bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intensive Care to Facilitate Organ Donation: A Report on the Experience of 2 Spanish Centers With a Common Protocol
Authors: Martínez-Soba Fernando , Pérez-Villares José M. , Martínez-Camarero Lidia , Lara Ramón , Monzón José L. , Fernández-Carmona Alberto , Marco Pedro , Coll Elisabeth , Domínguez-Gil Beatriz 
Published: July 2018

Background.
The aim of this study is to report the experience with a program of Intensive Care to facilitate Organ Donation (ICOD) in 2 Spanish centers based on a common protocol.

Methods.
Retrospective review of clinical charts of patients with a devastating brain injury whose families were approached to discuss the possibility of ICOD once further treatment was deemed futile by the treating team. Study period is from January 1, 2011, to December 31, 2015.

Results.
ICOD was discussed with families of 131 patients. Mean age of possible donors was 75 years (SD = 11 years). The main cause of brain injury was an intracranial hemorrhage (72%). Interviews with families were held after the decision had been made not to intubate/ventilate in 50% of cases, and after the decision not to continue with invasive ventilation in the remaining cases. Most interviews (66%) took place in the emergency department. The majority of families (95%) consented to ICOD. Of the 125 consented cases, 101 (81%) developed brain death (BD), most in 72 hours or less. Ninety-nine (98%) patients transitioned to actual donation after BD, with 1.2 organs transplanted per donor. Of patients who did not evolve to BD, 4 died after an unexpected cardiac arrest and 18 after the withdrawal of life-sustaining measures. ICOD contributed to 33% of actual donors registered at both centers.

Conclusions.
ICOD is well accepted by families. Most patients evolve to BD within a short period of time. The practice substantially contributes to increasing organ donation and offers more patients the chance of donating their organs after death.
Filtration-induced production of conductive/robust Cu films on cellulose paper by low-temperature sintering in air
Authors: Sakurai Shintaro , Akiyama Yusuke , Kawasaki Hideya 
Published: July 2018

Cellulose paper is an attractive substrate for paper electronics because of its advantages of flexibility, biodegradability, easy incorporation into composites, low cost and eco-friendliness. However, the micrometre-sized pores of cellulose paper make robust/conductive films difficult to deposit onto its surface from metal-nanoparticle-based inks. We developed a Cu-based composite ink to deposit conductive Cu films onto cellulose paper via low-temperature sintering in air. The Cu-based inks consisted of a metallo-organic decomposition ink and formic-acid-treated Cu flakes. The composite ink was heated in air at 100°C for only 15 s to give a conductive Cu film (7 × 10
−5
Ω cm) on the cellulose paper. Filtration of the Cu-based composite ink accumulated Cu flakes on the paper, which enabled formation of a sintered Cu film with few defects. A strategy was developed to enhance the bending stability of the sintered Cu films on paper substrates using polyvinylpyrrolidone-modified Cu flakes and amine-modified paper. The resistance of the Cu films increased only 1.3-fold and 1.1-fold after 1000 bending cycles at bending radii of 5 mm and 15 mm, respectively. The results of this study provide an approach to increasing the bending stability of Cu films on cellulose paper.
Translating genotype data of 44,000 biobank participants into clinical pharmacogenetic recommendations: challenges and solutions
Authors: Reisberg Sulev , Krebs Kristi , Kals Mart , Mägi Reedik , Metsalu Kristjan , Lauschke Volker M. , Vilo Jaak , Milani Lili 
Published: July 2018

ABSTRACTPurposeBiomedical databases combining electronic medical records, phenotypic and genomic data constitute a powerful resource for the personalization of treatment. To leverage the wealth of information provided, algorithms are required that systematically translate the contained information into treatment recommendations based on existing genotype-phenotype associations.MethodsWe developed and tested algorithms for translation of pre-existing genotype data of over 44,000 participants of the Estonian biobank into pharmacogenetic recommendations. We compared the results obtained by whole genome sequencing, whole exome sequencing and genotyping using microarrays, and evaluated the impact of pharmacogenetic reporting based on drug prescription statistics in the Nordic countries and Estonia.ResultsOur most striking result was that the performance of genotyping arrays is similar to that of whole genome sequencing, whereas exome sequencing is not suitable for pharmacogenetic predictions. Interestingly, 99.8% of all assessed individuals had a genotype associated with increased risks to at least one medication, and thereby the implementation of pharmacogenetic recommendations based on genotyping affects at least 50 daily drug doses per 1000 inhabitants.ConclusionWe find that microarrays are a cost-effective solution for creating pre-emptive pharmacogenetic reports, and with slight modifications, existing databases can be applied for automated pharmacogenetic decision support for clinicians.
Infant and adult brains are coupled to the dynamics of natural communication
Authors: Piazza Elise A. , Hasenfratz Liat , Hasson Uri , Lew-Williams Casey 
Published: July 2018

AbstractInfancy is the foundational period for learning from adults, and the dynamics of the social environment have long been proposed as central to children’s development. Here we reveal a novel, highly naturalistic approach for studying live interactions between infants and adults. Using functional near-infrared spectroscopy (fNIRS), we simultaneously and continuously measured the brains of infants (9-15 months) and an adult while they communicated and played with each other in real time. We found that time-locked neural coupling within dyads was significantly greater when they interacted with each other than with control individuals. In addition, we found that both infant and adult brains continuously tracked the moment-to-moment fluctuations of mutual gaze, infant emotion, and adult speech prosody with high temporal precision. This investigation advances what is currently known about how the brains and behaviors of infants both shape and reflect those of adults during real-life communication.
Unfold: An integrated toolbox for overlap correction, non-linear modeling, and regression-based EEG analysis
Authors: Ehinger Benedikt V. , Dimigen Olaf 
Published: July 2018

ABSTRACTElectrophysiological research with event-related brain potentials (ERPs) is increasingly moving from simple, strictly orthogonal stimulation paradigms towards more complex, quasi-experimental designs and naturalistic situations that involve fast, multisensory stimulation and complex motor behavior. As a result, electrophysiological responses from subsequent events often overlap with each other. In addition, the recorded neural activity is typically modulated by numerous covariates, which influence the measured responses in a linear or nonlinear fashion. Examples of paradigms where systematic temporal overlap variations and low-level confounds between conditions cannot be avoided include combined EEG/eye-tracking experiments during natural vision, fast multisensory stimulation experiments, and mobile brain/body imaging studies. However, even “traditional”, highly controlled ERP datasets often contain a hidden mix of overlapping activity (e.g. from stimulus onsets, involuntary microsaccades, or button presses) and it is helpful or even necessary to disentangle these components for a correct interpretation of the results. In this paper, we introduceunfold, a powerful, yet easy-to-use MATLAB toolbox for regression-based EEG analyses that combines existing concepts of massive univariate modeling (“regression ERPs”), linear deconvolution modeling, and non-linear modeling with the generalized additive model (GAM) into one coherent and flexible analysis framework. The toolbox is modular, compatible with EEGLAB and can handle even large datasets efficiently. It also includes advanced options for regularization and the use of temporal basis functions (e.g. Fourier sets). We illustrate the advantages of this approach for simulated data as well as data from a standard face recognition experiment. In addition to traditional and non-conventional EEG/ERP designs,unfoldcan also be applied to other overlapping physiological signals, such as pupillary or electrodermal responses. It is available as open-source software athttp://www.unfoldtoolbox.org.
Quantifying metacognitive thresholds using signal-detection theory
Authors: Sherman M.T. , Seth A.K. , Barrett A.B 
Published: July 2018

AbstractHow sure are we about what we know? Confidence, measured via self-report, is often interpreted as a subjective probabilistic estimate on having made a correct judgement. The neurocognitive mechanisms underlying the construction of confidence and the information incorporated into these judgements are of increasing interest. Investigating these mechanisms requires principled and practically applicable measures of confidence and metacognition. Unfortunately, current measures of confidence are subject to distortions from decision biases and task performance. Motivated by a recent signal-detection theoretic behavioural measure of metacognitive sensitivity, known as meta-ď, here we present a quantitative behavioural measure of confidence that is invariant to decision bias and task performance. This measure, which we call m-distance, captures in a principled way the propensity to report decisions with high (or low) confidence. Computational simulations demonstrate the robustness of m-distance to decision bias and task performance, as well as its behaviour under conditions of high and low metacognitive sensitivity and under dual-channel and hierarchical models of metacognition. The introduction of the m-distance measure will enhance systematic quantitative studies of the behavioural expression and neurocognitive basis of subjective confidence.
Mitogen-Activated Protein Kinase-Dependent Fiber-Type Regulation in Skeletal Muscle
Authors: Boyer Justin G. , Song Taejeong , Lee Donghoon , Fu Xing , Sadayappan Sakthivel , Molkentin Jeffery D. 
Published: July 2018

AbstractMitogen-activated protein kinases (MAPK) are conserved protein kinases that regulate a diverse array of cellular activities. Stress or mitogenic signals activate three primary branches of the greater MAPK cascade, each of which consists of a phosphorylation-dependent array of successively acting kinases. The extracellular signal-regulated kinase 1/2 (ERK1/2) branch is regulated by growth factory signaling at the cell membrane, leading to phosphorylation of the dual-specificity kinase MEK1, which is dedicated to ERK1/2 phosphorylation. Previous studies have established a link between MAPK activation and endurance exercise, but whether a single MAPK is responsible for establishing muscle metabolic fate is unclear. Using mouse genetics we observed that muscle-specific expression of a constitutively active MEK1 promotes greater ERK1/2 signaling that mediates fiber-type switching in mouse skeletal muscle to a slow, oxidative phenotype with type I myosin heavy chain expression. Induced expression of the activated MEK1 mutant using either a MyoD-Cre or myosin light chain-Cre strategy equally increased the number of type I fibers in skeletal muscle with significantly reduced size compared to controls. Moreover, activation of MEK1 in mature myofibers of an adult mouse using a transgene containing a tamoxifen inducible MerCreMer cDNA under the control of a skeletal α-actin promoter produced a similar phenotype of switching towards a slow-oxidative program. Physiologic assessment of mice with greater skeletal muscle slow-oxidative fibers showed enhanced metabolic activity and oxygen consumption with greater fatigue resistance of individual muscles. In summary, these results show that sustained MEK1-ERK1/2 activity in skeletal muscle produces a fast-to-slow fiber-type switch, suggesting that modulation of this signaling pathway may represent a therapeutic approach to enhance the long-term metabolic effectiveness of musclein vivo.
A Universal Probe Set for Targeted Sequencing of 353 Nuclear Genes from Any Flowering Plant Designed Using k-medoids Clustering
Authors: Johnson Matthew G. , Pokorny Lisa , Dodsworth Steven , Botigue Laura R. , Cowan Robyn S. , Devault Alison , Eiserhardt Wolf L. , Epitawalage Niroshini , Forest Félix , Kim Jan T. , Leebens-Mack James H. , Leitch Ilia J. , Maurin Olivier , Soltis Douglas E. , Soltis Pamela S. , Wong Gane Ka-Shu , Baker William J. , Wickett Norman J. 
Published: July 2018

AbstractSequencing of target-enriched libraries is an efficient and cost-effective method for obtaining DNA sequence data from hundreds of nuclear loci for phylogeny reconstruction. Much of the cost associated with developing targeted sequencing approaches is preliminary data needed for identifying orthologous loci for probe design. In plants, identifying orthologous loci has proven difficult due to a large number of whole-genome duplication events, especially in the angiosperms (flowering plants). We used multiple sequence alignments from over 600 angiosperms for 353 putatively single-copy protein-coding genes to design a set of targeted sequencing probes for phylogenetic studies of any angiosperm lineage. To maximize the phylogenetic potential of the probes while minimizing the cost of production, we introduce a k-medoids clustering approach to identify the minimum number of sequences necessary to represent each coding sequence in the final probe set. Using this method, five to 15 representative sequences were selected per orthologous locus, representing the sequence diversity of angiosperms more efficiently than if probes were designed using available sequenced genomes alone. To test our approximately 80,000 probes, we hybridized libraries from 42 species spanning all higher-order lineages of angiosperms, with a focus on taxa not present in the sequence alignments used to design the probes. Out of a possible 353 coding sequences, we recovered an average of 283 per species and at least 100 in all species. Differences among taxa in sequence recovery could not be explained by relatedness to the representative taxa selected for probe design, suggesting that there is no phylogenetic bias in the probe set. Our probe set, which targeted 260 kbp of coding sequence, achieved a median recovery of 137 kbp per taxon in coding regions, a maximum recovery of 250 kbp, and an additional median of 212 kbp per taxon in flanking non-coding regions across all species. These results suggest that the Angiosperms353 probe set described here is effective for any group of flowering plants and would be useful for phylogenetic studies from the species level to higher-order lineages, including all angiosperms.
Start-Stop Assembly: a functionally scarless DNA assembly system optimised for metabolic engineering
Authors: Taylor George M. , Mordaka Paweł M. , Heap John T. 
Published: July 2018

ABSTRACTDNA assembly allows individual DNA constructs or designed mixtures to be assembled quickly and reliably. Most methods are either: (i) Modular, easily scalable and suitable for combinatorial assembly, but leave undesirable ‘scar’ sequences; or (ii) bespoke (non-modular), scarless but less suitable for construction of combinatorial libraries. Both have limitations for metabolic engineering. To overcome this trade-off we devised Start-Stop Assembly, a multi-part, modular DNA assembly method which is both functionally scarless and suitable for combinatorial assembly. Crucially, 3 bp overhangs corresponding to start and stop codons are used to assemble coding sequences into expression units, avoiding scars at sensitive coding sequence boundaries. Building on this concept, a complete DNA assembly framework was designed and implemented, allowing assembly of up to 15 genes from up to 60 parts (or mixtures); monocistronic, operon-based or hybrid configurations; and a new streamlined assembly hierarchy minimising the number of vectors. Only one destination vector is required per organism, reflecting our optimisation of the system for metabolic engineering in diverse organisms. Metabolic engineering using Start-Stop Assembly was demonstrated by combinatorial assembly of carotenoid pathways inE. coliresulting in a wide range of carotenoid production and colony size phenotypes indicating the intended exploration of design space.GRAPHICAL ABSTRACT
Lateral Root Priming Synergystically Arises from Root Growth and Auxin Transport Dynamics
Authors: van den Berg Thea , ten Tusscher Kirsten H. 
Published: July 2018

AbstractThe root system is a major determinant of plant fitness. Its capacity to supply the plant with sufficient water and nutrients strongly depends on root system architecture, which arises from the repeated branching off of lateral roots. A critical first step in lateral root formation is priming, which prepatterns sites competent of forming a lateral root. Priming is characterized by temporal oscillations in auxin, auxin signalling and gene expression in the root meristem, which through growth become transformed into a spatially repetitive pattern of competent sites. Previous studies have demonstrated the importance of auxin synthesis, transport and perception for the amplitude of these oscillations and their chances of producing an actual competent site. Additionally, repeated lateral root cap apoptosis was demonstrated to be strongly correlated with repetitive lateral root priming. Intriguingly, no single mutation has been identified that fully abolishes lateral root formation, and thusfar the mechanism underlying oscillations has remained unknown. In this study, we investigated the impact of auxin reflux loop properties combined with root growth dynamics on priming, using a computational approach. To this end we developed a novel multi-scale root model incorporating a realistic root tip architecture and reflux loop properties as well as root growth dynamics. Excitingly, in this model, repetitive auxin elevations automatically emerge. First, we show that root tip architecture and reflux loop properties result in an auxin loading zone at the start of the elongation zone, with preferential auxin loading in narrow vasculature cells. Second, we demonstrate how meristematic root growth dynamics causes regular alternations in the sizes of cells arriving at the elongation zone, which subsequently become amplified during cell expansion. These cell size differences translate into differences in cellular auxin loading potential. Combined, these properties result in temporal and spatial fluctuations in auxin levels in vasculature and pericycle cells. Our model predicts that temporal priming frequency predominantly depends on cell cycle duration, while cell cycle duration together with meristem size control lateral root spacing.
Instability in 18S and 5.8S rDNA copy numbers and 18S:5.8S ratios in longitudinally-collected human DNA samples detected by monochrome multiplex qPCR
Authors: Ligerman Chris B. , Baird Lisa , Leppert Mark F. , Cawthon Richard M. 
Published: July 2018

AbstractRibosomal DNA encodes the structural RNAs of the ribosomes. Ribosomal DNA instability is a major contributor to aging in yeast, but its role in human aging and longevity is largely unknown. Human 45S rDNA encodes the 18S, 5.8S, and 28S ribosomal RNAs; ranges in copy number from 60 to > 800 per cell, distributed as tandem repeats along the short arms of the five acrocentric chromosomes (p13, p14, p15, p21, and p22); and is prone to frequent homologous and non-homologous recombination. Here we present two multiplex quantitative PCR assays, one for 18S rDNA normalized to the single copy gene beta-globin (HBB), and the other for 5.8S rDNA normalized to the single copy gene albumin (ALB). Longitudinally-collected pairs of DNAs from bloods drawn approximately 16 years apart from 40 females and 39 males, aged < 1 to 77 years at first blood draw, from the Utah CEPH families were assayed. Ribosomal DNA copy number varied over a four-fold range between subjects and increased approximately 14% across the lifespan. Longitudinal within-individual gains in copy number up to +68% and losses down to ‐25% were observed, while repeated assays of single DNA samples varied approximately +/- 10%. While 18S and 5.8S rDNA tended to be gained and lost together, the 18S:5.8S ratio was also unstable longitudinally, with increases up to +19% and decreases down to ‐15% observed. The 18S:5.8S ratio at second draw, relative to that at first draw, increased significantly across the lifespan in males, but not in females. To our knowledge this is the first report of within-individual longitudinal changes in the human 18S and 5.8S rDNA copy numbers. These assays will facilitate investigations of the biology of ribosomal RNA genes and their roles in health and disease across the human lifespan.
Mitochondrial genetics of exceptional longevity in multigeneration matrilineages
Authors: Kerber Richard A. , O’Brien Elizabeth , Munger Ron , Smith Ken R. , Cawthon Richard M. 
Published: July 2018

AbstractSome heritable mitochondrial DNA (mtDNA) sequence variants may slow the rate of aging. The European mitochondrial haplogroup K has previously been reported to be increased in frequency in centenarians and nonagenarians relative to its frequency in younger individuals, by standard case/control study designs. To select for mitochondrial genomes likely to carry beneficial genetic variants, we screened a large genealogical database (the Utah Population Database, UPDB) for mitochondrial lineages in which the frequency of survival past 90 years was significantly higher than in the general population, and also significantly higher than in close non-matrilineal relatives. We ranked 14,900 distinct matrilineages by the strength of their association with longevity. Full sequencing of the mtDNAs from a single individual from each of 53 matrilineages in the top longevity ranks and each of 374 control matrilineages from the general Utah population, followed by analyses of the mtDNA haplogroup frequencies, identified haplogroup K2 as the haplogroup most enriched in frequency by the longevity selection (Odds Ratio = 23.05). We then analyzed overall survival and cause-specific mortality in the several thousand individuals aged 40 years or older whose mtDNA genotypes could be imputed from the 374 fully sequenced control mtDNAs. In these control matrilineages Haplogroup K2 individuals (n=332) enjoyed a significantly lower all-cause mortality risk than the general population (HR=0.81), attributable in part to a significantly lower risk of dying from heart disease (HR=0.50), as well as lower (though not significantly lower) risks of dying from cancer (HR=0.72) and diabetes (HR=0.74). Furthermore, K2 was the only haplogroup in which mortality was reduced for all three of these common causes of death.