bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pitfalls and Rewards for Implementing Ocular Motor Testing in Acute Vestibular Syndrome
Authors: Dumitrascu Oana M. , Torbati Sam , Tighiouart Mourad , Newman-Toker David E. , Song Shlee S. 
Published: February 2017

Objectives:
Isolated acute vestibular syndrome (iAVS) presentations to the emergency department (ED) pose management challenges, given the concerns for posterior circulation strokes. False-negative brain imaging may erroneously reassure clinicians, whereas HINTS-plus examination outperforms imaging to screen for strokes in iAVS. We studied the feasibility of implementing HINTS-plus testing in the ED, aiming to reduce neuroimaging in patients with iAVS.

Methods:
We launched an institutional Quality Improvement initiative, using DMAIC methodology. The outcome measures [proportion of iAVS subjects who had HINTS-plus examinations and underwent neuroimaging by computed tomography/magnetic resonance imaging (CT/MRI)] were compared before and after the established intervention. The intervention consisted of formal training for neurologists and emergency physicians on how to perform, document, and interpret HINTS-plus and implementation of novel iAVS management algorithm. Neuroimaging was not recommended if HINTS-plus suggested peripheral vestibular etiology. If a central process was suspected, brain MRI/MR angiogram was performed. Head CT was reserved only for thrombolytic time-window cases.

Results:
In the first 2 months postimplementation, HINTS-plus testing performance by neurologists increased from 0% to 80% (P=0.007), and by ED providers from 0% to 9.09% (P=0.367). Head CT scans were reduced from 18.5% to 6.25%. Brain MRI use was reduced from 51.8% to 31.2%. About 60% of the iAVS subjects were discharged from the ED; none were readmitted or had another ED presentation in the ensuing 30 days.

Conclusions:
Implementation of HINTS-plus evaluation in the ED is valuable and feasible for neurologists, but challenging for emergency physicians. Future studies should determine the “dose-response” curve of educational interventions.
“Phacing” a New Cause of Carotid Artery Dissection
Authors: Kulyk Caterina , Farina Filippo , Palmieri Anna , Viaro Federica , Causin Francesco , Laverda Anna M. , Baracchini Claudio 
Published: February 2017

Introduction:
Cervical arterial dissection (CAD) is a frequent and preventable cause of ischemic stroke in young patients. Several arguments suggest that genetic and developmental disorders could play an important role as part of a multifactorial predisposition of sporadic CAD.
We present 2 cases of young patients with CAD in association with cutaneous lesions and nonatherosclerotic multivessel arteriopathy.

Case Reports:
Our first patient was a 17-year-old white girl with sudden onset of weakness in her right upper limb. A magnetic resonance angiogram showed a severe stenosis along the extracranial and intracranial segments of the left internal carotid artery and the left middle cerebral artery. A complete ultrasound study confirmed the stenoses with characteristics suggestive of dissection.
Our second patient was a 7-year old white girl with a past history of left middle cerebral artery ischemic stroke. During the follow-up, an ultrasonographical examination discovered an asymptomatic dissection of the right internal carotid artery.
Both patients reported a history of large unilateral hemangiomas; in the first case a coloboma of the left optic disc and an aortic aneurysm were also present. These findings were suggestive of PHACE—a neurocutaneous developmental syndrome associated with constitutional arteriopathy of the major cerebral vessels.

Conclusions:
Noteworthy, among vascular abnormalities of PHACE, CADs have never been reported before. Our 2 cases suggest that CAD is an underecognized cerebrovascular manifestation of PHACE and it should be searched for in these patients. Ultrasound, being noninvasive and portable, is a useful tool for the assessment and follow-up of these patients.
Mechanisms of saccade suppression revealed in the anti-saccade task
Authors: Coe Brian C. , Munoz Douglas P. 
Published: February 2017

The anti-saccade task has emerged as an important tool for investigating the complex nature of voluntary behaviour. In this task, participants are instructed to suppress the natural response to look at a peripheral visual stimulus and look in the opposite direction instead. Analysis of saccadic reaction times (SRT: the time from stimulus appearance to the first saccade) and the frequency of direction errors (i.e. looking toward the stimulus) provide insight into saccade suppression mechanisms in the brain. Some direction errors are reflexive responses with very short SRTs (express latency saccades), while other direction errors are driven by automated responses and have longer SRTs. These different types of errors reveal that the anti-saccade task requires different forms of suppression, and neurophysiological experiments in macaques have revealed several potential mechanisms. At the start of an anti-saccade trial, pre-emptive top-down inhibition of saccade generating neurons in the frontal eye fields and superior colliculus must be present before the stimulus appears to prevent express latency direction errors. After the stimulus appears, voluntary anti-saccade commands must compete with, and override, automated visually initiated saccade commands to prevent longer latency direction errors. The frequencies of these types of direction errors, as well as SRTs, change throughout the lifespan and reveal time courses for development, maturation, and ageing. Additionally, patients diagnosed with a variety of neurological and/or psychiatric disorders affecting the frontal lobes and/or basal ganglia produce markedly different SRT distributions and types of direction errors, which highlight specific deficits in saccade suppression and inhibitory control. The anti-saccade task therefore provides valuable insight into the neural mechanisms of saccade suppression and is a valuable tool in a clinical setting.
This article is part of the themed issue ‘Movement suppression: brain mechanisms for stopping and stillness’.
Models of inhibitory control
Authors: Schall Jeffrey D. , Palmeri Thomas J. , Logan Gordon D. 
Published: February 2017

We survey models of response inhibition having different degrees of mathematical, computational and neurobiological specificity and generality. The independent race model accounts for performance of the stop-signal or countermanding task in terms of a race between GO and STOP processes with stochastic finishing times. This model affords insights into neurophysiological mechanisms that are reviewed by other authors in this volume. The formal link between the abstract GO and STOP processes and instantiating neural processes is articulated through interactive race models consisting of stochastic accumulator GO and STOP units. This class of model provides quantitative accounts of countermanding performance and replicates the dynamics of neural activity producing that performance. The interactive race can be instantiated in a network of biophysically plausible spiking excitatory and inhibitory units. Other models seek to account for interactions between units in frontal cortex, basal ganglia and superior colliculus. The strengths, weaknesses and relationships of the different models will be considered. We will conclude with a brief survey of alternative modelling approaches and a summary of problems to be addressed including accounting for differences across effectors, species, individuals, task conditions and clinical deficits.
This article is part of the themed issue ‘Movement suppression: brain mechanisms for stopping and stillness’.
Inhibitory dysfunction contributes to some of the motor and non-motor symptoms of movement disorders and psychiatric disorders
Authors: Jahanshahi Marjan , Rothwell John C. 
Published: February 2017

Recently, it has been proposed that similar to goal-directed and habitual action mediated by the fronto-striatal circuits, the fronto-striato-subthalamic-pallidal-thalamo-cortical network may also mediate goal-directed and habitual (automatic) inhibition in both the motor and non-motor domains. Within this framework, some of the clinical manifestations of Parkinson's disease, dystonia, Tourette syndrome and obsessive–compulsive disorder can be considered to represent an imbalance between goal-directed and habitual action and inhibition. It is possible that surgical interventions targeting the basal ganglia nuclei, such as deep brain stimulation of the subthalamic nucleus or the internal segment of the globus pallidus, improve these disorders by restoring a functional balance between facilitation and inhibition in the fronto-striatal networks. These proposals require investigation in future studies.
This article is part of the themed issue ‘Movement suppression: brain mechanisms for stopping and stillness’.
Unchanging visions: the effects and limitations of ocular stillness
Authors: Martinez-Conde Susana , Macknik Stephen L. 
Published: February 2017

Scientists have pondered the perceptual effects of ocular motion, and those of its counterpart, ocular stillness, for over 200 years. The unremitting ‘trembling of the eye’ that occurs even during gaze fixation was first noted by Jurin in 1738. In 1794, Erasmus Darwin documented that gaze fixation produces perceptual fading, a phenomenon rediscovered in 1804 by Ignaz Paul Vital Troxler. Studies in the twentieth century established that Jurin's ‘eye trembling’ consisted of three main types of ‘fixational’ eye movements, now called microsaccades (or fixational saccades), drifts and tremor. Yet, owing to the constant and minute nature of these motions, the study of their perceptual and physiological consequences has met significant technological challenges. Studies starting in the 1950s and continuing in the present have attempted to study vision during retinal stabilization—a technique that consists on shifting any and all visual stimuli presented to the eye in such a way as to nullify all concurrent eye movements—providing a tantalizing glimpse of vision in the absence of change. No research to date has achieved perfect retinal stabilization, however, and so other work has devised substitute ways to counteract eye motion, such as by studying the perception of afterimages or of the entoptic images formed by retinal vessels, which are completely stable with respect to the eye. Yet other research has taken the alternative tack to control eye motion by behavioural instruction to fix one's gaze or to keep one's gaze still, during concurrent physiological and/or psychophysical measurements. Here, we review the existing data—from historical and contemporary studies that have aimed to nullify or minimize eye motion—on the perceptual and physiological consequences of perfect versus imperfect fixation. We also discuss the accuracy, quality and stability of ocular fixation, and the bottom–up and top–down influences that affect fixation behaviour.
This article is part of the themed issue ‘Movement suppression: brain mechanisms for stopping and stillness’.
Neuronal control of fixation and fixational eye movements
Authors: Krauzlis Richard J. , Goffart Laurent , Hafed Ziad M. 
Published: February 2017

Ocular fixation is a dynamic process that is actively controlled by many of the same brain structures involved in the control of eye movements, including the superior colliculus, cerebellum and reticular formation. In this article, we review several aspects of this active control. First, the decision to move the eyes not only depends on target-related signals from the peripheral visual field, but also on signals from the currently fixated target at the fovea, and involves mechanisms that are shared between saccades and smooth pursuit. Second, eye position during fixation is actively controlled and depends on bilateral activity in the superior colliculi and medio-posterior cerebellum; disruption of activity in these circuits causes systematic deviations in eye position during both fixation and smooth pursuit eye movements. Third, the eyes are not completely still during fixation but make continuous miniature movements, including ocular drift and microsaccades, which are controlled by the same neuronal mechanisms that generate larger saccades. Finally, fixational eye movements have large effects on visual perception. Ocular drift transforms the visual input in ways that increase spatial acuity; microsaccades not only improve vision by relocating the fovea but also cause momentary changes in vision analogous to those caused by larger saccades.This article is part of the themed issue ‘Movement suppression: brain mechanisms for stopping and stillness’.
Freeze for action: neurobiological mechanisms in animal and human freezing
Authors: Roelofs Karin 
Published: February 2017

Upon increasing levels of threat, animals activate qualitatively different defensive modes, including freezing and active fight-or-flight reactions. Whereas freezing is a form of behavioural inhibition accompanied by parasympathetically dominated heart rate deceleration, fight-or-flight reactions are associated with sympathetically driven heart rate acceleration. Despite the potential relevance of freezing for human stress-coping, its phenomenology and neurobiological underpinnings remain largely unexplored in humans. Studies in rodents have shown that freezing depends on amygdala projections to the brainstem (periaqueductal grey). Recent neuroimaging studies in humans have indicated that similar brain regions may be involved in human freezing. In addition, flexibly shifting between freezing and active defensive modes is critical for adequate stress-coping and relies on fronto-amygdala connections. This review paper presents a model detailing these neural mechanisms involved in freezing and the shift to fight-or-flight action. Freezing is not a passive state but rather a parasympathetic brake on the motor system, relevant to perception and action preparation. Study of these defensive responses in humans may advance insights into human stress-related psychopathologies characterized by rigidity in behavioural stress reactions. The paper therefore concludes with a research agenda to stimulate translational animal–human research in this emerging field of human defensive stress responses.
This article is part of the themed issue ‘Movement suppression: brain mechanisms for stopping and stillness’.
And the best task is …? Using Task potency to infer task specificity
Authors: Chauvin Roselyne J. , Mennes Maarten , Llera Alberto , Buitelaar Jan K. , Beckmann Christian F. 
Published: February 2017

AbstractWhen an individual engages in a task, the associated evoked activities build upon already ongoing activity, itself shaped by an underlying functional connectivity baseline (Fox et al., 2009; Smith et al., 2009; Tavor et al., 2016). To facilitate understanding the building blocks of cognition we incorporate the idea that task-induced functional connectivity modulation with respect to its underlying resting state functional connectivity is task-specific. Here, we introduce a framework incorporatingtask potency, providing direct access to task-specificity through enabling direct comparison between task paradigms. In particular, to study functional connectivity modulations related to cognitive involvement in a task we define task potency as the amplitude of connectivity modulations away from the brain’s baseline functional connectivity architecture as observed during a resting state acquisition. We demonstrate the use of our framework by comparing three tasks (visuo-spatial working memory, reward processing, and stop signal task) available within a large cohort. Using task potency, we demonstrate that cognitive operations are supported by a common baseline of within-network interactions, supplemented by connections between large-scale networks in order to solve a specific task.Highlights-Task potency framework defines modulation of functional connectivity away from baseline resting state-More within-than between-network modulations are induced by task performance-Between-network modulations are task-specific-Edges modulated by multiple tasks are mostly within-network-The task potency can be used to define the most potent task
Dynamics of ASC speck formation during skin inflammatory responsesin vivo
Authors: Kuri Paola , Schieber Nicole L. , Thumberger Thomas , Wittbrodt Joachim , Schwab Yannick , Leptin Maria 
Published: February 2017

AbstractActivated danger or pathogen sensors trigger assembly of the inflammasome adaptor ASC into specks, large signalling platforms considered hallmarks of inflammasome activation. Because a lack ofin vivotools has prevented the study of endogenous ASC dynamics, we generated a live ASC reporter through CRISPR/Cas9 tagging of the endogenous gene in zebrafish. We see strong ASC expression in the skin and other epithelia that act as barriers to insult. A toxic stimulus triggered speck formation and rapid pyroptosis in keratinocytesin vivo. Macrophages engulfed and digested this speck-containing pyroptotic debris. A 3D ultrastructural reconstruction based on CLEM ofin vivoassembled specks revealed a compact network of highly intercrossed filaments, whereas PYD or CARD alone formed filamentous aggregates. The effector caspase is recruited through PYD, whose overexpression induced pyroptosis, but after substantial delay. Therefore, formation of a single compact speck and rapid cell death inductionin vivorequires full-length ASC.One Sentence SummaryWith a new endogenous ASC real-time reporter we characterize speck dynamicsin vivoas well as the concomitant pyroptosis speck formation causes in keratinocytes.
STPGA: Selection of training populations with a genetic algorithm
Authors: Akdemir Deniz 
Published: February 2017

AbstractOptimal subset selection is an important task that has numerous algorithms designed for it and has many application areas. STPGA contains a special genetic algorithm supplemented with a tabu memory property (that keeps track of previously tried solutions and their fitness for a number of iterations), and with a regression of the fitness of the solutions on their coding that is used to form the ideal estimated solution (look ahead property) to search for solutions of generic optimal subset selection problems. I have initially developed the programs for the specific problem of selecting training populations for genomic prediction or association problems, therefore I give discussion of the theory behind optimal design of experiments to explain the default optimization criteria in STPGA, and illustrate the use of the programs in this endeavor. Nevertheless, I have picked a few other areas of application: supervised and unsupervised variable selection based on kernel alignment, supervised variable selection with design criteria, influential observation identification for regression, solving mixed integer quadratic optimization problems, balancing gains and inbreeding in a breeding population. Some of these illustrations pertain new statistical approaches.
Functional genomic analysis of corals from natural CO2-seeps reveals core molecular responses involved in acclimatization to ocean acidification
Authors: Kenkel CD , Moya A , Strahl J , Humphrey C , Bay LK 
Published: February 2017

ABSTRACTLittle is known about the potential for acclimatization or adaptation of corals to ocean acidification and even less about the molecular mechanisms underpinning these processes. Here we examine global gene expression patterns in corals and their intracellular algal symbionts from two replicate population pairs in Papua New Guinea that have undergone long-term acclimatization to natural variation in pCO2. In the coral host, only 61 genes were differentially expressed in response to pCO2environment, but the pattern of change was highly consistent between replicate populations, likely reflecting the core expression homeostasis response to ocean acidification. Functional annotations highlight lipid metabolism and a change in the stress response capacity of corals as a key part of this process. Specifically, constitutive downregulation of molecular chaperones was observed, which may impact response to combined climate-change related stressors. Elevated CO2has been hypothesized to benefit photosynthetic organisms but expression changes ofin hospite Symbiodiniumin response to acidification were greater and less consistent among reef populations. This population-specific response suggests hosts may need to adapt not only to an acidified environment, but also to changes in theirSymbiodiniumpopulations that may not be consistent among environments. This process adds another challenging dimension to the physiological process of coping with climate change.
Understanding inhibitor resistance in Mps1 kinase through novel biophysical assays and structures
Authors: Hiruma Yoshitaka , Koch Andre , Hazraty Nazila , Tsakou Foteini , Medema René H. , Joosten Robbie P. , Perrakis Anastassis 
Published: February 2017

AbstractMonopolar spindle 1 (Mps1/TTK) is a protein kinase essential in mitotic checkpoint signalling, preventing anaphase until all chromosomes are properly attached to spindle microtubules. Mps1 has emerged as a potential target for cancer therapy, and a variety of compounds have been developed to inhibit its kinase activity. Mutations in the catalytic domain of Mps1 that give rise to inhibitor resistance, but retain catalytic activity and do not display cross-resistance to other Mps1 inhibitors, have been described. Here we characterize the interactions of two such mutants, Mps1 C604Y and C604W, which raise resistance to two closely related compounds, NMS-P715 and its derivative Cpd-5, but not to the well-characterised Mps1 inhibitor, reversine. We show that estimates of the IC50(employing a novel specific and efficient assay that utilizes a fluorescently labelled substrate) and of the binding affinity (KD) indicate that in both mutants, Cpd-5 should be better tolerated than the closely related NMS-P715. To gain further insight, we determined the crystal structure of the Mps1 kinase mutants bound to Cpd-5 and NMS-P715, and compare the binding modes of Cpd-5, NMS-P715 and reversine. The difference in steric hindrance between Tyr/Trp604 and the trifluoromethoxy moiety of NMS-P715, the methoxy moiety of Cpd-5, and complete absence of such a group in reversine, account for differences we observein vitro. Our analysis enforces the notion that inhibitors targeting Mps1 drug-resistant mutations can emerge as a feasible intervention strategy based on existing scaffolds, if the clinical need arises.Summary statementThe inhibition of specific Mps1 kinase inhibitors towards the wild-type protein and inhibitor-resistant mutants is explained by a novel specific activity assay, biophysical characterisation, and X-ray structures.AbbreviationsATPadenosine triphosphateBub1/Bub3budding uninhibited by benzimidazoles 1 / budding uninhibited by benzimidazoles 3Cpd-5Compound-5 (N-(2,6-diethylphenyl)-8-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide)FPfluorescence polarizationGSTGlutathione S-transferaseIC50half maximal inhibitory concentrationKDdissociation constantΔGcalccalculated Gibbs energy difference for ligand bindingKNL1kinetochore null protein 1KPi(inorganic) potassium phosphateMps1monopolar spindle 1MSTmicroscale thermophoresisNMS-P715N-(2,6-diethylphenyl)-1-methyl-8-({4-[(1-methylpiperidin-4-yl)carbamoyl]-2-(trifluoromethoxy)phenyl}amino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamideTMRtetramethylrhodamineWTwild-type