rudyvdbrink/CitationDatabase huggingface dataset:
Selective role for the COMT polymorphism in a trans-diagnostic compulsivity phenotype.
Psychological medicine, 2018

Impulsivity and compulsivity are central to understanding a range of psychiatric disorders but also to understanding the spectrum of normative human behavior. It was recently shown that separable latent phenotypes of impulsivity and compulsivity could be fractionated. The possible genetic contributions to these latent phenotypes have yet to be elicited. The catechol-o-methyl transferase (COMT) Val158Met polymorphism (rs4680) regulates cortical dopamine degradation and is a key area of interest in this context.
Inhibiting the NLRP3 inflammasome with MCC950 ameliorates retinal neovascularization and leakage by reversing the IL-1β/IL-18 activation pattern in an oxygen-induced ischemic retinopathy mouse model.
Cell death & disease, 2020

Activation of the nucleotide-binding domain leucine-rich repeat and pyrin domain containing receptor 3 (NLRP3) inflammasome plays an important role in ocular neovascularization. In our study, we found that the expression and activation levels of NLRP3 inflammasome components, including NLRP3, an apoptosis-associated speck-like protein (ASC) containing caspase activation and recruitment domain (CARD) and caspase-1 (CAS1), were significantly upregulated. In addition, we found interleukin (IL)-1β activity increased while IL-18 activity decreased in the retinas of oxygen-induced ischemic retinopathy (OIR) mice. MCC950, an inhibitor of NLRP3, reversed the IL-1β/IL-18 activation pattern, inhibited the formation of retinal neovascularization (RNV), decreased the number of acellular capillaries and reduced leakage of retinal vessels. Moreover, MCC950 could regulate the expression of endothelial cell- and pericyte function-associated molecules, such as vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)1, VEGFR2, matrix metalloproteinase (MMP)2, MMP9, tissue inhibitor of metalloproteinases (TIMP)1, TIMP2, platelet-derived growth factor receptor-β (PDGFR-β), platelet-derived growth factor-B (PDGF-B), and angiopoietin2 (Ang2). In vitro, recombinant human (r)IL-18 and rIL-1β regulated the expression of endothelial cell- and pericyte function-associated molecules and the proliferation and migration of endothelial cells and pericytes. We therefore determined that inhibiting the NLRP3 inflammasome with MCC950 can regulate the function of endothelial cells and pericytes by reversing the IL-1β/IL-18 activation pattern to ameliorate RNV and leakage; thereby opening new avenues to treat RNV-associated ocular diseases.
HDAC inhibition ameliorates cone survival in retinitis pigmentosa mice.
Cell death and differentiation, 2021

Cone photoreceptor cell death in inherited retinal diseases, such as Retinitis Pigmentosa (RP), leads to the loss of high acuity and color vision and, ultimately to blindness. In RP, a vast number of mutations perturb the structure and function of rod photoreceptors, while cones remain initially unaffected. Extensive rod loss in advanced stages of the disease triggers cone death by a mechanism that is still largely unknown. Here, we show that secondary cone cell death in animal models for RP is associated with increased activity of histone deacetylates (HDACs). A single intravitreal injection of an HDAC inhibitor at late stages of the disease, when the majority of rods have already degenerated, was sufficient to delay cone death and support long-term cone survival in two mouse models for RP, affected by mutations in the phosphodiesterase 6b gene. Moreover, the surviving cones remained light-sensitive, leading to an improvement in visual function. RNA-seq analysis of protected cones demonstrated that HDAC inhibition initiated multi-level protection via regulation of different pro-survival pathways, including MAPK, PI3K-Akt, and autophagy. This study suggests a unique opportunity for targeted pharmacological protection of secondary dying cones by HDAC inhibition and creates hope to maintain vision in RP patients even in advanced disease stages.
The migraineur's brain networks: Continuous resting state fMRI over 30 days.
Cephalalgia : an international journal of headache, 2020

The aim of the current study was to identify typical alterations in resting state connectivity within different stages of the migraine cycle and to thus explore task-free mechanisms of headache attack generation in migraineurs.
Neural encoding of spectro-temporal cues at slow and near speech-rate in cochlear implant users.
Hearing research, 2021

The ability to process rapid modulations in the spectro-temporal structure of sounds is critical for speech comprehension. For users of cochlear implants (CIs), spectral cues in speech are conveyed by differential stimulation of electrode contacts along the cochlea, and temporal cues in terms of the amplitude of stimulating electrical pulses, which track the amplitude-modulated (AM'ed) envelope of speech sounds. Whilst survival of inner-ear neurons and spread of electrical current are known factors that limit the representation of speech information in CI listeners, limitations in the neural representation of dynamic spectro-temporal cues common to speech are also likely to play a role. We assessed the ability of CI listeners to process spectro-temporal cues varying at rates typically present in human speech. Employing an auditory change complex (ACC) paradigm, and a slow (0.5Hz) alternating rate between stimulating electrodes, or different AM frequencies, to evoke a transient cortical ACC, we demonstrate that CI listeners-like normal-hearing listeners-are sensitive to transitions in the spectral- and temporal-domain. However, CI listeners showed impaired cortical responses when either spectral or temporal cues were alternated at faster, speech-like (6-7Hz), rates. Specifically, auditory change following responses-reliably obtained in normal-hearing listeners-were small or absent in CI users, indicating that cortical adaptation to alternating cues at speech-like rates is stronger under electrical stimulation. In CI listeners, temporal processing was also influenced by the polarity-behaviourally-and rate of presentation of electrical pulses-both neurally and behaviorally. Limitations in the ability to process dynamic spectro-temporal cues will likely impact speech comprehension in CI users.
A multiorganism pipeline for antiseizure drug discovery: Identification of chlorothymol as a novel γ-aminobutyric acidergic anticonvulsant.
Epilepsia, 2020

Current medicines are ineffective in approximately one-third of people with epilepsy. Therefore, new antiseizure drugs are urgently needed to address this problem of pharmacoresistance. However, traditional rodent seizure and epilepsy models are poorly suited to high-throughput compound screening. Furthermore, testing in a single species increases the chance that therapeutic compounds act on molecular targets that may not be conserved in humans. To address these issues, we developed a pipeline approach using four different organisms.
COVID-19 pandemic-related anxiety, distress and burnout: prevalence and associated factors in healthcare workers of North-West Italy.
BJPsych open, 2021

The COVID-19 pandemic caused drastic changes in healthcare and severe social restrictions. Healthcare workers (HCWs) are on the front line against the virus and have been highly exposed to pandemic-related stressors, but there are limited data on their psychological involvement for a large sample in Italy.
Generation of induced pluripotent stem cells (iPSCs) from a hereditary spastic paraplegia patient carrying a homozygous R486C mutation in CYP7B1 (SPG5).
Stem cell research, 2016

Skin fibroblasts were obtained from a 47-year-old hereditary spastic paraplegia patient carrying a homozygous mutation R486C in CYP7B1 (Cytochrome P450, Family 7, Subfamily B, Polypeptide 1), responsible for causing hereditary spastic paraplegia type 5 (SPG5). Induced pluripotent stem cells (iPSCs) were generated by transfection with episomal plasmids carrying hOCT4, hSOX2, hKLF4, hL-MYC and hLIN28. The generated line iPS-SPG5-R486C was transgene-free, retained the specific mutation with no additional genomic aberrations, expressed pluripotency markers and was able to differentiate into cells of all germ layers in vitro. The generated iPS-SPG5-R486C line may be a useful resource for disease modelling of SPG5.
Development of EpiRisk: An online clinical tool for estimating the risk of major congenital malformations in pregnant women treated for epilepsy.
Epilepsia open, 2018

Antiepileptic drugs (AEDs) are known to associate with an increased risk of major congenital malformations (MCMs) in children born to women who become pregnant while taking them. As the indications for AEDs continue to diversify, novel AEDs emerge, and polytherapy becomes more prevalent, the volume and complexity of the information relating to teratogenic risk can become unmanageable for the clinician. This in turn makes accurate education of pregnant women treated with AEDs regarding the risk of MCMs challenging. To enable clinicians to provide better information regarding the potential teratogenic risk of AEDs, we outline here the method we have employed to underpin a new system of real-time risk analysis, "
Prevalence of childhood exposure to intimate partner violence and associations with mental distress in Cambodia, Malawi and Nigeria: A cross-sectional study.
Child abuse & neglect, 2021

Research from high-income countries shows that witnessing intimate partner violence (IPV) between caregivers is experienced by up to a third of all children and is related to poor mental health outcomes. Much less is known about the burden of witnessing IPV in low- and middle-income countries.
Transplantation of Human Neural Precursor Cells Reverses Syrinx Growth in a Rat Model of Post-Traumatic Syringomyelia.
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2021

Posttraumatic syringomyelia (PTS) is a serious condition of progressive expansion of spinal cord cysts, affecting patients with spinal cord injury years after injury. To evaluate neural cell therapy to prevent cyst expansion and potentially replace lost neurons, we developed a rat model of PTS. We combined contusive trauma with subarachnoid injections of blood, causing tethering of the spinal cord to the surrounding vertebrae, resulting in chronically expanding cysts. The cysts were usually located rostral to the injury, extracanalicular, lined by astrocytes. T2*-weighted magnetic resonance imaging (MRI) showed hyperintense fluid-filled cysts but also hypointense signals from debris and iron-laden macrophages/microglia. Two types of human neural stem/progenitor cells-fetal neural precursor cells (hNPCs) and neuroepithelial-like stem cells (hNESCs) derived from induced pluripotent stem cells-were transplanted to PTS cysts. Cells transplanted into cysts 10 weeks after injury survived at least 10 weeks, migrated into the surrounding parenchyma, but did not differentiate during this period. The cysts were partially obliterated by the cells, and cyst walls often merged with thin layers of cells in between. Cyst volume measurements with MRI showed that the volumes continued to expand in sham-transplanted rats by 102%, while the cyst expansion was effectively prevented by hNPCs and hNESCs transplantation, reducing the cyst volumes by 18.8% and 46.8%, respectively. The volume reductions far exceeded the volume of the added human cells. Thus, in an animal model closely mimicking the clinical situation, we provide proof-of-principle that transplantation of human neural stem/progenitor cells can be used as treatment for PTS.
Cell-based approaches towards treating age-related macular degeneration.
Cell and tissue banking, 2020

Age-related macular degeneration as one of the most common causes of worldwide vision loss needs a proper approach for treatment. Therein, cell therapy and regenerative medicine can hold a great promise to be an effective approach. Accordingly, some preclinical and clinical studies were conducted to search around the therapeutic influence of stem cells in Age-related macular degeneration models and subjects. Hereupon, the purpose of the current review is to discuss the mechanisms of age-related macular degeneration, appropriate animal models along with suitable dosage and route of stem cell administration for its treatment.
Repetitive behaviors in chronic schizophrenia: using the Japanese version of the Elgin Behavior Rating Scale (JEBRS).
The International journal of neuroscience, 2003

The main aim of this study was to test the reliability and value of the Japanese Elgin Behavior Rating Scale (JEBRS) with 92 schizophrenia patients. Cronbach's alpha for the JEBRS was 0.61. All inter-rater reliability coefficients were in the satisfactory range. The JEBRS had a high stability over time. Almost all of the correlations among the nine item scores and total score in the JEBRS were significant. The total score for nine repetitive behaviors in the JEBRS was positively correlated with positive and negative symptoms. This study showed that the JEBRS is a useful and reliable scale.
Differential effects of Foxp2 disruption in distinct motor circuits.
Molecular psychiatry, 2019

Disruptions of the FOXP2 gene cause a speech and language disorder involving difficulties in sequencing orofacial movements. FOXP2 is expressed in cortico-striatal and cortico-cerebellar circuits important for fine motor skills, and affected individuals show abnormalities in these brain regions. We selectively disrupted Foxp2 in the cerebellar Purkinje cells, striatum or cortex of mice and assessed the effects on skilled motor behaviour using an operant lever-pressing task. Foxp2 loss in each region impacted behaviour differently, with striatal and Purkinje cell disruptions affecting the variability and the speed of lever-press sequences, respectively. Mice lacking Foxp2 in Purkinje cells showed a prominent phenotype involving slowed lever pressing as well as deficits in skilled locomotion. In vivo recordings from Purkinje cells uncovered an increased simple spike firing rate and decreased modulation of firing during limb movements. This was caused by increased intrinsic excitability rather than changes in excitatory or inhibitory inputs. Our findings show that Foxp2 can modulate different aspects of motor behaviour in distinct brain regions, and uncover an unknown role for Foxp2 in the modulation of Purkinje cell activity that severely impacts skilled movements.
Award for Distinguished Scientific Early Career Contributions to Psychology: Luke W. Hyde.
The American psychologist, 2020

The Early Career Awards, given for the first time in 1974, recognize the large number of excellent early career psychologists. Recipients of this award may not have held a doctoral degree for more than nine years. For purposes of this award, psychology has been divided into 10 areas: animal learning and behavior, comparative; developmental; health; cognition/human learning; psychopathology; behavioral and cognitive neuroscience; perception/motor performance; social; applied research; and individual differences. Five areas are considered each year, with areas rotated in two-year cycles. The areas considered in 2020 were animal learning and behavior, comparative; developmental; health; cognition/ human learning; and psychopathology. Each year, panels are selected for the areas under consideration, and these panels recommend nominees to the Committee on Scientific Awards. The 2020 recipients of the APA Scientific Contribution Awards were recognized by the 2019 Board of Scientific Affairs and selected by the 2019 Committee on Scientific Awards. For outstanding contributions to developmental psychopathology in particular and clinical and developmental psychology broadly. Luke W. Hyde's programmatic and novel empirical work has changed how we view the development of antisocial behavior and callous-unemotional (CU) traits. His research also highlights how familial and neighborhood factors may sculpt brain development and increase risk for psychopathology. His theoretical work has drawn on many areas of psychology and other disciplines to lay out novel directions for understanding the roles that genes, context, and the brain play in the development of risk and resilience. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
ACE2 and SCARF expression in human dorsal root ganglion nociceptors: implications for SARS-CoV-2 virus neurological effects.
Pain, 2020

SARS-CoV-2 has created a global crisis. COVID-19, the disease caused by the virus, is characterized by pneumonia, respiratory distress, and hypercoagulation and can be fatal. An early sign of infection is loss of smell, taste, and chemesthesis-loss of chemical sensation. Other neurological effects of the disease have been described, but not explained. It is now apparent that many of these neurological effects (for instance joint pain and headache) can persist for at least months after infection, suggesting a sensory neuronal involvement in persistent disease. We show that human dorsal root ganglion (DRG) neurons express the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 at the RNA and protein level. We also demonstrate that SARS-CoV-2 and coronavirus-associated factors and receptors are broadly expressed in human DRG at the lumbar and thoracic level as assessed by bulk RNA sequencing. ACE2 mRNA is expressed by a subset of nociceptors that express MRGPRD mRNA, suggesting that SARS-CoV-2 may gain access to the nervous system through entry into neurons that form free nerve endings at the outermost layers of skin and luminal organs. Therefore, DRG sensory neurons are a potential target for SARS-CoV-2 invasion of the peripheral nervous system, and viral infection of human nociceptors may cause some of the persistent neurological effects seen in COVID-19.
Risk attitude and personality in people with multiple sclerosis facing the choice of different disease-modifying therapy scenarios.
Journal of the neurological sciences, 2020

As available disease-modifying therapies (DMTs) increase, evaluating benefit/risk presents greater difficulties, requiring people with MS (PwMS) to play crucial roles in choosing treatment. Although individual attitude toward risk may predict this evaluation, its relation to personality is little studied in MS literature.
The Reciprocity of Brain and Behavior.
Journal of the American Academy of Child and Adolescent Psychiatry, 2018

The rise of neuroscience in our field has raised legitimate questions about the relative value of brain versus behavioral data to inform our understanding of the etiology and treatment of childhood mental disorders. There is no doubt that data on brain function and structure have wielded unique power and influence in mental health research during the past two decades. This could be based in part on its inherent objective and quantitative features in a field that has searched for, and thus far has generally failed to find, clearly measurable markers of psychopathology for clinical use. However, it also could be based on a reductionist philosophy that posits that the brain is the source and driver of all human emotions and behavior and therefore should be of central importance. Contrasting this view, recent neuroscience perspectives have emphasized that detailed studies of behavior are essential to inform neuroscience.
Self-Organized Structuring of Recurrent Neuronal Networks for Reliable Information Transmission.
Biology, 2021

Our brains process information using a layered hierarchical network architecture, with abundant connections within each layer and sparse long-range connections between layers. As these long-range connections are mostly unchanged after development, each layer has to locally self-organize in response to new inputs to enable information routing between the sparse in- and output connections. Here we demonstrate that this can be achieved by a well-established model of cortical self-organization based on a well-orchestrated interplay between several plasticity processes. After this self-organization, stimuli conveyed by sparse inputs can be rapidly read out from a layer using only very few long-range connections. To achieve this information routing, the neurons that are stimulated form feed-forward projections into the unstimulated parts of the same layer and get more neurons to represent the stimulus. Hereby, the plasticity processes ensure that each neuron only receives projections from and responds to only one stimulus such that the network is partitioned into parts with different preferred stimuli. Along this line, we show that the relation between the network activity and connectivity self-organizes into a biologically plausible regime. Finally, we argue how the emerging connectivity may minimize the metabolic cost for maintaining a network structure that rapidly transmits stimulus information despite sparse input and output connectivity.
Adaptation to Noise in Human Speech Recognition Depends on Noise-Level Statistics and Fast Dynamic-Range Compression.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2020

Human hearing adapts to background noise, as evidenced by the fact that listeners recognize more isolated words when words are presented later rather than earlier in noise. This adaptation likely occurs because the leading noise shifts ("adapts") the dynamic range of auditory neurons, which can improve the neural encoding of speech spectral and temporal cues. Because neural dynamic range adaptation depends on stimulus-level statistics, here we investigated the importance of "statistical" adaptation for improving speech recognition in noisy backgrounds. We compared the recognition of noised-masked words in the presence and in the absence of adapting noise precursors whose level was either constant or was changing every 50 ms according to different statistical distributions. Adaptation was measured for 28 listeners (9 men) and was quantified as the recognition improvement in the precursor relative to the no-precursor condition. Adaptation was largest for constant-level precursors and did not occur for highly fluctuating precursors, even when the two types of precursors had the same mean level and both activated the medial olivocochlear reflex. Instantaneous amplitude compression of the highly fluctuating precursor produced as much adaptation as the constant-level precursor did without compression. Together, results suggest that noise adaptation in speech recognition is probably mediated by neural dynamic range adaptation to the most frequent sound level. Further, they suggest that auditory peripheral compression per se, rather than the medial olivocochlear reflex, could facilitate noise adaptation by reducing the level fluctuations in the noise.