bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endovascular Coil Retrieval Using Dual Synchronous Solitaire Revascularization Devices
Authors: Nerva John D , Morton Ryan P , Kelly Cory M , Hallam Danial K , Levitt Michael R 
Published: November 2017

Abstract

BACKGROUND AND IMPORTANCE
Coil migration is a potential complication of endovascular aneurysm treatment. Dislodged coils into the parent artery require retrieval to prevent thromboembolic complications. A variety of techniques for coil retrieval have been described, including the use of single stentrievers and aspiration catheters.

CLINICAL PRESENTATION
The use of 2 stentrievers, as opposed to a single device, was thought to be advantageous in coil removal by the additional point of friction due to the extensive length of coil stretching and earlier failure of a single device.

CONCLUSION
In this report, 2 synchronous Solitaire FR Revascularization Devices (Covidien/Medtronic, Dublin, Ireland) were deployed, 1 distal and 1 proximal, to retrieve an inadvertently deployed coil.
Alteration of Bile Acid and Cholesterol Biosynthesis and Transport by Perfluorononanoic Acid (PFNA) in Mice
Authors: Zhang Yue , Zhang Youcai , Klaassen Curtis D , Cheng Xingguo 
Published: November 2017

Abstract
Perfluorochemicals produce hepatotoxic effects via activation of peroxisome proliferator-activated receptor alpha (PPARα) and constitutive androstane receptor (CAR) nuclear receptors in animals. Bile formation is one major liver function. But it remains unknown whether perfluorochemicals alter metabolism of bile acids (BAs) in liver. The present study was designed to determine the impact of perfluorononanoic acid (PFNA) on BA and cholesterol homeostasis in mice. A single dose of PFNA (0.1 mmol/kg) was intraperitoneally administered to adult male wild-type (WT), PPARα-null, and CAR-null mice. PFNA caused cholestasis in the WT mice, indicated by increased serum alanine aminotransferase, hyperbilirubinemia, elevated BA concentrations in mouse serum, and appearance of bile plugs in mouse liver. In addition, PFNA decreased total and some individual BAs in mouse liver. PFNA increased the concentrations of total and taurine-conjugated, as well as some individual BAs in the serum of WT and CAR-null mice but not in PPARα-null mice, indicating a PPARα-dependent mechanism. PFNA decreased mRNA expression of most BA-related transporters (sodium-taurocholate cotransporting polypeptide, organic anion transporting polypeptide [Oatp]1a1, Oatp1b2, and bile salt export pump) and BA biosynthetic enzymes (Cyp7a1, 7b1, 8b1, and 27a1) in mouse liver, but increased mRNA expression of some efflux transporters (breast cancer resistance protein, multidrug resistance transporter 2, multidrug resistance-associated protein [Mrp] 2, Mrp3, and Mrp4), primarily via a PPARα-dependent mechanism. Moreover, PFNA increased free and total cholesterol in mouse liver but not in mouse serum. Furthermore, PFNA increased mRNA expression of sterol transporters, namely Abca1, g1, g5/g8, and steroidogenic acute regulatory protein via PPARα. In conclusion, PFNA produced cholestasis in mouse liver, and the activation of PPARα plays a central role in regulating BA and cholesterol metabolism and transport in mouse serum and liver.
Electrographic and Clinical Natural History of Lateralized Periodic Discharges
Authors: Punia Vineet , Vakani Ravi , Burgess Richard , Hantus Stephen 
Published: November 2017

Purpose:
The long-term electrographic features of lateralized periodic discharges (LPD) and their impact on clinical management are unclear. The authors investigated routine EEGs (rEEG) to analyze the delayed natural history of LPDs, and studied the clinical care of these patients.

Methods:
After IRB approval, the prospectively maintained continuous EEG (cEEG) database was searched to identify patients fulfilling the following criteria: LPDs on cEEG, age ≥18 years, no epilepsy history, and rEEG completed within 1 to 12 months of hospital discharge. Their rEEGs were reviewed followed by clinical data extraction. Appropriate statistical tools were used for data analysis.

Results:
Thirty-nine patients (20 females) with a mean age of 63.3 ± 16.8 years at the time of cEEG fulfilled the study criteria. Thirty-three (85%) had associated electrographic seizures. rEEG was performed 4.7 ± 3.5 months after cEEG. Seven (18%) patients had interictal epileptiform discharges (IEDs) on the rEEG. The LPDs on cEEG of these patients were more often continuous, with an amplitude >2 times their background compared with 10 (26%) patients with normal rEEGs findings. After a mean follow-up of 19.8 ± 9.9 months, 11 (31%) patients developed epilepsy, but only 3 had IEDs on their rEEG. Majority (86%) of patients were on AEDs at the time of last follow-up.

Conclusions:
LPDs lead to markers of epileptogenicity in around 18% of patients. One-third of the study population developed epilepsy. rEEG findings were not found to be good indicators of epilepsy development in our small, retrospective study limited by its sampling bias. Indiscriminate, long-term use of AEDs in these patients is a concerning finding.
Germline determinants of the somatic mutation landscape in 2,642 cancer genomes
Authors: Waszak Sebastian M , Tiao Grace , Zhu Bin , Rausch Tobias , Muyas Francesc , Rodríguez-Martín Bernardo , Rabionet Raquel , Yakneen Sergei , Escaramis Georgia , Li Yilong , Saini Natalie , Roberts Steven A , Demidov German M , Pitkänen Esa , Delaneau Olivier , Heredia-Genestar Jose Maria , Weischenfeldt Joachim , Shringarpure Suyash S , Chen Jieming , Nakagawa Hidewaki , Alexandrov Ludmil B , Drechsel Oliver , Dursi L Jonathan , Segre Ayellet V , Garrison Erik , Erkek Serap , Habermann Nina , Urban Lara , Khurana Ekta , Cafferkey Andy , Hayashi Shuto , Imoto Seiya , Aaltonen Lauri A , Alvarez Eva G , Baez-Ortega Adrian , Bailey Matthew , Bosio Mattia , Bruzos Alicia L , Buchhalter Ivo , Bustamante Carlos D. , Calabrese Claudia , DiBiase Anthony , Gerstein Mark , Holik Aliaksei Z , Hua Xing , Huang Kuan-lin , Letunic Ivica , Klimczak Leszek J , Koster Roelof , Kumar Sushant , McLellan Mike , Mashl Jay , Mirabello Lisa , Newhouse Steven , Prasad Aparna , Rätsch Gunnar , Schlesner Matthias , Schwarz Roland , Sharma Pramod , Shmaya Tal , Sidiropoulos Nikos , Song Lei , Susak Hana , Tanskanen Tomas , Tojo Marta , Wedge David C , Wright Mark , Wu Ying , Ye Kai , Yellapantula Venkata D , Zamora Jorge , Butte Atul J , Getz Gad , Simpson Jared , Ding Li , Marques-Bonet Tomas , Navarro Arcadi , Brazma Alvis , Campbell Peter , Chanock Stephen J , Chatterjee Nilanjan , Stegle Oliver , Siebert Reiner , Ossowski Stephan , Harismendy Olivier , Gordenin Dmitry A , Tubio Jose MC , Vega Francisco M De La , Easton Douglas F , Estivill Xavier , Korbel Jan O ,   on behalf of the PCAWG Germline Working group%,   and the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Network
Published: November 2017

AbstractCancers develop through somatic mutagenesis, however germline genetic variation can markedly contribute to tumorigenesis via diverse mechanisms. We discovered and phased 88 million germline single nucleotide variants, short insertions/deletions, and large structural variants in whole genomes from 2,642 cancer patients, and employed this genomic resource to study genetic determinants of somatic mutagenesis across 39 cancer types. Our analyses implicate damaging germline variants in a variety of cancer predisposition and DNA damage response genes with specific somatic mutation patterns. Mutations in the MBD4 DNA glycosylase gene showed association with elevated C>T mutagenesis at CpG dinucleotides, a ubiquitous mutational process acting across tissues. Analysis of somatic structural variation exposed complex rearrangement patterns, involving cycles of templated insertions and tandem duplications, in BRCA1-deficient tumours. Genome-wide association analysis implicated common genetic variation at the APOBEC3 gene cluster with reduced basal levels of somatic mutagenesis attributable to APOBEC cytidine deaminases across cancer types. We further inferred over a hundred polymorphic L1/LINE elements with somatic retrotransposition activity in cancer. Our study highlights the major impact of rare and common germline variants on mutational landscapes in cancer.
Size-reduced embryos reveal a gradient scaling based mechanism for zebrafish somite formation
Authors: Ishimatsu Kana , Hiscock Tom W. , Collins Zach M. , Sari Dini Wahyu Kartika , Lischer Kenny , Richmond David L. , Bessho Yasumasa , Matsui Takaaki , Megason Sean G. 
Published: November 2017

AbstractLittle is known about how the sizes of animal tissues are controlled. A prominent example is somite size which varies widely both within an individual and across species. Despite intense study of the segmentation clock governing the timing of somite generation, how it relates to somite size is poorly understood. Here we examine somite scaling and find that somite size at specification scales with the length of the presomitic mesoderm (PSM) despite considerable variation in PSM length across developmental stages and in surgically size-reduced embryos. Measurement of clock period, axis elongation speed, and clock gene expression patterns demonstrate that existing models fail to explain scaling. We posit a “clock and scaled gradient” model, in which somite boundaries are set by a dynamically scaling signaling gradient across the PSM. Our model not only explains existing data, but also makes a unique prediction that we experimentally confirm—the formation of periodic “echoes” in somite size following perturbation of the size of one somite. Our findings demonstrate that gradient scaling plays a central role both in progression and size control of somitogenesis.Summary statementBy comparing patterning in zebrafish embryos of different size we show that a dynamically scaling gradient in the presomitic mesoderm regulates somite size control.
A note on measuring natural selection on principal component scores
Authors: Chong Veronica K. , Fung Hannah F. , Stinchcombe John R. 
Published: November 2017

AbstractMeasuring natural selection through the use of multiple regression has transformed our understanding of selection, although the methods used remain sensitive to the effects of multicollinearity due to highly correlated traits. While measuring selection on principal component scores is an apparent solution to this challenge, this approach has been heavily criticized due to difficulties in interpretation and relating PC axes back to the original traits. We describe and illustrate how to transform selection gradients for PC scores back into selection gradients for the original traits, addressing issues of multicollinearity and biological interpretation. We demonstrate this approach with empirical data and examples from the literature, highlighting how selection estimates for PC scores can be interpreted while reducing the consequences of multicollinearity.
Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies
Authors: Zhou Wei , Nielsen Jonas B. , Fritsche Lars G. , Dey Rounak , Gabrielsen Maiken E. , Wolford Brooke N. , LeFaive Jonathon , VandeHaar Peter , Gagliano Sarah A. , Gifford Aliya , Bastarache Lisa A. , Wei Wei-Qi , Denny Joshua C. , Lin Maoxuan , Hveem Kristian , Kang Hyun Min , Abecasis Goncalo R. , Willer Cristen J. , Lee Seunggeun 
Published: November 2017

AbstractIn genome-wide association studies (GWAS) for thousands of phenotypes in large biobanks, most binary traits have substantially fewer cases than controls. Both of the widely used approaches, linear mixed model and the recently proposed logistic mixed model, perform poorly – producing large type I error rates – in the analysis of phenotypes with unbalanced case-control ratios. Here we propose a scalable and accurate generalized mixed model association test that uses the saddlepoint approximation (SPA) to calibrate the distribution of score test statistics. This method, SAIGE, provides accurate p-values even when case-control ratios are extremely unbalanced. It utilizes state-of-art optimization strategies to reduce computational time and memory cost of generalized mixed model. The computation cost linearly depends on sample size, and hence can be applicable to GWAS for thousands of phenotypes by large biobanks. Through the analysis of UK Biobank data of 408,961 white British European-ancestry samples for >1400 binary phenotypes, we show that SAIGE can efficiently analyze large sample data, controlling for unbalanced case-control ratios and sample relatedness.
Determining the genetic basis of anthracycline-cardiotoxicity by molecular response QTL mapping in induced cardiomyocytes
Authors: Knowles David A , Burrows Courtney K , Blischak John D , Patterson Kristen M , Ober Carole , Pritchard Jonathan K , Gilad Yoav 
Published: November 2017

AbstractAnthracycline-induced cardiotoxicity (ACT) is a key limiting factor in setting optimal chemotherapy regimes for cancer patients, with almost half of patients expected to ultimately develop congestive heart failure given high drug doses. However, the genetic basis of sensitivity to anthracyclines such as doxorubicin remains unclear. To begin addressing this, we created a panel of iPSC-derived cardiomyocytes from 45 individuals and performed RNA-seq after 24h exposure to varying levels of doxorubicin. The transcriptomic response to doxorubicin is substantial, with the majority of genes being differentially expressed across treatments of different concentrations and over 6000 genes showing evidence of differential splicing. Overall, our observations indicate that splicing fidelity decreases in the presence of doxorubicin. We detect 376 response-expression QTLs and 42 response-splicing QTLs, i.e. genetic variants that modulate the individual transcriptomic response to doxorubicin in terms of expression and splicing changes respectively. We show that inter-individual variation in transcriptional response is predictive of cell damage measuredin vitrousing a cardiac troponin assay, which in turn is shown to be associated within vivoACT risk. Finally, the molecular QTLs we detected are enriched in lower ACT GWASp-values, further supporting thein vivorelevance of our map of genetic regulation of cellular response to anthracyclines.
Natural selection interacts with the local recombination rate to shape the evolution of hybrid genomes
Authors: Schumer Molly , Xu Chenling , Powell Daniel L. , Durvasula Arun , Skov Laurits , Holland Chris , Sankararaman Sriram , Andolfatto Peter , Rosenthal Gil G. , Przeworski Molly 
Published: November 2017

AbstractWhile hybridization between species is increasingly appreciated to be a common occurrence, little is known about the forces that govern the subsequent evolution of hybrid genomes. We considered this question in three independent, naturally-occurring hybrid populations formed between swordtail fish speciesXiphophorus birchmanniandX. malinche.To this end, we built a fine-scale genetic map and inferred patterns of local ancestry along the genomes of 690 individuals sampled from the three populations. In all three cases, we found hybrid ancestry to be more common in regions of high recombination and where there is linkage to fewer putative targets of selection. These same patterns are also apparent in a reanalysis of human-Neanderthal admixture. Our results lend support to models in which ancestry from the “minor” parental species persists only where it is rapidly uncoupled from alleles that are deleterious in hybrids, and show the retention of hybrid ancestry to be at least in part predictable from genomic features. Our analyses further indicate that in swordtail fish, the dominant source of selection on hybrids stems from deleterious combinations of epistatically-interacting alleles.One sentence summaryThe persistence of hybrid ancestry is predictable from local recombination rates, in three replicate hybrid populations as well as in humans.
Neural mechanisms of speed-accuracy tradeoff of visual search: Saccade vigor, targeting errors, superior colliculus and frontal eye field
Authors: Reppert Thomas R. , Servant Mathieu , Heitz Richard P. , Schall Jeffrey D. 
Published: November 2017

AbstractBalancing the speed-accuracy tradeoff (SAT) is necessary for successful behavior. Using a visual search task with interleaved cues emphasizing speed or accuracy, we recently reported diverse contributions of frontal eye field (FEF) neurons instantiating salience evidence and response preparation. Here we report replication of visual search SAT performance in two macaque monkeys, new information about variation of saccade dynamics with SAT, extension of the neurophysiological investigation to describe processes in the superior colliculus, and description of the origin of search errors in this task. Saccade vigor varied idiosyncratically across SAT conditions and monkeys, but tended to decrease with response time. As observed in the FEF, speed-accuracy tradeoff was accomplished through several distinct adjustments in the superior colliculus. Visually-responsive neurons modulated baseline firing rate and the time course of salience evidence. Unlike FEF, the magnitude of visual responses in SC did not vary across SAT conditions, but the time to locate the target was longer in Accurate as compared to Fast trials. Also unlike FEF, the activity of SC movement neurons when saccades were initiated was equivalent in Fast and Accurate trials. Search errors occurred when visual salience neurons in FEF and SC treated distractors as targets, even in the Accurate condition. Saccade-related neural activity in SC but less FEF varied with saccade peak velocity. These results extend our understanding of the cortical and subcortical contributions to SAT.Significance statementNeurophysiological mechanisms of speed-accuracy tradeoff (SAT) have only recently been investigated. This paper reports the first replication of SAT performance in nonhuman primates, the first report of variation of saccade dynamics with SAT, the first description of superior colliculus contributions to SAT, and the first description of the origin of errors during SAT. These results inform and constrain new models of distributed decision-making.
Species and Cell-Type Properties of Classically Defined Human and Rodent Neurons and Glia
Authors: Xu Xiao , Stoyanova Elitsa I. , Lemiesz Agata , Xing Jie , Mash Deborah C. , Heintz Nathaniel 
Published: November 2017

SummaryDetermination of the molecular properties of genetically targeted cell types has led to fundamental insights into mouse brain function and dysfunction. Here, we report an efficient strategy for precise exploration of gene expression events in specific cell types in a broad range of species, including postmortem human brain. We demonstrate that classically defined, homologous neuronal and glial cell types differ between rodent and human by the expression of hundreds of orthologous, cell specific genes. Confirmation that these genes are differentially active was obtained using epigenetic mapping and immunofluorescence localization. Studies of sixteen human postmortem brains revealed cell-specific molecular responses to aging, and the induction of a shared, robust response to an unknown external event experienced by three donors. Our data establish a comprehensive approach for analysis of unique molecular events associated with specific circuits and cell types in a wide variety of human conditions.
Widespread dynamic and pleiotropic expression of the melanocortin-1-receptor (MC1R) system is conserved across chick, mouse and human embryonic development
Authors: Thomas Anna C. , Heux Pauline , Santos Chloe , Arulvasan Wisenave , Solanky Nita , Carey Magalie E. , Gerrelli Dianne , Kinsler Veronica A. , Etchevers Heather C. 
Published: November 2017

AbstractBackgroundMC1R, a G-protein coupled receptor with high affinity for alpha-melanocyte stimulating hormone (αMSH), modulates pigment production in melanocytes from many species and is associated with human melanoma risk.MC1Rmutations affecting human skin and hair color also have pleiotropic effects on the immune response and analgesia. Variants affecting human pigmentationin uteroalter the congenital phenotype of both oculocutaneous albinism and congenital melanocytic naevi, and have a possible effect on birthweight.Methods and ResultsByin situhybridization, RT-PCR and immunohistochemistry, we show thatMC1Ris widely expressed during human, chick and mouse embryonic and fetal stages in many somatic tissues, particularly in the musculoskeletal and nervous systems, and conserved across evolution in these three amniotes. Its dynamic pattern differs from that ofTUBB3, a gene overlapping the same locus in humans and encoding class III β-tubulin. The αMSH peptide and the transcript for its precursor, pro-opiomelanocortin (POMC), are similarly present in numerous extra-cutaneous tissues.MC1Rgenotyping of variants p.(V60M) and p.(R151C) was undertaken for 867 healthy children from the Avon Longitudinal Study of Parent and Children (ALSPAC) cohort, and birthweight modelled using multiple logistic regression analysis. A significant positive association initially found between R151C and birth weight, independent of known birth weight modifiers, was not reproduced when combined with data from an independent genome-wide association study of 6,459 additional members of the same cohort.ConclusionsThese data clearly show a new and hitherto unsuspected role for MC1R in non-cutaneous solid tissues before birth.
Post-catalytic spliceosome structure reveals mechanism of 3'-splice site selection
Authors: Wilkinson Max E. , Fica Sebastian M. , Galej Wojciech P. , Norman Christine M. , Newman Andrew J. , Nagai Kiyoshi 
Published: November 2017

AbstractIntrons are removed from eukaryotic mRNA precursors by the spliceosome in two transesterification reactions – branching and exon ligation. Following branching, the 5'-exon remains paired to U5 snRNA loop 1, but the mechanism of 3'-splice site recognition during exon ligation has remained unclear. Here we present the 3.7Å cryo-EM structure of the yeast P complex spliceosome immediately after exon ligation. The 3'-splice site AG dinucleotide is recognised through non-Watson-Crick pairing with the 5'-splice site and the branch point adenosine. A conserved loop of Prp18 together with the α-finger and the RNaseH domain of Prp8 clamp the docked 3'-splice site and 3'-exon. The step 2 factors Prp18 and Slu7 and the C-terminal domain of Yju2 stabilise a conformation competent for 3'-splice site docking and exon ligation. The structure accounts for the strict conservation of the GU and AG dinucleotides of the introns and provides insight into the catalytic mechanism of exon ligation.
A Noninvasive Molecular Clock for Fetal Development Predicts Gestational Age and Preterm Delivery
Authors: Ngo Thuy T. M. , Moufarrej Mira N. , Rasmussen Marie-Louise H. , Camunas-Soler Joan , Pan Wenying , Okamoto Jennifer , Neff Norma F. , Liu Keli , Wong Ronald J. , Downes Katheryne , Tibshirani Robert , Shaw Gary M. , Skotte Line , Stevenson David K. , Biggio Joseph R. , Elovitz Michal A. , Melbye Mads , Quake Stephen R. 
Published: November 2017

AbstractWe performed a high time-resolution, longitudinal study of normal pregnancy development by measuring cell-free RNA (cfRNA) in blood from women during each week of pregnancy. Analysis of tissue-specific transcripts in these samples enabled us to follow fetal and placental development with high resolution and sensitivity, and also to detect gene-specific responses of the maternal immune system to pregnancy. We established a “clock” for normal pregnancy development and enabled a direct molecular approach to determine expected delivery dates with comparable accuracy to ultrasound, creating the basis for a portable, inexpensive fetal dating method. We also identified a related gene set that accurately discriminated women at risk for spontaneous preterm delivery up to two months in advance of labor, forming the basis of a potential screening test for risk of preterm delivery.