rudyvdbrink/CitationDatabase huggingface dataset:
Transcriptome analysis of a ring chromosome 20 patient cohort.
Epilepsia, 2021

Ring chromosomes occur when the ends of normally rod-shaped chromosomes fuse. In ring chromosome 20 (ring 20), intellectual disability and epilepsy are usually present, even if there is no deleted coding material; the mechanism by which individuals with complete ring chromosomes develop seizures and other phenotypic abnormalities is not understood. We investigated altered gene transcription as a contributing factor by performing RNA-sequencing (RNA-seq) analysis on blood from seven patients with ring 20, and 11 first-degree relatives (all parents). Geographic analysis did not identify altered expression in peritelomeric or other specific chromosome 20 regions. RNA-seq analysis revealed 97 genes potentially differentially expressed in ring 20 patients. These included one epilepsy gene, NPRL3, but this finding was not confirmed on reverse transcription Droplet Digital polymerase chain reaction analysis. Molecular studies of structural chromosomal anomalies such as ring chromosome are challenging and often difficult to interpret because many patients are mosaic, and there may be genome-wide chromosomal instability affecting gene expression. Our findings nevertheless suggest that peritelomeric altered transcription is not the likely pathogenic mechanism in ring 20. Underlying genetic mechanisms are likely complex and may involve differential expression of many genes, the majority of which may not be located on chromosome 20.
Found in translation? Commentary on a BJP themed issue about animal models in neuropsychiatry research.
British journal of pharmacology, 2014

This themed issue of Br J Pharmacol is dedicated to the utility and needs of animal models in psychiatry research. The following articles document strengths and weaknesses, indicate areas where better models are sorely needed and provide examples where pharmacological studies may result in mechanistic breakthrough and aid in drug development. In addition, complicating factors both in disease and treatment strategies are canvassed, such as sex differences, genetic and environmental influences. While not exhaustive, the intention was to use a number of exemplars to stimulate discussion around how animal models can aid in improving our understanding and treatment of many devastating conditions.
Heterogeneous release probabilities and activity-dependent short-term synaptic depression.
Communicative & integrative biology, 2011

Synaptic transmission is a major mechanism by which neurons communicate with each other. Basic steps in neurotransmitter release are similar in all synapses. However, many properties of release vary between synapses and reflect specific structural and functional requirements, endowing synapses with specialized functions. Recently, Gelman et al.1 described properties of release and short-term depression at specialized nicotinic synapses in the brainstem of goldfish, Carassius auratus (Linnaeus). These axo-axonic synapses between the Mauthner cell collaterals and their targets, cranial relay neurons (CRNs), exhibit strong short-term depression, even at stimulation frequencies as low as 0.33 Hz. In short, amplitudes of post-synaptic responses, evoked by presynaptic trains of action potentials, were depressed with a time course approximated by a sum of two exponential functions. Initially, fast depression reduced the amplitude of EPSP(2) (response after the second stimulus), to less than 50% of EPSP(1) (response after the first stimulus). This was followed by a slow component of depression that produced an additional 10-30% amplitude reduction over a time-span of tens to hundreds of seconds. Interestingly, depressed EPSPs exhibited longer latencies than that of the "undepressed" EPSP1. Additionally, fast and slow calcium chelators (BAPTA and EGTA), injected pre-synaptically, were equally potent in reducing release. These data are consistent with a previously proposed general mechanism that assumes a change in release probability after the initial release. However, in an alternative interpretation the results could be coherently explained by postulating two releasable pools of vesicles, with high and low release probabilities, and a generally accepted depletion scheme. This latter interpretation will be discussed in this article.
Atypical and inflexible visual encoding in autism spectrum disorder.
PLoS biology, 2021

Encoding, which involves translating sensory information into neural representations, is a critical first step in the sensory-perceptual pathway. Using a visual orientation task, a new study found both lower encoding capacity and less flexible adaptation in people with autism spectrum disorder.
[Suicidal risk prevention in schizophrenia: Importance of family psychoeducation].
L'Encephale, 2020

Although mortality by suicide in schizophrenia seems to have decreased in some countries over the last 30 years, it remains much higher than in the general population. Studies have shown this risk to impact around 5% of patients, corresponding to a risk almost 2.5 times higher than in the general population. Family psychoeducation in schizophrenia has been demonstrated to lead to symptom reductions and to an improvement of the quality of life, two factors that should contribute to decreasing the suicidal risk. Therefore, if families attend an efficient psychoeducation program, we can expect a decrease in the patient suicidal risk. Attending a family psychoeducation program at the beginning of the disease would also be associated with a stronger preventive effect on suicidal mortality. The objective of this study is to describe the suicide attempt rate of patients who suffer from schizophrenia before and one year after one of their relatives participated to the family psychoeducation program Profamille.
General population ZBTB18 missense variants influence DNA binding and transcriptional regulation.
Human mutation, 2020

Genetic variation of the multi-zinc finger BTB domain transcription factor ZBTB18 can cause a spectrum of human neurodevelopmental disorders, but the underlying mechanisms are not well understood. Recently, we reported that pathogenic, de novo ZBTB18 missense mutations alter its DNA-binding specificity and gene regulatory functions, leading to human neurodevelopmental disease. However, the functional impact of the general population ZBTB18 missense variants is unknown. Here, we investigated such variants documented in the Genome Aggregation Database (gnomAD) to discover that ZBTB gene family members are intolerant to loss-of-function and missense mutations, but not synonymous mutations. We studied ZBTB18 as a protein-DNA complex to find that general population missense variants are rare, and disproportionately map to non-DNA-contact residues, in contrast to the majority of disease-associated variants that map to DNA-contact residues, essential to motif binding. We studied a selection of variants (n = 12), which spans the multi-zinc finger region to find 58.3% (7/12) of variants displayed altered DNA binding, 41.6% (5/12) exhibited altered transcriptional activity in a luciferase reporter assay, 33.3% (4/12) exhibited altered DNA binding and transcriptional activity, whereas 33.3% (4/12) displayed a negligible functional impact. Our results demonstrate that general population variants, while rare, can influence ZBTB18 function, with potential consequences for neurodevelopment, homeostasis, and disease.
Rat cardiomyocyte H9c2(2-1)-based sulforhodamine B assay as a promising in vitro method to assess the biological component of effluent toxicity.
Journal of environmental sciences (China), 2020

The treatment of wastewaters is crucial to maintain the ecological status of receiving waters, and thereby guarantee the protection of aquatic life and human health. Wastewater quality evaluation is conventionally based on physicochemical parameters, but increasing attention has been paid to integrate physicochemical and biological data. Nevertheless, the regulatory use of fish in biological testing methods has been subject to various ethical and cost concerns, and in vitro cell-based assays have thus become an important topic of interest. Hence, the present study intends: (a) to evaluate the efficiency of two different sample pre-concentration techniques (lyophilisation and solid phase extraction) to assess the toxicity of municipal effluents on rat cardiomyoblast H9c2(2-1) cells, and (b) maximizing the use of the effluent sample collected, to estimate the environmental condition of the receiving environment. The gathered results demonstrate that the H9c2(2-1) sulforhodamine B-based assay is an appropriate in vitro method to assess biological effluent toxicity, and the best results were attained by lyophilising the sample as pre-treatment. Due to its response, the H9c2(2-1) cell line might be a possible alternative in vitro model for fish lethal testing to assess the toxicity of municipal effluents. The physicochemical status of the sample suggests a high potential for eutrophication, and iron exceeded the permissible level for wastewater discharge, possibly due to the addition of ferric chloride for wastewater treatment. In general, the levels of carbamazepine and sulfamethoxazole are higher than those reported for other countries, and both surpassed the aquatic protective values for long-term exposure.
Meeting of Minds around Food Addiction: Insights from Addiction Medicine, Nutrition, Psychology, and Neurosciences.
Nutrients, 2020

This review, focused on food addiction (FA), considers opinions from specialists with different expertise in addiction medicine, nutrition, health psychology, and behavioral neurosciences. The concept of FA is a recurring issue in the clinical description of abnormal eating. Even though some tools have been developed to diagnose FA, such as the Yale Food Addiction Scale (YFAS) questionnaire, the FA concept is not recognized as an eating disorder (ED) so far and is even not mentioned in the Diagnostic and Statistical Manuel of Mental Disorders version 5 (DSM-5) or the International Classification of Disease (ICD-11). Its triggering mechanisms and relationships with other substance use disorders (SUD) need to be further explored. Food addiction (FA) is frequent in the overweight or obese population, but it remains unclear whether it could articulate with obesity-related comorbidities. As there is currently no validated therapy against FA in obese patients, FA is often underdiagnosed and untreated, so that FA may partly explain failure of obesity treatment, addiction transfer, and weight regain after obesity surgery. Future studies should assess whether a dedicated management of FA is associated with better outcomes, especially after obesity surgery. For prevention and treatment purposes, it is necessary to promote a comprehensive psychological approach to FA. Understanding the developmental process of FA and identifying precociously some high-risk profiles can be achieved via the exploration of the environmental, emotional, and cognitive components of eating, as well as their relationships with emotion management, some personality traits, and internalized weight stigma. Under the light of behavioral neurosciences and neuroimaging, FA reveals a specific brain phenotype that is characterized by anomalies in the reward and inhibitory control processes. These anomalies are likely to disrupt the emotional, cognitive, and attentional spheres, but further research is needed to disentangle their complex relationship and overlap with obesity and other forms of SUD. Prevention, diagnosis, and treatment must rely on a multidisciplinary coherence to adapt existing strategies to FA management and to provide social and emotional support to these patients suffering from highly stigmatized medical conditions, namely overweight and addiction. Multi-level interventions could combine motivational interviews, cognitive behavioral therapies, and self-help groups, while benefiting from modern exploratory and interventional tools to target specific neurocognitive processes.
The effects of lacosamide on cognitive function and psychiatric profiles in patients with epilepsy.
Epilepsy & behavior : E&B, 2020

Cognitive and psychiatric problems are common in people with epilepsy. They can have multiple causes, including structural brain lesions, the active epilepsy, and the effect of anti-epileptic therapy. Since patients' treatment compliance and quality of life are affected by cognitive and emotional status, it is crucial for clinicians to understand how anti-seizure medications (ASMs) affect cognition and mood, and to choose the proper ASM.
Influence of thrombectomy volume on non-physician staff burnout and attrition in neurointerventional teams.
Journal of neurointerventional surgery, 2020

Burnout takes a heavy toll on healthcare providers. We sought to assess the prevalence and risk factors for burnout among neurointerventional (NI) non-physician procedural staff (nurses and technologists) given increasing thrombectomy demands.
Emotional responses of parents participating for the first time in caregiving for their baby in a neonatal unit.
Paediatric and perinatal epidemiology, 2021

Parents of term and preterm infants hospitalised at birth experience a stressful situation. They are considered as primary caregivers in neonatal units and are encouraged to participate in their child's care.
Coping styles of parents of children and adolescents with acquired brain injury in the chronic phase.
Journal of rehabilitation medicine, 2015

To investigate the types of coping strategies used by parents of children with acquired brain injury in the chronic phase and the relationship between their coping styles and psychosocial functioning.
Correction to: Striatal-frontal network activation during voluntary task selection under conditions of monetary reward.
Cognitive, affective & behavioral neuroscience, 2019

Conflict of interest statement: Although co-author Marie T. Banich is the Editor-in-Chief of Cognitive, Affective, and Behavioral Neuroscience, Stan Floresco served as the action editor for this manuscript.
Muscle spasm-induced exothermia in dystonic cerebral palsy: uncommon and frequently misdiagnosed condition.
BMJ case reports, 2019

A known cerebral palsy young man presented with prolonged bouts of generalised body movements associated with high-grade fever without any localising signs of infection, requiring multiple hospital admissions over several months. All septic work-ups, including a lumbar puncture, were negative. Serum chemistry was consistent with rhabdomyolysis. Repeated electroencephalograms showed no epileptiform discharges. Cranial MRI with gadolinium contrast revealed left cerebral atrophy with hyperintensities at the left basal ganglia. Uncontrolled dystonia with concomitant rhabdomyolysis was considered. Subsequent aggressive hydration and administration of muscle relaxant afforded abrupt resolution of symptoms.
Asymmetry of Hippocampal Tau Pathology in Primary Age-Related Tauopathy and Alzheimer Disease.
Journal of neuropathology and experimental neurology, 2021

Primary age-related tauopathy (PART) is a neurodegenerative entity defined as neurofibrillary degeneration generally restricted to the medial temporal region (Braak stage I-IV) with complete or near absence of diffuse and neuritic plaques. Symptoms range in severity but are generally milder and later in onset than in Alzheimer disease (AD). Recently, an early predilection for neurofibrillary degeneration in the hippocampal CA2 subregion has been demonstrated in PART, whereas AD neuropathologic change (ADNC) typically displays relative sparing of CA2 until later stages. In this study, we utilized a semiquantitative scoring system to evaluate asymmetry of neurofibrillary degeneration between left and right hippocampi in 67 PART cases and 17 ADNC cases. 49% of PART cases demonstrated asymmetric findings in at least one hippocampal subregion, and 79% of the asymmetric cases displayed some degree of CA2 asymmetry. Additionally, 19% of cases revealed a difference in Braak score between the right and left hippocampi. There was a significant difference in CA2 neurofibrillary degeneration (p = 0.0006) and CA2/CA1 ratio (p < 0.0001) when comparing the contralateral sides, but neither right nor left was more consistently affected. These data show the importance of analyzing bilateral hippocampi in the diagnostic evaluation of PART and potentially of other neurodegenerative diseases.
Preliminary Evidence for Aortopathy and an X-Linked Parent-of-Origin Effect on Aortic Valve Malformation in a Mouse Model of Turner Syndrome.
Journal of cardiovascular development and disease, 2015

Turner syndrome (TS), most frequently caused by X-monosomy (45,X), is characterized in part by cardiovascular abnormalities, including aortopathy and bicuspid aortic valve (BAV). There is a need for animal models that recapitulate the cardiovascular manifestations of TS. Extracellular matrix (ECM) organization and morphometrics of the aortic valve and proximal aorta were examined in adult 39,XO mice (where the parental origin of the single X was paternal (39,X
MicroRNAs and Ascl1 facilitate direct conversion of porcine fibroblasts into induced neurons.
Stem cell research, 2020

Direct neuronal conversion describes the process of generating induced neurons from somatic cells such as fibroblasts by overexpressing cell type-specific transcription factors, microRNAs or by culturing in the presence of small molecules. This was first achieved by expressing Brn2, Ascl1 and Myt1L in mouse fibroblasts, and was later achieved in human cells by the inclusion of additional factors such as NeuroD1. Here, we present the first protocol for directly converting porcine fibroblasts into induced neurons. We used lentivirus-mediated delivery of previously identified neuron-specifying transcription factors and microRNAs and evaluated morphology and neuron marker expression after ten days of conversion. We found that Ascl1 and microRNAs, miR-9/9* and miR-124 together generated more neuronal cells than other conditions tested. The porcine induced neurons expressed common mature markers such as MAP2 and Synaptophysin after four weeks of conversion. Transcriptomic analysis revealed that fibroblast-specific signatures were silenced early in the conversion process, while the neuron-specific genes became more abundant during conversion. We generated a heterogeneous population of glutamatergic and GABAergic neurons.
The interaction of the circadian and immune system: Desynchrony as a pathological outcome to traumatic brain injury.
Neurobiology of sleep and circadian rhythms, 2020

Traumatic brain injury (TBI) is a complex and costly worldwide phenomenon that can lead to many negative health outcomes including disrupted circadian function. There is a bidirectional relationship between the immune system and the circadian system, with mammalian coordination of physiological activities being controlled by the primary circadian pacemaker in the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN receives light information from the external environment and in turn synchronizes rhythms throughout the brain and body. The SCN is capable of endogenous self-sustained oscillatory activity through an intricate clock gene negative feedback loop. Following TBI, the response of the immune system can become prolonged and pathophysiological. This detrimental response not only occurs in the brain, but also within the periphery, where a leaky blood brain barrier can permit further infiltration of immune and inflammatory factors. The prolonged and pathological immune response that follows TBI can have deleterious effects on clock gene cycling and circadian function not only in the SCN, but also in other rhythmic areas throughout the body. This could bring about a state of circadian desynchrony where different rhythmic structures are no longer working together to promote optimal physiological function. There are many parallels between the negative symptomology associated with circadian desynchrony and TBI. This review discusses the significant contributions of an immune-disrupted circadian system on the negative symptomology following TBI. The implications of TBI symptomology as a disorder of circadian desynchrony are discussed.
The correlation of serum adiponectin and insulin resistance with the presence and severity of dementia in non-obese Alzheimer's patients.
Clinical nutrition ESPEN, 2020

Alteration in the insulin signaling could contribute to the development of Alzheimer's disease (AD) through metabolic or inflammatory processes, adipokines could affect insulin dysregulation. This study aimed to investigate whether there is a correlation between serum adiponectin level alteration and insulin resistance with the presence and severity of AD, compared to normal controls.
Expression of Mutant Ubiquitin and Proteostasis Impairment in Kii Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex Brains.
Journal of neuropathology and experimental neurology, 2020

Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) is a progressive neurodegenerative disorder that is endemic to the Kii peninsula of Japan. The disorder is clinically characterized by a variable combination of parkinsonism, dementia, and motor neuron symptoms. Despite extensive investigations, the etiology and pathogenesis of ALS/PDC remain unclear. At the neuropathological level, Kii ALS/PDC is characterized by neuronal loss and tau-dominant polyproteinopathy. Here, we report the accumulation of several proteins involved in protein homeostasis pathways, that is, the ubiquitin-proteasome system and the autophagy-lysosome pathway, in postmortem brain tissue from a number of Kii ALS/PDC cases (n = 4). Of particular interest is the presence of a mutant ubiquitin protein (UBB+1), which is indicative of disrupted ubiquitin homeostasis. The findings suggest that abnormal protein aggregation is linked to impaired protein homeostasis pathways in Kii ALS/PDC.
Activity of Alzheimer's γ-secretase is linked to changes of interferon-induced transmembrane proteins (IFITM) in innate immunity.
Molecular neurodegeneration, 2020

The activity of γ-secretase is critical to the pathogenesis of Alzheimer's disease (AD). How its activity is regulated is intriguing and highly important for any AD therapy that focuses on reduction of toxic amyloid peptides and amyloid deposition in patients. Recently, interferon-induced transmembrane protein 3 (IFITM3) has been identified as a novel regulator of γ-secretase through a specific interaction. This commentary highlights this exciting study and provides an updated link of γ-secretase activity to innate immunity through IFITM3.
Neurosurgery in the age of Cushing: the achievement of Leonard Lindon.
ANZ journal of surgery, 2012

Leonard Lindon was the first neurosurgeon on the staff of the Royal Adelaide Hospital, and headed this hospital's neurosurgical service from 1931 to 1951, with an interruption from war service. Like other early neurosurgeons, Lindon began as a general surgeon. In 1929, when he was well established in his surgical practice, he took unpaid leave from his hospital duties to undertake a study tour of neurosurgical centres in Europe and North America. Lindon visited the London Hospital, where Hugh Cairns, like him, an Adelaide medical graduate and veteran of Gallipoli, was establishing a modern neurosurgical service. Lindon also visited Harvey Cushing in Boston, USA. Cushing was then at the zenith of his reputation as the master of a safe neurosurgical operative technique; he was also famous for his contributions in the neurosciences. Lindon was deeply impressed by Cushing's philosophy and his operative methods. When Lindon returned to Adelaide in 1930, he prepared a plan for a neurosurgical unit in Adelaide, and over the next 20 years, he achieved some of his aims. In this plan, Lindon gave priority to the management of head injuries as a role for neurosurgeons.