bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leveraging the Incidence, Burden, and Fiscal Implications of Unplanned Hospital Revisits for the Prioritization of Prevention Efforts in Pediatric Surgery
Authors: Cameron Danielle B. , Serres Stephanie K. , Glass Charity C. , Milliren Carly E. , Graham Dionne A. , Anandalwar Seema , Thangarajah Hariharan , Goldin Adam B. , Hall Matthew , Rangel Shawn J. 
Published: June 2018

Objective:
To characterize procedure-level burden of revisit-associated resource utilization in pediatric surgery with the goal of establishing a prioritization framework for prevention efforts.

Summary of Background Data:
Unplanned hospital revisits are costly to the health care system and associated with lost productivity on behalf of patients and their families. Limited objective data exist to guide the prioritization of prevention efforts within pediatric surgery.

Methods:
Using the Pediatric Health Information System (PHIS) database, 30-day unplanned revisits for the 30 most commonly performed pediatric surgical procedures were reviewed from 47 children's hospitals between January 1, 2012 and March 31, 2015. The relative contribution of each procedure to the cumulative burden of revisit-associated length of stay and cost from all procedures was calculated as an estimate of public health relevance if prevention efforts were successfully applied (higher relative contribution = greater potential public health relevance).

Results:
159,675 index encounters were analyzed with an aggregate 30-day revisit rate of 10.8%. Four procedures contributed more than half of the revisit-associated length of stay burden from all procedures, with the highest relative contributions attributable to complicated appendicitis (18.4%), gastrostomy (13.4%), uncomplicated appendicitis (13.0%), and fundoplication (9.4%). Four procedures contributed more than half of the revisit-associated cost burden from all procedures, with the highest relative contributions attributable to complicated appendicitis (18.8%), gastrostomy (14.6%), fundoplication (10.4%), and uncomplicated appendicitis (10.2%).

Conclusions and Relevance:
A small number of procedures account for a disproportionate burden of revisit-associated resource utilization in pediatric surgery. Gastrostomy, fundoplication, and appendectomy should be considered high-priority targets for prevention efforts within pediatric surgery.
S-CAP extends clinical-grade pathogenicity prediction to genetic variants that affect RNA splicing
Authors: Jagadeesh Karthik A. , Paggi Joseph M. , Ye James S. , Stenson Peter D. , Cooper David N. , Bernstein Jonathan A. , Bejerano Gill 
Published: June 2018

AbstractThere are over 15,000 known variants that cause human inherited disease by disrupting RNA splicing. While severalin silicomethods such as CADD, EIGEN and LINSIGHT are commonly used to predict the pathogenicity of noncoding variants, we introduce S-CAP, a tool developed specially for splicing which is better able to effectively distinguish pathogenic splicing-relevant variants from benign variants. S-CAP is a novel splicing pathogenicity predictor that reduces the number of splicing-relevant variants of uncertain significance in patient exomes by 41%, a nearly 3-fold improvement over existing noncoding pathogenicity measures while correctly classifying known pathogenic splicing-relevant variants with a clinical-grade 95% sensitivity.
Lineage segregation, pluripotency and X-chromosome inactivation in the pig pre-gastrulation embryo
Authors: Ramos-Ibeas Priscila , Sang Fei , Zhu Qifan , Tang Walfred W.C. , Withey Sarah , Klisch Doris , Loose Matt , Surani M. Azim , Alberio Ramiro 
Published: June 2018

AbstractHigh-resolution molecular programs delineating the cellular foundations of mammalian embryogenesis have emerged recently. Similar analysis of human embryos is limited to pre-implantation stages, since early post-implantation embryos are inaccessible. Notwithstanding, we previously suggested conserved principles of pig and human early development. For further insight on pluripotent states and lineage delineation, we analysed pig embryos at single cell resolution. Here we show progressive segregation of inner cell mass and trophectoderm in early blastocysts, and then of epiblast and hypoblast in late blastocysts. We detected distinct pluripotent states, first as a short ‘naïve’ state followed by a protracted primed state. Dosage compensation with respect to the X-chromosome in females is attained via X-inactivation in late epiblasts. Detailed human-pig comparison is a basis towards comprehending early human development and a foundation for further studies of human pluripotent stem cell differentiation in pig interspecies chimeras.
Applying biophysical models to understand the role of white matter in cognitive development
Authors: Huber Elizabeth , Henriques Rafael Neto , Owen Julia P. , Rokem Ariel , Yeatman Jason D. 
Published: June 2018

AbstractDiffusion MRI (dMRI) holds great promise for illuminating the biological changes that underpin cognitive development. The diffusion of water molecules probes the cellular structure of brain tissue, and biophysical modeling of the diffusion signal can be used to make inferences about specific tissue properties that vary over development or predict cognitive performance. However, applying these models to study development requires that the parameters can be reliably estimated given the constraints of data collection with children. Here we collect repeated scans using a multi-shell diffusion MRI protocol in a group of children (ages 7-12) and use two popular biophysical models to characterize axonal properties. We first assess the scan-rescan reliability of model parameters and show that axon water faction can be reliably estimated from a relatively fast acquisition, without applying spatial smoothing or de-noising. We then investigate developmental changes in the white matter, and individual differences in white matter that correlate with reading skill. Specifically, we test the hypothesis that previously reported correlations between reading skill and diffusion anisotropy in the corpus callosum reflect increased axon density in poor readers. Both models support this interpretation, highlighting the utility of biophysical models for testing specific hypotheses about cognitive development.
Complexin cooperates with Bruchpilot to tether synaptic vesicles to the active zone cytomatrix
Authors: Scholz Nicole , Ehmann Nadine , Sachidanandan Divya , Imig Cordelia , Cooper Benjamin H. , Jahn Olaf , Reim Kerstin , Brose Nils , Pauli Martin , Heckmann Manfred , Stigloher Christian , Langenhan Tobias , Kittel Robert J. 
Published: June 2018

ABSTRACTInformation processing by the nervous system depends on the release of neurotransmitter from synaptic vesicles (SVs) at the presynaptic active zone. Molecular components of the cytomatrix at the active zone (CAZ) regulate the final stages of the SV cycle preceding exocytosis and thereby shape the efficacy and plasticity of synaptic transmission. Part of this regulation is reflected by a physical association of SVs with filamentous CAZ structures. However, our understanding of the protein interactions underlying SV tethering by the CAZ is far from complete. The very C-terminal region of Bruchpilot (Brp), a key component of theDrosophilaCAZ, participates in SV tethering. Yet so far, no vesicular or cytoplasmic molecules have been reported to engage in an interaction with Brp’s C-terminus. Here, we carried out an in vivo screen for molecules that link the Brp C-terminus to SVs. This strategy identified the conserved SNARE (solubleN-ethylmaleimide-sensitive factor (NSF) attachment protein receptor) regulator Complexin (Cpx) as a vesicular interaction partner of Brp. We show that Brp and Cpx interact genetically and functionally. Interfering with Cpx targeting to SVs mirrored distinctive features of a C-terminal Brp truncation: impaired SV recruitment to the CAZ and enhanced short-term synaptic depression. Extending the study beyondDrosophilasynapses, we interrogated active zones of mouse rod bipolar cells. Here, too, we collected evidence for an evolutionarily conserved role of Cpx upstream of SNARE complex assembly where it participates in SV tethering to the CAZ.
Reannotation of eight Drosophila genomes
Authors: Yang Haiwang , Jaime Maria , Polihronakis Maxi , Kanegawa Kelvin , Markow Therese , Kaneshiro Kenneth , Oliver Brian 
Published: June 2018

AbstractThe sequenced genomes in the Drosophila phylogeny is a central resource for comparative work supporting the understanding of the Drosophila melanogaster non-mammalian model system. These have also facilitated studying the selected and random differences that distinguish the thousands of extant species of Drosophila. However, full utility has been hampered by uneven genome annotation. We have generated a large expression profile dataset for nine species of Drosophila and trained a transcriptome assembly approach on Drosophila melanogaster to develop a pipeline that best matched the extensively curated annotation. We then applied this to the other species to add tens of thousands of new gene models per species. We also developed new orthologs to facilitate cross-species comparisons. We validated the new annotation of the distantly related Drosophila grimshawi with an extensive collection of newly sequenced cDNAs. This reannoation will facilitate understanding both the core commonalities and the species differences in this important group of model organisms.
A fast and cost-effective microsampling protocol incorporating reduced animal usage for time-series transcriptomics in rodent malaria parasites
Authors: Ramaprasad Abhinay , Subudhi Amit Kumar , Culleton Richard , Pain Arnab 
Published: June 2018

AbstractThe transcriptional regulation occurring in malaria parasites during the clinically important life stages within host erythrocytes can be studied in vivo with rodent malaria parasites propagated in mice. Time-series transcriptome profiling commonly involves the euthanasia of groups of mice at specific time points followed by the extraction of parasite RNA from whole blood samples. Current methodologies for parasite RNA extraction involve several steps and when multiple time points are profiled, these protocols are laborious, time consuming, and require the euthanisation of large cohorts of mice. We designed a simplified protocol for parasite RNA extraction from blood volumes as low as 20 microliters (microsamples), serially bled from mice via tail snips and directly lysed with TRIzol reagent. Gene expression data derived from microsampling using RNA-seq were closely matched to those derived from larger volumes of leucocyte-depleted and saponin-treated blood obtained from euthanized mice and also tightly correlated between biological replicates. Transcriptome profiling of microsamples taken at different time points during the intra-erythrocytic developmental cycle of the rodent malaria parasite Plasmodium vinckei revealed the transcriptional cascade commonly observed in malaria parasites. Microsampling is a quick, robust and cost-efficient approach to sample collection for in vivo time-series transcriptomic studies in rodent malaria parasites.
DiverseEscherichia colilineages, from domestic animals and humans in a household, carry colistin resistance genemcr-1in Ecuador
Authors: Loayza María Fernanda , Salinas Liseth , Villavicencio Fernando , Rafael Tamayo , Salas Stephanie , Villacís José , Satan Carolina , Ushiña Liliana , Rivera Ruth , Muñoz Olga , Zurita Jeannete , Nathalie Tijet , Melano Roberto , Reyes Jorge , Trueba Gabriel 
Published: June 2018

AbstractThe aim of this study was to investigate the presence ofEscherichia colicarryingmcr-1gene in domestic animals close to a child who suffered a peritoneal infection by amcr-1positiveE. coli. Rectal or cloacal swabs and fecal samples from domestic animals were plated on selective media to isolate colistin-resistantE. coliand isolates were submitted to detection ofmcr-1gene, pulsed field gel electrophoresis (PFGE), multi-locus sequence typing (MLST), replicon typing and S1-PFGE. Fourmcr-1positiveE. coliisolates (from chicken, turkey and dog) were recovered. No shared PFGE pattern or MLST sequence type were observed among isolates. A 60Kb IncI1γmcr-1-carrying plasmid was detected in all isolates. Our results suggest thatmcr-1gene was horizontally disseminated amongst different lineages ofE. colifrom domestic animals in the child’s household.ImportanceHorizontally transferable colistin resistance (mcr-1 gene) is thought to have originated in domestic animals and transferred to humans through meat and dairy products. In the present report we show evidence that themcr-1 gene could be transferred to differentE. colistrains colonizing different hosts (humans and pets) in the same household.
The transferable resistome of produce
Authors: Blau Khald , Bettermann Antje , Jechalke Sven , Fornefeld Eva , Vanrobaeys Yann , Stalder Thibault , Top Eva , Smalla Kornelia 
Published: June 2018

ABSTRACTProduce is increasingly recognized as a reservoir of human pathogens and transferable antibiotic resistance genes. This study aimed to explore methods to characterize the transferable resistome of bacteria associated with produce. Mixed salad, arugula, and cilantro purchased from supermarkets were analyzed by means of cultivation- and DNA-based methods. Before and after a nonselective enrichment step, tetracycline (tet) resistantEscherichia coliwere isolated and plasmids conferring tet resistance were captured by exogenous plasmid isolation. Tet resistantE. coliisolates, transconjugants and total community (TC)-DNA from the microbial fraction detached from leaves or after enrichment were analyzed for the presence of resistance genes, class 1 integrons and various plasmids by real-time PCR and PCR-Southern blot hybridization. Real-time PCR primers were developed for IncI and IncF plasmids. Tet resistantE. coliisolated from arugula and cilantro carried IncF, IncI1, IncN, IncH11, IncU and IncX1 plasmids. Three isolates from cilantro were positive for IncN plasmids andblaCTX-M-1. From mixed salad and cilantro, IncF, Inc11, and IncP-1β plasmids were captured exogenously. Importantly, whereas direct detection of IncI and IncF plasmids in TC-DNA failed, these plasmids became detectable in DNA extracted from enrichment cultures. This confirms that cultivation-independent DNA-based methods are not always sufficiently sensitive to detect the transferable resistome in the rare microbiome. In summary, this study showed that an impressive diversity of self-transmissible multiple resistance plasmids was detected in bacteria associated with produce that is consumed raw, and exogenous capturing intoE. colisuggests that they could transfer to gut bacteria as well.
Staged developmental mapping and X chromosome transcriptional dynamics during mouse spermatogenesis
Authors: Ernst Christina , Eling Nils , Martinez-Jimenez Celia P , Marioni John C , Odom Duncan T 
Published: June 2018

SUMMARYUnderstanding male fertility requires an in-depth characterisation of spermatogenesis, the developmental process by which male gametes are generated. Spermatogenesis occurs continuously throughout a male’s reproductive window and involves a complex sequence of developmental steps, both of which make this process difficult to decipher at the molecular level. To overcome this, we transcriptionally profiled single cells from multiple distinct stages during the first wave of spermatogenesis, where the most mature germ cell type is known. This naturally enriches for spermatogonia and somatic cell types present at very low frequencies in adult testes. Our atlas, available as a shiny app (https://marionilab.cruk.cam.ac.uk/SpermatoShiny), allowed us to reconstruct the three main processes of spermatogenesis: spermatogonial differentiation, meiosis, and spermiogenesis. Additionally, we profiled the chromatin changes associated with meiotic silencing of the X chromosome, revealing a set of genes specifically and strongly repressed by H3K9me3 in the spermatocyte stage, but which escape post-meiotic silencing in spermatids.
Trade-offs in provisioning and stability of multiple ecosystem services in agroecosystems
Authors: Montoya Daniel , Haegeman Bart , Gaba Sabrina , Mazancourt Claire de , Bretagnolle Vincent , Loreau Michel 
Published: June 2018

AbstractChanges in land use generate trade-offs in the delivery of ecosystem services in agricultural landscapes. However, we know little about how the stability of ecosystem services responds to landscape composition, and what ecological mechanisms underlie these trade-offs. Here, we develop a model to investigate the dynamics of three ecosystem services in intensively-managed agroecosystems, i.e. pollination-independent crop yield, crop pollination, and biodiversity. Our model reveals trade-offs and synergies imposed by landscape composition that affect not only the magnitude but also the stability of ecosystem service delivery. Trade-offs involving crop pollination are strongly affected by the degree to which crops depend on pollination and by their relative requirement for pollinator densities. We show conditions for crop production to increase with biodiversity and decreasing crop area, reconciling farmers’ profitability and biodiversity conservation. Our results further suggest that, for pollination-dependent crops, management strategies that focus on maximising yield will often overlook its stability. Given that agriculture has become more pollination-dependent over time, it is essential to understand the mechanisms driving these trade-offs to ensure food security.
A framework for offline evaluation and optimization of real-time algorithms for use in neurofeedback, demonstrated on an instantaneous proxy for correlations
Authors: Ramot Michal , Gonzalez-Castillo Javier 
Published: June 2018

AbstractInterest in real-time fMRI neurofeedback has grown exponentially over the past few years, both for use as a basic science research tool, and as part of the search for novel clinical interventions for neurological and psychiatric illnesses. In order to expand the range of questions which can be addressed with this tool however, new neurofeedback methods must be developed, going beyond feedback of activations in a single region. These new methods, several of which have already been proposed, are by their nature complex, involving many possible parameters. Here we suggest a framework for evaluating and optimizing algorithms for use in a real-time setting, before beginning the neurofeedback experiment, by offline simulations of algorithm output using a previously collected dataset. We demonstrate the application of this framework on the instantaneous proxy for correlations which we developed for training connectivity between different network nodes, identify the optimal parameters for use with this algorithm, and compare it to more traditional correlation methods. We also examine the effects of advanced imaging techniques, such as multi-echo acquisition, and the integration of these into the realtime processing stream.
A mechanism for synaptic copy between neural circuits
Authors: Shao Yuxiu , Wang Binxu , Sornborger Andrew T. , Tao Louis 
Published: June 2018

The brain has a central, short-term learning module, the hippocampus, which transfers what it has learned to long-term memory in cortex during non-REM sleep. The putative mechanism responsible for this type of memory consolidation invokes hierarchically nested hippocampal ripples (100-250 Hz), thalamo-cortical spindles (7-15 Hz), and cortical slow oscillations (< 1 Hz) to enable transfer. Suppression of, for instance, thalamic spindles has been shown to impair hippocampus-dependent memory consolidation. Cortical oscillations are central to information transfer in neural systems. Significant evidence supports the idea that coincident spike input can allow the neural threshold to be overcome, and spikes to be propagated downstream in a circuit. Thus, an observation of oscillations in neural circuits would be an indication that repeated synchronous spiking is enabling information transfer. However, for memory transfer, in which synaptic weights must be being transferred from one neural circuit (region) to another, what is the mechanism? Here, we present a synaptic transfer mechanism whose structure provides some understanding of the phenomena that have been implicated in memory transfer, including the nested oscillations at various frequencies. The circuit is based on the principle of pulse-gated, graded information transfer between neural populations.PACS numbers: 87.18.Sn,87.19.lj,87.19.lm,87.19.lq
Coping-Style Behavior Identified by a Survey of Parent-of-Origin Effects in the Rat
Authors: Mont Carme , Pilego Polinka Hernandez , Cañete Toni , Oliveras Ignasi , Río-Álamos Cristóbal , Blázquez Gloria , López-Aumatell Regina , Martínez-Membrives Esther , Tobeña Adolf , Flint Jonathan , Fernández-Teruel Alberto , Mott Richard 
Published: June 2018

AbstractWe develop theory, based on earlier work, to partition heritability into a component due to a combination of parent of origin, maternal, paternal and shared environment, and another component that estimates classical additive genetic variance. We then investigate the effects on heritability of the parental origin of alleles in outbred heterogeneous stock rats across 199 complex traits. Parent-of-origin-like heritability was on average 2.7-fold larger than classical additive heritability. Among the phenotypes with the most enhanced parent-of-origin heritability were 10 coping style behaviors, with average 3.2-fold heritability enrichment. To confirm these findings on coping behaviour, and to eliminate the possibility that the parent of origin effects are due to confounding with shared environment, we performed a reciprocal F1 cross between the behaviourally divergent RHA and RLA rat strains. We observed parent-of-origin effects on F1 rat anxiety/coping-related behavior in the Elevated Zero Maze test. Our results are the first to assess genetic parent-of-origin effects in rats, and confirm earlier findings in mice that such effects influence mammalian coping and impulsive behavior.
Exploration of miRNA-mediated fertility regulation network of cytoplasmic male sterility during flower bud development in soybean
Authors: Xianlong Ding , Hao Zhang , Hui Ruan , Yanwei Li , Linfeng Chen , Tanliu Wang , Ling Jin , Xiaoqiang Li , Shouping Yang , Junyi Gai 
Published: June 2018

ABSTRACTCytoplasmic male sterility (CMS) plays an important role in the production of soybean hybrid seeds. MicroRNAs (miRNAs) are a class of non-coding endogenous ~21 nt small RNAs that play crucial roles in flower and pollen development by targeting genes in plants. Here, two small RNA libraries and two degradome libraries were constructed from the flower buds of the soybean CMS line NJCMS1A and its restorer (Rf) line NJCMS1C. Following high-throughput sequencing, 558 known miRNAs, 103 novel miRNAs on the other arm of known pre-miRNAs, 10 novel miRNAs, and a number of base-edited miRNAs were identified. Among the identified miRNAs, 76 differentially expressed miRNAs were discovered with greater than two-fold changes between NJCMS1A and NJCMS1C. By degradome analysis, a total of 466 distinct transcripts targeted by 200 miRNAs and 122 distinct transcripts targeted by 307 base-edited miRNAs were detected. Further integrated analysis of transcriptome and small RNA found some miRNAs and their targets’ expression patterns showing a negative correlation, such as miR156b-GmSPL and miR4413b-GmPPR. Previous reports showed that these targets might be related to flower bud development, suggesting that miRNAs might act as regulators of soybean CMS fertility. These findings may provide a better understanding of the miRNA-mediated regulatory networks in CMS mechanisms of soybean.