bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Financial Impact of Living in Canada With an Ostomy
Authors: LeBlanc Kimberly , Heerschap Corey , Martins Lina , Butt Britney , Wiesenfeld Samantha , Woo Kevin 
Published: October 2019

PURPOSE:
The aim of this study was to explore how living with an ostomy financially impacts Canadians.

METHODS:
A descriptive, pan-Canadian, cross-sectional online and paper-based survey was conducted using a convenience sample.

RESULTS:
Surveys were completed by 467 individuals. Seventy-six percent (n = 355) reported spending more than $1000 annually on ostomy supplies, with 58% (n = 271) paying partially out of pocket. Atlantic regions relied primarily on insurance (n = 81), and the central, prairies, and western regions used a combination of funding (provincial government funding and/or insurance) (n = 385) with no significant out-of-pocket funding differences between regions (χ2 = 18.267, P = .079). Fifteen percent (n = 70) reported frequent peristomal skin problems, and 19% (n = 89) indicated that having an ostomy negatively affected their ability to work. When experiencing ostomy-related problems, 60% (n = 280) sought assistance from a nurse specialized in wound, ostomy, and continence (NSWOC) and spent significantly less on ostomy supplies (χ2 = 231.267, P < .001).

CONCLUSION:
This study demonstrated that living with an ostomy may result in financial burden and that Canadian regional variations in funding and access to an NSWOC should be explored.
Functional MRI connectivity accurately distinguishes cases with psychotic disorders from healthy controls, based on cortical features associated with neurodevelopment
Authors: Morgan Sarah E , Young Jonathan , Patel Ameera X , Whitaker Kirstie J , Scarpazza Cristina , van Amelsvoort Therese , Marcelis Machteld , van Os Jim , Donohoe Gary , Mothersill David , Corvin Aiden , Arango Celso , Mechelli Andrea , van den Heuvel Martijn , Kahn René S , McGuire Philip , Brammer Michael , Bullmore Edward T 
Published: October 2019

AbstractBackgroundMachine learning (ML) can distinguish cases with psychotic disorder from healthy controls based on magnetic resonance imaging (MRI) data, with reported accuracy in the range 60-100%. It is not yet clear which MRI metrics are the most informative for case-control ML.MethodsWe analysed multi-modal MRI data from two independent case-control studies of patients with psychotic disorders (cases, N = 65, 28; controls, N = 59, 80) and compared ML accuracy across 5 MRI metrics. Cortical thickness, mean diffusivity and fractional anisotropy were estimated at each of 308 cortical regions, as well as functional and structural connectivity between each pair of regions. Functional connectivity data were also used to classify non-psychotic siblings of cases (N=64) and to distinguish cases from controls in a third independent study (cases, N=67; controls, N = 81).ResultsIn both principal studies, the most diagnostic metric was fMRI connectivity: the areas under the receiver operating characteristic curve were 92% and 77%, respectively. The cortical map of diagnostic connectivity features was replicable between studies (r = 0.31, P < 0.001); correlated with replicable case-control differences in fMRI degree centrality, and with prior cortical maps of aerobic glycolysis and adolescent development of functional connectivity; predicted intermediate probabilities of psychosis in siblings; and replicated in the third case-control study.ConclusionsML most accurately distinguished cases from controls by a replicable pattern of fMRI connectivity features, highlighting abnormal hubness of cortical nodes in an anatomical pattern consistent with the concept of psychosis as a disorder of network development.
Evaluation of the General Practice Pharmacist (GPP) intervention to optimise prescribing in Irish primary care: a non-randomised pilot study
Authors: Cardwell Karen , Smith Susan M , Clyne Barbara , McCullagh Laura , Wallace Emma , Kirke Ciara , Fahey Tom , Moriarty Frank 
Published: October 2019

AbstractObjectiveLimited evidence suggests integration of pharmacists into the general practice team could improve medicines management for patients, particularly those with multimorbidity and polypharmacy. This study aimed to develop and assess the feasibility of an intervention involving pharmacists, working within general practices, to optimise prescribing in Ireland.DesignNon-randomised pilot studySettingPrimary care in IrelandParticipantsFour general practices, purposively sampled and recruited to reflect a range of practice sizes and demographic profiles.InterventionA pharmacist joined the practice team for six months (10 hours/week) and undertook medication reviews (face-to-face or chart-based) for adult patients, provided prescribing advice, supported clinical audits, and facilitated practice-based education.Outcome measuresAnonymised practice-level medication (e.g. medication changes) and cost data were collected. Patient-Reported Outcome Measure (PROM) data were collected on a subset of older adults (aged ≥65 years) with polypharmacy using patient questionnaires, before and six weeks after medication review by the pharmacist.ResultsAcross four practices, 787 patients were identified as having 1,521 prescribing issues by the pharmacists. Issues relating to potentially inappropriate or high-risk prescribing were addressed most often by the prescriber (51.8%), compared to cost-related issues (7.5%). Medication changes made during the study equated to approximately €57,000 in cost savings assuming they persisted for 12 months. Ninety-six patients aged ≥65 years with polypharmacy were recruited from the four practices for PROM data collection and 64 (66.7%) were followed up. There were no changes in patients’ treatment burden or attitudes to deprescribing following medication review, and there were conflicting changes in patients’ self-reported quality of life.ConclusionsThis non-randomised pilot study demonstrated that an intervention involving pharmacists, working within general practices is feasible to implement and has potential to improve prescribing quality. This study provides rationale to conduct a randomised controlled trial to evaluate the clinical and cost-effectiveness of this intervention.Article summaryStrengths and limitations of this studyThis is the first study examining the role of general practice-based pharmacists in Ireland and the feasibility of evaluating this role.Integration of pharmacists was limited to four general practices, although these were diverse in terms of practice characteristics.A range of medication and patient-reported outcome measures data were collected, although because this was a pilot study there was no control group to compare these to.
DeepProg: an ensemble of deep-learning and machine-learning models for prognosis prediction using multi-omics data
Authors: Poirion Olivier , Jing Zheng , Chaudhary Kumardeep , Huang Sijia , Garmire Lana X. 
Published: October 2019

AbstractMulti-omics data are good resources for prognosis and survival prediction, however, these are difficult to integrate computationally. We introduce DeepProg, a novel ensemble framework of deep-learning and machine-learning approaches that robustly predicts patient survival subtypes using multi-omics data. It identifies two optimal survival subtypes in most cancers and yields significantly better risk-stratification than other multi-omics integration methods. DeepProg is highly predictive, exemplified by two liver cancer (C-index 0.73-0.80) and five breast cancer datasets (C-index 0.68-0.73). Pan-cancer analysis associates common genomic signatures in poor survival subtypes with extracellular matrix modeling, immune deregulation, and mitosis processes. DeepProg is freely available at https://github.com/lanagarmire/DeepProg
An iterative and automated computational pipeline for untargeted strain-level identification using MS/MS spectra from pathogenic samples
Authors: Kuhring Mathias , Doellinger Joerg , Nitsche Andreas , Muth Thilo , Renard Bernhard Y. 
Published: October 2019

AbstractUntargeted accurate strain-level classification of a priori unidentified organisms using tandem mass spectrometry is a challenging task. Reference databases often lack taxonomic depth, limiting peptide assignments to the species level. However, the extension with detailed strain information increases runtime and decreases statistical power. In addition, larger databases contain a higher number of similar proteomes.We present TaxIt, an iterative workflow to address the increasing search space required for MS/MS-based strain-level classification of samples with unknown taxonomic origin. TaxIt first applies reference sequence data for initial identification of species candidates, followed by automated acquisition of relevant strain sequences for low level classification. Furthermore, proteome similarities resulting in ambiguous taxonomic assignments are addressed with an abundance weighting strategy to improve candidate confidence.We apply our iterative workflow on several samples of bacterial and viral origin. In comparison to non-iterative approaches using unique peptides or advanced abundance correction, TaxIt identifies microbial strains correctly in all examples presented (with one tie), thereby demonstrating the potential for untargeted and deeper taxonomic classification. TaxIt makes extensive use of public, unrestricted and continuously growing sequence resources such as the NCBI databases and is available under open-source license at https://gitlab.com/rki_bioinformatics.
RNase 2/EDN cleaves the anticodon loops of tRNAs to produce immunostimulatory tRNA halves in asthma
Authors: Shigematsu Megumi , Kawamura Takuya , Shah Sushrut D. , Deshpande Deepak A. , Kirino Yohei 
Published: October 2019

AbstractAsthma, the most prevalent chronic inflammatory airway disease, develops due to allergen-induced airway inflammation driven by various mediators, including proinflammatory cytokines. Our research shows that inhalation of house dust mite (HDM) in mice leads to a significant increase in the levels of tRNA half molecules in asthmatic lungs. Transcriptomic analyses of ribonucleases unequivocally identifiedEar11(RNase 2a/Edn) as the most responsive endoribonuclease to HDM exposure. Indeed, human EDN is taken up by lung epithelial cells and cleaves the anticodon loops of mature tRNAs to produce tRNA halves. These tRNA halves, abundantly generated by EDN, include immunostimulatory species that promote the production of proinflammatory cytokine by activating Toll-like receptor 7. Reconstitution of thein vitroEDN-mediated RNA cleavage system elucidated specific positional and nucleotide preferences within the tRNA anticodon loop, providing a molecular basis for the generation of specific tRNA halves. These findings represent a previously overlooked, yet potentially critical, factor in the induction of cytokines during the pathogenesis of asthma.
Combining metabarcoding and morphological approaches to identify phytoplankton taxa associated with harmful algal blooms
Authors: Esenkulova Svetlana , Sutherland Ben J.G. , Tabata Amy , Haigh Nicola , Pearce Christopher M. , Miller Kristina M. 
Published: October 2019

AbstractMolecular techniques are expected to be highly useful in detecting taxa causing harmful algal blooms (HABs). This is the first report in Canada evaluating HABs-related species identification using a combination of morphological and molecular approaches. Microscopy, quantitative polymerase chain reaction (qPCR), and metabarcoding with multiple markers (i.e.16S, 18S-dinoflagellate and 18S-diatom, large subunit (28S) rDNA) were applied on samples (n=54) containing suspected harmful algae (e.g.Alexandriumspp.,Chattonellasp.,Chrysochromulinaspp.,Dictyochaspp.,Heterosigma akashiwo,Protoceratium reticulatum,Pseudochattonella verruculosa, Pseudo-nitzschiaspp.,Pseudopedinellasp.). Due to methodology limitations, qPCR result interpretation was limited, although good detectability occurred using previously published assays forAlexandrium tamarense,H. akashiwo, andP. verruculosa. Overall, the multiple-marker metabarcoding results were superior to the morphology-based methods, with the exception of taxa from the silicoflagellate group. The combined results using both 18S markers and the 28S marker together closely corresponded with morphological identification of targeted species, providing the best overall taxonomic coverage and resolution. The most numerous unique taxa were identified using the 18S-dinoflagellate amplicon, and the best resolution to the species level occurred using the 28S amplicon. Molecular techniques are therefore highly useful for HABs taxa detection, but currently depend on deploying multiple markers for metabarcoding.
Constitutive Expression of the Progesterone Receptor Isoforms Promotes Hormone-Dependent Development of Ovarian Neoplasms
Authors: Wetendorf Margeaux , Li Rong , Wu San-Pin , Liu Jian , Creighton Chad J. , Wang Tianyuan , Janardhan Kyathanahalli S. , Willson Cynthia J. , Lanz Rainer B. , Murphy Bruce D. , Lydon John P. , DeMayo Francesco J. 
Published: October 2019

AbstractAbnormal expression of the progesterone receptor (PGR) isoforms, PGRA and PGRB, is often observed in women with reproductive tract cancer. To assess the importance of the PGR isoform ratio in the maintenance of the healthy reproductive tract, mice with Cre recombinase- activated PGRA and PGRB transgenes were bred with the PGRCremouse model to generate strains expressing either PGRA or PGRB in PGR positive tissues. The PGRB mice developed ovarian neoplasms at 23 weeks of age derived from ovarian luteal cells, while the PGRA expressing mice displayed a reduced frequency of tumor development. Transcriptomic analyses of the ovarian tumors revealed an enhanced AKT pathway signature, which is in agreement with expression changes found in human ovarian adenocarcinoma. Effective treatment with the PGR antagonist RU486 reduced tumor growth and the expression of cell cycle genes. We concluded that tumor growth and proliferation is hormone and PGR isoform dependent. Further analysis of the PGRB cistrome identified binding events of critical mitotic phase entry genes. This work suggests an intriguing mechanism whereby the expression of the PGR isoforms determinesin vivoneoplasia through high-jacking of the cell cycle pathway.
A CTP-dependent gating mechanism enables ParB spreading on DNA
Authors: Jalal Adam S. B. , Tran Ngat T. , Stevenson Clare. E. M. , Chimthanawala Afroze , Badrinarayanan Anjana , Lawson David M. , Le Tung B. K. 
Published: October 2019

ABSTRACTProper chromosome segregation is essential in all living organisms. The ParA-ParB-parS system is widely employed for chromosome segregation in bacteria. Previously, we showed that Caulobacter crescentus ParB requires cytidine triphosphate to escape the nucleation site parS and spread by sliding to the neighboring DNA 1. Here, we provide the structural basis for this transition from nucleation to spreading by solving co-crystal structures of a C-terminal domain truncated C. crescentus ParB with parS and with a CTP analog. Nucleating ParB is an open clamp, in which parS is captured at the DNA-binding domain (the DNA-gate). Upon binding CTP, the N-terminal domain (NTD) self-dimerizes to close the NTD-gate of the clamp. The DNA-gate also closes, thus driving parS into a compartment between the DNA-gate and the C-terminal domain. CTP hydrolysis and/or the release of hydrolytic products are likely associated with re-opening of the gates to release DNA and to recycle ParB. Overall, we suggest a CTP-operated gating mechanism that regulates ParB nucleation, spreading, and recycling.
A consensus phylogenomic approach highlights paleopolyploid and rapid radiation in the history of Ericales
Authors: Larson Drew A. , Walker Joseph F. , Vargas Oscar M. , Smith Stephen A. 
Published: October 2019

ABSTRACTPremise of studyLarge genomic datasets offer the promise of resolving historically recalcitrant species relationships. However, different methodologies can yield conflicting results, especially when clades have experienced ancient, rapid diversification. Here, we analyzed the ancient radiation of Ericales and explored sources of uncertainty related to species tree inference, conflicting gene tree signal, and the inferred placement of gene and genome duplications.MethodsWe used a hierarchical clustering approach, with tree-based homology and orthology detection, to generate six filtered phylogenomic matrices consisting of data from 97 transcriptomes and genomes. Support for species relationships was inferred from multiple lines of evidence including shared gene duplications, gene tree conflict, gene-wise edge-based analyses, concatenation, and coalescent-based methods and is summarized in a consensus framework.Key ResultsOur consensus approach supported a topology largely concordant with previous studies, but suggests that the data are not capable of resolving several ancient relationships due to lack of informative characters, sensitivity to methodology, and extensive gene tree conflict correlated with paleopolyploidy. We found evidence of a whole genome duplication before the radiation of all or most ericalean families and demonstrate that tree topology and heterogeneous evolutionary rates impact the inferred placement of genome duplications.ConclusionsOur approach provides a novel hypothesis regarding the history of Ericales and confidently resolves most nodes. We demonstrate that a series of ancient divergences are unresolvable with these data. Whether paleopolyploidy is a major source of the observed phylogenetic conflict warrants further investigation.
Dopamine buffering capacity imaging: A pharmacodynamic fMRI method for staging Parkinson disease
Authors: Black Kevin J. , Acevedo Haley K. , Koller Jonathan M. 
Published: October 2019

AbstractWe propose a novel brain imaging method for objectively quantifying disease severity in Parkinson disease (PD). Levodopa pharmacological fMRI (phMRI) hysteresis mapping is based on the clinical observation that the benefit from a dose of levodopa wears off more quickly as PD progresses. Biologically this has been thought to represent decreased buffering capacity for dopamine as nigrostriatal cells die. Buffering capacity has been modeled previously based on clinical effects, but clinical measurements are influenced by confounding factors such as patient fatigue. The new method proposes to measure the effect directly and objectively based on the timing of the known metabolic and blood flow response of several brain regions to exogenous levodopa. Such responses are robust and can be quantified without ionizing radiation using perfusion MRI.Here we present simulation studies based on published clinical dose-response data and an intravenous levodopa infusion. Standard pharmacokinetic-pharmacodynamic methods were used to model the response. Then the effect site rate constant ke was estimated from simulated response data plus Gaussian noise.Predicted time:effect curves sampled at times consistent with phMRI differ substantially based on clinical severity. Estimated ke from noisy input data was recovered with good accuracy.These simulation results support the feasibility of levodopa phMRI hysteresis mapping to measure the severity of dopamine denervation objectively and simultaneously in several brain regions.
Correlating surface plasmon resonance microscopy of living and fixated cells with electron microscopy allows for investigation of potential preparation artifacts
Authors: Kreysing Eva , Seyock Silke , Hassani Hossein , Brauweiler-Reuters Elke , Neumann Elmar , Offenhäusser Andreas 
Published: October 2019

AbstractThe investigation of the cell-substrate interface is of great importance for a broad spectrum of areas such as biomedical engineering, brain-chip interfacing and fundamental research. Due to its unique resolution and the prevalence of instruments, electron microscopy (EM) is used as one of the standard techniques for the analysis of the cell-substrate interface. However, possible artifacts that might be introduced by the required sample preparation have been the subject of speculation for decades. Due to recent advances in Surface plasmon resonance microscopy (SPRM), the technique now offers a label-free alternative for the interface characterization with nanometer resolution in axial direction. In contrast to EM, SPRM studies do not require fixation and can therefore be performed on living cells. Here, we present a workflow that allows us to quantify the impact of chemical fixation on the cell-substrate interface. These measurements confirmed that chemical fixation preserved the average cell-substrate distances in the majority of studied cells. Furthermore, we were able to correlate the SPRM measurements with EM images of the cell-substrate interface of the exact same cells allowing us to identify regions with good agreement between the two methods and reveal artifacts introduced during further sample preparation.
Meta-analysis of the General Coral Stress Response:Acroporacorals show opposing responses depending on stress intensity
Authors: Dixon Groves , Abbott Evelyn , Matz Mikhail 
Published: October 2019

AbstractAs climate change progresses, reef-building corals must contend more often with suboptimal conditions, motivating a need to understand coral stress response. Here we test the hypothesis that there is a stereotyped transcriptional response that corals enact under any stressful conditions, functionally characterized by downregulation of growth and activation of cell death, response to reactive oxygen species, immunity, and protein homeostasis. We analyze RNA-seq and Tag-Seq data from 14 previously published studies and supplement them with four new experiments involving different stressors, totaling over 600 gene expression profiles from the genusAcropora. Contrary to expectations, we found not one, but two distinct types of response. The type A response was observed under all kinds of high-intensity stress, showed strong correlations between independent projects, and was functionally consistent with the hypothesized stereotyped response. Higher similarity of type A responses irrespective of stress type supports its role as the General Coral Stress Response providing a blanket solution to severely stressful conditions. The distinct type B response was observed under lower intensity stress and was weaker and more variable among studies than type A. Unexpectedly, the type B response was broadly opposite the type A response: biological processes up-regulated under type A response tended to be down-regulated under type B response, and vice versa. Gene network analysis indicated that type B response does not involve specific co-regulated gene groups and is simply the opposite of type A response. We speculate that these paradoxically opposing responses may result from an inherent negative association between stress response and cell proliferation.