the cues that preceded the to-be-memorised objects violated the studied rule. At test, participants performed an old/new recognition task with old items (targets) and a set of parametrically manipulated (very similar to dissimilar) new foils for each object. We explored the effects of both contextual expectation, manipulated at initial encoding, and mnemonic-attribution expectation, driven by the mnemonic decisions taken on previous retrieval trials. For example, a target would be unexpected if in a previous trial a similar foil had been erroneously accepted as old. Memory was found to be better for foils of high and mid similarity to contextually unexpected targets at encoding, compared to expected ones. Additionally, violations of mnemonic-attribution expectation also yielded improved memory performance when the level of foil similarity was high. These results suggest that violations of both contextual expectation and mnemonic-attribution expectation engage pattern separation, resulting in better discrimination performance for these items. Importantly, this mechanism is engaged when input differentiation is required in order to make a correct recognition decision.
Age Differences in Hemispheric Lateralization in Spatial and Verbal Visual Working Memory
Authors: Sander Myriam C. , Maier Patrizia M. , Napiórkowski Natan , Finke Kathrin , Töllner Thomas , Müller Hermann J. , Lindenberger Ulman , Werkle-Bergner Markus , Wiegand Iris 
Published: March 2019

AbstractDue to hemispheric specialization of the human brain, neural signatures of visual working memory (WM) performance are expected to differ between tasks involving verbal versus spatial memoranda. Theories of cognitive aging suggest a reduction of hemispheric specialization in older adults. Using behavioral and neural WM capacity markers, we assessed hemispheric lateralization in younger and older adults performing a spatial or verbal visual WM task. Participants encoded information presented in the left or right hemifield. We observed behavioral advantages for spatial stimuli processed in the right hemisphere and for verbal stimuli processed in the left hemisphere. While younger adults showed lateralization in both tasks, older adults showed lateralization only in the verbal task. Lateralization was assessed by the contralateral delay activity (CDA) on the neural level. CDA amplitudes displayed hemispheric lateralization for verbal versus spatial material, but this effect was age-invariant. While our findings support right-hemispheric specialization for spatial information maintenance, and left-hemispheric specialization for verbal information maintenance, we could not confirm a generalized reduction in hemispheric lateralization at older ages.
Host metabolic reprogramming of Pseudomonas aeruginosa by phage-based quorum sensing modulation
Authors: Hendrix H. , Kogadeeva M. , Zimmermann M. , Sauer U. , De Smet J. , Muchez L. , Lissens M. , Staes I. , Voet M. , Wagemans J. , Ceyssens P-J. , Noben J-P. , Aertsen A. , Lavigne R. 
Published: March 2019

AbstractThe Pseudomonas quinolone signal (PQS) is a multifunctional quorum sensing molecule of key importance to the P. aeruginosa metabolism. We here describe that the lytic Pseudomonas bacterial virus LUZ19 targets this population-density-dependent signaling system by expressing quorum sensing-associated acyltransferase (Qst) during early infection. Qst interacts with a key biosynthesis pathway enzyme PqsD, resulting in decreased metabolites levels of PQS and its precursor 2-heptyl-4(1H)-quinolone. The lack of a functional PqsD enzyme impairs the normal LUZ19 infection but is restored by external supplementation of 2-heptyl-4(1H)-quinolone, showing that LUZ19 exploits PQS to successfully achieve its infection. A functional interaction network, which includes enzymes of the central carbon metabolism (CoaC/ThiD) and a novel non-ribosomal peptide synthetase pathway (PA1217), suggests a broader functional context for Qst, which blocks P. aeruginosa cell division. Qst represents an exquisite example of intricate reprogramming of the bacterium, which may be exploited towards antibiotic target discovery for this bacterial pathogen.
Resilience Analysis for Competing Populations
Authors: César Fassoni Artur , de Carvalho Braga Denis 
Published: March 2019

AbstractEcological resilience refers to the ability of a system to retain its state when subject to state variables perturbations or parameter changes. While understanding and quantifying resilience is crucial to anticipate the possible regime shifts, characterizing the influence of the system parameters on resilience is the first step towards controlling the system to avoid undesirable critical transitions. In this paper, we apply tools of qualitative theory of differential equations to study the resilience of competing populations as modeled by the classical Lotka-Volterra system. Within the high interspecific competition regime, such model exhibits bistability, and the boundary between the basins of attraction corresponding to exclusive survival of each population is the stable manifold of a saddle-point. Studying such manifold and its behavior in terms of the model parameters, we characterized the populations resilience: while increasing competitiveness leads to higher resilience, it is not always the case with respect to reproduction. Within a pioneering context where both populations initiate with few individuals, increasing reproduction leads to an increase in resilience; however, within an environment previously dominated by one population and then invaded by the other, an increase in resilience is obtained by decreasing the reproduction rate. Besides providing interesting insights for the dynamics of competing population, this work brings near to each other the theoretical concepts of ecological resilience and the mathematical methods of differential equations and stimulates the development and application of new mathematical tools for ecological resilience.
Short-Term Synaptic Dynamics Control the Activity Phase of Neurons in an Oscillatory Network
Authors: Martinez Diana , Anwar Haroon , Bose Amitabha , Bucher Dirk , Nadim Farzan 
Published: March 2019

AbstractIn oscillatory systems, neuronal activity phase is often independent of network frequency. Such phase maintenance requires adjustment of synaptic input with network frequency, a relationship that we explored using the crab,Cancer borealis, pyloric network. The burst phase of pyloric neurons is relatively constant despite a >2-fold variation in network frequency. We used noise input to characterize how input shape influences burst delay of a pyloric neuron, and then used dynamic clamp to examine how burst phase depends on the period, amplitude, duration, and shape of rhythmic synaptic input. Phase constancy across a range of periods required a proportional increase of synaptic duration with period. However, phase maintenance was also promoted by an increase of amplitude and peak phase of synaptic input with period. Mathematical analysis shows how short-term synaptic plasticity can coordinately change amplitude and peak phase to maximize the range of periods over which phase constancy is achieved.
Hearing impairment due toMir183/96/182mutations suggests both loss and gain of function effects
Authors: Lewis Morag A. , Di Domenico Francesca , Ingham Neil J. , Prosser Haydn M. , Steel Karen P. 
Published: March 2019

AbstractThe microRNA miR-96 is important for hearing, as point mutations in humans and mice result in dominant progressive hearing loss.Mir96is expressed in sensory cells along withMir182andMir183, but the roles of these closely-linked microRNAs are as yet unknown. Here we analyse mice carrying null alleles ofMir182, and ofMir183andMir96together to investigate their roles in hearing. We found thatMir183/96heterozygous mice had normal hearing and homozygotes were completely deaf with abnormal hair cell stereocilia bundles and reduced numbers of inner hair cell synapses at four weeks old.Mir182knockout mice developed normal hearing then exhibited progressive hearing loss. Our transcriptional analyses revealed significant changes in a range of other genes, but surprisingly there were fewer genes with altered expression in the organ of Corti ofMir183/96null mice compared with our previous findings inMir96Dmdomutants, which have a point mutation in the miR-96 seed region. This suggests the more severe phenotype ofMir96Dmdomutants compared withMir183/96mutants, including progressive hearing loss inMir96Dmdoheterozygotes, is likely to be mediated by the gain of novel target genes in addition to the loss of its normal targets. We propose three mechanisms of action of mutant miRNAs; loss of targets that are normally completely repressed, loss of targets whose transcription is normally buffered by the miRNA, and gain of novel targets. Any of these mechanisms could lead to a partial loss of a robust cellular identity and consequent dysfunction.
Efficient parameterization of large-scale dynamic models based on relative measurements
Authors: Schmiester Leonard , Schälte Yannik , Fröhlich Fabian , Hasenauer Jan , Weindl Daniel 
Published: March 2019

AbstractMotivationMechanistic models of biochemical reaction networks facilitate the quantitative understanding of biological processes and the integration of heterogeneous datasets. However, some biological processes require the consideration of comprehensive reaction networks and therefore large-scale models. Parameter estimation for such models poses great challenges, in particular when the data are on a relative scale.ResultsHere, we propose a novel hierarchical approach combining (i) the efficient analytic evaluation of optimal scaling, offset, and error model parameters with (ii) the scalable evaluation of objective function gradients using adjoint sensitivity analysis. We evaluate the properties of the methods by parameterizing a pan-cancer ordinary differential equation model (>1000 state variables,>4000 parameters) using relative protein, phospho-protein and viability measurements. The hierarchical formulation improves optimizer performance considerably. Furthermore, we show that this approach allows estimating error model parameters with negligible computational overhead when no experimental estimates are available, pro-viding an unbiased way to weight heterogeneous data. Overall, our hierarchical formulation is applicable to a wide range of models, and allows for the efficient parameterization of large-scale models based on heterogeneous relative measurements.Contactjan.hasenauer@helmholtz-muenchen.deSupplementary informationSupplementary information are available atbioRxivonline. Supplementary code and data are available online athttp://doi.org/10.5281/zenodo.2593839andhttp://doi.org/10.5281/zenodo.2592186.
Genomic dissection of maternal, additive and non-additive genetic effects for growth and carcass traits in Nile tilapia
Authors: Joshi Rajesh , Woolliams John , Meuwissen Theodorus , Gjøen Hans Magnus 
Published: March 2019

AbstractBackgroundThe availability of both pedigree and genomic sources of information for animal breeding and genetics has created new challenges in understanding how best they may be utilized and how they may be interpreted. This study computed the variance components obtained using genomic information and compared these to the variances obtained using pedigree in a population generated to estimate non-additive genetic variance. Further, the impact of assumptions concerning Hardy-Weinberg Equilibrium (HWE) on the component estimates was examined. The magnitude of inbreeding depression for important commercial traits in Nile tilapia was estimated for the first time, here using genomic data.ResultsThe non-additive genetic variance in a Nile tilapia population was estimated from fullsib families and, where present, was found to be almost entirely additive by additive epistatic variance, although in pedigree studies this source is commonly assumed to arise from dominance. For body depth (BD) and body weight at harvest (BWH), the estimates of the additive by additive epistatic ratio (P<0.05) were found to be 0.15 and 0.17 in the current breeding population using genomic data. In addition, we found maternal variance (P<0.05) for BD, BWH, body length (BL) and fillet weight (FW), explaining approximately 10% of the observed phenotypic variance, which are comparable to the pedigree-based estimates. This study also disclosed detrimental effects of inbreeding in commercial traits of tilapia, which were estimated to cause 1.1%, 0.9%, 0.4% and 0.3% decrease in the trait value with 1% increase in the individual homozygosity for FW, BWH, BD and BL, respectively. The inbreeding depression and lack of dominance variance was consistent with an infinitesimal dominance modelConclusionsAn eventual utilisation of non-additive genetic effects in breeding schemes is not evident or straightforward from our findings, but inbreeding depression suggests for cross-breeding, although commercially this conclusion will depend on cost structures. However, the creation of maternal lines in Tilapia breeding schemes may be a possibility if this variation is found to be heritable.
ADrosophilamodel of neuronal ceroid lipofuscinosisCLN4reveals a hypermorphic gain of function mechanism
Authors: Imler Elliot , Pyon Jin Sang , Kindelay Selina , Zhang Yong-quan , Chandra Sreeganga S. , Zinsmaier Konrad E. 
Published: March 2019

AbstractThe autosomal dominant neuronal ceroid lipofuscinoses (NCL)CLN4is caused by mutations in the synaptic vesicle (SV) protein CSPα, which is a critical co-chaperone of Hsc70 protecting synapses from activity-dependent degeneration. We developed the first animal models ofCLN4by expressing eitherCLN4mutant human CSPα (hCSPα) orDrosophilaCSP (dCSP) in fly neurons. Similar to patients,CLN4mutations induced excessive oligomerization of mutant hCSPα and premature lethality in a dose-dependent manner. Instead of being localized to SVs, mostCLN4mutant hCSPα abnormally accumulated in axons and somata, and co-localized with ubiquitinated proteins and the prelysosomal markers HRS and LAMP1. Ultrastructurally, abnormal multi-laminar membrane structures were frequently observed in axons and somata next to degenerative abnormalities. The lethality, oligomerization and prelysosomal accumulation induced byCLN4mutations was attenuated by reducing wild type (WT) dCSP levels and enhanced by increasing WT dCSP or hCSPα levels, which indicates that bothCLN4alleles resemble dominant hypermorphic gain of function mutations. Furthermore, reducing the gene dosage of Hsc70 also attenuatedCLN4phenotypes. Taken together, we suggest thatCLN4alleles resemble dominant hypermorphic gain of function mutations that drive excessive oligomerization and impair membrane trafficking.