bluuebunny/crossref_metadata_2025_split huggingface dataset:
Applying Inter-rater Reliability to Improve Consistency in Classifying PhD Career Outcomes
Authors: Stayart C. Abigail , Brandt Patrick D. , Brown Abigail M. , Hutto Tamara , Layton Rebekah L. , Petrie Kimberly A. , Flores-Kim Emma N. , Peña Christopher G. , Fuhrmann Cynthia N. , Monsalve Gabriela C. 
Published: July 2018

ABSTRACTIn the past year, there has been an exciting groundswell of national efforts to integrate multiple taxonomies for the transparent dissemination and analysis of PhD career outcomes. In this study, we leveraged the unique resources of the Broadening Experiences in Scientific Training Consortium to examine the reliability of the three-tiered Unified Career Outcomes Taxonomy (UCOT v.2017) that was collaboratively developed at a meeting convened by Rescuing Biomedical Research in August 2017. Using an amended version of the UCOT v.2017 (UCOT v.2017-rev1) and a new Supplementary Guidance document, we categorized over 570 PhD alumni records from three different universities. Utilizing Krippendorff’s alpha to measure the interrater reliability from nine different individuals, we determined moderate to robust reproducibility within the first two tiers of the taxonomy (Workforce Sector and Career Type); however, the reliability for the third tier (Job Function) did not meet established standards. The team identified significant sources of error, revised category definitions, improved coder training materials and processes, and tested for improved reliability through coding 219 PhD alumni records using the revised taxonomy, UCOT v.2017-rev2. Our results revealed that the changes introduced in UCOT v.2017-rev2 improved inter-rater reliability in all three tiers, and either met or exceeded the acceptable standards for reliability. A final set of clarifications were made to UCOT v.2017-rev2, resulting in UCOT v.2018 and a Finalized Guidance document. Our findings underscore the importance of carefully developing guidance documents to aid coders in the reliable and consistent categorization of alumni career outcomes. We propose periodic assessment of the UCOT v.2018 to address the natural evolution of PhD careers in the global workforce. Ultimately, we hope that UCOT v.2018 will aid in the classification and dissemination of alumni career outcomes that is essential to educating trainees, institutions, and agencies about the diversity of career options for PhDs, and therein empower all PhDs to pursue the careers of their choice.
Integration and modularity in Procrustes shape data: is there a risk of spurious results?
Authors: Cardini Andrea 
Published: July 2018

AbstractStudies of morphological integration and modularity are a hot topic in evolutionary developmental biology. Geometric morphometrics using Procrustes methods offers powerful tools to quantitatively investigate morphological variation and, within this methodological framework, a number of different methods has been put forward to test if different regions within an anatomical structure behave like modules or,vice versa, are highly integrated and covary strongly. Although some exploratory techniques do not requirea priorimodules, commonly modules are specified in advance based on prior knowledge. Once this is done, most of the methods can be applied either by subdividing modules and performing separate Procrustes alignments or by splitting shape coordinates of anatomical landmarks into modules after a common superimposition. This second approach is particularly interesting because, contrary to completely separate blocks analyses, it preserves information on relative size and position of the putative modules. However, it also violates one of the fundamental assumptions on which Procrustes methods are based, which is that one should not analyse or interpret subsets of landmarks from a common superimposition, because the choice of that superimposition is purely based on statistical convenience (although with sound theoretical foundations) and not on a biological model of variance and covariance. In this study, I offer a first investigation of the effects of testing integration and modularity within a configuration of commonly superimposed landmarks using some of the most widely employed statistical methods available to this aim. When applied to simulated shapes with random non-modular isotropic variation, standard methods frequently recovered significant but arbitrary patterns of integration and modularity. Re-superimposing landmarks within each module, before testing integration or modularity, generally removes this artifact. The study, although preliminary and exploratory in nature, raises an important issue and indicates an avenue for future research. It also suggests that great caution should be exercised in the application and interpretation of findings from analyses of modularity and integration using Procrustes shape data, and that issues might be even more serious using some of the most common methods for handling the increasing popular semilandmark data used to analyse 2D outlines and 3D surfaces.
Multivariate Stochastic Volatility Modeling of Neural Data
Authors: Phan Tung D. , Wacther Jessica A. , Solomon Ethan A. , Kahana Michael J. 
Published: July 2018

AbstractBecause multivariate autoregressive models have failed to adequately account for the complexity of neural signals, researchers have predominantly relied on non-parametric methods when studying the relations between brain and behavior. Using medial temporal lobe (MTL) recordings from 96 neurosurgical patients, we show that time series models with volatility described by a multivariate stochastic latent-variable process and lagged interactions between signals in different brain regions provide new insights into the dynamics of brain function. The implied volatility inferred from our process positively correlates with high-frequency spectral activity, a signal that correlates with neuronal activity. We show that volatility features derived from our model can reliably decode memory states, and that this classifier performs as well as those using spectral features. Using the directional connections between brain regions during complex cognitive process provided by the model, we uncovered perirhinal-hippocampal desynchronization in the MTL regions that is associated with successful memory encoding.
Towards personalized computer simulation of breast cancer treatment: a multi-scale pharmacokinetic and pharmacodynamic model informed by multi-type patient data
Authors: Lai Xiaoran , Geier Oliver M , Fleischer Thomas , Garred Øystein , Borgen Elin , Funke Simon Wolfgang , Kumar Surendra , Elisabeth Rognes Marie , Seierstad Therese , Børresen-Dale Anne-Lise , Kristensen Vessela N. , Engebraaten Olav , Köhn-Luque Alvaro , Frigessi Arnoldo 
Published: July 2018

AbstractMathematical modeling and simulation have emerged as a potentially powerful, time and cost effective approach to personalized cancer treatment. The usefulness of mechanistic models to disentangle complex multi-scale cancer processes such as treatment response has been widely acknowledged. However, a major barrier for multi-scale models to predict the outcomes of therapeutic regimens in a particular patient lies in their initialization and parameterization which need to reflect individual cancer characteristics accurately. In this study we use multi-type routinely acquired measurements on a single breast tumor, including histopathology, magnetic resonance imaging, and molecular profiling to personalize parts of a complex multi-scale model of breast cancer treated with chemotherapeutic and anti-angiogenic agents. We model the dynamics of drugs in tissue (pharmacokinetics) and the corresponding effects on their targets (pharmacodynamics). We developed a open-source computer program that simulates cross-sections of tumors under 12-week therapy regimes and use it to individually reproduce and elucidate treatment outcomes of four patients. For two of the tumors that did not respond to therapy, we used model simulations to suggest alternative regimes, depending on their individual characteristics, with improved outcomes. We found that more frequent doses of chemothereapy reduce tumor burden in a low proliferative tumor while lower doses of anti-angiogenic agents improve drug penetration in a poorly perfused tumor. In addition to bridge multi-type clinical data to shed light on individual treatment outcomes, our approach identified a few tumor-related aspects that need to be clinically portraited better to allow for future model-driven personalized cancer therapy.
State-specific individualized functional networks form a predictive signature of brain state
Authors: Salehi Mehraveh , Karbasi Amin , Barron Daniel S. , Scheinost Dustin , Todd Constable R. 
Published: July 2018

AbstractThere is extensive evidence that human brain functional organization is dynamic, varying within a subject as the brain switches between tasks demands. This functional organization also varies across subjects, even when they are all engaged in similar tasks. Currently, we lack a comprehensive model that unifies the two dimensions of variation (brain state and subject). Using fMRI data obtained across multiple task-evoked and rest conditions (which we operationally define as brain states) and across multiple subjects, we develop a state-and subject-specific functional network parcellation (the assignment of nodes to networks). Our parcellation approach provides a measure of how node-to-network assignment (NNA) changes across states and across subjects. We demonstrate that the brain’s functional networks are not spatially fixed, but reconfigure with brain state. This reconfiguration is robust and reliable to such an extent that it can be used to predict brain state with accuracies up to 97%.
A genome-wide association study of mitochondrial DNA copy number in two population-based cohorts
Authors: Guyatt Anna L. , Brennan Rebecca R. , Burrows Kimberley , Guthrie Philip A. I. , Ascione Raimondo , Ring Susan , Gaunt Tom R. , Pyle Angela , Cordell Heather J. , Lawlor Debbie A. , Chinnery Patrick , Hudson Gavin , Rodriguez Santiago 
Published: July 2018

AbstractMitochondrial DNA copy number (mtDNA CN) exhibits interindividual and intercellular variation, but few genome-wide association studies (GWAS) of directly assayed mtDNA CN exist.We undertook a GWAS of qPCR-assayed mtDNA CN in the Avon Longitudinal Study of Parents and Children (ALSPAC), and the UK Blood Service (UKBS) cohort. After validating and harmonising data, 5461 ALSPAC mothers (16-43 years at mtDNA CN assay), and 1338 UKBS females (17-69 years) were included in a meta-analysis. Sensitivity analyses restricted to females with white cell-extracted DNA, and adjusted for estimated or assayed cell proportions. Associations were also explored in ALSPAC children, and UKBS males.A neutrophil-associated locus approached genome-wide significance (rs709591 [MED24], β[SE] −0.084 [0.016], p=1.54e-07) in the main meta-analysis of adult females. This association was concordant in magnitude and direction in UKBS males and ALSPAC neonates. SNPs in and around ABHD8 were associated with mtDNA CN in ALSPAC neonates (rs10424198, β[SE] 0.262 [0.034], p=1.40e-14), but not other study groups. In a meta-analysis of unrelated individuals (N=11253), we replicated a published association in TFAM β[SE] 0.046 [0.017], p=0.006), with an effect size much smaller than that observed in the replication analysis of a previous in silico GWAS.In a hypothesis-generating GWAS, we confirm an association between TFAM and mtDNA CN, and present putative loci requiring replication in much larger samples. We discuss the limitations of our work, in terms of measurement error and cellular heterogeneity, and highlight the need for larger studies to better understand nuclear genomic control of mtDNA copy number.
Ventromedial prefrontal cortex is not critical for behavior change without external reinforcement
Authors: Aridan Nadav , Pelletier Gabriel , Fellows Lesley K , Schonberg Tom 
Published: July 2018

AbstractCue-approach training (CAT) is a novel paradigm that has been shown to induce preference changes towards items without external reinforcements. In the task the mere association of a neutral cue and a speeded button response has been shown to induce a behavioral change lasting months. This paradigm includes several phases whereby after the training of individual items, behavior change is manifested through binary choices of items with similar initial values. Neuroimaging data have implicated the ventromedial prefrontal cortex (vmPFC) during the choice phase of this task. However, it still remains unclear what are the underlying neural mechanisms during training. Here, we sought to determine whether the ventromedial frontal cortex (VMF) is critical for the non-reinforced preference change induced by CAT. For this purpose, eleven participants with focal lesions involving the VMF and 30 healthy age-matched controls performed the CAT. We found that at the individual level, a similar proportion of VMF and healthy participants showed a preference shift following CAT. The VMF group performed similarly to the healthy age-matched control group in the ranking and training phases. As a group the healthy age-matched controls exhibited a behavior change, but the VMF participants as a group did not. We did not find an association between individual lesion patterns and performance in the task. We conclude that a fully intact VMF is not critical to induce non-externally reinforced preference change and suggest potential mechanisms for this novel type of behavioral change.
The architecture of functional lateralisation and its relationship to callosal connectivity in the human brain
Authors: Karolis VR , Corbetta M , Thiebaut de Schotten M 
Published: July 2018

AbstractFunctional lateralisation is a fundamental principle of the human brain. However, a comprehensive taxonomy of functional lateralisation and its organisation in the brain is missing. We report the first complete map of functional hemispheric asymmetries in the human brain, reveal its low dimensional structure, and its relationship with structural inter-hemispheric connectivity. Our results suggest that the lateralisation of brain functions is distributed along four functional axes: symbolic communication, perception/action, emotion, and decision-making, and that cortical regions showing asymmetries in task-evoked activity have reduced connections with the opposite hemisphere.
Large propulsion demands increase locomotor learning at the expense of step length symmetry
Authors: Sombric Carly J. , Calvert Jonathan S. , Torres-Oviedo Gelsy 
Published: July 2018

AbstractThere is a clinical interest in increasing the extent of locomotor learning induced by split-belt treadmills that move each leg at different speeds. However, factors facilitating locomotor learning are poorly understood. We hypothesized that augmenting the braking forces, rather than propulsion forces, experienced at the feet would increase locomotor adaptation and learning. To test this, forces were modulated during split-belt walking with distinct slopes: inclined (larger propulsion than braking), declined (larger braking than propulsion), and flat (similar propulsion and braking). These groups were compared using step length asymmetry, which is a clinically relevant measure robustly adapted on split-belt treadmills. Unexpectedly, the group with larger propulsion demands (i.e., the incline group) adapted faster and more, and had larger after-effects when the split-belt perturbation was removed. We also found that subjects who propelled more during baseline and experienced larger disruptions of propulsion forces in early adaptation exhibited greater after-effects, which further highlights the catalytic role of propulsion on locomotor learning. The relevance of mechanical demands on shaping our movements was also indicated by the steady state split-belt behavior, during which each group recovered their baseline leg orientation to meet leg-specific force demands at the expense of step length symmetry. Notably, the flat group was nearly symmetric, whereas the incline and decline group overshot and undershot symmetry, respectively. Taken together, our results indicate that forces propelling the body facilitate gait adaptation during split-belt walking. Therefore, interventions that increase propulsion demands may be a viable strategy for augmenting locomotor learning in individuals with hemiparesis.Key Points SummarySplit-belt walking (i.e., legs moving at different speeds) can induce locomotor learning and even improve hemiparetic gait, but little is known about how to facilitate this process.We investigated the effect of braking and propulsion forces on locomotor learning by testing young unimpaired subjects on the split-belt condition at different slopes (i.e., flat, decline, and incline), which distinctively modified these forces.Propulsion forces facilitated locomotor learning indicated by 1) greater adaptation and after-effects following split-belt walking of the inclined group, which experienced larger propulsion demands and 2) a positive correlation between individual after-effects and subject-specific propulsion during regular walking and initial steps in the split condition.Interestingly, incline and decline groups self-selected asymmetric step lengths at steady state in the split condition, challenging the prominent view that step length asymmetry is a biomarker for inefficient gait.Our results suggest that interventions augmenting propulsion demands could correct hemiparetic gait more effectively.
Working-memory disruption by task-irrelevant talkers depends on degree of talker familiarity
Authors: Kreitewolf Jens , Wöstmann Malte , Tune Sarah , Plöchl Michael , Obleser Jonas 
Published: July 2018

AbstractWhen listening, familiarity with an attended talker’s voice improves speech comprehension. Here, we instead investigated the effect of familiarity with a distracting talker. In an irrelevant-speech task, we assessed listeners’ working memory for the serial order of spoken digits when a task-irrelevant, distracting sentence was produced by either a familiar or an unfamiliar talker (with rare omissions of the task-irrelevant sentence). We tested two groups of listeners using the same experimental procedure. The first group were undergraduate psychology students (N=66) who had attended an introductory statistics course. Critically, each student had been taught by one of two course instructors, whose voices served as familiar and unfamiliar task-irrelevant talkers. The second group of listeners were family members and friends (N=20) who had known either one of the two talkers for more than ten years. Students, but not family members and friends, made more errors when the task-irrelevant talker was familiar versus unfamiliar. Interestingly, the effect of talker familiarity was not modulated by the presence of task-irrelevant speech: students experienced stronger working-memory disruption by a familiar talker irrespective of whether they heard a task-irrelevant sentence during memory retention or merely expected it. While previous work has shown that familiarity with an attended talker benefits speech comprehension, our findings indicate that familiarity with an ignored talker deteriorates working memory for target speech. The absence of this effect in family members and friends suggests that the degree of familiarity modulates memory disruption.
Requirements for efficient cotranscriptional regulatory switching in designed variants of the Bacillus subtilis pbuE adenine-responsive riboswitch
Authors: Drogalis Lea K. , Batey Robert T. 
Published: July 2018

AbstractRiboswitches, generally located in the 5’-leader of bacterial mRNAs, direct expression via a small molecule-dependent structural switch informing the transcriptional or translational machinery. While the structure and function of riboswitch effector-binding (aptamer) domains have been intensely studied, only recently have the requirements for efficient linkage between small molecule binding and the structural switch in the cellular and cotranscriptional context begun to be actively explored. To address this, we have performed a structure-guided mutagenic analysis of the B. subtilis pbuE adenine-responsive riboswitch, one of the simplest riboswitches containing a secondary structural switch. Using a cell-based fluorescent protein reporter assay to assess ligand-dependent regulatory activity in E. coli, these studies revealed previously unrecognized features of the riboswitch. Most importantly, it was found that local and long-range conformational dynamics in two regions of the aptamer domain have a significant effect upon efficient regulatory switching. Further, sequence features of the expression platform including the pre-aptamer leader sequence, a nucleation helix and a putative programmed pause have clear affects upon ligand-dependent regulation. Together, these data point to sequence and structural features distributed throughout the riboswitch required to strike a balance between rates of ligand binding, transcription and secondary structural switching via a strand exchange mechanism.
Conservation and Variations of BimodalHoxDGene Regulation During Tetrapod Limb Development
Authors: Yakushiji-Kaminatsui Nayuta , Lopez-Delisle Lucille , Bolt Christopher Chase , Andrey Guillaume , Beccari Leonardo , Duboule Denis 
Published: July 2018

ABSTRACTIn all tetrapods examined thus far, the development and patterning of limbs require the activation of gene members of theHoxDcluster. In mammals, they are controlled by a complex bimodal regulation, which controls first the proximal patterning, then the distal structure, allowing at the same time the formation of the wrist and ankle articulations. We analyzed the implementation of this regulatory mechanism in chicken, i.e. in an animal where large morphological differences exist between fore-and hindlimbs. We report that while this bimodal regulation is globally conserved between mammals and avian, some important modifications evolved at least between these two model systems, in particular regarding the activity of specific enhancers, the width of the TAD boundary separating the two regulations and the comparison between the forelimbversushindlimb regulatory controls. Some aspects of these regulations seem to be more conserved between chick and bats than with the mouse situation, which may relate to the extent to which forelimbs and hindlimbs of these various animals differ in their functions.AUTHOR SUMMARYThe morphologies of limbs largely vary either amongst tetrapod species, or even between the fore-and hindlimbs of the same animal species. In order to try and evaluate whether variations in the complex regulation ofHoxdgenes during limb development may contribute to these differences, we compared their transcriptional controls during both fore-and hindlimb buds development in either the mouse, or the chicken embryos. We combined transcriptome analyses with 3D genome conformation, histone modification profiles and mouse genetics and found that the regulatory mechanism underlyingHoxdgene expression was highly conserved in all contexts, though with some clear differences. For instance, we observed a variation in the TAD boundary interval between the mouse and the chick, as well as differences in the activity of a conserved enhancer element (CS93) situated within the T-DOM regulatory landscape. In contrast to the mouse, the chicken enhancer indeed displayed a stronger activity in fore-than in hindlimb buds, coinciding with the observed striking differences in the mRNA levels. Altogether, differences in both the timing and duration of TAD activities and in the width of their boundary may parallel the important decrease inHoxdgene transcription in chick hindlimbversusforelimb buds. These differences may also account for the slightly distinct regulatory strategies implemented by mammals and birds at this locus, potentially leading to substantial morphological variations.