bluuebunny/crossref_metadata_2025_split huggingface dataset:
Breast Cancer Assessment With Pulse-Echo Speed of Sound Ultrasound From Intrinsic Tissue Reflections
Authors: Ruby Lisa , Sanabria Sergio J. , Martini Katharina , Dedes Konstantin J. , Vorburger Denise , Oezkan Ece , Frauenfelder Thomas , Goksel Orcun , Rominger Marga B. 
Published: March 2019

Purpose
The aim of this study was to differentiate malignant and benign solid breast lesions with a novel ultrasound (US) technique, which measures speed of sound (SoS) using standard US transducers and intrinsic tissue reflections and scattering (speckles) as internal reference.

Materials and Methods
This prospective, institutional review board–approved, Health Insurance Portability and Accountability Act-compliant prospective comparison study was performed with prior written informed consent from 20 women. Ten women with histological proven breast cancer and 10 with fibroadenoma were measured. A conventional US system with a linear probe was used for SoS-US (SonixTouch; Ultrasonix, Richmond, British Columbia, Canada). Tissue speckle reflections served as a timing reference for the US signals transmitted through the breasts. Relative phase inconsistencies were detected using plane wave measurements from different angular directions, and SoS images with 0.5-mm resolution were generated using a spatial domain reconstruction algorithm. The SoS of tumors were compared with the breast density of a larger cohort of 106 healthy women.

Results
Breast lesions show focal increments ΔSoS (meters per second) with respect to the tissue background. Peak ΔSoS values were evaluated. Breast carcinoma showed significantly higher ΔSoS than fibroadenomas (∆SoS > 41.64 m/s: sensitivity, 90%; specificity, 80%; area under curve, 0.910) and healthy breast tissue of different densities (area under curve, 0.938; sensitivity, 90%; specificity, 96.5%). The lesion localization in SoS-US images was consistent with B-mode imaging and repeated SoS-US measurements were reproducible.

Conclusions
Using SoS-US, based on conventional US and tissue speckles as timing reference, breast carcinoma showed significantly higher SoS values than fibroadenoma and healthy breast tissue of different densities. The SoS presents a promising technique for differentiating solid breast lesions.
Extent of Intraprotocol and Intersite Variability of Thoracic Magnetic Resonance Acquisition Times at a Large Quaternary Institution
Authors: Ackman Jeanne B. , Nitiwarangkul Chayanin , Mercaldo Sarah F. 
Published: March 2019

Purpose:
The purpose of this study was to describe Thoracic magnetic resonance (MR) acquisition time (AT) variability, associations, and technologist insights as to its causes at a large quaternary institution, by MR protocol and imaging site.

Materials and Methods:
A retrospective review of our 2017 QI database of 1.5 T MR imaging ATs for adults 19 years and above at the main hospital and outpatient (OPT) satellites was performed for all 5 Thoracic MR protocols. Summary statistics were calculated for ATs. Multivariable linear regression was adjusted for age, sex, body mass index, time of examination relative to shift change, technologist experience, and language interpreter. An anonymous REDCap survey of our MR technologists sought their assessment of reasons for AT variability and techniques that help reduce it.

Results:
A total of 174 adult OPT 1.5 T mediastinal, pleural, and lung MR examinations were analyzed, revealing high variability of median AT by protocol and site (P<0.001)—for example, mean, median, slowest, and fastest ATs for Thymus I− protocol (n=38) were 34, 32, 66, and 8 minutes, respectively. OPT site with fewest MR technologists and a single MR scanner had shortest mean AT across all protocols (35±15 min). Full Chest I− protocol had shortest AT across all sites (mean AT=33±13 min), compared with focused imaging protocols. All I−/I+ protocols had greater than expected AT, compared with the same protocol performed (I−). Surveyed MR technologists noted limited Thoracic MR training/experience, discomfort with thoracic anatomy and Thoracic MR performance, and AT-related benefit of effective communication with the radiologist with regard to lesion location.

Conclusions:
There was tremendous intraprotocol and intersite variability of Thoracic MR ATs. Increased technologist training, amplified experience, and a solid understanding of lesion location for focused examinations may all help reduce Thoracic MR AT.
ntEdit: scalable genome assembly polishing
Authors: Warren René L , Coombe Lauren , Mohamadi Hamid , Zhang Jessica , Jaquish Barry , Isabel Nathalie , Jones Steven JM , Bousquet Jean , Bohlmann Joerg , Birol Inanç 
Published: March 2019

AbstractIn the modern genomics era, genome sequence assemblies are routine practice. However, depending on the methodology, resulting drafts may contain considerable base errors. Although utilities exist for genome base polishing, they work best with high read coverage and do not scale well. We developed ntEdit, a Bloom filter-based genome sequence editing utility that scales to large mammalian and conifer genomes.We first tested ntEdit and the state-of-the-art assembly improvement tools GATK, Pilon and Racon on controlled E. coli and C. elegans sequence data. Generally, ntEdit performs well at low sequence depths (<20X), fixing the majority (>97%) of base substitutions and indels, and its performance is largely constant with increased coverage. In all experiments conducted using a single CPU, the ntEdit pipeline executed in <14s and <3m, on average, on E. coli and C. elegans, respectively. We performed similar benchmarks on a sub-20X coverage human genome sequence dataset, inspecting accuracy and resource usage in editing chromosomes 1 and 21, and whole genome. ntEdit scaled linearly, executing in 30-40m on those sequences. We show how ntEdit ran in <2h20m to improve upon long and linked read human genome assemblies of NA12878, using high coverage (54X) Illumina sequence data from the same individual, fixing frame shifts in coding sequences. We also generated 17-fold coverage spruce sequence data from haploid sequence sources (seed megagametophyte), and used it to edit our pseudo haploid assemblies of the 20 Gbp interior and white spruce genomes in <4 and <5h, respectively, making roughly 50M edits at a (substitution+indel) rate of 0.0024.Availabilityhttps://github.com/bcgsc/nteditSupplemental materialavailable online.
SVCurator: A Crowdsourcing app to visualize evidence of structural variants for the human genome
Authors: Chapman Lesley M , Spies Noah , Pai Patrick , Lim Chun Shen , Carroll Andrew , Narzisi Giuseppe , Watson Christopher M. , Proukakis Christos , Clarke Wayne E. , Nariai Naoki , Dawson Eric , Jones Garan , Blankenberg Daniel , Brueffer Christian , Xiao Chunlin , Kolora Sree Rohit Raj , Alexander Noah , Wolujewicz Paul , Ahmed Azza , Smith Graeme , Shehreen Saadlee , Wenger Aaron M. , Salit Marc , Zook Justin M. 
Published: March 2019

AbstractA high quality benchmark for small variants encompassing 88 to 90% of the reference genome has been developed for seven Genome in a Bottle (GIAB) reference samples. However a reliable benchmark for large indels and structural variants (SVs) is yet to be defined. In this study, we manually curated 1235 SVs which can ultimately be used to evaluate SV callers or train machine learning models. We developed a crowdsourcing app – SVCurator – to help curators manually review large indels and SVs within the human genome, and report their genotype and size accuracy.SVCurator is a Python Flask-based web platform that displays images from short, long, and linked read sequencing data from the GIAB Ashkenazi Jewish Trio son [NIST RM 8391/HG002], We asked curators to assign labels describing SV type (deletion or insertion), size accuracy, and genotype for 1235 putative insertions and deletions sampled from different size bins between 20 and 892,149 bp. The crowdsourced results were highly concordant with 37 out of the 61 curators having at least 78% concordance with a set of ‘expert’ curators, where there was 93% concordance amongst ‘expert’ curators. This produced high confidence labels for 935 events. When compared to the heuristic-based draft benchmark SV callset from GIAB, the SVCurator crowdsourced labels were 94.5% concordant with the benchmark set. We found that curators can successfully evaluate putative SVs when given evidence from multiple sequencing technologies.
The dot-compartment revealed? Diffusion MRI with ultra-strong gradients and spherical tensor encoding in the living human brain
Authors: Tax Chantal M.W. , Szczepankiewicz Filip , Nilsson Markus , Jones Derek K. 
Published: March 2019

AbstractThe so-called “dot-compartment” is conjectured in diffusion MRI to represent small spherical spaces, such as cell bodies, in which the diffusion is restricted in all directions. Previous investigations inferred its existence from data acquired with directional diffusion encoding which does not permit a straightforward separation of signals from ‘sticks’ (axons) and signals from ‘dots’. Here we combine isotropic diffusion encoding with ultra-strong diffusion gradients (240 mT/m) to achieve high diffusion-weightings with high signal to noise ratio, while suppressing signal arising from anisotropic water compartments with significant mobility along at least one axis (e.g., axons). A dot-compartment, defined to have apparent diffusion coefficient equal to zero and no exchange, would result in a non-decaying signal at very high b-values (b ≳ 7000 s/mm2). With this unique experimental setup, a residual yet slowly decaying, signal above the noise floor for b-values as high as 15000 s/mm2was seen clearly in the cerebellar grey matter (GM), and in several white matter (WM) regions to some extent. Upper limits of the dot-signal-fraction were estimated to be ~2% in cerebellar GM and ~0.2% in WM. By relaxing the assumption of zero diffusivity, the signal at high b-values in cerebellar GM could be represented more accurately by an isotropic water pool with a low apparent diffusivity of 0.11 µm2/ms and a substantial signal fraction of ~7-16%. This remaining signal at high b-values has potential to serve as a novel and simple marker for isotropically-restricted water compartments in cerebellar GM.
Herpesvirus infection reduces Pol II occupancy of host promoters but spares viral promoters
Authors: Hartenian Ella N , Glaunsinger Britt A 
Published: March 2019

AbstractIn mammalian cells, widespread acceleration of cytoplasmic mRNA degradation is linked to impaired RNA polymerase II (Pol II) transcription. This mRNA decay-induced transcriptional repression occurs during infection with gammaherpesviruses including Kaposi’s sarcoma-associated herpesvirus (KSHV) and murine gammaherpesvirus 68 (MHV68), which encode an mRNA endonuclease that initiates widespread RNA decay. Here, we show that MHV68-induced mRNA decay leads to a genome-wide reduction of Pol II occupancy at mammalian promoters. Viral genes, despite the fact that they require Pol II for transcription, escape this transcriptional repression. Protection is not governed by viral promoter sequences; instead, location on the viral genome is both necessary and sufficient to escape the transcriptional repression effects of mRNA decay. We hypothesize that the ability to escape from transcriptional repression is linked to the localization of viral DNA in replication compartments, providing a means for these viruses to counteract decay-induced viral transcript loss.
The PIWI/piRNA response is relaxed in a rodent that lacks mobilizing transposable elements
Authors: Vandewege Michael W. , Patt Roy N. , Merriman Dana K. , Ray David A. , Hoffmann Federico G. 
Published: March 2019

AbstractTransposable elements (TEs) are genomic parasites that can propagate by inserting copies of themselves into host genomes. Mammalian genomes are typically dominated by LINE retrotransposons and their associated SINEs, and their mobilization in the germline is a challenge to genome integrity. There are genomic defenses against TE proliferation and the PIWI/piRNA defense is among the most well understood. However, the PIWI/piRNA system has been investigated largely in animals with abundant and actively mobilizing TEs and it is unclear how the PIWI/piRNA system functions in the absence of mobilizing TEs. The 13-lined ground squirrel provides an excellent opportunity to examine PIWI/piRNA and TE dynamics within the context of minimal, and possibly nonexistent, TE accumulation. We sequenced RNA and small RNAs pools from the testes of juvenile and adult squirrels and compared results to TE and PIWI/piRNA dynamics in the European rabbit and house mouse. Interestingly in squirrels, despite a lack of young insertions, TEs were still actively transcribed at higher levels compared to mouse and rabbit. All three PIWI proteins were either not expressed, or only minimally expressed, prior to P8 in squirrel testis, but there was little TE expression change with the onset of PIWI expression. We found PIWIs largely did not reduce TE transcription, and the ping-pong cycle was significantly reduced among squirrel LINEs and SINEs compared to the mouse and rabbit. We speculate that, although the PIWI/piRNA system is adaptable to novel TE threats, transcripts from TEs that are no longer threatening receive less attention from PIWI proteins.
Chloroplasts Require Glutathione Reductase to Balance Reactive Oxygen Species and Maintain Efficient Photosynthesis
Authors: Müller-Schüssele Stefanie J. , Wang Ren , Gütle Desirée D. , Romer Jill , Rodriguez-Franco Marta , Scholz Martin , Lüth Volker M. , Kopriva Stanislav , Dörmann Peter , Schwarzländer Markus , Reski Ralf , Hippler Michael , Meyer Andreas J. 
Published: March 2019

SummaryThiol-based redox-regulation is vital to coordinate chloroplast functions depending on illumination. Yet, how the redox-cascades of the thioredoxin and glutathione redox machineries integrate metabolic regulation and reactive oxygen species (ROS) detoxification remains largely unresolved. We investigate if maintaining a highly reducing stromal glutathione redox potential (EGSH) via glutathione reductase (GR) is necessary for functional photosynthesis and plant growth.Since absence of the plastid/mitochondrial GR is embryo-lethal in Arabidopsis thaliana, we used the model moss Physcomitrella patens to create knock-out lines. We dissect the role of GR in chloroplasts by in vivo monitoring stromal EGSH dynamics, and reveal changes in protein abundances by metabolic labelling.Whereas stromal EGSH is highly reducing in wildtype and clearly responsive to light, the absence of GR leads to a partial oxidation, which is not rescued by light. Photosynthetic performance and plant growth are decreased with increasing light intensities, while ascorbate and zeaxanthin levels are elevated. An adjustment of chloroplast proteostasis is pinpointed by the induction of plastid protein repair and degradation machineries.Our results indicate that the plastid thioredoxin and glutathione redox systems operate largely independently. They reveal a critical role of GR in maintaining efficient photosynthesis.
Scientific evaluation of negative exome sequencing followed by systematic scoring of candidate genes to decipher the genetics of neurodevelopmental disorders
Authors: Büttner Benjamin , Martin Sonja , Finck Anja , Arelin Maria , Baade-Büttner Carolin , Bartolomaeus Tobias , Bauer Peter , Bertsche Astrid , Bernhard Matthias K. , Biskup Saskia , Donato Nataliya Di , Elgizouli Magdeldin , Ewald Roland , Heine Constanze , Hellenbroich Yorck , Hentschel Julia , Hoffjan Sabine , Horn Susanne , Hornemann Frauke , Huhle Dagmar , Kamphausen Susanne B. , Kiess Wieland , Krey Ilona , Kuechler Alma , Liesfeld Ben , Merkenschlager Andreas , Mitter Diana , Muschke Petra , Pfäffle Roland , Polster Tilman , Schanze Ina , Schlump Jan-Ulrich , Syrbe Steffen , Wieczorek Dagmar , Zenker Martin , Lemke Johannes R. , Duc Diana Le , Platzer Konrad , Jamra Rami Abou 
Published: March 2019

AbstractBackgroundDeciphering the monogenetic causes of neurodevelopmental disorders (NDD) is an important milestone to offer personalized care. But the plausibility of reported candidate genes in exome studies often remains unclear, which slows down progress in the field.MethodsWe performed exome sequencing (ES) in 198 cases of NDD. Cases that remained unresolved (n=135) were re-investigated in a research setting. We established a candidate scoring system (CaSc) based on 12 different parameters reflecting variant and gene attributes as well as current literature to rank and prioritize candidate genes.ResultsIn this cohort, we identified 158 candidate variants in 148 genes with CaSc ranging from 2 to 11.7. Only considering the top 15% of candidates, 14 genes were already published or funneled into promising validation studies.ConclusionsWe promote that in an approach of case by case re-evaluation of primarily negative ES, systematic and standardized scoring of candidate genes can and should be applied. This simple framework enables better comparison, prioritization, and communication of candidate genes within the scientific community. This would represent an enormous benefit if applied to the tens of thousands of negative ES performed in routine diagnostics worldwide and speed up deciphering the monogenetic causes of NDD.
The Human Exonuclease-1 Interactome And Phosphorylation Sites
Authors: Eid Wassim , Hess Daniel , König Christiane , Gentili Christian , Ferrari Stefano 
Published: March 2019

ABSTRACTError-free repair of DNA double-strand break is orchestrated by homologous recombination (HR) pathways and requires the concerted action of several factors. Among these, EXO1 and DNA2/BLM execute extensive resection of DNA ends to produce 3’-overhangs, which are key intermediates for downstream steps of HR. To help shedding light on regulatory aspects of DNA repair pathways in which EXO1 participates, we set out to identify proteins interacting with EXO1. Affinity purification of EXO1 followed by Orbitrap mass spectrometry led to the identification of novel partners that are involved in RNA processing or that are the causative agents of rare X-linked disorders. Depletion of a selected subset of EXO1 interacting proteins led to reduction of the DNA damage response. Among those, we examined the RRP5-homologue and NFκB-interacting protein PDCD11/ALG-4, which has roles in apoptosis and is a putative driver gene in cutaneous T-cell lymphoma. We provide evidence that depletion of PDCD11 decreased the formation of γH2AX foci and the phosphorylation of DNA damage response signaling intermediates in response to camptothecin or bleomycin, resulting in increased cellular resistance to DNA damage. Furthermore, extensive coverage of EXO1 sequence (>85%) by mass spectrometry allowed conducting an in-depth analysis of its phosphorylation sites, with the identification of 26 residues that are differentially modified in untreated conditions or upon induction of DNA damage.As a whole, these results provide the basis for future in-depth studies on novel roles of EXO1 in genome stability and indicate targets for pharmacological inhibition of pathways of cancer development.HIGHLIGHTSProteome-wide analysis of Exonuclease-1 (EXO1) interacting proteins revealed novel partners involved in RNA processing or that are the causative agents of rare X-linked disorders.We provide evidence for a role of PDCD11 in the DNA Damage Response.We conducted a comprehensive identification of EXO1 phosphorylation sites.
A Polybasic Domain in aPKC Mediates Par6-Dependent Control of Membrane Targeting and Kinase Activity
Authors: Dong Wei , Lu Juan , Zhang Xuejing , Wu Yan , Lettieri Kaela , Hammond Gerald R. , Hong Yang 
Published: March 2019

SUMMARYMechanisms coupling the atypical PKC (aPKC) kinase activity to its subcellular localization are essential for cell polarization. Unlike other members of the PKC family, aPKC has no well-defined plasma membrane (PM) or calcium binding domains, leading to the assumption that its subcellular localization relies exclusively on protein-protein interactions. Here we show that in both Drosophila and mammalian cells the pseudosubstrate region (PSr) of aPKC acts as a polybasic domain capable of targeting aPKC to the PM via electrostatic binding to PM PI4P and PI(4,5)P2. However, physical interaction between aPKC and Par-6 is required for the PM-targeting of aPKC, likely by allosterically exposing the PSr to bind PM. Binding of Par-6 also inhibits aPKC kinase activity and such inhibition can be relieved through Par-6 interaction with apical polarity protein Crumbs. Our data suggest a potential mechanism in which allosteric regulation of polybasic PSr by Par-6 couples the control of both aPKC subcellular localization and spatial activation of its kinase activity.eTOC SummaryDong et al. discover that the pseudo-substrate region (PSr) in aPKC is a polybasic domain capable of electrostatically targeting aPKC to plasma membrane. Allosteric regulation of PSr by Par-6 couples the control of both aPKC subcellular localization and spatial activation of kinase activity.
An RNA guanine quadruplex regulated pathway to TRAIL-sensitization by DDX21
Authors: McRae Ewan K.S. , Dupas Steven J. , Booy Evan P. , Piragasam Ramanaguru S. , Fahlman Richard P. , McKenna Sean A. 
Published: March 2019

AbstractDDX21 is a newly discovered RNA G-quadruplex (rG4) binding protein with no known biological rG4 targets. In this study we identified 26 proteins that are expressed at significantly different levels in cells expressing wild type DDX21 relative to an rG4 binding deficient DDX21 (M4). From this list we validate MAGED2 as a protein that is regulated by DDX21 through rG4 in its 5’UTR. MAGED2 protein levels, but not mRNA levels, are reduced by half in cells expressing only DDX21 M4. MAGED2 has a repressive effect on TRAIL-R2 expression that is relieved under these conditions, resulting in elevated TRAIL-R2 mRNA and protein in cells expressing only DDX21 M4, and rendering previously resistant cells sensitive to TRAIL mediated apoptosis. Our work identifies the role of DDX21 in regulation at the translational level through biologically relevant rG4 and shows that MAGED2 protein levels are regulated, at least in part, by a rG4 forming potential in their 5’UTRs.