bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retrospective, Multicenter Comparison of the Clinical Presentation of Patients Presenting With Diplopia From Giant Cell Arteritis vs Other Causes
Authors: Ross Ahmara G. , Jivraj Imran , Rodriguez Geoffrey , Pistilli Maxwell , Chen John J. , Sergott Robert C. , Moster Mark , Sheldon Claire A. , Liu Grant T. , Foroozan Rod , Ko Melissa W. , Francis Courtney E. , Williams Zoë R. , Lee Andrew G. , McClelland Collin M. , Shindler Kenneth S. , Yalamanchili Sushma , Osborne Benjamin , Hedges Thomas R. , Van Stavern Gregory P. , Puckett Ernest , Rigi Mohammed , García-Basterra Ignacia , Tamhankar Madhura A. 
Published: April 2018

Background:
Although giant cell arteritis (GCA) is a well-known cause of transient and permanent vision loss, diplopia as a presenting symptom of this condition is uncommon. We compared symptoms and signs of patients presenting with diplopia from GCA to those from other causes.

Methods:
This was a multicenter, retrospective study comparing the clinical characteristics of patients presenting with diplopia from GCA with age-matched controls. Demographic information, review of symptoms, ophthalmic examination, and laboratory data of biopsy-proven patients with GCA were compared with those of age-matched controls presenting with diplopia.

Results:
A total of 27 patients presented with diplopia from GCA, 19 with constant diplopia, and 8 with transient diplopia. All patients with constant diplopia from GCA were matched with 67 control subjects who had diplopia from other etiologies. Patients with GCA were more likely to describe other accompanying visual symptoms (58% vs 25%, P = 0.008), a greater number of systemic GCA symptoms (3.5, GCA vs 0.6, controls, P < 0.001) such as headache (94% [17/18] vs 39% [23/67]; P < 0.001), jaw claudication (80% [12/15] vs 0% [0/36]; P < 0.001), and scalp tenderness (44% [7/16] vs 7% [3/43]; P < 0.001). Ocular ischemic lesions (26% vs 1%, P < 0.001) were also common in patients with diplopia from GCA. Inflammatory markers were elevated significantly in patients with GCA vs controls (erythrocyte sedimentation rate: 91% [10/11] vs 12% [3/25], P < 0.001; C-reactive protein: 89% [8/9] vs 11% [2/19], P < 0.001).

Conclusions:
GCA is a rare but serious cause of diplopia among older adults and must be differentiated from other more common benign etiologies. Our study suggests that most patients with diplopia from GCA have concerning systemic symptoms and/or elevated inflammatory markers that should trigger further work-up. Moreover, careful ophthalmoscopic examination should be performed to look for presence of ocular ischemic lesions in older patients presenting with acute diplopia.
Leishmania naiffiandLeishmania guyanensisreference genomes highlight genome structure and gene evolution in theVianniasubgenus
Authors: Coughlan Simone , Taylor Ali Shirley , Feane Eoghan , Sanders Mandy , Schonian Gabriele , Cotton James A. , Downing Tim 
Published: April 2018

The unicellular protozoan parasiteLeishmaniacauses the neglected tropical disease leishmaniasis, affecting 12 million people in 98 countries. In South America, where theVianniasubgenus predominates, so far onlyL.(Viannia)braziliensisandL.(V.)panamensishave been sequenced, assembled and annotated as reference genomes. Addressing this deficit in molecular information can inform species typing, epidemiological monitoring and clinical treatment. Here,L.(V.)naiffiandL.(V.)guyanensisgenomic DNA was sequenced to assemble these two genomes as draft references from short sequence reads. The methods used were tested using short sequence reads forL. braziliensisM2904 against its published reference as a comparison. This assembly and annotation pipeline identified 70 additional genes not annotated on the original M2904 reference. Phylogenetic and evolutionary comparisons ofL. guyanensisandL. naiffiwith 10 otherVianniagenomes revealed four traits common to allViannia: aneuploidy, 22 orthologous groups of genes absent in otherLeishmaniasubgenera, elevated TATE transposon copies and a high NADH-dependent fumarate reductase gene copy number. Within theViannia, there were limited structural changes in genome architecture specific to individual species: a 45 Kb amplification on chromosome 34 was present in all barL. lainsoni,L. naiffihad a higher copy number of the virulence factor leishmanolysin, and laboratory isolateL. shawiM8408 had a possible minichromosome derived from the 3’ end of chromosome 34.This combination of genome assembly, phylogenetics and comparative analysis across an extended panel of diverseVianniahas uncovered new insights into the origin and evolution of this subgenus and can help improve diagnostics for leishmaniasis surveillance.
Ndr/Lats kinases bind specific Mob-family coactivators through a conserved and modular interface
Authors: Parker Benjamin W. , Gógl Gergő , Bálint Mónika , Hetenyi Csaba , Remenyi Attila , Weiss Eric L. 
Published: April 2018

AbstractNdr/Lats kinases bind Mob coactivator proteins to form complexes that are essential and deeply conserved components of “Hippo” signaling pathways, which control cell proliferation and morphogenesis in eukaryotes. All Ndr/Lats kinases have a characteristic N-terminal region (NTR) that binds a specific Mob co-factor: Lats kinases associate with Mob1 proteins, and Ndr kinases associate with Mob2 proteins. To better understand the functional significance of Mob protein association with Ndr/Lats kinases and selective binding of Ndr and Lats to distinct Mob co-factors, we solved crystal structures of Saccharomyces cerevisiae Cbk1(NTR)-Mob2 and Dbf2(NTR)-Mob1 and experimentally assessed determinants of Mob cofactor binding and specificity. This significantly refines the previously determined structure of Cbk1 kinase bound to Mob2, presently the only crystallographic model of a full length Ndr/Lats kinase complexed with a Mob cofactor. Our analysis indicates that the Ndr/Lats NTR-Mob interface provides a distinctive kinase regulation mechanism, in which Mob co-factor organizes the Ndr/Lats NTR to interact with the AGC kinase C-terminal hydrophobic motif (HM) activation segment. The Mob-organized NTR appears to mediate HM association with an allosteric site on the kinase N-lobe. We also found that Cbk1 and Dbf2 associated highly specifically with Mob2 and Mob1, respectively. Alteration of specific positions in the Cbk1 NTR allows association of non-cognate Mob co-factor, indicating that cofactor specificity is restricted by discrete sites rather than broadly distributed. Overall, our analysis provides a new picture of the functional role of Mob association and indicates that the Ndr/Lats(NTR)-Mob interface overall is largely a common structural platform that mediates kinase-cofactor binding.
GOcats: A tool for categorizing Gene Ontology into subgraphs of user-defined concepts
Authors: Hinderer Eugene W. , Moseley Hunter N.B. 
Published: April 2018

AbstractGene Ontology is used extensively in scientific knowledgebases and repositories to organize the wealth of available biological information. However, interpreting annotations derived from differential gene lists is difficult without manually sorting into higher-order categories. To address these issues, we present GOcats, a novel tool that organizes the Gene Ontology (GO) into subgraphs representing user-defined concepts, while ensuring that all appropriate relations are congruent with respect to scoping semantics. We tested GOcats performance using subcellular location categories to mine annotations from GO-utilizing knowledgebases and evaluating their accuracy against immunohistochemistry datasets in the Human Protein Atlas (HPA).In comparison to mappings generated from UniProt’s controlled vocabulary and from GO slims via OWLTools’ Map2Slim, GOcats outperforms these methods without reliance on a human-curated set of GO terms. By identifying and properly defining relations with respect to semantic scope, GOcats can use traditionally problematic relations without encountering erroneous term mapping. We applied GOcats in the comparison of HPA-sourced knowledgebase annotations to experimentally-derived annotations provided by HPA directly. During the comparison, GOcats improved correspondence between the annotation sources by adjusting semantic granularity. Utilized in this way, GOcats can perform an accurate knowledgebase-level evaluation of curated HPA-based annotations.
The genome ofEctocarpus subulatus– a highly stress-tolerant brown alga
Authors: Dittami Simon M. , Corre Erwan , Brillet-Guéguen Loraine , Lipinska Agnieszka P. , Pontoizeau Noé , Aite Meziane , Avia Komlan , Caron Christophe , Cho Chung Hyun , Collén Jonas , Cormier Alexandre , Delage Ludovic , Doubleau Sylvie , Frioux Clémence , Gobet Angélique , González-Navarrete Irene , Groisillier Agnès , Hervé Cécile , Jollivet Didier , KleinJan Hetty , Leblanc Catherine , Liu Xi , Marie Dominique , Markov Gabriel V. , Minoche André E. , Monsoor Misharl , Pericard Pierre , Perrineau Marie-Mathilde , Peters Akira F. , Siegel Anne , Siméon Amandine , Trottier Camille , Yoon Hwan Su , Himmelbauer Heinz , Boyen Catherine , Tonon Thierry 
Published: April 2018

AbstractBrown algae are multicellular photosynthetic stramenopiles that colonize marine rocky shores worldwide.Ectocarpussp. Ec32 has been established as a genomic model for brown algae. Here we present the genome and metabolic network of the closely related species,Ectocarpus subulatusKützing, which is characterized by high abiotic stress tolerance. Since their separation, both strains show new traces of viral sequences and the activity of large retrotransposons, which may also be related to the expansion of a family of chlorophyll-binding proteins. Further features suspected to contribute to stress tolerance include an expanded family of heat shock proteins, the reduction of genes involved in the production of halogenated defence compounds, and the presence of fewer cell wall polysaccharide-modifying enzymes. Overall,E. subulatushas mainly lost members of gene families down-regulated in low salinities, and conserved those that were up-regulated in the same condition. However, 96% of genes that differed between the two examinedEctocarpusspecies, as well as all genes under positive selection, were found to encode proteins of unknown function. This underlines the uniqueness of brown algal stress tolerance mechanisms as well as the significance of establishingE. subulatusas a comparative model for future functional studies.
Quantitative photoacoustic imaging study of tumours in vivo: baseline variations in quantitative measurements
Authors: Costa Márcia Martinho , Shah Anant , Rivens Ian , Box Carol , O’Shea Tuathan , Papaevangelou Efthymia , Bamber Jeffrey , ter Haar Gail 
Published: April 2018

AbstractPhotoacoustic imaging (PAI) provides information on haemoglobin levels and blood oxygenation (sO2). To facilitate assessment of the variability in sO2 and haemoglobin in tumours, for example in response to therapies, the baseline variability of these parameters was evaluated in subcutaneous head and neck tumours in mice, using a PAI system (MSOT-inVision-256TF). Tumours of anaesthetized animals (midazolam-fentanyl-medetomidine) were imaged for 75 minutes; in varying positions; and repeatedly over 6 days. An increasing linear trend for average tumoural haemoglobin and blood sO2 was observed, when imaging over 75 minutes. There were no significant differences in these temporal trends, when re-positioning tumours. A negative correlation was found between the percent decrease in blood sO2 over 6 days and tumour growth rate. This paper shows the potential of PAI to provide baseline data for assessing the significance of intra- and inter-tumoural variations that may eventually have value for predicting and/or monitoring cancer treatment response.
Kinome expansion in theFusarium oxysporumspecies complex driven by accessary chromosomes
Authors: DeIulio Gregory A. , Guo Li , Zhang Yong , Goldberg Jonathan , Kistler H. Corby , Ma Li-Jun 
Published: April 2018

ABSTRACTTheFusarium oxysporumspecies complex (FOSC) is a group of soil-borne pathogens causing severe disease in over one hundred plant hosts, while individual strains exhibit strong host specificity. Both chromosome transfer and comparative genomics experiments have demonstrated that lineage-specific (LS) chromosomes contribute to the host specific pathogenicity. However, little is known about the functional importance of genes encoded in these LS chromosomes. Focusing on signaling transduction, this study compared kinomes of 12F. oxysporumisolates, including both plant and human pathogens and one non-pathogenic biocontrol strain, with seven additional publicly available ascomycete genomes. Overall,F. oxysporumkinomes are the largest, facilitated in part by the acquisitions of the LS chromosomes. The comparative study identified 99 kinases that are present in almost all examined fungal genomes, forming the core signaling network of ascomycete fungi. Compared to the conserved ascomycete kinome, the expansion of theF. oxysporumkinome occurs in several kinases families such as Histidine kinases that are involved in environmental signal sensing and TOR kinase that mediates cellular responses. Comparative kinome analysis suggests a convergent evolution that shapes individualF. oxysporumisolates with an enhanced and unique capacity for environmental perception and associated downstream responses.IMPORTANCEIsolates ofF. oxysporumare adapted to survive a wide range of host and non-host conditions. In addition,F. oxysporumwas recently recognized as the top emerging opportunistic fungal pathogen infecting immunocompromised humans. The sensory and response networks of these fungi undoubtedly play a fundamental role in establishing the adaptability of this group. We have examined the kinomes of 12F. oxysporumisolates and highlighted kinase families that distinguishF. oxysporumfrom other fungi, as well as different isolates from one another. The amplification of kinases involved in environmental signal relay and regulating downstream cellular responses clearly setsFusariumapart from other Ascomycetes. Though the function of many of these kinases is still unclear, their specific proliferation highlights them as a result of the evolutionary forces which have shaped this species complex, and clearly marks them as targets for exploitation in order to combat disease.
The HCP 7T Retinotopy Dataset: Description and pRF Analysis
Authors: Benson Noah C. , Jamison Keith W. , Arcaro Michael J. , Vu An , Glasser Matthew F. , Coalson Timothy S. , Van Essen David C. , Yacoub Essa , Ugurbil Kamil , Winawer Jonathan , Kay Kendrick 
Published: April 2018

AbstractAbout a quarter of human cerebral cortex is dedicated mainly to visual processing. The large-scale organization of visual cortex can be measured with functional magnetic resonance imaging (fMRI) while subjects view spatially modulated visual stimuli, also known as ‘retinotopic mapping’. One of the datasets collected by the Human Connectome Project (HCP) involved ultra-high-field (7 Tesla) fMRI retinotopic mapping in 181 healthy young adults (1.6-mm resolution), yielding the largest freely available collection of retinotopy data. Here, we describe the experimental paradigm and the results of model-based analysis of the fMRI data. These results provide estimates of population receptive field position and size. Our analyses include both results from individual subjects as well as results obtained by averaging fMRI time-series across subjects at each cortical and subcortical location and then fitting models. Both the group-average and individual-subject results reveal robust signals across much of the brain, including occipital, temporal, parietal, and frontal cortex as well as subcortical areas. The group-average results agree well with previously published parcellations of visual areas. In addition, split-half analyses show strong within-subject reliability, further demonstrating the high quality of the data. We make publicly available the analysis results for individual subjects and the group average, as well as associated stimuli and analysis code. These resources provide an opportunity for studying fine-scale individual variability in cortical and subcortical organization and the properties of high-resolution fMRI. In addition, they provide a set of observations that can be compared with other HCP measures acquired in these same participants.
Detection of viral pathogens with multiplex Nanopore MinION sequencing: be careful with cross-talk
Authors: Xu Yifei , Lewandowski Kuiama , Lumley Sheila , Pullan Steven , Vipond Richard , Carroll Miles , Foster Dona , Matthews Philippa C , Peto Timothy , Crook Derrick 
Published: April 2018

AbstractMetagenomic sequencing with the Oxford Nanopore MinION sequencer offers potential for point-of-care testing of infectious diseases in clinical settings. To improve cost-effectiveness, multiplexing of several, barcoded samples upon a single flow cell will be required during sequencing. We generated a unique sequencing dataset to assess the extent and source of cross barcode contamination caused by multiplex MinION sequencing. Sequencing libraries for three different viruses, including influenza A, dengue and chikungunya, were prepared separately and sequenced on individual flow cells. We also pooled the respective libraries and performed multiplex sequencing. We identified 0.056% of total reads in the multiplex sequencing data that were assigned to incorrect barcodes. Chimeric reads were the predominant source of this error. Our findings highlight the need for careful filtering of multiplex sequencing data before downstream analysis, and the trade-off between sensitivity and specificity that applies to the barcode demultiplexing methods.
Ablation of proliferating neural stem cells during early life is sufficient to reduce adult hippocampal neurogenesis
Authors: Youssef Mary , Krish Varsha S. , Kirshenbaum Greer S. , Atsak Piray , Lass Tamara J. , Lieberman Sophie R. , Leonardo E. David , Dranovsky Alex 
Published: April 2018

AbstractEnvironmental exposures during early life, but not during adolescence or adulthood, lead to persistent reductions in neurogenesis in the adult hippocampal dentate gyrus (DG). The mechanisms by which early life exposures lead to long-term deficits in neurogenesis remain unclear. Here, we investigated whether targeted ablation of dividing neural stem cells during early life is sufficient to produce long-term decreases in DG neurogenesis. Having previously found that the stem cell lineage is resistant to long-term effects of transient ablation of dividing stem cells during adolescence or adulthood (Kirshenbaum et al., 2014), we used a similar pharmacogenetic approach to target dividing neural stem cells for elimination during early life periods sensitive to environmental insults. We then assessed the Nestin stem cell lineage in adulthood. We found that the adult neural stem cell reservoir was depleted following ablation during the first postnatal week, when stem cells were highly proliferative, but not during the third postnatal week, when stem cells were more quiescent. Remarkably, ablating proliferating stem cells during either the first or third postnatal week led to reduced adult neurogenesis out of proportion to the changes in the stem cell pool, indicating a disruption of the stem cell function or niche following stem cell ablation in early life. These results highlight the first three postnatal weeks as a series of sensitive periods during which elimination of dividing stem cells leads to lasting alterations in adult DG neurogenesis and stem cell function. These findings contribute to our understanding of the relationship between DG development and adult neurogenesis, as well as suggest a possible mechanism by which early life experiences may lead to lasting deficits in adult hippocampal neurogenesis.
Replicate Engineered Virtual Patient Populations as Surrogates for Real Patient-Level Data
Authors: Alenghat Francis J. 
Published: April 2018

AbstractObjectivesTo demonstrate a new method for generating virtual, individual-level data by testing it on a known clinical trial population.DesignVirtualization of aggregate data from a clinical trial.SettingVirtualParticipants936,100 virtual patientsInterventionsNoneMain Outcomes MeasuresOdds ratios for adverse outcomes in virtual patient populations compared to clinical trial participants.MethodsThe replicate engineered virtual patient populations (RE-ViPPs) method, based on aggregate cross-tabulated categorical population data, does not require access to individual-level data. Using sequential regression combined with randomization, it generates virtual individual patients to comprise populations that, on average, closely resemble the real population in question. The method is validated by applying it to aggregated data from the seminal SPRINT trial, which compared intensive versus standard blood pressure treatment goals on major adverse cardiovascular events.ResultsThe method yields virtual populations, each with 9361 patients, faithfully mimicking the real SPRINT participants. Multiple logistic regression on 100 such populations shows that factors with the highest odds ratios for the primary event are, in descending order, past clinical cardiovascular disease, age ≥ 75, chronic kidney disease, high non-HDL, and smoking history. Intensive blood pressure treatment, the trial’s intervention, had an odds ratio of 0.74 [0.63-0.87]. On all these measures, the 100 RE-ViPPs mirrored the real SPRINT participants, including the intensive therapy result (actual SPRINT odds ratio: 0.74 [0.62-0.88]).ConclusionsClinical data dissemination has limitations. The most coveted data is descriptive at the individual level but comes with significant cost, effort, and time. There is potential for privacy breaches, and the open-data movement has progressed slowly due to data-ownership concerns. RE-ViPPs closely matched the true SPRINT population. Applied to trials, registries, and databases, RE-ViPPs could reduce open-data burdens by encouraging dissemination of aggregate cross-tabulated real data that allow investigators to generate and measure virtual patients.
Genotyping by sequencing of 393Sorghum bicolorBTx623 × IS3620C recombinant inbred lines improves sensitivity and resolution of QTL detection
Authors: Kong WenQian , Kim Changsoo , Zhang Dong , Guo Hui , Tan Xu , Jin Huizhe , Zhou Chengbo , Shuang Lan-shuan , Goff Valorie , Sezen Uzay , Pierce Gary , Compton Rosana , Lemke Cornelia , Robertson Jon , Rainville Lisa , Auckland Susan , Paterson Andrew H. 
Published: April 2018

AbstractWe describe a genetic map with a total of 381 bins of 616 genotyping by sequencing (GBS)-based SNP markers in a F6-F8recombinant inbred line (RIL) population of 393 individuals derived from crossingS. bicolorBTx623 toS. bicolorIS3620C, a guinea line substantially diverged from BTx623. Five segregation distorted regions were found with four showing enrichment forS. bicoloralleles, suggesting possible selection during formation of this RIL population. A quantitative trait locus (QTL) study with this number of individuals, tripled relative to prior studies of this cross, provided resources, validated previous findings, and demonstrated improved power to detect plant height and flowering time related QTLs relative to other published studies. An unexpected low correlation between flowering time and plant height permitted us to separate QTLs for each trait and provide evidence against pleiotropy. Ten non-random syntenic regions conferring QTLs for the same trait suggest that those QTLs may represent alleles at genes functioning in the same manner since the 96 million year ago genome duplication that created these syntenic relationships, while syntenic regions conferring QTLs for different trait may suggest sub-functionalization after duplication. Collectively, this study provides resources for marker-assisted breeding, as well as a framework for fine mapping and subsequent cloning of major genes for important traits such as plant height and flowering time in sorghum.