bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of Extracorporeal Membrane Oxygenation and Mortality in Pediatric Cardiac Surgery Patients With Genetic Conditions: A Multicenter Analysis*
Authors: Furlong-Dillard Jamie M. , Amula Venugopal , Bailly David K. , Bleyl Steven B. , Wilkes Jacob , Bratton Susan L. 
Published: June 2017

Objective:
Congenital heart disease is commonly a manifestation of genetic conditions. Surgery and/or extracorporeal membrane oxygenation were withheld in the past from some patients with genetic conditions. We hypothesized that surgical care of children with genetic conditions has increased over the last decade, but their cardiac extracorporeal membrane oxygenation use remains lower and mortality greater.

Design:
Retrospective cohort study.

Setting:
Patients admitted to the Pediatric Health Information System database 18 years old or younger with cardiac surgery during 2003–2014. Genetic conditions identified by International Classification of Diseases, 9th Edition codes were grouped as follows: trisomy 21, trisomy 13 or 18, 22q11 deletion, and all “other” genetic conditions and compared with patients without genetic condition.

Patients:
A total of 95,253 patients met study criteria, no genetic conditions (85%), trisomy 21 (10%), trisomy 13 or 18 (0.2%), 22q11 deletion (1%), and others (5%).

Interventions:
None.

Measurements and Main Results:
Annual surgical cases did not vary over time. Compared to patients without genetic conditions, trisomy 21 patients, extracorporeal membrane oxygenation use was just over half (odds ratio, 0.54), but mortality with and without extracorporeal membrane oxygenation were similar. In trisomy 13 or 18 patients, extracorporeal membrane oxygenation use was similar to those without genetic condition, but all five treated with extracorporeal membrane oxygenation died. 22q11 patients compared with those without genetic condition had similar extracorporeal membrane oxygenation use, but greater odds of extracorporeal membrane oxygenation mortality (odds ratio, 3.44). Other genetic conditions had significantly greater extracorporeal membrane oxygenation use (odds ratio, 1.22), mortality with extracorporeal membrane oxygenation (odds ratio, 1.42), and even greater mortality odds without (odds ratio, 2.62).

Conclusions:
The proportion of children undergoing cardiac surgery who have genetic conditions did not increase during the study. Excluding trisomy 13 or 18, all groups of genetic conditions received and benefited from extracorporeal membrane oxygenation, although extracorporeal membrane oxygenation mortality was greater for those with 22q11 deletion and other genetic conditions.
Observational Study of the Effect of Patient Outreach on Return to Care: The Earlier the Better
Authors: Rebeiro Peter F. , Bakoyannis Giorgos , Musick Beverly S. , Braithwaite Ronald S. , Wools-Kaloustian Kara K. , Nyandiko Winstone , Some Fatma , Braitstein Paula , Yiannoutsos Constantin T. 
Published: June 2017

Background:
The burden of HIV remains heaviest in resource-limited settings, where problems of losses to care, silent transfers, gaps in care, and incomplete mortality ascertainment have been recognized.

Methods:
Patients in care at Academic Model Providing Access to Healthcare (AMPATH) clinics from 2001–2011 were included in this retrospective observational study. Patients missing an appointment were traced by trained staff; those found alive were counseled to return to care (RTC). Relative hazards of RTC were estimated among those having a true gap: missing a clinic appointment and confirmed as neither dead nor receiving care elsewhere. Sample-based multiple imputation accounted for missing vital status.

Results:
Among 34,522 patients lost to clinic, 15,331 (44.4%) had a true gap per outreach, 2754 (8.0%) were deceased, and 837 (2.4%) had documented transfers. Of 15,600 (45.2%) remaining without active ascertainment, 8762 (56.2%) with later RTC were assumed to have a true gap. Adjusted cause-specific hazard ratios (aHRs) showed early outreach (a ≤8-day window, defined by grid-search approach) had twice the hazard for RTC vs. those without (aHR = 2.06; P < 0.001). HRs for RTC were lower the later the outreach effort after disengagement (aHR = 0.86 per unit increase in time; P < 0.001). Older age, female sex (vs. male), antiretroviral therapy use (vs. none), and HIV status disclosure (vs. none) were also associated with greater likelihood of RTC, and higher enrollment CD4 count with lower likelihood of RTC.

Conclusion:
Patient outreach efforts have a positive impact on patient RTC, regardless of when undertaken, but particularly soon after the patient misses an appointment.
Addressing current challenges in cancer immunotherapy with mathematical and computational modeling
Authors: Konstorum Anna , Vella Anthony T. , Adler Adam J. , Laubenbacher Reinhard 
Published: June 2017

AbstractThe goal of cancer immunotherapy is to boost a patient’s immune response to a tumor. Yet, the design of an effective immunotherapy is complicated by various factors, including a potentially immunosuppressive tumor microenvironment, immune-modulating effects of conventional treatments, and therapy-related toxicities. These complexities can be incorporated into mathematical and computational models of cancer immunotherapy that can then be used to aid in rational therapy design. In this review, we survey modeling approaches under the umbrella of the major challenges facing immunotherapy development, which encompass tumor classification, optimal treatment scheduling, and combination therapy design. Although overlapping, each challenge has presented unique opportunities for modelers to make contributions using analytical and numerical analysis of model outcomes, as well as optimization algorithms. We discuss several examples of models that have grown in complexity as more biological information has become available, showcasing how model development is a dynamic process interlinked with the rapid advances in tumor-immune biology. We conclude the review with recommendations for modelers both with respect to methodology and biological direction that might help keep modelers at the forefront of cancer immunotherapy development.
Cameo: A Python Library for Computer Aided Metabolic Engineering and Optimization of Cell Factories
Authors: Cardoso João G. R. , Jensen Kristian , Lieven Christian , Hansen Anne Sofie Lærke , Galkina Svetlana , Beber Moritz , Özdemir Emre , Herrgård Markus J. , Redestig Henning , Sonnenschein Nikolaus 
Published: June 2017

ABSTRACTComputational systems biology methods enable rational design of cell factories on a genomescale and thus accelerate the engineering of cells for the production of valuable chemicals and proteins. Unfortunately, for the majority of these methods’ implementations are either not published, rely on proprietary software, or do not provide documented interfaces, which has precluded their mainstream adoption in the field. In this work we present cameo, a platform-independent software that enablesin silicodesign of cell factories and targets both experienced modelers as well as users new to the field. It is written in Python and implements state-of-the-art methods for enumerating and prioritizing knock-out, knock-in, over-expression, and down-regulation strategies and combinations thereof. Cameo is an open source software project and is freely available under the Apache License 2.0. A dedicated website including documentation, examples, and installation instructions can be found athttp://cameo.bio. Users can also give cameo a try athttp://try.cameo.bio.
Differential Mast Cell Outcomes Are Sensitive to FcεRI-Syk Binding Kinetics
Authors: Schwartz Samantha L. , Cleyrat Cédric , Olah Mark , Relich Peter , Phillips Genevieve , Hlavacek William S. , Lidke Keith A. , Wilson Bridget S. , Lidke Diane S. 
Published: June 2017

AbstractCrosslinking of IgE-bound FcεRI triggers multiple cellular responses, including degranulation and cytokine production. Signaling is dependent on recruitment of Syk via docking of its dual SH2 domains to phosphorylated tyrosines within the FcεRI immunoreceptor tyrosine-based activation motifs. Using single molecule imaging in live cells, we directly visualized and quantified the binding of individual mNeonGreen-tagged Syk molecules as they associated with the plasma membrane after FcεRI activation. We found that Syk colocalizes transiently to FcεRI and that Syk-FcεRI binding dynamics are independent of receptor aggregate size. Substitution of glutamic acid for tyrosine between the Syk SH2 domains (SykY130E) led to an increased Syk-FcεRI off-rate, loss of site-specific Syk autophosphorylation, and impaired downstream signaling. CRISPR-Cas9 engineered cells expressing only SykY130E were deficient in antigen-stimulated calcium release, degranulation and production of some cytokines (TNF-a, IL-3) but not others (MCP-1, IL-4). We propose that kinetic discrimination along the FcεRI signaling pathway occurs at the level of Syk-FcεRI interactions, with key outcomes dependent upon sufficiently long-lived Syk binding events.SummarySchwartz et al. use single molecule imaging to quantify the transient nature of FcεRI-Syk interactions in live mast cells. A functional mutation that increases Syk off-rate leads to loss of site-specific Syk phosphorylation and impaired signaling, highlighting the importance of finely tuned protein interactions in directing cellular outcomes.
De-novoassembly of zucchini genome reveals a whole genome duplication associated with the origin of theCucurbitagenus
Authors: Montero-Pau Javier , Blanca José , Bombarely Aureliano , Ziarsolo Peio , Esteras Cristina , Martí-Gómez Carlos , Ferriol María , Gómez Pedro , Jamilena Manuel , Mueller Lukas , Picó Belén , Cañizares Joaquín 
Published: June 2017

AbstractTheCucurbitagenus (squashes, pumpkins, gourds) includes important domesticated species such asC. pepo,C. maximaandC. moschata. In this study, we present a high-quality draft of the zucchini (C. pepo) genome. The assembly has a size of 263 Mb, a scaffold N50 of 1.8 Mb, 34,240 gene models, includes 92% of the conserved BUSCO core gene set, and it is estimated to cover 93.0% of the genome. The genome is organized in 20 pseudomolecules, that represent 81.4% of the assembly, and it is integrated with a genetic map of 7,718 SNPs. Despite its small genome size three independent evidences support that theC. pepogenome is the result of a Whole Genome Duplication: the topology of the gene family phylogenies, the karyotype organization, and the distribution of 4DTv distances. Additionally, 40 transcriptomes of 12 species of the genus were assembled and analyzed together with all the other published genomes of the Cucurbitaceae family. The duplication was detected in all theCucurbitaspecies analyzed, includingC. maximaandC. moschata, but not in the more distant cucurbits belonging to theCucumisandCitrullusgenera, and it is likely to have happened 30 ± 4 Mya in the ancestral species that gave rise to the genus.
Single-cell RNA-seq of mouse dopaminergic neurons informs candidate gene selection for sporadic Parkinson’s disease
Authors: Hook Paul W. , McClymont Sarah A. , Cannon Gabrielle H. , Law William D. , Morton A. Jennifer , Goff Loyal A. , McCallion Andrew S. 
Published: June 2017

ABSTRACTGenetic variation modulating risk of sporadic Parkinson’s disease (PD) has been primarily explored through genome wide association studies (GWAS). However, like many other common genetic diseases, the impacted genes remain largely unknown. Here, we used single-cell RNA-seq to characterize dopaminergic (DA) neuron populations in the mouse brain at embryonic and early postnatal timepoints. These data facilitated unbiased identification of DA neuron subpopulations through their unique transcriptional profiles, including a novel postnatal neuroblast population andsubstantia nigra(SN) DA neurons. We use these population-specific data to develop a scoring system to prioritize candidate genes in all 49 GWAS intervals implicated in PD risk, including known PD genes and many with extensive supporting literature. As proof of principle, we confirm that the nigrostriatal pathway is compromised inCplx1null mice. Ultimately, this systematic approach establishes biologically pertinent candidates and testable hypotheses for sporadic PD, informing a new era of PD genetic research.
Population genomics of bank vole populations reveals associations between immune related genes and the epidemiology of Puumala hantavirus in Sweden
Authors: Rohfritsch Audrey , Galan Maxime , Gautier Mathieu , Gharbi Karim , Olsson Gert , Gschloessl Bernhard , Zeimes Caroline , VanWambeke Sophie , Vitalis Renaud , Charbonnel Nathalie 
Published: June 2017

AbstractInfectious pathogens are major selective forces acting on individuals. The recent advent of high-throughput sequencing technologies now enables to investigate the genetic bases of resistance/susceptibility to infections in non-model organisms. From an evolutionary perspective, the analysis of the genetic diversity observed at these genes in natural populations provides insight into the mechanisms maintaining polymorphism and their epidemiological consequences. We explored these questions in the context of the interactions between Puumala hantavirus (PUUV) and its reservoir host, the bank voleMyodes glareolus. Despite the continuous spatial distribution ofM. glareolusin Europe, PUUV distribution is strongly heterogeneous. Different defence strategies might have evolved in bank voles as a result of co-adaptation with PUUV, which may in turn reinforce spatial heterogeneity in PUUV distribution. We performed a genome scan study of six bank vole populations sampled along a North/South transect in Sweden, including PUUV endemic and non-endemic areas. We combined candidate gene analyses (Tlr4,Tlr7,Mx2genes) and high throughput sequencing of RAD (Restriction-site Associated DNA) markers. We found evidence for outlier loci showing high levels of genetic differentiation. Ten outliers among the 52 that matched to mouse protein-coding genes corresponded to immune related genes and were detected using ecological associations with variations in PUUV prevalence. One third of the enriched pathways concerned immune processes, including platelet activation and TLR pathway. In the future, functional experimentations should enable to confirm the role of these these immune related genes with regard to the interactions betweenM. glareolusand PUUV.
SNP Data Quality Control in a National Beef and Dairy Cattle System and Highly Accurate SNP Based Parentage Verification and Identification
Authors: McClure M.C. , McCarthy J. , Flynn P. , McClure J. , O’Connell K. , Kearney J.F. 
Published: June 2017

AbstractA major use of genetic data is parentage verification and identification as inaccurate pedigrees negatively affect genetic gain. Since 2012 the international standard for single nucleotide polymorphism (SNP) based verification inBos tauruscattle has been the ISAG 100 and 200 SNP panels. While these SNP sets have provided an increased level of parentage accuracy over microsatellite markers (MS), they can validate the wrong parent for an animal at ≤1% misconcordance rate levels, indicating that more SNP are needed if a more accurate pedigree is required. With rapidly increasing numbers of cattle being genotyped in Ireland that represent 61Bos taurusbreeds from a wide range of farm types: beef/dairy, AI/pedigree/commercial, purebred/crossbred, and large to small herd size the Irish Cattle Breeding Federation (ICBF) analysed different SNP densities to determine that at a minimum ≥500 SNP are needed to consistently predict only one set of parents at a ≤1% misconcordance rate. For parentage validation and prediction ICBF uses 800 SNP selected based on SNP clustering quality, ISAG200 inclusion, call rate (CR), and minor allele frequency (MAF) in the Irish cattle population. Large datasets require sample and SNP quality control (QC). Most publications only deal with SNP QC via CR, MAF, parent-progeny conflicts, and Hardy-Weinberg deviation, but not sample QC. We report here a genomic sample QC pipeline to deal with the unique challenges of >1,000,000 genotypes from a national herd such as SNP genotype errors from mis-tagging of animals, lab errors, farm errors, and multiple other issues that can arise.
Post-transcriptional modulation of Dscam1 enhances axonal growth in development and after injury
Authors: Koch Marta , Nicolas Maya , Zschaetzsch Marlen , de Geest Natalie , Claeys Annelies , Yan Jiekun , Morgan Matthew , Erfurth Marie-Luise , Holt Matthew , Schmucker Dietmar , Hassan Bassem A 
Published: June 2017

AbstractInjury to the adult central nervous systems (CNS) results in severe long-term disability because damaged CNS connections rarely regenerate. Although several axon regeneration regulators have been proposed, intrinsic regenerative mechanisms remain largely unexplored. Here, we use aDrosophilaCNS injury model to identify a novel pro-regeneration signaling pathway. We conducted a genetic screen of approximately three hundred candidate genes and identified three strong inducers of axonal growth and regeneration: the Down Syndrome Cell Adhesion Molecule (Dscam1), the de-ubiquitinating enzyme Fat Facets (Faf)/Usp9x and the Jun N-Terminal Kinase (JNK) pathway transcription factor Kayak (Kay)/Fos. Genetic and biochemical analyses link these genes in a common signaling pathway whereby Faf stabilizes Dscam1 protein levels, by acting on the 3’-UTR of its mRNA, and Dscam1 acts upstream of the growth-promoting JNK signal. The mammalian homolog of Faf, Usp9x/FAM, shares both the regenerative and Dscam1 stabilizing activities, suggesting a conserved mechanism.
Hammondia hammondihas a developmental programin vitrothat mirrors its stringent two host life cycle
Authors: Sokol Sarah L. , Primack Abby S. , Nair Sethu C. , Wong Zhee S. , Tembo Maiwase , Dubey J.P. , Verma Shiv K. , Boyle Jon P. 
Published: June 2017

AbstractHammondia hammondiis the nearest relative ofToxoplasma gondii,but unlikeT. gondiiis obligately heteroxenous. We have comparedH. hammondiandT. gondiidevelopmentin vitroand identified multipleH. hammondi-specific growth states. Despite replicating slower thanT. gondii,H. hammondiwas resistant to pH-induced tissue cyst formation early after excystation. However, in the absence of stressH. hammondispontaneously converted to a terminally differentiated tissue cyst stage whileT. gondiidid not. CulturedH. hammondicould infect new host cells for up to 8 days following excystation, and this period was exploited to generate stably transgenicH. hammondi. Coupled with RNAseq analyses, our data clearly show thatH. hammondizoites grow as stringently regulated life stages that are fundamentally distinct fromT. gondiitachyzoites and bradyzoites.
Metabolic engineering ofEscherichia colifor production of valerenadiene
Authors: Eric Nybo S. , Saunders Jacqueline , McCormick Sean P. 
Published: June 2017

AbstractValeriana officinalisis a medicinal herb which produces a suite of compounds in its root tissue useful for treatment of anxiety and insomnia. The sesquiterpene components of the root extract, valerenic acid and valerena-1,10-diene, are thought to contribute to most of the observed anxiolytic of Valerian root preparations. However, valerenic acid and its biosynthetic intermediates are only produced in low quantities in the roots ofV. officinalis. Thus, in this report,Escherichia coliwas metabolically engineered to produce substantial quantities of valerena-1,10-diene in shake flask fermentations with decane overlay. Expression of the wildtype valerenadiene synthase gene (pZE-wvds) resulted in production of 12 μg/mL in LB cultures using endogenous FPP metabolism. Expression of a codon-optimized version of the valerenadiene synthase gene (pZE-cvds) resulted in 3-fold higher titers of valerenadiene (32 μg/mL). Co-expression of pZE-cvdswith an engineered methyl erythritol phosphate (MEP) pathway improved valerenadiene titers 65-fold to 2.09 mg/L valerenadiene. Optimization of the fermentation medium to include glycerol supplementation enhanced yields by another 5.5-fold (11.0 mg/L valerenadiene). The highest production of valerenadiene resulted from engineering the codon-optimized valerenadiene synthase gene under strong Ptrcand PT7promoters and via co-expression of an exogenous mevalonate (MVA) pathway. These efforts resulted in anE. coliproduction strain that produced 62.0 mg/L valerenadiene (19.4 mg/L/OD600specific productivity). ThisE. coliproduction platform will serve as the foundation for the synthesis of novel valerenic acid analogues potentially useful for the treatment of anxiety disorders.
Challenges in estimating the motility parametersn of single processive motor proteins
Authors: Ruhnow F. , Kloß L. , Diez S. 
Published: June 2017

AbstractCytoskeletal motor proteins are essential to the function of a wide range of intracellular mechanosystems. The biophysical characterization of their movement along their filamentous tracks is therefore of large importance. Towards this end, single-molecule,in vitrostepping-motility assays are commonly used to determine motor velocity and run length. However, comparing results from such experiments has proved difficult due to influences from variations in the experimental conditions and the data analysis methods. Here, we investigate the movement of fluorescently-labeled, processive, dimeric motor proteins and propose a unified algorithm to correct the measurements for finite filament length as well as photobleaching. Particular emphasis is put on estimating the statistical errors associated with the proposed evaluation method as knowledge of these values is crucial when comparing measurements from different experiments. Testing our approach with simulated and experimental data from GFP-labeled kinesin-1 motors stepping along immobilized microtubules, we show (i) that velocity distributions should be fitted by atlocation-scale probability density function rather than by a norm*al distribution, (ii) that the impossibility to measure events shorter than the image acquisition time needs to be accounted for, (iii) that the interaction time and run length of the motors can be estimated independent of the filament length distribution, and (iv) that the dimeric nature of the motors needs to be considered when correcting for photobleaching. Moreover, our analysis reveals that controlling the temperature during the experiments with a precision below 1 K is of importance. We believe, our method will not only improve the evaluation of experimental data, but will also allow for better statistical comparisons between different populations of motor proteins (e.g. with distinct mutations or linked to different cargos) and filaments (e.g. in distinct nucleotide states or with different posttranslational modifications).
Gaining insights from RNA-Seq data using iDEP
Authors: Ge Steven Xijin , Son Eun Wo 
Published: June 2017

AbstractThe analysis and interpretation of the RNA-Seq data can be time-consuming and challenging. We aim to streamline the bioinformatic analyses of gene-level data by developing a user-friendly web application for exploratory data analysis, differential expression, and pathway analysis. iDEP (integrated Differential Expression and Pathway analysis) seamlessly connects 63 R/Bioconductor packages, 208 annotation databases for plant and animal species, and 2 web services. The workflow can be reproduced by downloading customized R code and related files. As demonstrated by two examples, iDEP (http://ge-lab.org/idep/) democratizes access to bioinformatics resources and empowers biologists to easily gain actionable insights from transcriptomic data.