bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a Patient-Centered Pelvic Floor Complication Scale
Authors: Fitzgerald Jocelyn , Siddique Moiuri , Miranne Jeannine Marie , Saunders Pamela , Gutman Robert 
Published: March 2019

Objective
The aim of the study was to evaluate patient responses on a survey of knowledge, perceptions, concerns, and fears about complications related to pelvic reconstructive surgery (PRS). This is the first step to create a simplified, patient-centered Pelvic Floor Complication Scale that evaluates complications from both the patient and surgeon perspective.

Methods
Subjects for this prospective study included women older than 18 years planning surgery within 12 weeks or who had undergone PRS more than 6 months ago. Patients were asked open-ended questions about postoperative complications as well as to rank the severity of potential PRS complications (as mild, moderate, severe). Using thematic analysis, responses were coded and analyzed using Dedoose (Version 8.0.35).

Results
Thirty-three women (16 preop, 17 postop) participated in telephone interviews (n = 26) and focus groups (n = 7). There were no differences in age, race, education, marital status, and previous surgery. Specific complications such as a single urinary tract infection, short-term constipation (<2 weeks), persistent constipation (present preop), bladder injury not requiring repair or catheterization, vascular injury without sequelae, and extra office visits were considered minor. New recurrent urinary tract infections, new persistent constipation, worsening postop constipation (present preop), blood transfusion, readmission, and reoperation were considered severe complications.
The most common themes included the following: fears of surgical failure, anesthesia, mesh erosion, discharge with a catheter, and pain. Patients were overall very trusting of their female pelvic medicine and reconstructive surgery surgeons and potential risks did not impact surgical decisions.

Conclusions
Our research findings provide significant insight into patient perceptions of complications related to PRS that will aid in future development of a patient-centered Pelvic Floor Complication Scale.
Single cell multi-omics analysis reveals novel roles for DNA methylation in sensory neuron injury responses
Authors: Hu Youjin , An Qin , Fan Guoping 
Published: March 2019

AbstractDNA methylation is implicated in neuronal injury response and regeneration, but its role in regulating stable transcription changes in different types of dorsal root ganglion (DRG) neurons is unclear. In this study, we simultaneously profiled both the DNA methylome and mRNA transcriptome from single DRG neurons at different ages under either control or peripheral nerve injury condition. We found that age-related expression changes in Notch signaling genes and methylation changes at Notch receptor binding sites are associated with the age-dependent decline in peripheral nerve regeneration potential. Moreover, selective hypomethylation of AP-1 complex binding sites on regeneration-associated gene (RAG) promoters coincides with RAG transcriptional upregulation after injury. Consistent with the findings that different subtypes of DRG neurons exhibit distinct methylome changes upon injury responses, in a hybrid CAST/Ei; C57BL/6 genetic background, we further observed allele-specific gene regulation and methylation changes for many RAGs after injury. We suggest that the genetic background determines distinct allele-specific DNA methylomes, which contribute to age-dependent regulation and neuronal subtype-specific injury-responses in different mouse strains.
Integrating electric field modelling and neuroimaging to explain inter-individual variability of tACS effects
Authors: Kasten Florian H. , Duecker Katharina , Maack Marike C. , Meiser Arnd , Herrmann Christoph S. 
Published: March 2019

AbstractUnderstanding variability of transcranial electrical stimulation (tES) effects is one of the major challenges in the brain stimulation community. Promising candidates to explain this variability are individual anatomy and the resulting differences of electric fields inside the brain. We integrated individual simulations of electric fields during tES with source-localization to predict variability of transcranial alternating current stimulation (tACS) aftereffects on α-oscillations. In two experiments, participants received 20 minutes of either α-tACS (1 mA) or sham stimulation. Magnetoencephalogram was recorded for 10 minutes before and after stimulation. tACS caused a larger power increase in the α-band as compared to sham. The variability of this effect was significantly predicted by measures derived from individual electric field modelling. Our results directly link electric field variability to variability of tACS outcomes, stressing the importance of individualizing stimulation protocols and providing a novel approach to analyze tACS effects in terms of dose-response relationships.
Immune profiling in M. tuberculosis infection enables stratification of patients with active disease
Authors: Duffy Darragh , Nemes Elisa , Llibre Alba , Rouilly Vincent , Filander Elizabeth , Africa Hadn , Mabwe Simbarashe , Jaxa Lungisa , Charbit Bruno , Musvosvi Munyaradzi , Mulenga Humphrey ,   the Milieu Intérieur Consortium, Thomas Stephanie , Hatherill Mark , Bilek Nicole , Scriba Thomas J , Albert Matthew L 
Published: March 2019

AbstractTuberculosis (TB) is caused byMycobacterium tuberculosis(Mtb) infection and is a major public health problem with an estimated 1.7 billion persons infected worldwide. Clinical challenges in TB include the lack of a blood-based test for active disease, and the absence of prognostic biomarkers for early treatment response. Current blood based tests, such as QuantiFERON-TB Gold (QFT), are based on an IFNγ readout followingMtbantigen stimulation. However, they do not distinguish active TB disease from asymptomaticMtbinfection. We hypothesized that the use of TruCulture, an improved immunomonitoring method for whole blood collection and immune stimulation, could improve the discrimination of active disease from latentMtbinfection. To test our hypothesis, we stimulated whole blood from active TB patients (before and after successful treatment), comparing them to asymptomatic latently infected individuals.Mtb-specific antigens (ESAT-6, CFP-10, TB7.7) and live bacillus Calmette-Guerin (BCG) were used for TruCulture stimulation conditions, with direct comparison to QFT. Protein analyses were performed on the culture supernatants using ELISA and Luminex multi-analyte profiling. TruCulture showed an ability to discriminate active TB cases from latent controls (p < 0.0001, AUC = 0.81, 95% CI: 0.69-0.93) as compared to QFT (p = 0.47 AUC = 0.56, 95% CI: 0.40-0.72), based on an IFNγ readout afterMtbantigen stimulation. The stratification of the two groups could be further improved by using theMtbAg/BCG IFNγ ratio response (p < 0.0001, AUC = 0.918, 95% CI: 0.84-0.98). We also identified additional cytokines that distinguished latent infection from TB disease; and show that the primary differences between the TruCulture and QFT systems were a result of higher levels of non-specific innate immune activation in QFT tubes, due to the lack of a buffering solution in the latter. We conclude that TruCulture offers a next-generation solution for whole blood stimulation and immunomonitoring with the possibility to discriminate active and latently infected persons.
Inter-individual genomic heterogeneity within European population isolates
Authors: Anagnostou Paolo , Dominici Valentina , Battaggia Cinzia , Sarno Stefania , Boattini Alessio , Calò Carla , Francalacci Paolo , Vona Giuseppe , Tofanelli Sergio , Vilar Miguel G. , Colonna Vincenza , Pagani Luca , Bisol Giovanni Destro 
Published: March 2019

AbstractA number of studies carried out since the early ‘70s has investigated the effects of isolation on genetic variation within and among human populations in diverse geographical contexts. However, no extensive analysis has been carried out on the heterogeneity among genomes within isolated populations. This issue is worth exploring since events of recent admixture and/or subdivision could potentially disrupt the genetic homogeneity which is to be expected when isolation is prolonged and constant over time. Here, we analyze literature data relative to 87,818 autosomal single-nucleotide polymorphisms, which were obtained from a total of 28 European populations. Our results challenge the traditional paradigm of population isolates as genetically (and genomically) uniform entities. In fact, focusing on the distribution of variance of intra-population diversity measures across individuals, we show that the inter-individual heterogeneity of isolated populations is at least comparable to the open ones. More in particular, three small and highly inbred isolates (Sappada, Sauris and Timau in Northeastern Italy) were found to be characterized by levels of this parameter largely exceeding that of all other populations, possibly due to relatively recent events of genetic introgression. Finally, we propose a way to monitor the effects of inter-individual heterogeneity in disease-gene association studies.
Transient upregulation of translational efficiency in prodromal Tg2576 mice precipitates AD symptoms
Authors: Borreca Antonella , Valeri Francesco , De Luca Mariassunta , Ernst Lysianne , Russo Arianna , Cordella Alberto , Corsetti Veronica , Nobili Annalisa , Amadoro Giusy , Mercuri Nicola Biagio , D’Amelio Marcello , Ammassari-Teule Martine 
Published: March 2019

ABSTRACTTg2576 mice overexpressing APPK670/671L exhibit elevated hAPP levels from birth but remain at a prodromal stage until 3 months of age. Whether variations in hAPP mRNA specific and overall translation occur during development and precipitates the transition from an asymptomatic to a symptomatic stage is unknown. By performing polysome profiling and distribution of hAPP, and measuring the levels of eukaryotic initial translation factors in hippocampal extracts from pre- and early symptomatic Tg2576 mice, we found that the presence of mRNA and protein polysomal signals was associated with decreased levels of the phosphorylated form of the initial translation factor eIF2α (p-eIF2α), revealing a transient upregulation of overall translation. Differently, the reduction of hAPP mRNA polysomal signals was associated with increased p-eIF2α levels – repressing translation-when mice were symptomatic, suggesting a compensatory mechanism aimed at downregulating hAPP mRNA. Confirming that prodromal upregulation of translational efficiency contributes to AD pathogenesis, pharmacological restoration of proper translational control in early symptomatic mice blocked the manifestation of neural and cognitive AD-like alterations.
Gene regulatory network reconstruction using single-cell RNA sequencing of barcoded genotypes in diverse environments
Authors: Jackson Christopher A , Castro Dayanne M , Saldi Giuseppe-Antonio , Bonneau Richard , Gresham David 
Published: March 2019

AbstractUnderstanding how gene expression programs are controlled requires identifying regulatory relationships between transcription factors and target genes. Gene regulatory networks are typically constructed from gene expression data acquired following genetic perturbation or environmental stimulus. Single-cell RNA sequencing (scRNAseq) captures the gene expression state of thousands of individual cells in a single experiment, offering advantages in combinatorial experimental design, large numbers of independent measurements, and accessing the interaction between the cell cycle and environmental responses that is hidden by population-level analysis of gene expression. To leverage these advantages, we developed a method for transcriptionally barcoding gene deletion mutants and performing scRNAseq in budding yeast (Saccharomyces cerevisiae). We pooled diverse genotypes in 11 different environmental conditions and determined their expression state by sequencing 38,285 individual cells. We developed, and benchmarked, a framework for learning gene regulatory networks from scRNAseq data that incorporates multitask learning and constructed a global gene regulatory network comprising 12,018 interactions. Our study establishes a general approach to gene regulatory network reconstruction from scRNAseq data that can be employed in any organism.
Dissociable neural circuits underlie the resolution of three discrete sources of competition during task-switching
Authors: Burke Kelly M. , Molholm Sophie , Butler John S. , Ross Lars A. , Foxe John J. 
Published: March 2019

AbstractHumans perform sub-optimally when juggling more than one task, but are nonetheless required to multitask during many daily activities. Rapidly and effectively switching attentional focus between tasks is fundamental to navigating complex environments. Task-switching paradigms in conjunction with neuroimaging have identified brain networks underpinning flexible reallocation of cognitive resources and a core network of neural regions is repeatedly implicated (i.e., posterior parietal, inferior frontal, anterior cingulate, and middle frontal cortex). Performance costs such as reduced accuracy and slowed responses accompany the first execution of a task following a task-switch. These costs stem from three main sources of competition: 1) the need to reconfigure task-rules, 2) the immediate history of motor responding, and 3) whether inputs to be acted upon provide congruent or incongruent information regarding the appropriate motor response, relative to the recently “switched-away-from” task. Here, we asked whether both common (domain-general) and non-overlapping (dissociable) neural circuits were involved in resolving these three distinct sources of competition under high-demand task-switching conditions. Dissociable neural circuits were active in resolving each of the three sources of competition. No domain-general regions were implicated in all three. Rather, two regions were common across rule-switching and stimulus incongruence, and five regions to incongruence and response-switching. Each source of conflict elicited activation from many regions including the posterior cingulate, thalamus, and cerebellum, regions not commonly implicated in the task-switching literature. These results suggest that dissociable neural networks are principally responsible for resolving different sources of competition, but with partial interaction of some overlapping domain-general circuitry.
Graphene nanoflakes for acute manipulation of membrane cholesterol and transmembrane signaling
Authors: Kitko Kristina E. , Hong Tu , Lazarenko Roman M. , Rafael Montenegro-Burke J. , Shah Amy T. , Zhang Yuchen , Raghunathan Krishnan , Kenworthy Anne K. , Skala Melissa C. , McLean A. , Xu Ya-Qiong , Zhang Qi 
Published: March 2019

ABSTRACTCholesterol is one of the most essential lipids in eukaryotic cell membranes. However, acute and selective manipulation of membrane cholesterol remains challenging. Here, we report that graphene nanoflakes (GNFs) insert into the plasma membrane and directly interact with cholesterol, resulting in acute cholesterol enrichment – and thus structural and functional changes. Using two representative cell preparations, we explore the utility of GNFs in modifying cell communication pathways sensitive to membrane cholesterol. In fibroblasts, GNFs enhance ATP-induced intracellular Ca2+-release by allosteric facilitation of P2Y receptors, a subtype of G protein-coupled receptors, in a cholesterol-dependent manner. In neurons, which possess higher membrane cholesterol levels than most cell types, GNFs further increase cholesterol. Consequently, GNFs change membrane fluidity, especially at synaptic boutons, and potentiate neurotransmitter release by accelerating synaptic vesicle turnover. Together, our results provide a molecular explanation for graphene’s cellular impacts and demonstrate its potential for membrane-oriented engineering of cell signaling.
REMI-seq: Development of methods and resources for functional genomics inDictyostelium
Authors: Gruenheit Nicole , Baldwin Amy , Stewart Balint , Jaques Sarah , Keller Thomas , Parkinson Katie , Chisholm Rex , Harwood Adrian , Thompson Christopher R. L. 
Published: March 2019

AbstractGenomes can be sequenced with relative ease, but ascribing gene function remains a major challenge. Genetically tractable model systems are crucial to meet this challenge. One powerful model is the social amoebaDictyostelium discoideum, a eukaryotic microbe widely used to study diverse questions in cell, developmental and evolutionary biology. However, its utility is hampered by the inefficiency with which sequence, transcriptome or proteome variation can be linked to phenotype. To address this, we have developed methods (REMI-seq) to (1) generate a near genome-wide resource of individual mutants (2) allow large-scale parallel phenotyping. We demonstrate that integrating these resources allows novel regulators of cell migration, phagocytosis and macropinocytosis to be rapidly identified. Therefore, these methods and resources provide a step change for high throughput gene discovery in a key model system, and the study of genes affecting traits associated with higher eukaryotes.
Determinants of transcription factor regulatory range
Authors: Chen Chen-Hao , Zheng Rongbin , Fan Jingyu , Brown Myles , Liu Jun S. , Meyer Clifford A. , Shirley Liu X. 
Published: March 2019

AbstractTo characterize the genomic distances over which transcription factors (TFs) influence gene expression, we examined thousands of TF and histone modification ChIP-seq datasets and thousands of gene expression profiles. A model integrating these data revealed two classes of TF: one with short-range regulatory influence, the other with long-range regulatory influence. The two TF classes also had distinct chromatin-binding preferences and auto-regulatory properties. The regulatory range of a single TF bound within different topologically associating domains (TADs) depended on intrinsic TAD properties such as local gene density and G/C content, but also on the TAD chromatin state in specific cell types. Our results provide evidence that most TFs belong to one of these two functional classes, and that the regulatory range of long-range TFs is chromatin-state dependent. Thus, consideration of TF type, distance-to-target, and chromatin context is likely important in identifying TF regulatory targets and interpreting GWAS and eQTL SNPs.
Butterfly assemblages from Amazonian flooded forests are not more species-poor than from unflooded forests
Authors: Rabelo Rafael M. , Magnusson William E. 
Published: March 2019

AbstractThe Amazonian flooded and upland forests harbour distinct assemblages of most taxonomic groups. These differences can be mainly attributed to flooding, which may affect directly or indirectly the persistence of species. Here, we compare the density, richness and composition of butterfly assemblages in vaórzea and terra firme forests, and evaluate whether terrain elevation and flooding can be used to predict the assemblage structure. We found that the total abundance and number of species per plot is higher in vaórzea than in terra firme forests. Vaórzea assemblages showed a higher dominance of abundant species than terra firme assemblages, in which low-flying Haeterini butterflies had higher abundance. After standardizing species richness by sample size and/or coverage, species richness estimates for vaórzea and terra firme forests were similar. There was strong turnover in species composition across vaórzea and terra firme forests associated with terrain elevation, most likely due to differences in the duration of flooding. Despite a smaller total area, less defined vegetation strata, more frequent disturbances and the younger geological age of floodplain forests, Nymphalid butterfly assemblages are not more species poor there than in unflooded forests.
SCHEMA
Authors: Stone Merlin , Woodcock Neil , Ekinci Yuksel , Aravopoulou Eleni , Parnell Brett David 
Published: March 2019

PurposeThis paper aims to review the development of thinking about the information needed by companies to create an accurate picture of how well they manage their engagement with customers, taking into account the evolution of thinking and practice in this area over the past three decades towards the idea of data-driven customer engagement. It then describes the evolution and use of an assessment and benchmarking process and tool which provide the needed information.Design/methodology/approachLiterature review, conceptual analysis and explanation of the management consulting process are used.FindingsCompanies can get an accurate picture of how well they manage customer engagement provided that a careful assessment approach is used where assessors are properly selected and trained and that there is a strong focus on compliance with requirements rather than “box-ticking” based upon managers’ perceptions.Research limitations/implicationsThe assessment and benchmarking process was developed mainly for use by larger companies, though the findings could be adapted for use by smaller companies.Practical implicationsCompanies whose success depends upon customer engagement should consider using the assessment and benchmarking tool to guide their planning and implementation. They should heed the warnings about the risks of inaccurate assessments which may arise because of the incentives by which managers are managed.Social implicationsThe assessment and benchmarking process has been used by the public sector and government, and given government’s desire to engage citizens better, they should consider adopting the ideas in this paper to reform citizen engagement.Originality/valueThis is the only paper which reviews the development of the assessment process for customer engagement.
The separation of directors and managers
Authors: Segrestin Blanche , Johnston Andrew , Hatchuel Armand 
Published: March 2019

PurposeThe purpose of this paper is to contrast the historical rise of the managerial function and its reception in law. It thus contributes to the debates on the separation of ownership and control, by showing that managers were never recognized in law. As a result, the managerial function was not protected in law.Design/methodology/approachThis paper brings together management history and the history of UK company law to study the emergence of management in the early twentieth century and the law’s response. The authors bring new historical evidence to bear on the company law reforms of the second half of the twentieth century and, in particular, on the changes inspired by the Cohen Committee report of 1945.FindingsScientific progress and innovation were important rationales for the emergence of managerial authority. They implied new economic models, new competencies and wider social responsibilities. The analysis of this paper shows that these rationales have been overlooked by company law. The lack of conceptualization of the management in law allowed reforms after 1945 that gave shareholders greater influence over corporate strategy, reducing managerial discretion and the scope for innovation.Research limitations/implicationsThis paper focuses on the UK. Further research is needed to confirm whether other countries followed a similar path, both in terms of the emergence of management and in terms of the law’s approach.Originality/valueThis paper is the first, to the authors’ knowledge, to examine the law’s historical approach to management. It calls for a reappraisal of the status of managers and the way corporate governance organizes the separation of ownership and control.