rudyvdbrink/CitationDatabase huggingface dataset:
The PAX-FOXO1s trigger fast trans-differentiation of chick embryonic neural cells into alveolar rhabdomyosarcoma with tissue invasive properties limited by S phase entry inhibition.
PLoS genetics, 2020

The chromosome translocations generating PAX3-FOXO1 and PAX7-FOXO1 chimeric proteins are the primary hallmarks of the paediatric fusion-positive alveolar subtype of Rhabdomyosarcoma (FP-RMS). Despite the ability of these transcription factors to remodel chromatin landscapes and promote the expression of tumour driver genes, they only inefficiently promote malignant transformation in vivo. The reason for this is unclear. To address this, we developed an in ovo model to follow the response of spinal cord progenitors to PAX-FOXO1s. Our data demonstrate that PAX-FOXO1s, but not wild-type PAX3 or PAX7, trigger the trans-differentiation of neural cells into FP-RMS-like cells with myogenic characteristics. In parallel, PAX-FOXO1s remodel the neural pseudo-stratified epithelium into a cohesive mesenchyme capable of tissue invasion. Surprisingly, expression of PAX-FOXO1s, similar to wild-type PAX3/7, reduce the levels of CDK-CYCLIN activity and increase the fraction of cells in G1. Introduction of CYCLIN D1 or MYCN overcomes this PAX-FOXO1-mediated cell cycle inhibition and promotes tumour growth. Together, our findings reveal a mechanism that can explain the apparent limited oncogenicity of PAX-FOXO1 fusion transcription factors. They are also consistent with certain clinical reports indicative of a neural origin of FP-RMS.
Pathway-selective adjustment of prefrontal-amygdala transmission during fear encoding.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014

Conditioned fear requires neural activity in the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC), structures that are densely interconnected at the synaptic level. Previous work has suggested that anatomical subdivisions of mPFC make distinct contributions to fear expression and inhibition, and that the functional output of this processing is relayed to the BLA complex. However, it remains unknown whether synaptic plasticity in mPFC-BLA networks contributes to fear memory encoding. Here we use optogenetics and ex vivo electrophysiology to reveal the impact of fear conditioning on BLA excitatory and feedforward inhibitory circuits formed by projections from infralimbic (IL) and prelimbic (PL) cortices. In naive mice, these pathways recruit equivalent excitation and feedforward inhibition in BLA principal neurons. However, fear learning leads to a selective decrease in inhibition:excitation balance in PL circuits that is attributable to a postsynaptic increase in AMPA receptor function. These data suggest a pathway-specific mechanism for fear memory encoding by adjustment of mPFC-BLA transmission. Upon reengagement of PL by conditioned cues, these modifications may serve to amplify emotional responses.
Summation of visual motion across eye movements reflects a nonspatial decision mechanism.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010

Human vision remains perceptually stable even though retinal inputs change rapidly with each eye movement. Although the neural basis of visual stability remains unknown, a recent psychophysical study pointed to the existence of visual feature-representations anchored in environmental rather than retinal coordinates (e.g., "spatiotopic" receptive fields; Melcher and Morrone, 2003). In that study, sensitivity to a moving stimulus presented after a saccadic eye movement was enhanced when preceded by another moving stimulus at the same spatial location before the saccade. The finding is consistent with spatiotopic sensory integration, but it could also have arisen from a probabilistic improvement in performance due to the presence of more than one motion signal for the perceptual decision. Here we show that this statistical advantage accounts completely for summation effects in this task. We first demonstrate that measurements of summation are confounded by noise related to an observer's uncertainty about motion onset times. When this uncertainty is minimized, comparable summation is observed regardless of whether two motion signals occupy the same or different locations in space, and whether they contain the same or opposite directions of motion. These results are incompatible with the tuning properties of motion-sensitive sensory neurons and provide no evidence for a spatiotopic representation of visual motion. Instead, summation in this context reflects a decision mechanism that uses abstract representations of sensory events to optimize choice behavior.
Human cortical θ during free exploration encodes space and predicts subsequent memory.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013

Spatial representations and walking speed in rodents are consistently related to the phase, frequency, and/or amplitude of θ rhythms in hippocampal local field potentials. However, neuropsychological studies in humans have emphasized the importance of parietal cortex for spatial navigation, and efforts to identify the electrophysiological signs of spatial navigation in humans have been stymied by the difficulty of recording during free exploration of complex environments. We resolved the recording problem and experimentally probed brain activity of human participants who were fully ambulant. On each of 2 d, electroencephalography was synchronized with head and body movement in 13 subjects freely navigating an extended virtual environment containing numerous unique objects. θ phase and amplitude recorded over parietal cortex were consistent when subjects walked through a particular spatial separation at widely separated times. This spatial displacement θ autocorrelation (STAcc) was quantified and found to be significant from 2 to 8 Hz within the environment. Similar autocorrelation analyses performed on an electrooculographic channel, used to measure eye movements, showed no significant spatial autocorrelations, ruling out eye movements as the source of STAcc. Strikingly, the strength of an individual's STAcc maps from day 1 significantly predicted object location recall success on day 2. θ was also significantly correlated with walking speed; however, this correlation appeared unrelated to STAcc and did not predict memory performance. This is the first demonstration of memory-related, spatial maps in humans generated during active spatial exploration.
A Bidirectional Neuromodulation Technology for Nerve Recording and Stimulation.
Micromachines, 2018

Electrical nerve recording and stimulation technologies are critically needed to monitor and modulate nerve activity to treat a variety of neurological diseases. However, current neuromodulation technologies presented in the literature or commercially available products cannot support simultaneous recording and stimulation on the same nerve. To solve this problem, a new bidirectional neuromodulation system-on-chip (SoC) is proposed in this paper, which includes a frequency-shaping neural recorder and a fully integrated neural stimulator with charge balancing capability. In addition, auxiliary circuits consisting of power management and data transmission circuits are designed to provide the necessary power supply for the SoC and the bidirectional data communication between the SoC and an external computer via a universal serial bus (USB) interface, respectively. To achieve sufficient low input noise for sensing nerve activity at a sub-10 μ V range, several noise reduction techniques are developed in the neural recorder. The designed SoC was fabricated in a 0.18 μ m high-voltage Bipolar CMOS DMOS (BCD) process technology that was described in a previous publication and it has been recently tested in animal experiments that demonstrate the proposed SoC is capable of achieving reliable and simultaneous electrical stimulation and recording on the same nerve.
Association of Peri-ictal Brainstem Posturing With Seizure Severity and Breathing Compromise in Patients With Generalized Convulsive Seizures.
Neurology, 2021

To analyze the association between peri-ictal brainstem posturing semiologies with postictal generalized electroencephalographic suppression (PGES) and breathing dysfunction in generalized convulsive seizures (GCS).
Auditory Exposure in the Neonatal Intensive Care Unit: Room Type and Other Predictors.
The Journal of pediatrics, 2017

To quantify early auditory exposures in the neonatal intensive care unit (NICU) and evaluate how these are related to medical and environmental factors. We hypothesized that there would be less auditory exposure in the NICU private room, compared with the open ward.
Understanding the Difference Between Standard Deviation and Standard Error of the Mean, and Knowing When to Use Which.
Indian journal of psychological medicine, 2020

Many authors are unsure of whether to present the mean along with the standard deviation (SD) or along with the standard error of the mean (SEM). The SD is a descriptive statistic that estimates the scatter of values around the sample mean; hence, the SD describes the sample. In contrast, the SEM is an estimate of how close the sample mean is to the population mean; it is an intermediate term in the calculation of the 95% confidence interval around the mean, and (where applicable) statistical significance; the SEM does not describe the sample. Therefore, the mean should always be accompanied by the SD when describing the sample. There are many reasons why the SEM continues to be reported, and it is argued that none of these is justifiable. In fact, presentation of SEMs may mislead readers into believing that the sample data are more precise than they actually are. Given that the standard error is not presented for other parameters, such as difference between means or proportions, and difference between proportions, it is suggested that presentation of SEM values can be done away with, altogether.
Differences in gut microbiome composition between persons with chronic schizophrenia and healthy comparison subjects.
Schizophrenia research, 2019

Intestinal microbiome and gut-brain axis have been receiving increasing attention for their role in the regulation of brain/behavior and possible biological basis of psychiatric disorders. Several recent clinical studies have linked the microbiome with neuropsychiatric conditions, although the literature on schizophrenia is quite limited. This study investigated gut microbiome composition in 50 individuals, including 25 persons with chronic schizophrenia and 25 demographically-matched non-psychiatric comparison subjects (NCs). Stool samples were collected and assayed using 16S rRNA sequencing of the V4 region. Examination of unweighted UniFrac and Bray-Curtis dissimilarity revealed significant community-level separation in microbiome composition between the two subject groups. At the phylum level, Proteobacteria were found to be relatively decreased in schizophrenia subjects compared to NCs. At the genus level, Anaerococcus was relatively increased in schizophrenia while Haemophilus, Sutterella, and Clostridium were decreased. Within individuals with schizophrenia, abundance of Ruminococcaceae was correlated with lower severity of negative symptoms; Bacteroides was associated with worse depressive symptoms; and Coprococcus was related to greater risk for developing coronary heart disease. Our findings provide evidence of altered gut microbial composition in persons with chronic schizophrenia and suggest a need for larger and longitudinal studies of microbiome in schizophrenia.
The neurobiology of brain and cognitive reserve: mental and physical activity as modulators of brain disorders.
Progress in neurobiology, 2009

The concept of 'cognitive reserve', and a broader theory of 'brain reserve', were originally proposed to help explain epidemiological data indicating that individuals who engaged in higher levels of mental and physical activity via education, occupation and recreation, were at lower risk of developing Alzheimer's disease and other forms of dementia. Subsequently, behavioral, cellular and molecular studies in animals (predominantly mice and rats) have revealed dramatic effects of environmental enrichment, which involves enhanced levels of sensory, cognitive and motor stimulation via housing in novel, complex environments. Furthermore, increasing levels of voluntary physical exercise, via ad libitum access to running wheels, can have significant effects on brain and behavior, thus informing the relative effects of mental and physical activity. More recently, animal models of brain disorders have been compared under environmentally stimulating and standard housing conditions, and this has provided new insights into environmental modulators and gene-environment interactions involved in pathogenesis. Here, we review animal studies that have investigated the effects of modifying mental and physical activity via experimental manipulations, and discuss their relevance to brain and cognitive reserve (BCR). Recent evidence suggests that the concept of BCR is not only relevant to brain aging, neurodegenerative diseases and dementia, but also to other neurological and psychiatric disorders. Understanding the cellular and molecular mechanisms mediating BCR may not only facilitate future strategies aimed at optimising healthy brain aging, but could also identify molecular targets for novel pharmacological approaches aimed at boosting BCR in 'at risk' and symptomatic individuals with various brain disorders.
In vivo evidence for decreased scyllo-inositol levels in the supplementary motor area of patients with Progressive Supranuclear Palsy: A proton MR spectroscopy study.
Parkinsonism & related disorders, 2019

Several structural and functional neuroimaging studies have shown that the Supplementary Motor Area (SMA) is affected by tau pathology in patients with Progressive Supranuclear Palsy (PSP). The aim of the study was to investigate the biochemical profile of SMA in PSP patients, using proton magnetic resonance spectroscopy (
Imaging fast neural traffic at fascicular level with electrical impedance tomography: proof of principle in rat sciatic nerve.
Journal of neural engineering, 2018

Understanding the coding of neural activity in nerve fascicles is a high priority in computational neuroscience, electroceutical autonomic nerve stimulation and functional electrical stimulation for treatment of paraplegia. Unfortunately, it has been little studied as no technique has yet been available to permit imaging of neuronal depolarization within fascicles in peripheral nerve.
Differential effects of oxytocin on social sensitivity in two distinct breeds of dogs (Canis familiaris).
Psychoneuroendocrinology, 2016

Dogs have been proven to show several human-analogue social behaviors, and recent research raises the possibility that the oxytocin system is related to these. However, despite dogs' general tendency to excel in the domain of social cognition, there is increasing evidence that dogs' ability to utilize human signals may vary with breed. Moreover, breeds may show differences not only in their 'inborn' communicative abilities, but also in their learning skills related to these. The aim of the present study was to explore breed differences and breed-specific effects of oxytocin administration on different aspects of social responsiveness. Dogs from two markedly different breeds, Border Collies (cooperative workers) and Siberian Huskies (independent workers) were tested. After having received intranasal administration of oxytocin or placebo, subjects participated in three behavioral tests measuring social responsiveness. Our results show that there are several behavioral differences between the two breeds and also that there are differential effects of the oxytocin treatment. Border Collies were in general more susceptible to the 'social' effects of oxytocin compared to Siberian Huskies: after oxytocin administration they (1) looked more at the experimenter in the 'Unreachable food' situation, (2) looked more at the owner and shifted their gaze more between the sound source and the owner in a potentially dangerous situation, and (3) looked longer at the experimenter's eyes in the 'Tolerance of prolonged eye contact' test. These findings suggest that selection for enhanced cooperative abilities, possibly complemented by the effect of different social environments the two breeds experience, affects dogs' performance in several behavioral tests and that the neurohormonal background differently modulates social behavior in different working breeds.
Forces exerted during microneurosurgery: a cadaver study.
The international journal of medical robotics + computer assisted surgery : MRCAS, 2014

A prerequisite for the successful design and use of robots in neurosurgery is knowledge of the forces exerted by surgeons during neurosurgical procedures. The aim of the present cadaver study was to measure the surgical instrument forces exerted during microneurosurgery.
An over-oxidized form of superoxide dismutase found in sporadic amyotrophic lateral sclerosis with bulbar onset shares a toxic mechanism with mutant SOD1.
Proceedings of the National Academy of Sciences of the United States of America, 2012

Recent studies suggest that Cu/Zn superoxide dismutase (SOD1) could be pathogenic in both familial and sporadic amyotrophic lateral sclerosis (ALS) through either inheritable or nonheritable modifications. The presence of a misfolded WT SOD1 in patients with sporadic ALS, along with the recently reported evidence that reducing SOD1 levels in astrocytes derived from sporadic patients inhibits astrocyte-mediated toxicity on motor neurons, suggest that WT SOD1 may acquire toxic properties similar to familial ALS-linked mutant SOD1, perhaps through posttranslational modifications. Using patients' lymphoblasts, we show here that indeed WT SOD1 is modified posttranslationally in sporadic ALS and is iper-oxidized (i.e., above baseline oxidation levels) in a subset of patients with bulbar onset. Derivatization analysis of oxidized carbonyl compounds performed on immunoprecipitated SOD1 identified an iper-oxidized SOD1 that recapitulates mutant SOD1-like properties and damages mitochondria by forming a toxic complex with mitochondrial Bcl-2. This study conclusively demonstrates the existence of an iper-oxidized SOD1 with toxic properties in patient-derived cells and identifies a common SOD1-dependent toxicity between mutant SOD1-linked familial ALS and a subset of sporadic ALS, providing an opportunity to develop biomarkers to subclassify ALS and devise SOD1-based therapies that go beyond the small group of patients with mutant SOD1.
Using real-time location devices (RTLD) to quantify off-unit adult intensive care registrar workload: a 1-year tertiary NHS hospital prospective observational study.
Journal of clinical monitoring and computing, 2020

UK national guidelines state deteriorating or at risk hospital ward patients should receive care from trained critical care outreach personnel. In most tertiary hospitals this involves a team led by an Intensive Care Unit (ICU) registrar. The ICU registrar must also review patients referred for possible ICU admission. These two responsibilities require work away from the ICU. To our knowledge the burden of this work has not been described, despite its importance in ICU workforce management and patient safety. A 12-month, prospective, observational study was carried out. The primary outcome measure was ICU registrar time spent on and off-unit. The study participants were senior and junior registrars on the rota of the 16 bed, Adult Intensive Care Unit at the John Radcliffe Hospital in Oxford. To measure their work patterns, this study used AeroScout 'T2' Real Time Location Device (RTLD) tags (Stanley Healthcare, Swindon). In our hospital, senior and junior ICU registrars spend roughly one-fifth of their time off-unit, half of which is spent in ED. This workload combines to leave the unit unattended at night up to 10% of the time. RTLDs provide a reliable, automated method for quantifying ICU registrar off-unit work patterns. This method may be adopted for quantifying other clinical staff work patterns in suitably equipped hospital environments.
A predictive coding account of bistable perception - a model-based fMRI study.
PLoS computational biology, 2017

In bistable vision, subjective perception wavers between two interpretations of a constant ambiguous stimulus. This dissociation between conscious perception and sensory stimulation has motivated various empirical studies on the neural correlates of bistable perception, but the neurocomputational mechanism behind endogenous perceptual transitions has remained elusive. Here, we recurred to a generic Bayesian framework of predictive coding and devised a model that casts endogenous perceptual transitions as a consequence of prediction errors emerging from residual evidence for the suppressed percept. Data simulations revealed close similarities between the model's predictions and key temporal characteristics of perceptual bistability, indicating that the model was able to reproduce bistable perception. Fitting the predictive coding model to behavioural data from an fMRI-experiment on bistable perception, we found a correlation across participants between the model parameter encoding perceptual stabilization and the behaviourally measured frequency of perceptual transitions, corroborating that the model successfully accounted for participants' perception. Formal model comparison with established models of bistable perception based on mutual inhibition and adaptation, noise or a combination of adaptation and noise was used for the validation of the predictive coding model against the established models. Most importantly, model-based analyses of the fMRI data revealed that prediction error time-courses derived from the predictive coding model correlated with neural signal time-courses in bilateral inferior frontal gyri and anterior insulae. Voxel-wise model selection indicated a superiority of the predictive coding model over conventional analysis approaches in explaining neural activity in these frontal areas, suggesting that frontal cortex encodes prediction errors that mediate endogenous perceptual transitions in bistable perception. Taken together, our current work provides a theoretical framework that allows for the analysis of behavioural and neural data using a predictive coding perspective on bistable perception. In this, our approach posits a crucial role of prediction error signalling for the resolution of perceptual ambiguities.
Sirolimus for progressive neurofibromatosis type 1-associated plexiform neurofibromas: a neurofibromatosis Clinical Trials Consortium phase II study.
Neuro-oncology, 2015

Plexiform neurofibromas (PNs) are benign peripheral nerve sheath tumors that arise in one-third of individuals with neurofibromatosis type 1 (NF1). They may cause significant disfigurement, compression of vital structures, neurologic dysfunction, and/or pain. Currently, the only effective management strategy is surgical resection. Converging evidence has demonstrated that the NF1 tumor suppressor protein, neurofibromin, negatively regulates activity in the mammalian Target of Rapamycin pathway.