bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genus trace reveals the topological complexity and domain structure of biomolecules
Authors: Zając Sebastian , Geary Cody , Andersen Ebbe Sloth , Dabrowski-Tumanski Pawel , Sulkowska Joanna I. , Sułkowski Piotr 
Published: November 2018

AbstractThe structure of bonds in biomolecules, such as base pairs in RNA chains or native interactions in proteins, can be presented in the form of a chord diagram. A given biomolecule is then characterized by the genus of an auxiliary two-dimensional surface associated to such a diagram. In this work we introduce the notion of the genus trace, which describes dependence of genus on the choice of a subchain of a given backbone chain. We find that the genus trace encodes interesting physical and biological information about a given biomolecule and its three dimensional structural complexity; in particular it gives a way to quantify how much more complicated a biomolecule is than its nested secondary structure alone would indicate. We illustrate this statement in many examples, involving both RNA and protein chains. First, we conduct a survey of all published RNA structures with better than 3 Å resolution in the PDB database, and find that the genus of natural structural RNAs has roughly linear dependence on their length. Then, we show that the genus trace captures properties of various types of base pairs in RNA, and enables the identification of the domain structure of a ribosome. Furthermore, we find that not only does the genus trace detect a domain structure, but it also predicts a cooperative folding pattern in multi-domain proteins. The genus trace turns out to be a useful and versatile tool, with many potential applications.
MSIpred: a python package for tumor microsatellite instability classification from tumor mutation annotation data using a support vector machine
Authors: Wang Chen , Liang Chun 
Published: November 2018

AbstractMicrosatellite instability (MSI) is characterized by high degree of polymorphism in microsatellite lengths due to deficiency in mismatch repair (MMR) system. MSI is associated with several tumor types and its status can be considered as an important indicator for patient prognosis. Conventional clinical diagnosis of MSI examines PCR products of a panel of microsatellite markers using electrophoresis (MSI-PCR), which is laborious, costly, and time consuming. We developed MSIpred, a python package for automatic MSI classification using a machine learning technology – support vector machine (SVM). MSIpred computes 22 features characterizing tumor somatic mutational load from mutation data in mutation annotation format (MAF) generated from paired tumor-normal exome sequencing data, subsequently using these features to predict tumor MSI status with a SVM classifier trained by MAF data of 1074 tumors belonging to four types. Evaluation of MSIpred on an independent testing set, MAF data of another 358 tumors, achieved overall accuracy of ≥98% and area under receiver operating characteristic (ROC) curve of 0.967. Further analysis on discrepant cases revealed that discrepancies were partially due to misclassification of MSI-PCR. Additional testing of MSIpred on non-TCGA data also validated its good classification performance. These results indicated that MSIpred is a robust pan-tumor MSI classification tool and can serve as a complementary diagnostic to MSI-PCR in MSI diagnosis.
Development and Characterization of a Spontaneously Metastatic Patient-Derived Xenograft Model of Human Prostate Cancer
Authors: Lange Tobias , Oh-Hohenhorst Su Jung , Joosse Simon A. , Pantel Klaus , Hahn Oliver , Gosau Tobias , Dyshlovoy Sergey A. , Wellbrock Jasmin , Feldhaus Susanne , Maar Hanna , Gehrcke Renate , Kluth Martina , Simon Ronald , Schlomm Thorsten , Huland Hartwig , Schumacher Udo 
Published: November 2018

AbstractHere we describe the establishment and characterization of an AR+, PSMA+, ERG+, PTEN−/−, CHD1+/− patient-derived xenograft (PDX) model termed ‘C5’, which has been developed from a 60 years old patient suffering from castration-resistant prostate cancer (CRPC). The patient underwent radical prostatectomy, showed early tumor marker PSA recurrence and, one year after surgery, abiraterone resistance. Subcutaneous C5 tumors can be serially transplanted between mice and grow within ~90 days to 1.5–2 cm³ tumors in SCID Balb/c mice (take rate 100%), NOD-scid IL2Rgnull (NSG) mice (100%) and C57BL/6 pfp−/−/rag2−/− mice (66%). In contrast, no tumor growth is observed in female mice. C5 tumors can be cryopreserved and show the same growth characteristics in vivo afterwards. C5 tumor cells do not grow stably in vitro, neither under two- nor three-dimensional cell culture conditions. Upon serial transplantation, some C5 tumors spontaneously disseminated to distant sites with an observable trend towards higher metastatic cell loads in scid compared to NSG mice. Lung metastases could be verified by histology by means of anti-PSMA immunohistochemistry, exclusively demonstrating single disseminated tumor cells (DTCs) and micro-metastases. Upon surgical resection of the primary tumors, such pulmonary foci rarely grew out to multi-cellular metastatic colonies despite doubled overall survival span. In the brain and bone marrow, the metastatic cell load present at surgery even disappeared during the post-surgical period. We provide shallow whole genome sequencing and whole exome sequencing data of C5 tumors demonstrating the copy number aberration/ mutation status of this PCa model and proving genomic stability over several passages. Moreover, we analyzed genomic and transcriptomic alterations during metastatic progression achieved by serial transplantation. This study describes a novel PCa PDX model that enables future research on several aspects of metastatic PCa, particularly for the AR+ , ERG+ , PTEN−/− PCa subtype.
Usefulness of Intravenous Gadolinium Inner Ear MR Imaging in Diagnosis of Ménière’s Disease
Authors: Cho Young Sang , Ahn Jung Min , Choi Ji Eun , Park Hyun Woo , Kim Yi-Kyung , Kim Hyung-Jin , Chung Won-Ho 
Published: November 2018

AbstractThis study aimed to investigate the usefulness of the intravenous gadolinium enhanced inner ear magnetic resonance imaging (IV-Gd inner ear MRI) in diagnosing Ménière’s disease(MD) and find a correlation between the degree of endolymphatic hydrops(EH) and the audiovestibular tests. Total 29 patients diagnosed with unilateral definite MD were enrolled. All patients underwent IV-Gd inner ear MRI and auditory and vestibular function tests such as pure tone audiometry (PTA), electrocochleography (ECoG), cervical vestibular evoked myogenic potential (cVEMP) and caloric test. The hydrops ratio in the cochlea and vestibule were significantly higher in the affected side than the unaffected side (p < 0.001). Average pure-tone thresholds for 0.5, 1 k, 2 k, and 4 k Hz correlated significantly with cochlear and vestibular hydrops (p < 0.01) in the affected side. When comparing the SP/AP ratio of ECoG with hydrops ratio in the vestibule, the affected and unaffected ears showed a significant difference (p < 0.05). Similarly, the results of the caloric test also showed a significant correlation (p < 0.05) with relative vestibular hydrops. However, the cVEMP response was not related to the hydrops ratio in the cochlea or vestibule. This study presents pertinent data with appropriate correlations with auditory vestibular functional testing which demonstrates the usefulness of IV-Gd inner ear MRI as a diagnostic method for visualizing the endolymphatic hydrops in MD.
Investigating the neuroprotective effect of AAV-mediated β-synuclein overexpression in a transgenic model of synucleinopathy
Authors: Sargent Dorian , Bétemps Dominique , Drouyer Matthieu , Verchere Jérémy , Gaillard Damien , Arsac Jean-Noël , Lakhdar Latifa , Salvetti Anna , Baron Thierry 
Published: November 2018

AbstractParkinson’s disease (PD) and multiple system atrophy (MSA) are neurodegenerative diseases characterized by inclusions mainly composed of α-synuclein (α-syn) aggregates. The objective of this study was to investigate if β-synuclein (β-syn) overexpression could have beneficial effects by inhibiting the aggregation of α-syn. The M83 transgenic mouse is a model of synucleinopathy, which develops severe motor symptoms associated with aggregation of α-syn. M83 neonate or adult mice were injected with adeno-associated virus vectors carrying the human β-syn gene (AAVβ-syn) or green fluorescent protein gene (AAVGFP) using different injection sites. The M83 disease was - or not - accelerated using extracts of M83 brains injected with brain extract from mouse (M83) or human (MSA) origins. AAV vectors expression was confirmed using Western blot and ELISA technics. AAV mediated β-syn overexpression did not delay the disease onset or reduce the α-syn phosphorylated at serine 129 levels detected by ELISA, regardless of the AAV injection route and the inoculation of brain extracts. Instead, a proteinase-K resistant β-syn staining was detected by immunohistochemistry, specifically in sick M83 mice overexpressing β-syn after inoculation of AAVβ-syn. This study indicated for the first time that viral vector-mediated β-syn overexpression could form aggregates in a model of synucleinopathy.
Capacitively Coupled Phase-based Dielectric Spectroscopy Tomography
Authors: Jiang Yandan , Soleimani Manuchehr 
Published: November 2018

AbstractImpedance imaging is an effective approach for non-intrusively reconstruct the distribution of dielectric parameters inside the region of interest. Most common form of impedance imaging is electrical impedance tomography (EIT), which requires direct contact with the medium via electrodes. In this work we present a novel impedance imaging using capacitive coupling which provides a contactless method, totally non-invasive and non-intrusive, by measuring the phase. There are less attentions in many prior works to the phase information of the voltage/current measurements. This work studies for the first time the capacitively coupled electrical phase spectroscopy for contactless dielectric parameter imaging. A 12-electrode capacitively coupled test phantom and a measurement system were used to obtain the phase measurements within a wideband frequency range from 200 kHz to 15 MHz. Background data with different conductivity levels were investigated in the experiments to show a broad application possibility. The forward modelling was implemented by simulation and the image reconstruction based on phase measurements was implemented with the total variation algorithm. The potentials, possibilities and challenges of such capacitively coupled dielectric spectroscopy tomography with phase data are discussed in this work.
Ninjurin1 Plays a Crucial Role in Pulmonary Fibrosis by Promoting Interaction between Macrophages and Alveolar Epithelial Cells
Authors: Choi Seungho , Woo Jong Kyu , Jang Yeong-Su , Kang Ju-Hee , Hwang Jong-Ik , Seong Je Kyung , Yoon Yeo Sung , Oh Seung Hyun 
Published: November 2018

AbstractThe transmembrane nerve injury-induced protein 1 (Ninjurin1 or Ninj1) is involved in progressing inflammatory diseases. In this study, we aimed to investigate a novel function of Ninj1 in pulmonary fibrosis. We found that the expression of Ninj1 in a patient cohort was upregulated in the lung specimens of idiopathic pulmonary fibrosis patients as well as mice with bleomycin-induced pulmonary fibrosis. In addition, the BLM-injected Ninj1 KO mice exhibited a mild fibrotic phenotype, as compared to WT mice. Therefore, we hypothesized that Ninj1 would play an important role in the development of pulmonary fibrosis. We discovered that Ninj1 expression increased in BLM-treated macrophages and alveolar epithelial cells (AECs). Interestingly, macrophages bound to BLM-treated AECs were activated. However, when Ninj1 expression was suppressed in either of AECs or macrophages, contact-dependent activation of macrophages with AECs was diminished. In addition, introduction of recombinant mouse Ninj11–50 to macrophages triggered an inflammatory response, but did not stimulate Ninj1-deficient macrophages. In conclusion, we propose that Ninj1 may contribute to activation of macrophages by enhancing interaction with AECs having elevated Ninj1 expression due to injury-inducing stimuli. Consequently, Ninj1 may be involved in the development of pulmonary fibrosis by enhancing inflammatory response of macrophages.
Pyrrolidines and piperidines bearing chiral tertiary alcohols by nickel-catalyzed enantioselective reductive cyclization of N-alkynones
Authors: Liu Guodu , Fu Wenzhen , Mu Xingye , Wu Ting , Nie Ming , Li Kaidi , Xu Xiaodong , Tang Wenjun 
Published: November 2018

AbstractPyrrolidines and piperidines are important building blocks in organic synthesis. Numerous methods exist for constructing substituted pyrrolidines and piperidines. However, efficient syntheses of pyrrolidines and piperidines bearing chiral tertiary alcohols are limited. Here we report an efficient enantioselective nickel-catalyzed intramolecular reductive cyclization of N-alkynones. A P-chiral bisphosphorus ligand DI-BIDIME is designed and applied in the synthesis of tertiary allylic siloxanes bearing pyrrolidine and piperidine rings in high yields and excellent enantioselectivities, with triethylsilane as reducing reagent. The highest turn over number achieved is 1000 (0.1 mol% catalyst loading) with > 99:1 er. This reaction provides a practical way to synthesize pyrrolidine and piperidine derivatives with chiral tertiary alcohols from easily accessible starting materials under mild conditions. The products can be scaled up and transformed to various useful chiral intermediates. The P-chiral bisphosphorus ligand developed in this study represents one of the few ligands for highly enantioselective cyclization of alkynones.
Transcriptomic study of Herpes simplex virus type-1 using full-length sequencing techniques
Authors: Boldogkői Zsolt , Szűcs Attila , Balázs Zsolt , Sharon Donald , Snyder Michael , Tombácz Dóra 
Published: November 2018

AbstractHerpes simplex virus type-1 (HSV-1) is a human pathogenic member of the Alphaherpesvirinae subfamily of herpesviruses. The HSV-1 genome is a large double-stranded DNA specifying about 85 protein coding genes. The latest surveys have demonstrated that the HSV-1 transcriptome is much more complex than it had been thought before. Here, we provide a long-read sequencing dataset, which was generated by using the RSII and Sequel systems from Pacific Biosciences (PacBio), as well as MinION sequencing system from Oxford Nanopore Technologies (ONT). This dataset contains 39,096 reads of inserts (ROIs) mapped to the HSV-1 genome (X14112) in RSII sequencing, while Sequel sequencing yielded 77,851 ROIs. The MinION cDNA sequencing altogether resulted in 158,653 reads, while the direct RNA-seq produced 16,516 reads. This dataset can be utilized for the identification of novel HSV RNAs and transcripts isoforms, as well as for the comparison of the quality and length of the sequencing reads derived from the currently available long-read sequencing platforms. The various library preparation approaches can also be compared with each other.
Overview and experience of the YODA Project with clinical trial data sharing after 5 years
Authors: Ross Joseph S. , Waldstreicher Joanne , Bamford Stephen , Berlin Jesse A. , Childers Karla , Desai Nihar R. , Gamble Ginger , Gross Cary P. , Kuntz Richard , Lehman Richard , Lins Peter , Morris Sandra A. , Ritchie Jessica D. , Krumholz Harlan M. 
Published: November 2018

AbstractThe Yale University Open Data Access (YODA) Project has facilitated access to clinical trial data since 2013. The purpose of this article is to provide an overview of the Project, describe key decisions that were made when establishing data sharing policies, and suggest how our experience and the experiences of our first two data generator partners, Medtronic, Inc. and Johnson & Johnson, can be used to enhance other ongoing or future initiatives.
Comprehensive geological dataset describing a crystalline rock mass for hydraulic stimulation experiments
Authors: Krietsch Hannes , Doetsch Joseph , Dutler Nathan , Jalali Mohammadreza , Gischig Valentin , Loew Simon , Amann Florian 
Published: November 2018

AbstractHigh-resolution 3D geological models are crucial for underground development projects and corresponding numerical simulations with applications in e.g., tunneling, hydrocarbon exploration, geothermal exploitation and mining. Most geological models are based on sparse geological data sampled pointwise or along lines (e.g., boreholes), leading to oversimplified model geometries. In the framework of a hydraulic stimulation experiment in crystalline rock at the Grimsel Test Site, we collected geological data in 15 boreholes using a variety of methods to characterize a decameter-scale rock volume. The experiment aims to identify and understand relevant thermo-hydro-mechanical-seismic coupled rock mass responses during high-pressure fluid injections. Prior to fluid injections, we characterized the rock mass using geological, hydraulic and geophysical prospecting. The combination of methods allowed for compilation of a deterministic 3D geological analog that includes five shear zones, fracture density information and fracture locations. The model may serve as a decameter-scale analog of crystalline basement rocks, which are often targeted for enhanced geothermal systems. In this contribution, we summarize the geological data and the resulting geological interpretation.
Genome-wide polyadenylation site mapping datasets in the rice blast fungus Magnaporthe oryzae
Authors: Marconi Marco , Sesma Ane , Rodríguez-Romero Julio Luis , González María Lourdes Rosano , Wilkinson Mark D. 
Published: November 2018

AbstractPolyadenylation plays an important role in gene regulation, thus affecting a wide variety of biological processes. In the rice blast fungus Magnaporthe oryzae the cleavage factor I protein Rpb35 is required for pre-mRNA polyadenylation and fungal virulence. Here we present the bioinformatic approach and output data related to a global survey of polyadenylation site usage in M. oryzae wild-type and

Δ

rbp35 strains under a variety of nutrient conditions, some of which simulate the conditions experienced by the fungus during part of its infection cycle.
Columbia Open Health Data, clinical concept prevalence and co-occurrence from electronic health records
Authors: Ta Casey N. , Dumontier Michel , Hripcsak George , Tatonetti Nicholas P. , Weng Chunhua 
Published: November 2018

AbstractColumbia Open Health Data (COHD) is a publicly accessible database of electronic health record (EHR) prevalence and co-occurrence frequencies between conditions, drugs, procedures, and demographics. COHD was derived from Columbia University Irving Medical Center’s Observational Health Data Sciences and Informatics (OHDSI) database. The lifetime dataset, derived from all records, contains 36,578 single concepts (11,952 conditions, 12,334 drugs, and 10,816 procedures) and 32,788,901 concept pairs from 5,364,781 patients. The 5-year dataset, derived from records from 2013–2017, contains 29,964 single concepts (10,159 conditions, 10,264 drugs, and 8,270 procedures) and 15,927,195 concept pairs from 1,790,431 patients. Exclusion of rare concepts (count ≤ 10) and Poisson randomization enable data sharing by eliminating risks to patient privacy. EHR prevalences are informative of healthcare consumption rates. Analysis of co-occurrence frequencies via relative frequency analysis and observed-expected frequency ratio are informative of associations between clinical concepts, useful for biomedical research tasks such as drug repurposing and pharmacovigilance. COHD is publicly accessible through a web application-programming interface (API) and downloadable from the Figshare repository. The code is available on GitHub.
Identification of Affective State Change in Adults With Aphasia Using Speech Acoustics
Authors: Gillespie Stephanie , Laures-Gore Jacqueline , Moore Elliot , Farina Matthew , Russell Scott , Haaland Benjamin 
Published: November 2018

PurposeThe current study aimed to identify objective acoustic measures related to affective state change in the speech of adults with post-stroke aphasia.MethodThe speech of 20 post-stroke adults with aphasia was recorded during picture description and administration of the Western Aphasia Battery–Revised (Kertesz, 2006). In addition, participants completed the Self-Assessment Manikin (Bradley & Lang, 1994) and the Stress Scale (Tobii Dynavox, 1981–2016) before and after the language tasks. Speech from each participant was used to detect a change in affective state test scores between the beginning and ending speech.ResultsMachine learning revealed moderate success in classifying depression, minimal success in predicting depression and stress numeric scores, and minimal success in classifying changes in affective state class between the beginning and ending speech.ConclusionsThe results suggest the existence of objectively measurable aspects of speech that may be used to identify changes in acute affect from adults with aphasia. This work is exploratory and hypothesis-generating; more work will be needed to make conclusive claims. Further work in this area could lead to automated tools to assist clinicians with their diagnoses of stress, depression, and other forms of affect in adults with aphasia.
Outflows in the inner kiloparsec of NGC 1566 as revealed by molecular (ALMA) and ionized gas (Gemini-GMOS/IFU) kinematics
Authors: Slater R. , Nagar N. M. , Schnorr-Müller A. , Storchi-Bergmann T. , Finlez C. , Lena D. , Ramakrishnan V. , Mundell C. G. , Riffel R. A. , Peterson B. , Robinson A. , Orellana G. 
Published: November 2018

Context. Tracing nuclear inflows and outflows in active galactic nuclei (AGNs), determining the mass of gas involved in them, and their impact on the host galaxy and nuclear black hole requires 3D imaging studies of both the ionized and molecular gas.
Aims. We map the distribution and kinematics of molecular and ionized gas in a sample of active galaxies to quantify the nuclear inflows and outflows. Here, we analyze the nuclear kinematics of NGC 1566 via ALMA observations of the CO J:2-1 emission at 24 pc spatial and ∼2.6 km s−1 spectral resolution, and Gemini-GMOS/IFU observations of ionized gas emission lines and stellar absorption lines at similar spatial resolution, and 123 km s−1 of intrinsic spectral resolution.
Methods. The morphology and kinematics of stellar, molecular (CO), and ionized ([N II]) emission lines are compared to the expectations from rotation, outflows, and streaming inflows.
Results. While both ionized and molecular gas show rotation signatures, there are significant non-circular motions in the innermost 200 pc and along spiral arms in the central kpc (CO). The nucleus shows a double-peaked CO profile (full width at zero intensity of 200 km s−1), and prominent (∼80 km s−1) blue- and redshifted lobes are found along the minor axis in the inner arcseconds. Perturbations by the large-scale bar can qualitatively explain all features in the observed velocity field. We thus favor the presence of a molecular outflow in the disk with true velocities of ∼180 km s−1 in the nucleus and decelerating to 0 by ∼72 pc. The implied molecular outflow rate is 5.6 M⊙ yr−1, with this gas accumulating in the nuclear 2″ arms. The ionized gas kinematics support an interpretation of a similar but more spherical outflow in the inner 100 pc, with no signs of deceleration. There is some evidence of streaming inflows of ∼50 km s−1 along specific spiral arms, and the estimated molecular mass inflow rate, ∼0.1 M⊙ yr−1, is significantly higher than the SMBH accretion rate (ṁ = 4.8 × 10−5 M⊙ yr−1).