rudyvdbrink/CitationDatabase huggingface dataset:
Predominant and novel de novo variants in 29 individuals with ALG13 deficiency: Clinical description, biomarker status, biochemical analysis, and treatment suggestions.
Journal of inherited metabolic disease, 2020

Asparagine-linked glycosylation 13 homolog (ALG13) encodes a nonredundant, highly conserved, X-linked uridine diphosphate (UDP)-N-acetylglucosaminyltransferase required for the synthesis of lipid linked oligosaccharide precursor and proper N-linked glycosylation. De novo variants in ALG13 underlie a form of early infantile epileptic encephalopathy known as EIEE36, but given its essential role in glycosylation, it is also considered a congenital disorder of glycosylation (CDG), ALG13-CDG. Twenty-four previously reported ALG13-CDG cases had de novo variants, but surprisingly, unlike most forms of CDG, ALG13-CDG did not show the anticipated glycosylation defects, typically detected by altered transferrin glycosylation. Structural homology modeling of two recurrent de novo variants, p.A81T and p.N107S, suggests both are likely to impact the function of ALG13. Using a corresponding ALG13-deficient yeast strain, we show that expressing yeast ALG13 with either of the highly conserved hotspot variants rescues the observed growth defect, but not its glycosylation abnormality. We present molecular and clinical data on 29 previously unreported individuals with de novo variants in ALG13. This more than doubles the number of known cases. A key finding is that a vast majority of the individuals presents with West syndrome, a feature shared with other CDG types. Among these, the initial epileptic spasms best responded to adrenocorticotropic hormone or prednisolone, while clobazam and felbamate showed promise for continued epilepsy treatment. A ketogenic diet seems to play an important role in the treatment of these individuals.
Interacting hepatic PAI-1/tPA gene regulatory pathways influence impaired fibrinolysis severity in obesity.
The Journal of clinical investigation, 2020

Fibrinolysis is initiated by tissue-type plasminogen activator (tPA) and inhibited by plasminogen activator inhibitor 1 (PAI-1). In obese humans, plasma PAI-1 and tPA proteins are increased, but PAI-1 dominates, leading to reduced fibrinolysis and thrombosis. To understand tPA-PAI-1 regulation in obesity, we focused on hepatocytes, a functionally important source of tPA and PAI-1 that sense obesity-induced metabolic stress. We showed that obese mice, like humans, had reduced fibrinolysis and increased plasma PAI-1 and tPA, due largely to their increased hepatocyte expression. A decrease in the PAI-1 (SERPINE1) gene corepressor Rev-Erbα increased PAI-1, which then increased the tPA gene PLAT via a PAI-1/LRP1/PKA/p-CREB1 pathway. This pathway was partially counterbalanced by increased DACH1, a PLAT-negative regulator. We focused on the PAI-1/PLAT pathway, which mitigates the reduction in fibrinolysis in obesity. Thus, silencing hepatocyte PAI-1, CREB1, or tPA in obese mice lowered plasma tPA and further impaired fibrinolysis. The PAI-1/PLAT pathway was present in primary human hepatocytes, and associations among PAI-1, tPA, and PLAT in livers from obese and lean humans were consistent with these findings. Knowledge of PAI-1 and tPA regulation in hepatocytes in obesity may suggest therapeutic strategies for improving fibrinolysis and lowering the risk of thrombosis in this setting.
Association between polygenic risk score of Alzheimer's disease and plasma phosphorylated tau in individuals from the Alzheimer's Disease Neuroimaging Initiative.
Alzheimer's research & therapy, 2021

Recent studies suggest that plasma phosphorylated tau181 (p-tau181) is a highly specific biomarker for Alzheimer's disease (AD)-related tau pathology. It has great potential for the diagnostic and prognostic evaluation of AD, since it identifies AD with the same accuracy as tau PET and CSF p-tau181 and predicts the development of AD dementia in cognitively unimpaired (CU) individuals and in those with mild cognitive impairment (MCI). Plasma p-tau181 may also be used as a biomarker in studies exploring disease pathogenesis, such as genetic or environmental risk factors for AD-type tau pathology. The aim of the present study was to investigate the relation between polygenic risk scores (PRSs) for AD and plasma p-tau181.
Duplication of the Alar Ligaments: A Case Report.
Cureus, 2018

The alar ligament is one of the two strongest ligaments stabilizing the craniocervical junction. The literature describes many variations of the attachment, insertion, shape, and orientation of the alar ligament and an understanding of these variations is vital as they can lead to altered biomechanics or misinterpretation on imaging. Herein, we report, to our knowledge, the first case of duplication of the alar ligaments and discuss the anatomical variations present in the literature.
Region-specific Foxp2 deletions in cortex, striatum or cerebellum cannot explain vocalization deficits observed in spontaneous global knockouts.
Scientific reports, 2020

FOXP2 has been identified as a gene related to speech in humans, based on rare mutations that yield significant impairments in speech at the level of both motor performance and language comprehension. Disruptions of the murine orthologue Foxp2 in mouse pups have been shown to interfere with production of ultrasonic vocalizations (USVs). However, it remains unclear which structures are responsible for these deficits. Here, we show that conditional knockout mice with selective Foxp2 deletions targeting the cerebral cortex, striatum or cerebellum, three key sites of motor control with robust neural gene expression, do not recapture the profile of pup USV deficits observed in mice with global disruptions of this gene. Moreover, we observed that global Foxp2 knockout pups show substantive reductions in USV production as well as an overproduction of short broadband noise "clicks", which was not present in the brain region-specific knockouts. These data indicate that deficits of Foxp2 expression in the cortex, striatum or cerebellum cannot solely explain the disrupted vocalization behaviours in global Foxp2 knockouts. Our findings raise the possibility that the impact of Foxp2 disruption on USV is mediated at least in part by effects of this gene on the anatomical prerequisites for vocalizing.
Increasing excitation versus decreasing inhibition in auditory cortex: consequences on the discrimination performance between communication sounds.
The Journal of physiology, 2020

Enhancing cortical excitability can be achieved by either reducing intracortical inhibition or by enhancing intracortical excitation. Here we compare the consequences of reducing intracortical inhibition and of enhancing intracortical excitation on the processing of communication sounds in the primary auditory cortex. Local application of gabazine and of AMPA enlarged the spectrotemporal receptive fields and increased the responses to communication to the same extent. The Mutual Information (an index of the cortical neurons' ability to discriminate between natural sounds) was increased in both cases, as were the noise and signal correlations. Spike-timing reliability was only increased after gabazine application and post-excitation suppression was affected in the opposite way: it was increased when reducing the intracortical inhibition but was eliminated by enhancing the excitation. A computational model suggests that these results can be explained by an additive effect vs. a multiplicative effect ABSTRACT: The level of excitability of cortical circuits is often viewed as one of the critical factors controlling perceptive performance. In theory, enhancing cortical excitability can be achieved either by reducing inhibitory currents or by increasing excitatory currents. Here, we evaluated whether reducing inhibitory currents or increasing excitatory currents in auditory cortex similarly affects the neurons' ability to discriminate between communication sounds. We attenuated the inhibitory currents by application of gabazine (GBZ), and increased the excitatory currents by applying AMPA in the auditory cortex while testing frequency receptive fields and responses to communication sounds. GBZ and AMPA enlarged the receptive fields and increased the responses to communication sounds to the same extent. The spike-timing reliability of neuronal responses was largely increased when attenuating the intracortical inhibition but not after increasing the excitation. The discriminative abilities of cortical cells increased in both cases but this increase was more pronounced after attenuating the inhibition. The shape of the response to communication sounds was modified in the opposite direction: reducing inhibition increased post-excitation suppression whereas this suppression tended to disappear when increasing the excitation. A computational model indicates that the additive effect promoted by AMPA vs. the multiplicative effect of GBZ on neuronal responses, together with the dynamics of spontaneous cortical activity, can explain these differences. Thus, although apparently equivalent for increasing cortical excitability, acting on inhibition vs. on excitation impacts differently the cortical ability to discriminate natural stimuli, and only modulating inhibition changed efficiently the cortical representation of communication sounds.
Caffeine-Induced Psychosis and a Review of Statutory Approaches to Involuntary Intoxication.
The journal of the American Academy of Psychiatry and the Law, 2020

Caffeine is the most commonly ingested psychoactive substance in the world. Although caffeine-use disorder is not recognized as a formal diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, five disorders related to caffeine use are enumerated therein. An evolving literature suggests that caffeine is one of many licit substances that may cause psychotic symptoms in higher doses. Here, we present a case in which a defendant ingested large quantities of caffeine, which result in transient psychosis and a successful affirmative defense of involuntary intoxication. The purpose of this article is to summarize states' statutory approaches to involuntary intoxication, given that the term is defined variably, if defined at all. Evaluators must be careful to apply jurisdictionally appropriate standards in involuntary intoxication defenses because the bar for this total defense differs across localities.
Need for systematic screening for IGD in adolescent psychiatric inpatients.
L'Encephale, 2020

Psychiatric comorbidities are frequent in adolescents with internet gaming disorder (IGD). In contrast, the proportion of IGD among adolescents hospitalized for a psychiatric disorder has not been documented yet. In addition, parental ratings of IGD could be useful for diagnosis, but very few data exist on this issue. The objectives of this study were to: (1) assess the prevalence of IGD among adolescent psychiatric inpatients, using the Ten-Item Internet Gaming Disorder Test (IGDT-10), and (2) assess the parental version developed for this study (IGDT-10-P). A total of 102 patients, aged from 12 to 17 years old, were included from four psychiatric units of the French region Auvergne-Rhône-Alpes, during a 6-month inclusion period. Adolescents completed the IGDT-10 while one of their parents completed the IGDT-10-P. The inclusion rate among the eligible population was 57.95%. The prevalence of IGD in the sample, based on the IGDT-10 and IGDT-10-P, was 6.00% and 12.79%, respectively. Psychometric features of the IGDT-10-P indicated excellent internal consistency, a good model fit to the one factor model in confirmatory factor analysis, a strong correlation with gaming time, and a moderate correlation with the IGDT-10. Our results support the need for a systematic screening of IGD among adolescents hospitalized for a psychiatric disorder. Future studies should aim to confirm and explain the prevalence gap between self- and parent-reported criteria.
Is Timing of Tracheotomy a Factor Influencing the Clinical Course in COVID-19 Patients?
Ear, nose, & throat journal, 2021

The timing of tracheotomy is a complex decision that requires understanding of the relative risks and benefits as compared with prolonging intubation. The role of tracheotomy during the COVID-19 pandemic remains to be determined. There is no evidence that early tracheostomy improves patient's clinical course and it is not impact on the natural history of these patients. In our opinion, the tracheotomy should be proposed in stable COVID-19 patients after 18th days after orotracheal intubation when the viral load is finished. Only in the case of patients with difficult of intubation do we perform earlier tracheotomies.
Correction to: Reducing task-based fMRI scanning time using simultaneous multislice echo planar imaging.
Neuroradiology, 2018

The original version of this article contained a mistake. The correct Affiliation 2 is Semmelweis University, János Szentágothai PhD School, MR Research Centre, Balassa Street 6, Budapest 1083, Hungary.
Drosophila Neuroscience: Should I Land or Should I Jump?
Current biology : CB, 2019

Information about behavioral states can be integrated in decision-making circuits. In Drosophila, the behavioral state - flying versus not flying - determines whether flies land or jump by dynamically coupling visual information to pre-motor descending neurons.
Take a Seat and Get Into Its Shoes! When Humans Spontaneously Represent Visual Scenes From the Point of View of Inanimate Objects.
Perception, 2020

Human description of the surrounding world may spontaneously rely on others' perspective, which is a crucial component of social cognition. In five studies, participants were asked to describe the spatial relations between objects in visual scenes including, or not, other agents. In Experiment 1, a substantial proportion of participants used an other-centered perspective in the presence of another agent, replicating classical findings. To our own surprise, we also observed that an even greater number of participants used an other-centered perspective when the human agent was replaced by an armchair. In order to explore this phenomenon, Experiments 2 to 5 compared the respective strength of chair-centered and agent-centered perspectives and/or set them into conflict. A significant proportion of participants spontaneously took the seat's perspective even when it may not be sat on (Experiments 3 and 4) and even when the seat was not referred to (Experiments 4 and 5). Altogether, these findings suggest that perspective taking may spontaneously apply to inanimate objects. These results question whether such tendencies originate from social cognitive skills-as classically assumed-or reveal a nonsocial phenomenon. Future works should specifically test the widely assumed social nature of spontaneous perspective-taking.
A Guide to Fluorescence Lifetime Microscopy and Förster's Resonance Energy Transfer in Neuroscience.
Current protocols in neuroscience, 2020

Fluorescence lifetime microscopy (FLIM) and Förster's resonance energy transfer (FRET) are advanced optical tools that neuroscientists can employ to interrogate the structure and function of complex biological systems in vitro and in vivo using light. In neurobiology they are primarily used to study protein-protein interactions, to study conformational changes in protein complexes, and to monitor genetically encoded FRET-based biosensors. These methods are ideally suited to optically monitor changes in neurons that are triggered optogenetically. Utilization of this technique by neuroscientists has been limited, since a broad understanding of FLIM and FRET requires familiarity with the interactions of light and matter on a quantum mechanical level, and because the ultra-fast instrumentation used to measure fluorescent lifetimes and resonance energy transfer are more at home in a physics lab than in a biology lab. In this overview, we aim to help neuroscientists overcome these obstacles and thus feel more comfortable with the FLIM-FRET method. Our goal is to aid researchers in the neuroscience community to achieve a better understanding of the fundamentals of FLIM-FRET and encourage them to fully leverage its powerful ability as a research tool. Published 2020. U.S. Government.
Virtual body ownership and its consequences for implicit racial bias are dependent on social context.
Royal Society open science, 2020

When people hold implicit biases against a group they typically engage in discriminatory behaviour against group members. In the context of the implicit racial bias of 'White' against 'Black' people, it has been shown several times that implicit bias is reduced after a short exposure of embodiment in a dark-skinned body in virtual reality. Embodiment usually leads to the illusion of ownership over the virtual body, irrespective of its skin colour. Previous studies have been carried out in virtual scenarios that are affectively neutral or positive. Here, we show that when the scenario is affectively negative the illusion of body ownership of White participants over a White body is lessened, and implicit bias is higher for White participants in a Black virtual body. The study was carried out with 92 White female participants, in a between-groups design with two factors: BodyType (their virtual body was White or Black) and a surrounding Crowd was Negative, Neutral or Positive towards the participant. We argue that negative affect prevents the formation of new positive associations with Black and distress leads to disownership of the virtual body. Although virtual reality is often thought of as an 'empathy machine' our results suggest caution, that this may not be universally the case.
Identifying and managing care for children with autism spectrum disorders in general practice: A systematic review and narrative synthesis.
Health & social care in the community, 2020

Many healthcare systems are organised such that General Practitioners (GPs) often have a key role in identifying autism spectrum disorders (hereafter collectively referred to as autism) in children. In this review, we explored what GPs know about autism and the factors that influence their ability to identify and manage care for their patients with autism in practice. We conducted a systematic narrative review using eight electronic databases. These included Embase and MEDLINE via Ovid, Web of Knowledge, PsycINFO via Ebscohost, PubMed, Scopus, ProQuest Dissertations and Thesis, and Applied Social Sciences Index and Abstracts (ASSIA) via ProQuest. Our search yielded 2,743 citations. Primary research studies were included, and we did not impose any geographical, language or date restrictions. We identified 17 studies that met our inclusion criteria. Studies included in the review were conducted between 2003 and 2019. We thematically synthesised the material and identified the following themes: the prototypical image of a child with autism; experience, sources of information, and managing care; barriers to identification; strategies to aid in identification; and characteristics that facilitate expertise. Together, the findings from this review present a mixed picture of GP knowledge and experiences in identifying autism and managing care for children with the condition. At one end of the continuum, there were GPs who had not heard of autism or endorsed outmoded aetiological theories. Others, however, demonstrated a sound knowledge of the conditions but had limited confidence in their ability to identify the condition. Many GPs and researchers alike called for more training and this might be effective. However, framing the problem as one of a lack of training risks silences the array of organisational factors that impact on a GP's ability to provide care for these patients.
Modeling behaviorally relevant neural dynamics enabled by preferential subspace identification.
Nature neuroscience, 2021

Neural activity exhibits complex dynamics related to various brain functions, internal states and behaviors. Understanding how neural dynamics explain specific measured behaviors requires dissociating behaviorally relevant and irrelevant dynamics, which is not achieved with current neural dynamic models as they are learned without considering behavior. We develop preferential subspace identification (PSID), which is an algorithm that models neural activity while dissociating and prioritizing its behaviorally relevant dynamics. Modeling data in two monkeys performing three-dimensional reach and grasp tasks, PSID revealed that the behaviorally relevant dynamics are significantly lower-dimensional than otherwise implied. Moreover, PSID discovered distinct rotational dynamics that were more predictive of behavior. Furthermore, PSID more accurately learned behaviorally relevant dynamics for each joint and recording channel. Finally, modeling data in two monkeys performing saccades demonstrated the generalization of PSID across behaviors, brain regions and neural signal types. PSID provides a general new tool to reveal behaviorally relevant neural dynamics that can otherwise go unnoticed.
Special, radical, failure of reduction in psychiatry.
The Behavioral and brain sciences, 2019

Use of network models to identify causal structure typically blocks reduction across the sciences. Entanglement of mental processes with environmental and intentional relationships, as Borsboom et al. argue, makes reduction of psychology to neuroscience particularly implausible. However, in psychiatry, a mental disorder can involve no brain disorder at all, even when the former crucially depends on aspects of brain structure. Gambling addiction constitutes an example.
A New Treatment for Local Adiposity with Ascorbic Acid and Ascorbyl-Palmitate Solution: Clinical and Histological Study.
Aesthetic plastic surgery, 2020

Localized adiposity (AL) is the accumulation of subcutaneous adipose tissue, placed in definite anatomic areas, building up an alteration of the body silhouette. The aim of the present clinical and histological study is to assess the effectiveness of an injectable solution containing sodium salt of ascorbic acid 0.24% and surfactant agent at 0.020% ascorbyl-palmitate (SAP) for treating local adiposity.
Altered Signaling in CB1R-5-HT2AR Heteromers in Olfactory Neuroepithelium Cells of Schizophrenia Patients is Modulated by Cannabis Use.
Schizophrenia bulletin, 2020

Schizophrenia (SCZ) has been associated with serotonergic and endocannabinoid systems dysregulation, but difficulty in obtaining in vivo neurological tissue has limited its exploration. We investigated CB1R-5-HT2AR heteromer expression and functionality via intracellular pERK and cAMP quantification in olfactory neuroepithelium (ON) cells of SCZ patients non-cannabis users (SCZ/nc), and evaluated whether cannabis modulated these parameters in patients using cannabis (SCZ/c). Results were compared vs healthy controls non-cannabis users (HC/nc) and healthy controls cannabis users (HC/c). Further, antipsychotic effects on heteromer signaling were tested in vitro in HC/nc and HC/c. Results indicated that heteromer expression was enhanced in both SCZ groups vs HC/nc. Additionally, pooling all 4 groups together, heteromer expression correlated with worse attentional performance and more neurological soft signs (NSS), indicating that these changes may be useful markers for neurocognitive impairment. Remarkably, the previously reported signaling properties of CB1R-5-HT2AR heteromers in ON cells were absent, specifically in SCZ/nc treated with clozapine. These findings were mimicked in cells from HC/nc exposed to clozapine, suggesting a major role of this antipsychotic in altering the quaternary structure of the CB1R-5-HT2AR heteromer in SCZ/nc patients. In contrast, cells from SCZ/c showed enhanced heteromer functionality similar to HC/c. Our data highlight a molecular marker of the interaction between antipsychotic medication and cannabis use in SCZ with relevance for future studies evaluating its association with specific neuropsychiatric alterations.