bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct-acting Antivirals for the Treatment of Kidney Transplant Patients With Chronic Hepatitis C Virus Infection in Spain: A Long-term Prospective Observational Study
Authors: González-Corvillo Carmen , Beneyto Isabel , Sánchez-Fructuoso Ana , Perelló Manel , Alonso Angel , Mazuecos Auxiliadora , Jiménez Carlos , Zárraga Sofía , Paul Javier , Lauzurica Ricardo , Hernández Domingo , Guirado Luis , Franco Antonio , Ruiz Juan Carlos , Llorente Santiago , Crespo Marta , Rodríguez-Benot Alberto , de Gracia Guindo María del Carmen , Díaz-Corte Carmen , Gentil Miguel Ángel 
Published: November 2019

Background.
Direct-acting antivirals (DAA) allow effective and safe eradication of hepatitis C virus (HCV) in most patients. There are limited data on the long-term effects of all-oral, interferon-free DAA combination therapies in kidney transplant (KT) patients infected with HCV. Here we evaluated the long-term tolerability, efficacy, and safety of DAA combination therapies in KT patients with chronic HCV infection.

Methods.
Clinical data from KT patients treated with DAA were collected before, during, and after the treatment, including viral response, immunosuppression regimens, and kidney and liver function.

Results.
Patients (N = 226) were mostly male (65.9%) aged 56.1 ± 10.9 years, with a median time from KT to initiation of DAA therapy of 12.7 years and HCV genotype 1b (64.6%). Most patients were treated with sofosbuvir-based therapies. Rapid virological response at 1 month was achieved by 89.4% of the patients and sustained virological response by week 12 by 98.1%. Liver function improved significantly after DAA treatment. Tacrolimus dosage increased 37% from the beginning of treatment (2.5 ± 1.7 mg/d) to 1 year after the start of DAA treatment (3.4 ± 1.9 mg/d, P < 0.001). Median follow-up was 37.0 months (interquartile range, 28.4–41.9) and death-censored graft survival was 91.1%. Adverse events resulting from DAA treatment, especially anemia, were reported for 31.0% of the patients.

Conclusions.
Chronic HCV infection can be treated efficiently and safely with DAA therapy in KT patients. Most patients retained stable kidney function and improved liver function. Tacrolimus dose had to be increased in most patients, potentially as a result of better liver function.
Quantifying uncertainty in brain-predicted age using scalar-on-image quantile regression
Authors: Palma Marco , Tavakoli Shahin , Brettschneider Julia , Nichols Thomas E. ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: November 2019

AbstractPrediction of subject age from brain anatomical MRI has the potential to provide a sensitive summary of brain changes, indicative of different neurodegenerative diseases. However, existing studies typically neglect the uncertainty of these predictions. In this work we take into account this uncertainty by applying methods of functional data analysis. We propose a penalised functional quantile regression model of age on brain structure with cognitively normal (CN) subjects in the Alzheimer’s Disease Neuroimaging Initiative (ADNI), and use it to predict brain age in Mild Cognitive Impairment (MCI) and Alzheimer’s Disease (AD) subjects. Unlike the machine learning approaches available in the literature of brain age prediction, which provide only point predictions, the outcome of our model is a prediction interval for each subject.
The Molecular Basis of Specific DNA Binding by the BRG1 AT-hook and Bromodomain
Authors: Sanchez Julio C. , Zhang Liyang , Evoli Stefania , Schnicker Nicholas J. , Nunez-Hernandez Maria , Yu Liping , Wereszczynski Jeff , Pufall Miles A. , Musselman Catherine A. 
Published: November 2019

AbstractThe ATP-dependent BAF chromatin remodeling complex plays a critical role in gene regulation by modulating chromatin architecture, and is frequently mutated in cancer. Indeed, subunits of the BAF complex are found to be mutated in >20% of human tumors. The mechanism by which BAF properly navigates chromatin is not fully understood, but is thought to involve a multivalent network of histone and DNA contacts. We previously identified a composite domain in the BRG1 ATPase subunit that is capable of associating with both histones and DNA in a multivalent manner. Mapping the DNA binding pocket revealed that it contains several cancer mutations. Here, we utilize SELEX-seq to identify the DNA specificity of this composite domain and NMR spectroscopy and molecular modelling to determine the structural basis of DNA binding. Finally, we demonstrate that cancer mutations in this domain alter the mode of DNA association.
Genetically variant human pluripotent stem cells selectively eliminate wild-type counterparts through YAP-mediated cell competition
Authors: Price Christopher J. , Stavish Dylan , Gokhale Paul J. , Sargeant Samantha , Lacey Joanne , Rodriguez Tristan A. , Barbaric Ivana 
Published: November 2019

AbstractThe appearance of genetic changes in human pluripotent stem cells (hPSCs) presents a concern for their use in research and regenerative medicine. Variant hPSCs harbouring recurrent culture-acquired aneuploidies display growth advantages over wild-type diploid cells, but the mechanisms yielding a drift from predominantly wild-type to variant cell populations remain poorly understood. Here we show that the dominance of variant clones in mosaic cultures is enhanced through competitive interactions resulting in elimination of wild-type cells. This elimination occurs through corralling and mechanical compression by faster growing variants, causing a redistribution of F-actin and sequestration of YAP in the cytoplasm that induces apoptosis in wild-type cells. Importantly, YAP overexpression in wild-type cells is sufficient to alleviate their loser phenotype. Our results demonstrate that hPSC fate is coupled to mechanical cues imposed by neighbouring cells and reveal that hijacking this mechanism allows variants to achieve clonal dominance in cultures.
Loss of histone H3.3 results in DNA replication defects and altered origin dynamics in C. elegans
Authors: Strobino Maude , Wenda Joanna M. , Steiner Florian A. 
Published: November 2019

AbstractHistone H3.3 is a replication-independent variant of histone H3 with important roles in development, differentiation and fertility. Here we show that loss of H3.3 results in replication defects in Caenorhabditis elegans embryos. To characterize these defects, we adapt methods to determine replication timing, map replication origins, and examine replication fork progression. Our analysis of the spatiotemporal regulation of DNA replication shows that despite the very rapid embryonic cell cycle, the genome is replicated from early and late firing origins and is partitioned into domains of early and late replication. We find that under temperature stress conditions, additional replication origins become activated. Moreover, loss of H3.3 results in impaired replication fork progression around origins, which is particularly evident at stress-activated origins. These replication defects are accompanied by replication checkpoint activation, a prolonged cell cycle, and increased lethality in checkpoint-compromised embryos. Our comprehensive analysis of DNA replication in C. elegans reveals the genomic location of replication origins and the dynamics of their firing, and uncovers a role of H3.3 in the regulation of replication origins under stress conditions.
AFM-based High-Throughput Nanomechanical Screening of Single Extracellular Vesicles
Authors: Ridolfi Andrea , Brucale Marco , Montis Costanza , Caselli Lucrezia , Paolini Lucia , Borup Anne , Boysen Anders T. , Loria Francesca , van Herwijnen Martijn J. C. , Kleinjan Marije , Nejsum Peter , Zarovni Natasa , Wauben Marca H. M. , Berti Debora , Bergese Paolo , Valle Francesco 
Published: November 2019

AbstractWe herein describe an Atomic Force Microscopy (AFM)-based experimental procedure which allows the simultaneous mechanical and morphological characterization of several hundred individual nanosized vesicles within the hour timescale.When deposited on a flat rigid surface from aqueous solution, vesicles are deformed by adhesion forces into oblate spheroids whose geometry is a direct consequence of their mechanical stiffness. AFM image analysis can be used to quantitatively measure the contact angle of individual vesicles, which is a size-independent descriptor of their deformation and, consequently, of their stiffness. The same geometrical measurements can be used to infer vesicle diameter in its original, spherical shape.We demonstrate the applicability of the proposed approach to natural vesicles obtained from different sources, recovering their size and stiffness distributions by simple AFM imaging in liquid. We show how the combined EV stiffness/size readout is able to discriminate between subpopulations of vesicular and non-vesicular objects in the same sample, and between populations of vesicles with similar sizes but different mechanical characteristics. We also discuss a force spectroscopy calibration procedure to quantitatively link the stiffness of EVs to their average contact angle.Finally, we discuss expected extensions and applications of the methodology.
Heterologous glycosyl hydrolase expression and cellular reprogramming resembling sucrose-induction enableZymomonas mobilisgrowth on cellobiose
Authors: Kurumbang Nagendra P. , Vera Jessica M. , Hebert Alexander S. , Coon Joshua J. , Landick Robert 
Published: November 2019

ABSTRACTPlant derived fuels and chemicals from renewable biomass have significant potential to replace reliance on petroleum and improve global carbon balance. However, plant biomass contains significant fractions of oligosaccharides that are not usable natively by many industrial microorganisms, includingEscherichia coli,Saccharomyces cerevisiae,andZymomonas mobilis. Even after chemical or enzymatic hydrolysis, some carbohydrate remains as non-metabolizable oligosaccharides (e.g., cellobiose or longer cellulose-derived oligomers), thus reducing the efficiency of conversion to useful products. To begin to address this problem forZ. mobilis, we engineered a strain (Z. mobilisGH3) that expresses a glycosyl hydrolase (GH) with β-glucosidase activity fromCaulobacter crescentusand subjected it to an adaptation in cellobiose medium. Growth on cellobiose was achieved after a prolonged lag phase in cellobiose medium that induced changes in gene expression and cell composition, including increased expression and secretion of GH. These changes were reversible upon growth in glucose-containing medium, meaning they did not result from genetic mutation but could be retained upon transfer of cells to fresh cellobiose medium. After adaptation to cellobiose, our GH-expressing strain was able to convert about 50% of cellobiose to glucose within 24 hours and use it for growth and ethanol production. Alternatively, pre-growth ofZ. mobilisGH3 in sucrose medium enabled immediate growth on cellobiose. Proteomic analysis of cellobiose- and sucrose-adapted strains revealed upregulation of secretion-, transport-, and outer membrane-related proteins, which may aid secretion or surface display of GHs, entry of cellobiose into the periplasm, or both. Our two key findings are thatZ. mobiliscan be reprogrammed to grow on cellobiose as a sole carbon source and that this reprogramming is related to a natural responseof Z. mobilisto sucrose that enables sucrose secretion.
clustifyr: An R package for automated single-cell RNA sequencing cluster classification
Authors: Fu Rui , Gillen Austin E. , Sheridan Ryan M. , Tian Chengzhe , Daya Michelle , Hao Yue , Hesselberth Jay R. , Riemondy Kent A. 
Published: November 2019

ABSTRACTBackgroundIn single-cell RNA sequencing (scRNA-seq) analysis, assignment of likely cell types remains a time-consuming, error-prone, and biased process. Current packages for identity assignment use limited types of reference data, and often have rigid data structure requirements. As such, a more flexible tool, capable of handling multiple types of reference data and data structures, would be beneficial.FindingsTo address difficulties in cluster identity assignment, we developed the clustifyr R package. The package leverages external datasets, including gene expression profiles from scRNA-seq, bulk RNA-seq, microarray expression data, and/or signature gene lists, to assign likely cell types. We benchmark various parameters of a correlation-based approach, and also implement a variety of gene list enrichment methods. By providing tools for exploratory data analysis, we demonstrate the feasibility of a simple and effective data-driven approach for cell type assignment in scRNA-seq cell clusters.Conclusionsclustifyr is a lightweight and effective cell type assignment tool developed for compatibility with various scRNA-seq analysis workflows. clustifyr is publicly available at https://github.com/rnabioco/clustifyr
Genome editing to model and reverse a prevalent mutation associated with myeloproliferative neoplasms
Authors: Baik Ron , Wyman Stacia K. , Kabir Shaheen , Corn Jacob E. 
Published: November 2019

AbstractMyeloproliferative neoplasms (MPNs) cause the over-production of blood cells such as erythrocytes (polycythemia vera) or platelets (essential thrombocytosis). JAK2 V617F is the most prevalent somatic mutation in many MPNs, but previous modeling of this mutation in mice relied on transgenic overexpression and resulted in diverse phenotypes that were in some cases attributed to expression level. CRISPR-Cas9 engineering offers new possibilities to model and potentially cure genetically encoded disorders via precise modification of the endogenous locus in primary cells. Here we develop “scarless” Cas9-based reagents to create and reverse the JAK2 V617F mutation in an immortalized human erythroid progenitor cell line (HUDEP-2), CD34+ adult human hematopoietic stem and progenitor cells (HSPCs), and immunophenotypic long-term hematopoietic stem cells (LT-HSCs). We find no overt in vitro increase in proliferation associated with an endogenous JAK2 V617F allele, but co-culture with wild type cells unmasks a competitive growth advantage provided by the mutation. Acquisition of the V617F allele also promotes terminal differentiation of erythroid progenitors, even in the absence of hematopoietic cytokine signaling. Taken together, these data are consistent with the gradually progressive manifestation of MPNs and reveals that endogenously acquired JAK2 V617F mutations may yield more subtle phenotypes as compared to transgenic overexpression models.
The metastable brain associated with autistic-like traits of typically developing individuals
Authors: Sase Takumi , Kitajo Keiichi 
Published: November 2019

AbstractMetastability in the brain is thought to be a mechanism involved in dynamic organization of cognitive and behavioral functions across multiple spatiotemporal scales. However, it is not clear how such organization is realized in underlying neural oscillations in a high-dimensional state space. It was shown that macroscopic oscillations often form phase-phase coupling (PPC) and phase-amplitude coupling (PAC) which result in synchronization and amplitude modulation, respectively, even without external stimuli. These oscillations can also make spontaneous transitions across synchronous states at rest. Using resting-state electroencephalographic signals and the autism-spectrum quotient scores acquired from healthy humans, we show experimental evidence that the PAC combined with PPC allows amplitude modulation to be transient, and that the metastable dynamics with this transient modulation is associated with autistic-like traits. In individuals with a longer attention span, such dynamics tended to show fewer transitions between states by forming delta-alpha PAC. We identified these states as two-dimensional metastable states that could share consistent patterns across individuals. Our findings suggest that the human brain dynamically organizes inter-individual differences in a hierarchy of macroscopic oscillations with multiple timescales by utilizing metastability.Author SummaryThe human brain organizes cognitive and behavioral functions dynamically. For decades, the dynamic organization of underlying neural oscillations has been a fundamental topic in neuroscience research. Even without external stimuli, macroscopic oscillations often form phase-phase coupling and phase-amplitude coupling (PAC) that result in synchronization and amplitude modulation, respectively, and can make spontaneous transitions across synchronous states at rest. Using resting-state electroencephalography signals acquired from healthy humans, we show evidence that these two neural couplings enable amplitude modulation to be transient, and that this transient modulation can be viewed as the transition among oscillatory states with different PAC strengths. We also demonstrate that such transition dynamics are associated with the ability to maintain attention to detail and to switch attention, as measured by autism-spectrum quotient scores. These individual dynamics were visualized as a trajectory among states with attracting tendencies, and involved consistent brain states across individuals. Our findings have significant implications for unraveling variability in the individual brains showing typical and atypical development.
Sustained modulation of emotion-related fibers after 8 weeks of mindfulness-based stress reduction training
Authors: Chen Chang-Le , Shih Yao-Chia , Hsu Yung-Chin , Wen Tzung-Kuen , Fang Shih-Chin , Tang Da-Lun , Lee Si-Chen , Tseng Wen-Yih Isaac 
Published: November 2019

AbstractAn 8-week mindfulness-based stress reduction (MBSR) program enables novices to learn and practice mindfulness meditation. A longitudinal study design has been used in prior research to investigate the effect of short-term mindfulness meditation training on brain structures. Many studies have demonstrated microstructural changes in the white matter by comparing baseline measurements with measurements obtained immediately after short-term meditation training. However, these studies did not clarify the evolution of the modulated microstructures several months after mindfulness meditation practice is discontinued. Therefore, in this study, we recruited 13 novice practitioners and administered an 8-week MBSR training program. We extended the span of the longitudinal study by adding a third measurement taken approximately 6 months after the second time point. Diffusion indices derived from diffusion spectrum imaging were used to quantify the temporal changes in modulation across three time points. The analysis identified four tract bundles that were significantly modulated after the 8-week MBSR training program, namely the callosal fibers connecting the bilateral amygdalae and bilateral hippocampi, right thalamic radiation of the auditory nerve, and right uncinate fasciculus. At the third time point, at which the participants had discontinued practice for approximately 6 months, the diffusion indices of the four tract bundles still presented a significant difference compared with the baseline. Our results indicate that the modulation of microstructural properties of the white matter tract induced by the 8-week MBSR program was sustained after completion of the program and support that neuroplasticity in brain connection persists after the discontinuation of meditation training.
Funders and stakeholders matter: a case study analysis
Authors: Murray Clare 
Published: November 2019

PurposeThe purpose of this paper is to understand how funders and stakeholders influence the performance of Spain’s most autonomous cultural institutions. As the first of its kind to focus on Spain’s independent cultural spaces, the paper is exploratory in nature. It seeks to contribute to the field of research on best practices in cultural management and marketing through its study of the performance of all seven independent cultural spaces that belong to the Red TransIbérica de Espacios Culturales Independientes.Design/methodology/approachThe paper employs a mixed-methods case study analysis. Relying on in-person observations and interviews, online surveying, online review analyses and cultural engagement data synthesis, it supports quantitative data with qualitative data, and uses methodological triangulation techniques to validate findings.FindingsThe paper indicates that despite their autonomy, the type of funding and the number of stakeholders that independent cultural spaces boast appear related to their marketability.Originality/valueUsing all seven member organizations as the sample group, this research is able to build generalized conclusions for the country’s population of independent cultural spaces. By highlighting key themes for further research, the paper offers insight into an understudied section of the sector.
Mission-driven arts organisations and initiatives
Authors: Carnegie Elizabeth , Drencheva Andreana 
Published: November 2019

Purpose
The purpose of this paper is to examine how mission-driven arts organisations respond to the complex set of economic and social conditions that the authors here term as a significant point of rupture. Drawing on the papers that form a part of the special section of this issue, the authors critically examine how the intersection of globalisation and neoliberalism creates multidimensional uncertainty that shapes the opportunities, responsibilities, work arrangements, and lived experiences of artists and artist-led initiatives and organisations.

Design/methodology/approach
In this introduction to the symposium on mission-driven arts organisations and initiatives, the authors explore how the included articles question and introduce key concerns that govern, limit and support mission-driven arts organisations.

Findings
Drawing on the papers in this set, the authors note that mission-driven arts organisations are diverse and employ numerous organising forms. However, at their core is the pursuit of social objectives, which also requires the management of often conflicting artistic, economic, cultural and social demands. The authors explicate how mission-driven arts organisations respond to local agendas and work best at the community level. As such, they may not play a key role in tourism or large-scale cultural regeneration of spaces, but rather seek to make creative use of sunken and redundant, often inner city spaces to address local needs. Yet, the uncertainty that these organisations face shapes temporary solutions that may enhance the precariaty and pressures for artists and creative producers with likely impact on wellbeing.

Originality/value
This paper brings together original insights into how mission-drive organisations seek to overcome and indeed flourish in a time of rupture. It moves beyond the notion of cultural regeneration as an instrument of tourism, and tourism as a focus of regeneration, to consider the value such organisations bring to localities evidenced in both creative practices and as local cultural engagement beyond economic impact. In doing so, mission-driven arts organisations play a vital role in a time of rapid change.