bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality Improvement and Performance Management Benefits of Public Health Accreditation: National Evaluation Findings
Authors: Siegfried Alexa , Heffernan Megan , Kennedy Mallory , Meit Michael 
Published: March 2018

Objective:
To identify the quality improvement (QI) and performance management benefits reported by public health departments as a result of participating in the national, voluntary program for public health accreditation implemented by the Public Health Accreditation Board (PHAB).

Design:
We gathered quantitative data via Web-based surveys of all applicant and accredited public health departments when they completed 3 different milestones in the PHAB accreditation process.

Participants:
Leadership from 324 unique state, local, and tribal public health departments in the United States.

Results:
Public health departments that have achieved PHAB accreditation reported the following QI and performance management benefits: improved awareness and focus on QI efforts; increased QI training among staff; perceived increases in QI knowledge among staff; implemented new QI strategies; implemented strategies to evaluate effectiveness and quality; used information from QI processes to inform decision making; and perceived achievement of a QI culture. The reported implementation of QI strategies and use of information from QI processes to inform decision making was greater among recently accredited health departments than among health departments that had registered their intent to apply but not yet undergone the PHAB accreditation process. Respondents from health departments that had been accredited for 1 year reported higher levels of staff QI training and perceived increases in QI knowledge than those that were recently accredited.

Conclusions:
PHAB accreditation has stimulated QI and performance management activities within public health departments. Health departments that pursue PHAB accreditation are likely to report immediate increases in QI and performance management activities as a result of undergoing the PHAB accreditation process, and these benefits are likely to be reported at a higher level, even 1 year after the accreditation decision.
Neurosurgical workload during US combat operations: 2002 to 2016
Authors: Turner Caryn A. , Stockinger Zsolt T. , Bell Randy S. , Gurney Jennifer M. 
Published: March 2018

BACKGROUND
Approximately 4.5% of surgical procedures performed at Role 2 (R2) (forward surgical) and Role 3 (R3) (theater) medical treatment facilities can be classified as neurosurgical. These procedures are foreign to the routine daily practice of the military general surgeon. The purpose of this study was to examine the neurosurgical workload in Iraq and Afghanistan in order to inform the future predeployment neurosurgical training needs of nonneurosurgical providers.

METHODS
Retrospective analysis of the Department of Defense Trauma Registry for all R2 and R3 medical facilities, from January 2002 to May 2016. The 103 neurosurgical International Classification of Diseases, Ninth Revision, Clinical Modification procedure codes identified were grouped by anatomic location. Select groups were further subdivided. Data analysis used Stata version 14 (College Station, TX).

RESULTS
A total of 7,509 neurosurgical procedures were identified. The majority (7,244 [96.5%]) occurred at R3 theater hospitals. Cranial procedures were the most common at both R2 (120, 45.3%) and R3 (4,483 [61.9%]), with craniotomy/craniectomy the most frequent procedure. Spine procedures were performed almost exclusively at R3, with 61.1% being fusions/stabilizations and 26.9% being spinal decompression alone. Neurosurgical caseload was variable over the 15-year study period, dropping to almost zero in 2016.

CONCLUSIONS
Neurosurgical procedures were performed primarily at larger R3 theater hospitals where neurosurgeons were assigned if present in theater; however, more than 100 cranial procedures were performed at forward R2 where neurosurgeons were not deployed. Considering that neurosurgeons are not everywhere available within the war zone, deploying general surgeons should have familiarity with trauma neurosurgery.

LEVEL OF EVIDENCE
Epidemiologic study, level III; Care Management, level IV.
Loss of CREST leads to neuroinflammatory responses and ALS-like motor defects in mice
Authors: Cheng Cheng , Yang Kan , Wu Xinwei , Zhang Yuefang , Shan Shifang , Gitler Aaron , Ghosh Anirvan , Qiu Zilong 
Published: March 2018

SUMMARYAmyotrophic lateral sclerosis (ALS) is a late onset neurodegenerative disease with fast progression. Mutations of the CREST gene (also known as SS18L1) are identified in sporadic ALS patients. Whether CREST mutations may lead to ALS remained largely unclear. In this study, we showed that the ALS-related CREST-Q388X mutation exhibited loss-of-function effects. Importantly, we found that microglial activation were prevalent in CREST haploinsufficieny mice and the Q394X mice mimicking the human CREST Q388X mutation. Furthermore, we showed that both CREST haploinsufficieny and the Q394X mice displayed deficits in motor coordination. Finally, we identified the critical role of CREST-BRG1 complex in repressing the expression of immune-related cytokines including Ccl2 and Cxcl10 in neurons, via histone deacetylation, providing the molecular mechanisms underlying inflammatory responses lack of CREST. These findings indicate that elevated inflammatory responses in a subset of ALS may be caused by neuron-derived factors, suggesting potential therapeutic methods through inflammation pathways.In BriefCheng et al. discovered that neuronal loss of CREST reduces the protein level of FUS, de-represses the transcriptional inhibition of chemokine genes which in turn causes microglial activation and proinflammation, and ultimately leads to axonal degeneration of motor neurons and impairment of locomotion.
The perception of color and material in naturalistic tasks
Authors: Brainard David H. , Cottaris Nicolas P. , Radonjić Ana 
Published: March 2018

AbstractPerceived object color and material properties help us to select and interact with objects. Because there is no simple mapping between the pattern of an object’s image on the retina and its physical reflectance, our perception of color and material are made more useful through sophisticated visual computations. A long-standing goal in vision science is to describe how these computations work, particularly as they act to stabilize perceived color and material against variation in scene factors extrinsic to object surface properties, such as the illumination. If we take seriously the notion that perceived color and material are useful because they help guide behavior in natural tasks, then we need experimental that measure and models that describe how they are used in such tasks. To this end, we have developed selection-based methods and accompanying perceptual models for studying perceived object color and material. This focused review highlights key aspects of our work. It includes a discussion of future directions and challenges, as well as an outline of a computational observer model that incorporates early, known, stages of visual processing and that clarifies how early vision shapes selection performance.
Biallelic Mutations in LRRC56 encoding a protein associated with intraflagellar transport, cause mucociliary clearance and laterality defects
Authors: Bonnefoy Serge , Watson Christopher M. , Kernohan Kristin D. , Lemos Moara , Hutchinson Sebastian , Poulter James A. , Crinnion Laura A. , O’Callaghan Chris , Hirst Robert A. , Rutman Andrew , Huang Lijia , Hartley Taila , Grynspan David , Moya Eduardo , Li Chunmei , Carr Ian M. , Bonthron David T. , Leroux Michel ,   Care4Rare Canada Consortium, Boycott Kym M. , Bastin Philippe , Sheridan Eamonn G. 
Published: March 2018

ABSTRACTDefective motile cilia are responsible for a group of heterogeneous genetic conditions characterised by dysfunction of the apparatus responsible for generating fluid flows. Primary ciliary dyskinesia (PCD) is the prototype for such disorders and presents with impaired pulmonary mucus clearance, susceptibility to chronic recurrent respiratory infections, male infertility and laterality defects in about 50 % of patients. Here we report biallelic variants in LRRC56 (also known as ODA8), identified in two unrelated consanguineous families. The phenotype comprises laterality defects and chronic pulmonary infections. High speed video microscopy of cultured patient epithelial cells showed severely dyskinetic cilia, but no obvious ultra-structural abnormalities on routine transmission electron microscopy (TEM). Further investigation revealed that LRRC56 interacts with the intraflagellar transport (IFT) protein IFT88. The link to IFT was interrogated in Trypanosoma brucei. In this protist, LRRC56 is recruited to the cilium during axoneme construction, where it co-localises with IFT trains and facilitates the addition of dynein arms to the distal end of the flagellum. In T. brucei carrying LRRC56 null mutations, or a mutation (p.Leu259Pro) corresponding to the p.Leu140Pro variant seen in one of the affected families, we observed abnormal ciliary beat patterns and an absence of outer dynein arms restricted to the distal portion of the axoneme. Together, our findings confirm that deleterious variants in LRRC56 result in a human disease, and suggest this protein has a likely role in dynein transport during cilia assembly that is evolutionarily important for cilia motility.
A study of phenotypic plasticity ofSaccharomyces cerevisiaein natural grape juices shed light on allelic variation under balanced selection
Authors: Peltier Emilien , Sharma Vikas , Martí Raga Maria , Roncoroni Miguel , Bernard Margaux , Jiranek Vladimir , Gibon Yves , Marullo Philippe 
Published: March 2018

AbstractThe ability of a genotype to produce different phenotypes according to its surrounding environment is known as phenotypic plasticity. Within different individuals of the same species, phenotypic plasticity can vary greatly. This contrasted response is due to allelic variations and is caused by gene-by-environment interactions (GxE). Finding the genes and the cellular functions that interact with the environment is a current challenge for better understanding the genetic bases of phenotypic plasticity. In order to study the impact of natural allelic variations having a contrasted but relevant effect in a changing environment, we investigated the phenotypic response of the wine yeastSaccharomyces cerevisiaefermented in various grape juices. In this study we implemented a QTL mapping program using two independent offspring (~100 progeny) in order to investigate the molecular basis of yeast phenotypic response in a wine fermentation context. Thanks to high throughput sequencing approaches, both populations were genotyped, providing saturated genetic maps of thousands of markers. Linkage analyses allowed the detection of 78 QTLs including 21 with significant interaction with the nature of the fermented juice or fermentation conditions. Molecular dissection of a major QTL showed that the sulfite pump Ssu1p has a pleiotropic effect and impacts the phenotypic plasticity of several traits. Both alleles have positive effect according to external condition in phenotypes related to yeast fitness suggesting an example of balanced selection. All together these results pave the way for exploiting and deciphering the genetic determinism of phenotypic plasticity.
Brainwide organization of neuronal activity and convergent sensorimotor transformations in larval zebrafish
Authors: Chen Xiuye , Mu Yu , Hu Yu , Kuan Aaron T. , Nikitchenko Maxim , Randlett Owen , Sompolinsky Haim , Engert Florian , Ahrens Misha B. 
Published: March 2018

AbstractSimultaneous recordings of large populations of neurons in behaving animals allow detailed observation of high-dimensional, complex brain activity. However, experimental design and analysis approaches have not sufficiently evolved to fully realize the potential of these methods. We recorded whole-brain neuronal activity for larval zebrafish presented with a battery of visual stimuli while recording fictive motor output. These data were used to develop analysis methods including regression techniques that leverage trial-to-trial variations and unsupervised clustering techniques that organize neurons into functional groups. We used these methods to obtain brain-wide maps of concerted activity, which revealed both known and heretofore uncharacterized brain nuclei. We also identified neurons tuned to each stimulus type and motor output, and revealed nuclei in the anterior hindbrain that respond to multiple stimuli that elicit the same behavior. However, these convergent sensorimotor representations were only weakly correlated to instantaneous motor behavior, suggesting that they inform, but do not directly generate, behavioral output. These findings motivate a novel model of sensorimotor transformation spanning distinct behavioral contexts, within which these hindbrain convergence neurons likely constitute a key step.
Tissue-specific transcriptome for Poeciliopsis prolifica reveals evidence for genetic adaptation related to the evolution of a placental fish
Authors: Jue Nathaniel K. , Foley Robert J. , Reznick David N. , O’Neill Rachel J. , O’Neill Michael J. 
Published: March 2018

ABSTRACTThe evolution of the placenta is an excellent model to examine the evolutionary processes underlying adaptive complexity due to the recent, independent derivation of placentation in divergent animal lineages. In fishes, the family Poeciliidae offers the opportunity to study placental evolution with respect to variation in degree of post-fertilization maternal provisioning among closely related sister species. In this study, we present a detailed examination of a new reference transcriptome sequence for the live-bearing, matrotrophic fish, Poeciliopsis prolifica, from multiple-tissue RNA-seq data. We describe the genetic components active in liver, brain, late-stage embryo, and the maternal placental/ovarian complex, as well as associated patterns of positive selection in a suite of orthologous genes found in fishes. Results indicate the expression of many signaling transcripts, “non-coding” sequences and repetitive elements in the maternal placental/ovarian complex. Moreover, patterns of positive selection in protein sequence evolution were found associated with live-bearing fishes, generally, and the placental P. prolifica, specifically, that appear independent of the general live-bearer lifestyle. Much of the observed patterns of gene expression and positive selection are congruent with the evolution of placentation in fish functionally converging with mammalian placental evolution and with the patterns of rapid evolution facilitated by the teleost-specific whole genome duplication event.
The formation of intramolecular secondary structure brings mRNA ends in close proximity
Authors: Lai Wan-Jung C. , Kayedkhordeh Mohammad , Cornell Erica V. , Farah Elie , Bellaousov Stanislav , Rietmeijer Robert , Mathews David H. , Ermolenko Dmitri N. 
Published: March 2018

ABSTRACTA number of protein factors regulate protein synthesis by bridging mRNA ends or untranslated regions (UTRs). Using experimental and computational approaches, we show that mRNAs from various organisms, including humans, have an intrinsic propensity to fold into structures in which the 5’ end and 3’ end are ≤ 7 nm apart irrespective of mRNA length. Computational estimates performed for ∼22,000 human transcripts indicate that the inherent proximity of the ends is a universal property of most, if not all, mRNA sequences. Only specific RNA sequences, which have low sequence complexity and are devoid of guanosines, are unstructured and exhibit end-to-end distances expected for the random coil conformation of RNA. Our results suggest that the intrinsic proximity of mRNA ends may facilitate binding of translation factors that bridge mRNA 5’ and 3’ UTRs. Furthermore, our studies provide the basis for measuring, computing and manipulating end-to-end distances and secondary structure in mRNAs in research and biotechnology.
A novel mutual information estimator to measure spike train correlations in a model thalamocortical network
Authors: Gribkova Ekaterina D. , Ibrahim Baher A. , Llano Daniel A. 
Published: March 2018

AbstractThe impact of thalamic state on information transmission to the cortex remains poorly understood. This limitation exists due to the rich dynamics displayed by thalamocortical networks and because of inadequate tools to characterize those dynamics. Here, we introduce a novel estimator of mutual information and use it to determine the impact of a computational model of thalamic state on information transmission. Using several criteria, this novel estimator, which uses an adaptive partition, is shown to be superior to other mutual information estimators with uniform partitions when used to analyze simulated spike train data with different mean spike rates, as well as electrophysiological data from simultaneously recorded neurons. When applied to a thalamocortical model, the estimator revealed that thalamocortical cell T-type calcium current conductance influences mutual information between the input and output from this network. In particular, a T-type calcium current conductance of about 40 nS appears to produce maximal mutual information between the input to this network (conceptualized as afferent input to the thalamocortical cell) and the output of the network at the level of a layer 4 cortical neuron. Furthermore, at particular combinations of inputs to thalamocortical and thalamic reticular nucleus cells, thalamic cell bursting correlated strongly with recovery of mutual information between thalamic afferents and layer 4 neurons. These studies suggest that the novel mutual information estimator has advantages over previous estimators, and that thalamic reticular nucleus activity can enhance mutual information between thalamic afferents and thalamorecipient cells in the cortex.
Behavior of homing endonuclease gene drives targeting genes required for viability or female fertility with multiplexed guide RNAs
Authors: Oberhofer Georg , Ivy Tobin , Hay Bruce A. 
Published: March 2018

AbstractA gene drive method of particular interest for population suppression utilizes homing endonuclease genes (HEGs), wherein a site-specific nuclease-encoding cassette is copied, in the germline, into a target gene whose loss of function results in loss of viability or fertility in homozygous, but not heterozygous progeny. Earlier work inDrosophilaand mosquitoes utilized HEGs consisting of Cas9 and a single gRNA that together target a specific gene for cleavage. Homing was observed, but resistant alleles, immune to cleavage, while retaining wildtype gene function, were also created through non-homologous end joining. Such alleles prevent drive and population suppression. Targeting a gene for cleavage at multiple positions has been suggested as a strategy to prevent the appearance of resistant alleles. To test this hypothesis, we generated two suppression HEGs, targeting genes required for embryonic viability or fertility, using a HEG consisting of CRISPR/Cas9 and guide RNAs (gRNAs) designed to cleave each gene at four positions. Rates of target locus cleavage were very high, and multiplexing of gRNAs prevented resistant allele formation. However, germline homing rates were modest, and the HEG cassette was unstable during homing events, resulting in frequent partial copying of HEGs that lacked gRNAs, a dominant marker gene, or Cas9. Finally, in drive experiments the HEGs failed to spread, due to the high fitness load induced in offspring as a result of maternal carry over of Cas9/gRNA complex activity. Alternative design principles are proposed that may mitigate these problems in future gene drive engineering.Significance statementHEG-based gene drive can bring about population suppression when genes required for viability or fertility are targeted. However, these strategies are vulnerable to failure through mechanisms that create alleles resistant to cleavage, but that retain wildtype gene function. We show that resistance allele creation can be prevented through the use of gRNAs designed to cleave a gene at four target sites. However, homing rates were modest, and the HEGs were unstable during homing. In addition, use of a promoter active in the female germline resulted in levels of HEG carryover that compromised the viability or fertility of HEG-bearing heterozygotes, thereby preventing drive. We propose strategies that can help to overcome these problems in next generation HEG systems.
Predicting the viability of archaic human hybrids using a mitochondrial proxy
Authors: Allen Richard , Ryan Hannah , Davis Brian W. , King Charlotte , Frantz Laurent , Barnett Ross , Linderholm Anna , Loog Liisa , Haile James , Lebrasseur Ophélie , White Mark , Kitchener Andrew C. , Murphy William J. , Larson Greger 
Published: March 2018

AbstractAncient DNA evidence has confirmed hybridization between humans and Neanderthals and revealed a complex pattern of admixture between hominin lineages. Many segments of the modern human genome are devoid of Neanderthal ancestry, however, and this non-random distribution has raised questions regarding the frequency and success of hybridisation between ancient human lineages. Here, we examine the hypothesis that hominin hybrid offspring suffered a reduction in fertility by comparing patterns of sequence divergence of mitochondrial and nuclear DNA from numerous hybridising pairs of mammals. Our results reveal a threshold separating species pairs whose divergence values fall within two categories: those whose hybrid offspring can successfully reproduce without backcrossing with their parent species, and those whose hybrid offspring cannot. Using this framework, we predict that the potential hybrid offspring of Neanderthals, Denisovans, the ancient individuals from the Sima de los Huesos and anatomically modern humans would not have suffered a reduction in fertility.
A Comparative Assessment of Human and Chimpanzee iPSC-derived Cardiomyocytes with Primary Heart Tissues
Authors: Pavlovic Bryan J. , Blake Lauren E. , Roux Julien , Chavarria Claudia , Gilad Yoav 
Published: March 2018

AbstractComparative genomic studies in primates have the potential to reveal the genetic and mechanistic basis for human specific traits. These studies may also help us better understand inter-species phenotypic differences that are clinically relevant. Unfortunately, the obvious limitation on sample collection and experimentation in humans and non-human apes severely restrict our ability to perform dynamic comparative studies in primates. Induced pluripotent stem cells (iPSCs), and their corresponding differentiated cells, may provide a suitable alternative system for dynamic comparative studies. Yet, to effectively use iPSCs and differentiated cells for comparative studies, one must characterize the extent to which these systems faithfully represent biological processes in primary tissues. To do so, we compared gene expression data from primary adult heart tissue and iPSC-derived cardiomyocytes from multiple human and chimpanzee individuals. We determined that gene expression in cultured cardiomyocytes from both human and chimpanzee is most similar to that of adult hearts compared to other adult tissues. Using a comparative framework, we found that 50% of gene regulatory differences between human and chimpanzee hearts are also observed between species in cultured cardiomyocytes; conversely, inter-species regulatory differences seen in cardiomyocytes are found significantly more often in hearts than in other primary tissues. Our work provides a detailed description of the utility and limitation of differentiated cardiomyocytes as a system for comparative functional genomic studies in primates.Data availability and resource sharingGene expression (RNA-seq) data are available at GEO under accession number GSE110471. All human and chimpanzee iPSCs are available upon request without restriction or limitation.