rudyvdbrink/CitationDatabase huggingface dataset:
ROM1 contributes to phenotypic heterogeneity in PRPH2-associated retinal disease.
Human molecular genetics, 2020

Peripherin 2 (PRPH2) is a retina-specific tetraspanin protein essential for the formation of rod and cone photoreceptor outer segments (OS). Patients with mutations in PRPH2 exhibit severe retinal degeneration characterized by vast inter- and intra-familial phenotypic heterogeneity. To help understand contributors to this within-mutation disease variability, we asked whether the PRPH2 binding partner rod OS membrane protein 1 (ROM1) could serve as a phenotypic modifier. We utilized knockin and transgenic mouse models to evaluate the structural, functional and biochemical effects of eliminating one allele of Rom1 (Rom1+/-) in three different Prph2 models which mimic human disease: C213Y Prph2 (Prph2C/+), K153Del Prph2 (Prph2K/+) and R172W (Prph2R172W). Reducing Rom1 in the absence of Prph2 mutations (Rom1+/-) had no effect on retinal structure or function. However, the effects of reducing Rom1 in the presence of Prph2 mutations were highly variable. Prph2K/+/Rom1+/- mice had improved rod and cone function compared with Prph2K/+ as well as amelioration of K153Del-associated defects in PRPH2/ROM1 oligomerization. In contrast, Prph2R172W/Rom1+/- animals had worsened rod and cone function and exacerbated retinal degeneration compared with Prph2R172W animals. Removing one allele of Rom1 had no effect in Prph2C/+. Combined, our findings support a role for non-pathogenic ROM1 null variants in contributing to phenotypic variability in mutant PRPH2-associated retinal degeneration. Since the effects of Rom1 reduction are variable, our data suggest that this contribution is specific to the type of Prph2 mutation.
Leukocyte dynamics after intracerebral hemorrhage in a living patient reveal rapid adaptations to tissue milieu.
JCI insight, 2021

Intracerebral hemorrhage (ICH) is a devastating form of stroke with a high mortality rate and few treatment options. Discovery of therapeutic interventions has been slow given the challenges associated with studying acute injury in the human brain. Inflammation induced by exposure of brain tissue to blood appears to be a major part of brain tissue injury. Here, we longitudinally profiled blood and cerebral hematoma effluent from a patient enrolled in the Minimally Invasive Surgery with Thrombolysis in Intracerebral Hemorrhage Evacuation trial, offering a rare window into the local and systemic immune responses to acute brain injury. Using single-cell RNA-Seq (scRNA-Seq), this is the first report to our knowledge that characterized the local cellular response during ICH in the brain of a living patient at single-cell resolution. Our analysis revealed shifts in the activation states of myeloid and T cells in the brain over time, suggesting that leukocyte responses are dynamically reshaped by the hematoma microenvironment. Interestingly, the patient had an asymptomatic rebleed that our transcriptional data indicated occurred prior to detection by CT scan. This case highlights the rapid immune dynamics in the brain after ICH and suggests that sensitive methods such as scRNA-Seq would enable greater understanding of complex intracerebral events.
Liquid-Liquid Phase Separation in Neuronal Development and Synaptic Signaling.
Developmental cell, 2020

Formation of biomolecular condensates that are not enclosed by membranes via liquid-liquid phase separation (LLPS) is a general strategy that cells adopt to organize membraneless subcellular compartments for diverse functions. Neurons are highly polarized with elaborate branching and functional compartmentalization of their neurites, thus, raising additional demand for the proper subcellular localization of both membraneless and membrane-based organelles. Recent studies have provided evidence that several protein assemblies involved in the establishment of neuronal stem cell (NSC) polarity and in the asymmetric division of NSCs form distinct molecular condensates via LLPS. In synapses of adult neurons, molecular apparatuses controlling presynaptic neurotransmitter release and postsynaptic signaling transmission are also likely formed via LLPS. These molecular condensates, though not enclosed by lipid bilayers, directly associate with plasma membranes or membrane-based organelles, indicating that direct communication between membraneless and membrane-based organelles is a common theme in neurons and other types of cells.
Patterns of benzodiazepine underdosing in the Established Status Epilepticus Treatment Trial.
Epilepsia, 2021

This study was undertaken to describe patterns of benzodiazepine use as first-line treatment of status epilepticus (SE) and test the association of benzodiazepine doses with response to second-line agents in patients enrolled in the Established Status Epilepticus Treatment Trial (ESETT).
Patrikios syndrome in two patients with treatable flail-leg weakness.
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia, 2012

Flail-leg syndrome or lower limb diplegia is a form of motor neuron disease characterized by a slower progression rate. The differential diagnosis with motor neuropathy is important. We present two patients with a previous diagnosis of amyotrophic lateral sclerosis (ALS)-flail-leg syndrome, in whom neurophysiological studies suggested proximal conduction block. Both patients responded to immunomodulatory therapy, which suggested an immunologically mediated, treatable flail-leg syndrome phenotype. We stress the importance of fasciculations in the diagnosis of ALS, and the study of nerve root conduction in the differential diagnosis.
Mutations disrupting neuritogenesis genes confer risk for cerebral palsy.
Nature genetics, 2020

In addition to commonly associated environmental factors, genomic factors may cause cerebral palsy. We performed whole-exome sequencing of 250 parent-offspring trios, and observed enrichment of damaging de novo mutations in cerebral palsy cases. Eight genes had multiple damaging de novo mutations; of these, two (TUBA1A and CTNNB1) met genome-wide significance. We identified two novel monogenic etiologies, FBXO31 and RHOB, and showed that the RHOB mutation enhances active-state Rho effector binding while the FBXO31 mutation diminishes cyclin D levels. Candidate cerebral palsy risk genes overlapped with neurodevelopmental disorder genes. Network analyses identified enrichment of Rho GTPase, extracellular matrix, focal adhesion and cytoskeleton pathways. Cerebral palsy risk genes in enriched pathways were shown to regulate neuromotor function in a Drosophila reverse genetics screen. We estimate that 14% of cases could be attributed to an excess of damaging de novo or recessive variants. These findings provide evidence for genetically mediated dysregulation of early neuronal connectivity in cerebral palsy.
Proposition of a corrected measure of the Lawton instrumental activities of daily living score.
BMC geriatrics, 2021

We aimed to propose a correction of the Lawton instrumental activity of daily living (IADL) score to take into account the possibility to have never done some activities, and measured its agreement and reliability with the usual IADL score.
Rejecting impulsivity as a psychological construct: A theoretical, empirical, and sociocultural argument.
Psychological review, 2021

We demonstrate through theoretical, empirical, and sociocultural evidence that the concept of impulsivity fails the basic requirements of a psychological construct and should be rejected as such. Impulsivity (or impulsiveness) currently holds a central place in psychological theory, research, and clinical practice and is considered a multifaceted concept. However, impulsivity falls short of the theoretical specifications for hypothetical constructs by having meaning that is not compatible with psychometric, neuroscience, and clinical data. Psychometric findings indicate that impulsive traits and behaviors (e.g., response inhibition, delay discounting) are largely uncorrelated and fail to load onto a single, superordinate latent variable. Modern neuroscience has also failed to identify a specific and central neurobehavioral mechanism underlying impulsive behaviors and instead has found separate neurochemical systems and loci that contribute to a variety of impulsivity types. Clinically, these different impulsivity types show diverging and distinct pathways and processes relating to behavioral and psychosocial health. The predictive validity and sensitivity of impulsivity measures to pharmacological, behavioral, and cognitive interventions also vary based on the impulsivity type evaluated and clinical condition examined. Conflation of distinct personality and behavioral mechanisms under a single umbrella of impulsivity ultimately increases the likelihood of misunderstanding at a sociocultural level and facilitates misled hypothesizing and artificial inconsistencies for clinical translation. We strongly recommend that, based on this comprehensive evidence, psychological scientists and neuroscientists reject the language of impulsivity in favor of a specific focus on the several well-defined and empirically supported factors that impulsivity is purported to cover. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
The role of isochrony in speech perception in noise.
Scientific reports, 2020

The role of isochrony in speech-the hypothetical division of speech units into equal duration intervals-has been the subject of a long-standing debate. Current approaches in neurosciences have brought new perspectives in that debate through the theoretical framework of predictive coding and cortical oscillations. Here we assess the comparative roles of naturalness and isochrony in the intelligibility of speech in noise for French and English, two languages representative of two well-established contrastive rhythm classes. We show that both top-down predictions associated with the natural timing of speech and to a lesser extent bottom-up predictions associated with isochrony at a syllabic timescale improve intelligibility. We found a similar pattern of results for both languages, suggesting that temporal characterisation of speech from different rhythm classes could be unified around a single core speech unit, with neurophysiologically defined duration and linguistically anchored temporal location. Taken together, our results suggest that isochrony does not seem to be a main dimension of speech processing, but may be a consequence of neurobiological processing constraints, manifesting in behavioural performance and ultimately explaining why isochronous stimuli occupy a particular status in speech and human perception in general.
Elevated exosomal secretion of miR-124-3p from spinal neurons positively associates with disease severity in ALS.
Experimental neurology, 2020

MicroRNAs (miRs) are powerful regulators of CNS development and diseases. Plasma and cerebrospinal fluid (CSF) miRs have recently been implicated as potential new sources for biomarker development. Previously we showed that miR-124-3p, an essential miR for neuronal identity, is highly abundant in neuronal exosomes and its expression decreases in spinal cord of ALS model SOD1G93A mice. In the current study, we found a disease associated reduction of miR-124-3p levels specifically in spinal neurons using in situ hybridization. By employing our recently developed exosome reporter mice in combination with sciatic nerve injections, we observed an increased association of miR-124-3p with spinal motor neuron-derived exosomes in SOD1G93A mice, even at the pre-symptomatic stage. Sciatic nerve injection delivered miR-124-3p is also more frequently localized outside of spinal motor neurons in SOD1G93A mice. Subsequent quantitative analysis of miR-124-3p levels in CSF exosomes from ALS patients found a significant correlation between CSF exosomal miR-124-3p levels and disease stage (indicated by the ALSFRS-R score) of (male) ALS patients. These results provide preliminary evidence to support the potential use of CSF exosomal miR-124-3p as a disease stage indicator in ALS.
Establishing criteria for pediatric epilepsy surgery center levels of care: Report from the ILAE Pediatric Epilepsy Surgery Task Force.
Epilepsia, 2020

Presurgical evaluation and surgery in the pediatric age group are unique in challenges related to caring for the very young, range of etiologies, choice of appropriate investigations, and surgical procedures. Accepted standards that define the criteria for levels of presurgical evaluation and epilepsy surgery care do not exist. Through a modified Delphi process involving 61 centers with experience in pediatric epilepsy surgery across 20 countries, including low-middle- to high-income countries, we established consensus for two levels of care. Levels were based on age, etiology, complexity of presurgical evaluation, and surgical procedure. Competencies were assigned to the levels of care relating to personnel, technology, and facilities. Criteria were established when consensus was reached (≥75% agreement). Level 1 care consists of children age 9 years and older, with discrete lesions including hippocampal sclerosis, undergoing lobectomy or lesionectomy, preferably on the cerebral convexity and not close to eloquent cortex, by a team including a pediatric epileptologist, pediatric neurosurgeon, and pediatric neuroradiologist with access to video-electroencephalography and 1.5-T magnetic resonance imaging (MRI). Level 2 care, also encompassing Level 1 care, occurs across the age span and range of etiologies (including tuberous sclerosis complex, Sturge-Weber syndrome, hypothalamic hamartoma) associated with MRI lesions that may be ill-defined, multilobar, hemispheric, or multifocal, and includes children with normal MRI or foci in/abutting eloquent cortex. Available Level 2 technologies includes 3-T MRI, other advanced magnetic resonance technology including functional MRI and diffusion tensor imaging (tractography), positron emission tomography and/or single photon emission computed tomography, source localization with electroencephalography or magnetoencephalography, and the ability to perform intra- or extraoperative invasive monitoring and functional mapping, by a large multidisciplinary team with pediatric expertise in epilepsy, neurophysiology, neuroradiology, epilepsy neurosurgery, neuropsychology, anesthesia, neurocritical care, psychiatry, and nursing. Levels of care will improve safety and outcomes for pediatric epilepsy surgery and provide standards for personnel and technology to achieve these levels.
The lifecycle of the neuronal microtubule transport machinery.
Seminars in cell & developmental biology, 2020

Neurons are incredibly reliant on their cytoskeletal transport machinery. During development the cytoskeleton is the primary driver of growth and remodelling. In mature neurons the cytoskeleton keeps all components in a constant state of movement, allowing both supply of newly synthesized proteins to distal locations as well as the removal of aging proteins and organelles for recycling or degradation. This process is most challenging within axons as large distances need to be covered between synthesis and degradation, but it is essential as the lifetime of any single protein is much shorter than the lifetime of the neuron and its synapses. However, the transport machinery itself also has to be actively transported, recycled and degraded in order to localise properly and perform within neurons. This review provides an overview of the lifecycle of cytoskeletal components in neurons, focusing on its spatial organisation over time in the axon.
Anatomy and Function of the Primate Entorhinal Cortex.
Annual review of vision science, 2020

The entorhinal cortex (EC) is a critical element of the hippocampal formation located within the medial temporal lobe (MTL) in primates. The EC has historically received attention for being the primary mediator of cortical information going into and coming from the hippocampus proper. In this review, we highlight the significance of the EC as a major player in memory processing, along with other associated structures in the primate MTL. The complex, convergent topographies of cortical and subcortical input to the EC, combined with short-range intrinsic connectivity and the selective targeting of EC efferents to the hippocampus, provide evidence for subregional specialization and integration of information beyond what would be expected if this structure were a simple conduit of information for the hippocampus. Lesion studies of the EC provide evidence implicating this region as critical for memory and the flexible use of complex relational associations between experienced events. The physiology of this structure's constituent principal cells mirrors the complexity of its anatomy. EC neurons respond preferentially to aspects of memory-dependent paradigms including object, place, and time. EC neurons also show striking spatial representations as primates explore visual space, similar to those identified in rodents navigating physical space. In this review, we highlight the great strides that have been made toward furthering our understanding of the primate EC, and we identify paths forward for future experiments to provide additional insight into the role of this structure in learning and memory.
Distinct neural mechanisms for reading Arabic vs. verbal numbers: An ERP study.
The European journal of neuroscience, 2020

In this electroencephalogram/event-related potential (EEG/ERP) study, 16 volunteers were asked to compare the numerical equality of 360 pairs of multidigit numbers presented in Arabic or verbal format. Behavioural data showed faster and more accurate responses for digit targets, with a right hand/left hemisphere advantage only for verbal numerals. Occipito-temporal N1, peaking at approximately 180 ms, was strongly left-lateralized during verbal number processing and bilateral during digit processing. A LORETA (low-resolution electromagnetic tomography) source reconstruction performed at the N1 latency stage (155-185 ms) revealed greater brain activation during coding of Arabic than of verbal stimuli. Digit perceptual coding was associated with the activation of the right angular gyrus (rAG), the left fusiform gyrus (FG,BA37), and left and right superior and medial frontal areas. N1 sources for verbal numerals included the left FG (BA37), the precuneus (BA31), the parahippocampal area and a small right prefrontal activation. In addition, verbal numerals elicited a late frontocentral negativity, possibly reflecting stimulus unfamiliarity or complexity. Overall, the data suggest distinct mechanisms for number reading through ciphers (digits) or words. Information about quantity was accessed earlier and more accurately if numbers were in a nonlinguistic code. Indeed, it can be speculated that numerosity processing would involve circuits originally involved in processing space (i.e., rAG/rIPS).
Early discharge and rehabilitation in paediatric acquired brain and neurological injury: a transferable model.
Archives of disease in childhood. Education and practice edition, 2018

Children and young people who require rehabilitation following sustaining an acquired brain injury often experience long lengths of stay (LOS) and potentially poorer recovery outcomes due to limited access to therapy and little proactive discharge planning. After stakeholder enquiry we launched a new team and pathway with a primary aim to reduce LOS. The secondary aims were to pilot an outreach model, reduce cost and improve patient and family satisfaction. We achieved a significantly improved change in quality care with a financial gain and increased patient and family satisfaction.
Trophoblast inclusions in the human placenta: Identification, characterization, quantification, and interrelations of subtypes.
Placenta, 2021

We sought to examine placentas enriched for trophoblast inclusions (TIs) in order to characterize, quantify, and examine the interrelations between subtypes of TIs to better understand their underlying biology. We examined a cohort of 600 placentas from deliveries between 20
Internalized psychopathology dimensions in middle childhood: Cross-sectional and temporal associations.
Journal of anxiety disorders, 2020

Anxiety, depression, and obsessive-compulsive symptoms often onset during middle childhood and are major causes of disability in young individuals. A better understanding of how these symptoms are linked and unfold over time is important to develop valid etiological models and effective prevention and treatment.
The role of hepatocyte-specific staining in liver pathology.
Expert review of gastroenterology & hepatology, 2011

The advantages of MRI in the investigation of liver disease are well documented. Recent developments, including fast scanning technique and new MRI contrast agents, enable improved detection and characterization of focal liver lesions. Therefore, a definitive diagnosis can be made avoiding invasive procedures, such as liver biopsy. In this article, a special emphasis is placed on the clinical use of combined perfusional and hepatocyte-selective MRI contrast agents, which allow us to obtain morphologic and vascular information, owing to the dynamic study, as well as functional information, owing to the hepatocyte-selective phase of enhancement. Different clinical scenarios are considered in order to highlight the proper use of the hepatocyte phase to noninvasively characterize and detect different focal liver lesions.
Viscoelasticity of striatal brain areas reflects variations in body mass index of lean to overweight male adults.
Brain imaging and behavior, 2020

Although a variety of MRI studies investigated the link between body mass index (BMI) and parameters of neural gray matter (GM), the technique applied in most of these studies, voxel-based morphometry (VBM), focusses on the regional GM volume, a macroscopic tissue property. Thus, the studies were not able to exploit the BMI-related information contained in the GM microstructure although PET studies suggest that these factors are important. Here, we used cerebral MR Elastography (MRE) to characterize features of tissue microstructure by evaluating the propagation of shear waves applied to the skull and to assess local tissue viscoelasticity to test the link between this parameter and BMI in 22 lean to overweight males. Unlike the majority of existing MRE studies investigating neural viscoelasticity signals averaged across large brain regions, we used the viscoelasticity of individual voxels for our experiment. Our technique revealed a negative link between BMI and viscoelasticity of two areas of the striatal reward system, i.e., right putamen (t = -8.2; p
Functional atropine sensitive purinergic responses in the healthy rat bladder.
Autonomic neuroscience : basic & clinical, 2020

While acetylcholine is regarded to be the main directly contractile transmitter substance in the urinary bladder, interactions with other transmitters likely occur. Presently, the interplay between purinergic and cholinergic signalling was investigated to unravel the involvement of the urothelium and efferent neurons in the functionally important purinergically evoked release of acetylcholine in vitro. Functional characterization of receptor subtypes involved in this interplay was also performed. In vitro organ bath experiments with electrical field stimulation (EFS) or administration of agonist were performed in the absence and presence of the neurotoxin tetrodotoxin (TTX; 5 × 10