bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes for Children With a Nonvisualized Appendix on Ultrasound
Authors: Williamson Kristy , Sherman Joshua M. , Fishbein Joanna Stein , Rocker Joshua 
Published: November 2018

Objectives
Oftentimes while pursing the diagnosis of appendicitis, an ultrasound cannot visualize the appendix, and physicians must utilize other resources for evaluation. The primary objective of this study was to determine if there was a lower rate of appendicitis when the appendix was not visualized on ultrasound. Furthermore, we assessed the importance of specific clinical predictors in this population.

Methods
We conducted a retrospective chart review of all children who presented to our pediatric emergency department from 2011 to 2013 and had an abdominal ultrasound. We identified total numbers of ultrasounds with a nonvisualized appendix and then assessed follow-up for a randomly selected group of patients. We performed logistic regression to assess the predictive value of different clinical factors.

Results
A total of 3245 ultrasounds were analyzed, and in 54% of these, the appendix was nonvisualized. In total, 28% of the total patients and 11.9% of patients who received a nonvisualized ultrasound had appendicitis (95% confidence interval [CI], 8.3%–16.2%). Among those patients who had follow-up studies performed during the same visit, 21.2% had appendicitis (95% CI, 14.9%–28.8%), and of those discharged without a diagnosis, 1.5% had appendicitis (95% CI, 0.2%–5.4%). Male sex, leukocytosis, and an elevated absolute neutrophil count were each significantly associated with appendicitis after a nonvisualized appendix on ultrasound.

Conclusions
A significant proportion of patients with suspected appendicitis who had an initial nonvisualized appendix on ultrasound were ultimately diagnosed with appendicitis. Clinicians must be vigilant about pursuing a definitive diagnosis if an initial ultrasound is nondiagnostic.
Depressive Symptoms During Childhood and Cardiovascular Risk Factors in Black and White Men
Authors: Matthews Karen A. , Jennings J. Richard , Lee Laisze , Pardini Dustin 
Published: November 2018

ABSTRACT

Objective
Depressive symptoms and major depression predict cardiovascular disease (CVD) and CVD risk factors in adulthood. Evidence regarding the role of depression in the development of CVD risk in youth is minimal. The study evaluated the prospective relationship of depressive symptoms in childhood and adolescence with adult CVD risk factors in black and white men.

Methods
Health behaviors and medical history were measured in 165 black and 146 white men (mean age = 32); a subset in the Pittsburgh area had a fasting blood draw to measure metabolic syndrome and inflammation. Adult CVD risk factors were related to depressive symptoms and childhood socioeconomic status (SES) prospectively measured annually from ages 7 to 16 years, followed by adjustments for adult SES and depressive symptoms.

Results
Men with higher depressive symptoms ages 7 to 16 smoked more cigarettes, B = 0.28 (standard error = 0.12), p = .015, and ate fewer servings of fruits and vegetables, B = −0.08 (0.04), p = .040, as adults. The association for smoking was independent of adult depressive symptoms (concurrent) and childhood and adult SES as well as race. Depressive symptoms during childhood were unrelated to the metabolic syndrome or biomarkers of inflammation in adulthood.

Conclusions
Depressive symptoms in childhood may predict later adverse health behaviors in black and white men. No evidence was found for an association between childhood depressive symptoms with metabolic syndrome or inflammation markers at ages approximately 32 years. The nature of the sample and lack of measurement of depressive disorder diagnosis tempers the conclusions, and future research is needed to determine associations with biological measures at later life span phases.
Locked Thumb Metacarpophalangeal Joint Caused by Entrapment of the Sesamoid Bone
Authors: Tsai Chia-Chin , Shieh Shyh-Jou 
Published: November 2018

Abstract
Locked thumb metacarpophalangeal joint caused by entrapment of the sesamoid bone is an uncommon entity. The intact volar plate, strong ligamentous attachment between the sesamoid bone and the joint, and altered axis of inserted muscle all contribute to failure of closed reduction. The patient's history, clinical presentation, and plain radiographic findings are all important clues to diagnosing this rare disease. We describe 2 patients with a similar mechanism of injury, where the sesamoid bones were displaced into the thumb metacarpophalangeal joint causing lock thumb. The anatomy, pathophysiology, and surgical management of the patients are also described and discussed. Both patients were successfully treated with meticulous open reduction.
VCF/Plotein: A web application to facilitate the clinical interpretation of genetic and genomic variants from exome sequencing projects
Authors: Ossio Raul , Anaya-Mancilla Diego Said , Garcia-Salinas O. Isaac , Garcia-Sotelo Jair S. , Aguilar Luis A. , Adams David J. , Robles-Espinoza Carla Daniela 
Published: November 2018

ABSTRACTPurposeTo create a user-friendly web application that allows researchers, medical professionals and patients to easily and securely view, filter and interact with human exome sequencing data in the Variant Call Format (VCF).MethodsWe have created VCF/Plotein, a web application written entirely in JavaScript using the Vue.js framework, available at http://vcfplotein.liigh.unam.mx. After a VCF is loaded, gene and variant information is extracted from Ensembl, and cross-referencing with external databases is performed via the Elasticsearch search engine. Support for application-based gene and variant filtering has also been implemented. Interactive graphs are created using the D3.js library. All data processing is done locally in the user’s CPU to ensure the security of patient data.ResultsVCF/Plotein allows users to interactively view and filter VCF files without needing any bioinformatics knowledge. A number of features make it especially suited for the medical community, such as its speed, security, the ability to filter by disease or gene function, and the ease with which information may be shared with collaborators/co-workers.ConclusionVCF/Plotein is a novel web application that allows users to easily and interactively filter and display exome sequencing information, and that is especially suited for bench researchers, medical professionals and patients.
Organoid single-cell profiling identifies a transcriptional signature of glomerular disease
Authors: Harder Jennifer L. , Menon Rajasree , Otto Edgar A. , Zhou Jian , Eddy Sean , Wys Noel L. , Nair Viji , Cebrian Cristina , Spence Jason R. , Troyanskaya Olga G. , Hodgin Jeffrey , Wiggins Roger C. , Freedman Benjamin S. , Kretzler Matthias ,   European Renal cDNA Bank, Nephrotic Syndrome Study Network
Published: November 2018

ABSTRACTPodocyte injury is central to many forms of kidney disease, but transcriptional signatures reflecting podocyte injury and compensation mechanisms are challenging to analyzein vivo. Human kidney organoids derived from pluripotent stem cells (PSCs), a new model for disease and regeneration, present an opportunity to explore the transcriptional plasticity of podocytes. Here, transcriptional profiling of over 12,000 single cells from human PSC-derived kidney organoid cultures was used to identify robust and reproducible cell-lineage gene expression signatures shared with developing human kidneys based on trajectory analysis. Surprisingly, the gene expression signature characteristic of developing glomerular epithelial cells was also observed in glomerular tissue from a kidney disease cohort. This signature correlated with proteinuria and inverse eGFR, and was confirmed in an independent podocytopathy cohort. Three genes in particular were further identified as critical components of the glomerular disease signature. We conclude that cells in human PSC-derived kidney organoids reliably recapitulate the developmental transcriptional program of podocytes and other cell lineages in the human kidney, and that the early transcriptional profile seen in developing podocytes is reactivated in glomerular disease. Our findings demonstrate an innovative approach to identifying novel molecular programs involved in the pathogenesis of glomerulopathies.
Bidirectional selection for body weight on standing genetic variation in a chicken model
Authors: Lillie Mette , Honaker Christa F. , Siegel Paul B. , Carlborg Örjan 
Published: November 2018

AbstractExperimental populations of model organisms provide valuable opportunities to unravel the genomic impact of selection in a controlled system. The Virginia body weight chicken lines represent a unique resource to investigate signatures of selection in a system where long-term, single-trait, bidirectional selection has been carried out for more than 60 generations. Using pooled genome resequencing of paired generations of these lines, we reveal the within and between-line genomic signatures of selection. At 55 generations of divergent selection, 14.2% of the genome showed extreme differentiation between the selected lines were contained within 395 genomic regions. The lines often displayed a duality of the sweep signatures: an extended region of homozygosity in one line, in contrast to mosaic pattern of heterozygosity in the other line. These haplotype mosaics consist of short, distinct haploblocks of variable between-line divergence. Formed during what probably was a complex history of bottlenecks, inbreeding, and introgressions, these mosaics represent the standing genetic variation available at the onset of selection in the founder population. Selection on standing genetic variation can thus result in different signatures depending on the intensity and direction of selection.
Exposure to graphene oxide sheets alters the expression of reference genes used for real-time RT-qPCR normalization
Authors: de Lázaro Irene , Kostarelos Kostas 
Published: November 2018

AbstractBackgroundstudies that unravel the interactions between thin, 2D graphene oxide (GO) sheets and the biological milieu, including cells and tissues, are multiplying quickly as the biomedical applications of those and other 2D materials continue to be explored. Many of such studies rely on real-time RT-qPCR as a powerful, yet relatively simple technique to determine gene expression. However, a systematic investigation of potential GO-induced changes in the expression of reference genes, crucial for appropriate normalization of qPCR data that ensures reliability of the results, is still lacking. In this study, we aimed to cover this gap by investigating the stability of the expression of ten (10) candidate reference genes upon exposure to increasing, but subtoxic, concentrations of GO, with two established algorithms (Bestkeeper and NormFinder). The study was performed in a human cancer cell line (MCF7) and in mouse, non-cancerous primary cells (mouse embryonic fibroblasts, MEFs), to assess different behaviors between cell types.ResultsBestkeeper and NormFinder algorithms evidenced significant deviations in the expression of various reference genes. Ribosomal proteins scored among the most significantly dysregulated targets in both cell types. Expression of ACTB and GAPDH, the most frequent calibrators in real-time RT-qPCR studies, was also affected, although differences existed between cell lines.Conclusionsthis study illustrates the need to validate reference genes for appropriate real-time RT-qPCR normalization, according to specific experimental conditions, when GO-cell interactions occur.
Dehydrojuncusol, a Natural Phenanthrene Compound Extracted fromJuncus maritimusIs a New Inhibitor of Hepatitis C Virus Replication
Authors: Sahuc Marie-Emmanuelle , Sahli Ramla , Rivière Céline , Pène Véronique , Lavie Muriel , Vandeputte Alexandre , Brodin Priscille , Rosenberg Arielle R. , Dubuisson Jean , Ksouri Riadh , Rouillé Yves , Sahpaz Sevser , Séron Karin 
Published: November 2018

AbstractRecent emergence of direct acting antivirals (DAAs) targeting hepatitis C virus (HCV) proteins has considerably enhanced the success of antiviral therapy. However, the appearance of DAA resistant-associated variants is a cause of treatment failure, and the high cost of DAAs renders the therapy not accessible in countries with inadequate medical infrastructures. Therefore, search for new inhibitors and with lower cost of production should be pursued. In this context, crude extract ofJuncus maritimusLam. was shown to exhibit high antiviral activity against HCV in cell culture. Bio-guided fractionation allowed isolating and identifying the active compound, dehydrojuncusol. A time-of-addition assay showed that dehydrojuncusol significantly inhibited HCV infection when added after virus inoculation of HCV genotype 2a (EC50= 1.35 µM). This antiviral activity was confirmed with a HCV subgenomic replicon and no effect on HCV pseudoparticle entry was observed. Antiviral activity of dehydrojuncusol was also demonstrated in primary human hepatocytes. Noin vitrotoxicity was observed at active concentrations. Dehydrojuncusol is also efficient on HCV genotype 3a and can be used in combination with sofosbuvir. Interestingly, dehydrojuncusol was able to inhibit replication of two frequent daclatasvir resistant mutants (L31M or Y93H in NS5A). Finally, resistant mutants to dehydrojuncusol were obtained and showed that HCV NS5A protein is the target of the molecule. In conclusion, dehydrojuncusol, a natural compound extracted fromJ. maritimus, inhibits infection of different HCV genotypes by targeting NS5A protein and is active against HCV resistant variants frequently found in patients with treatment failure.ImportanceTens of millions of people are infected with hepatitis C virus (HCV) worldwide. Recently marketed direct acting antivirals (DAAs) targeting HCV proteins have enhanced the efficacy of the treatment. However, due to its high cost, this new therapy is not accessible to the vast majority of infected patients. Furthermore, treatment failures have also been reported due to appearance of viral resistance. Here we report on the identification of a new HCV inhibitor, dehydrojuncusol that targets HCV NS5A and is able to inhibit replication of replicons harboring resistance mutations to anti-NS5A DAAs used in current therapy. Dehydrojuncusol is a natural compound isolated fromJuncus maritimus, a halophilic plant species very common in the coastlines worldwide. This molecule might serve as a lead for the development of new therapy more accessible to hepatitis C patients in the future.
Global transcriptional regulation of innate immunity in C. elegans
Authors: Fletcher Marissa , Tillman Erik J. , Butty Vincent L. , Levine Stuart S. , Kim Dennis H. 
Published: November 2018

AbstractThe nematode Caenorhabditis elegans has emerged as a genetically tractable animal host in which to study evolutionarily conserved mechanisms of innate immune signaling. We previously showed that the PMK-1 p38 mitogen-activated protein kinase (MAPK) pathway regulates innate immunity of C. elegans through phosphorylation of the CREB/ATF bZIP transcription factor, ATF-7. Here, we have undertaken a genomic analysis of the transcriptional response of C. elegans to infection by Pseudomonas aeruginosa, combining genome-wide expression analysis by RNA-seq with ATF-7 chromatin immunoprecipitation followed by sequencing (ChIP-Seq). We observe that PMK-1-ATF-7 activity regulates a majority of all genes induced by pathogen infection, and observe ATF-7 occupancy in regulatory regions of pathogen-induced genes in a PMK-1-dependent manner. Moreover, functional analysis of a subset of these ATF-7-regulated pathogen-induced target genes supports a direct role for this transcriptional response in host defense. The genome-wide regulation through PMK-1– ATF-7 signaling reveals global control over the innate immune response to infection through a single transcriptional regulator in a simple animal host.Author SummaryInnate immunity is the first line of defense against invading microbes across metazoans. Caenorhabditis elegans lacks adaptive immunity and is therefore particularly dependent on mounting an innate immune response against pathogens. A major component of this response is the conserved PMK-1/p38 MAPK signaling cascade, the activation of which results in phosphorylation of the bZIP transcription factor ATF-7. Signaling via PMK-1 and ATF-7 causes broad transcriptional changes including the induction of many genes that are predicted to have antimicrobial activity including C-type lectins and lysozymes. In this study, we show that ATF-7 directly regulates the majority of innate immune response genes upon pathogen infection of C. elegans, and demonstrate that many ATF-7 targets function to promote pathogen resistance.
The iPSC proteomic compendium
Authors: Brenes Alejandro , Bensaddek Dalila , Hukelmann Jens , Afzal Vackar , Lamond Angus I. 
Published: November 2018

AbstractInduced pluripotent stem cell (iPSC) technology holds great potential for therapeutic and research purposes. The Human Induced Pluripotent Stem Cell Initiative (HipSci) was established to generate a panel of high-quality iPSCs, from healthy and disease cohorts, with accompanying multi-omics and phenotypic data. Here, we present a proteomic analysis of 217 HipSci iPSC lines obtained from 163 donors.This dataset provides a comprehensive proteomic map of iPSCs, identifying >16,000 protein groups. We analyse how the expression profiles of proteins involved in cell cycle, metabolism and DNA repair contribute to key features of iPSC biology and we identify potential new regulators of the primed pluripotent state. To facilitate access, all these data have been integrated into the Encyclopedia of Proteome Dynamics (www.peptracker.com/epd), where it can be browsed interactively. Additionally, we generated an iPSC specific spectral library for DIA which we deposited in PRIDE along with the raw and processed mass-spectrometry data.
Revisiting tradeoffs in Rubisco kinetic parameters
Authors: Flamholz Avi I. , Prywes Noam , Moran Uri , Davidi Dan , Bar-On Yinon M. , Oltrogge Luke M. , Alves Rui , Savage David , Milo Ron 
Published: November 2018

AbstractRubisco is the most abundant enzyme in the biosphere and one of the best-characterized enzymes. Based on correlations between Rubisco kinetic parameters, it is widely posited that tradeoffs embedded in the catalytic mechanism constrain its specificity and maximum catalytic rate. However, the reasoning that established this view was based on data from ≈20 organisms. We re-examine these tradeoff models using a dataset from ≈300 organisms. Most correlations are substantially attenuated, with the inverse relationship between carboxylation kcat and specificity SC/O being a key example. Only one tradeoff model survives in our dataset. In this model, increasing catalytic efficiency (kcat/KM) for carboxylation requires increased catalytic efficiency for the competing oxygenation reaction, evidenced by strong power-law correlation between catalytic efficiencies. Our results imply that Rubisco evolution is constrained primarily by the physicochemical limits of O2/CO2 discrimination, which should reframe efforts to engineer this very central enzyme.
Chondroitin sulfate proteoglycan Windpipe modulates Hedgehog signaling inDrosophila
Authors: Takemura Masahiko , Noborn Fredrik , Nilsson Jonas , Nakato Eriko , Su Tsu-Yi , Larson Göran , Nakato Hiroshi 
Published: November 2018

AbstractProteoglycans, a class of carbohydrate-modified proteins, often modulate growth factor signaling on the cell surface. However, the molecular mechanism by which proteoglycans regulate signal transduction is largely unknown. In this study, using a recently-developed glycoproteomic method, we found that Windpipe (Wdp) is a novel chondroitin sulfate proteoglycan (CSPG) inDrosophila. Wdp is a single-pass transmembrane protein with leucin-rich repeat (LRR) motifs and bears three CS sugar chain attachment sites in the extracellular domain. Here we show that Wdp modulates the Hedgehog (Hh) pathway. Overexpression ofwdpinhibits Hh signaling in the wing disc, which is dependent on its CS chains and the LRR motifs. Conversely, loss ofwdpleads to the upregulation of Hh signaling. Furthermore, knockdown ofwdpincrease the cell surface accumulation of Smoothened (Smo), suggesting that Wdp inhibits Hh signaling by regulating Smo stability. Our study demonstrates a novel role of CSPG in regulating Hh signaling.
ManiNetCluster: A Manifold Learning Approach to Reveal the Functional Linkages Across Multiple Gene Networks
Authors: Nguyen Nam D. , Blaby Ian K. , Wang Daifeng 
Published: November 2018

AbstractThe coordination of genome encoded function is a critical and complex process in biological systems, especially across phenotypes or states (e.g., time, disease, organism). Understanding how the complexity of genome-encoded function relates to these states remains a challenge. To address this, we have developed a novel computational method based on manifold learning and comparative analysis, ManiNetCluster, which simultaneously aligns and clusters multiple molecular networks to systematically reveal function links across multiple datasets. Specifically, ManiNetCluster employs manifold learning to match local and non-linear structures among the networks of different states, to identify cross-network linkages. By applying ManiNetCluster to the developmental gene expression datasets across model organisms (e.g., worm, fruit fly), we found that our tool significantly better aligns the orthologous genes than existing state-of-the-art methods, indicating the non-linear interactions between evolutionary functions in development. Moreover, we applied ManiNetCluster to a series of transcriptomes measured in the green algaChlamy-domonas reinhardtii, to determine the function links between various metabolic processes between the light and dark periods of a diurnally cycling culture. For example, we identify a number of genes putatively regulating processes across each lighting regime, and how comparative analyses between ManiNetCluster and other clustering tools can provide additional insights. ManiNetCluster is available as an R package together with a tutorial athttps://github.com/namtk/ManiNetCluster.