rudyvdbrink/CitationDatabase huggingface dataset:
On the Clinical Pharmacology of Reactive Oxygen Species.
Pharmacological reviews, 2020

Reactive oxygen species (ROS) have been correlated with almost every human disease. Yet clinical exploitation of these hypotheses by pharmacological modulation of ROS has been scarce to nonexistent. Are ROS, thus, irrelevant for disease? No. One key misconception in the ROS field has been its consideration as a rather detrimental metabolic by-product of cell metabolism, and thus, any approach eliminating ROS to a certain tolerable level would be beneficial. We now know, instead, that ROS at every concentration, low or high, can serve many essential signaling and metabolic functions. This likely explains why systemic, nonspecific antioxidants have failed in the clinic, often with neutral and sometimes even detrimental outcomes. Recently, drug development has focused, instead, on identifying and selectively modulating ROS enzymatic sources that in a given constellation cause disease while leaving ROS physiologic signaling and metabolic functions intact. As sources, the family of NADPH oxidases stands out as the only enzyme family solely dedicated to ROS formation. Selectively targeting disease-relevant ROS-related proteins is already quite advanced, as evidenced by several phase II/III clinical trials and the first drugs having passed registration. The ROS field is expanding by including target enzymes and maturing to resemble more and more modern, big data-enhanced drug discovery and development, including network pharmacology. By defining a disease based on a distinct mechanism, in this case ROS dysregulation, and not by a symptom or phenotype anymore, ROS pharmacology is leaping forward from a clinical underperformer to a proof of concept within the new era of mechanism-based precision medicine. SIGNIFICANCE STATEMENT: Despite being correlated to almost every human disease, nearly no ROS modulator has been translated to the clinics yet. Here, we move far beyond the old-fashioned misconception of ROS as detrimental metabolic by-products and suggest 1) novel pharmacological targeting focused on selective modulation of ROS enzymatic sources, 2) mechanism-based redefinition of diseases, and 3) network pharmacology within the ROS field, altogether toward the new era of ROS pharmacology in precision medicine.
Selective breeding for high alcohol preference is associated with increased sensitivity to cannabinoid reward within the nucleus accumbens shell.
Pharmacology, biochemistry, and behavior, 2020

The rate of cannabinoid intake by those with alcohol use disorder (AUD) exceeds that of the general public. The high prevalence of co-abuse of alcohol and cannabis has been postulated to be predicated upon both a common predisposing genetic factor and the interaction of the drugs within the organism. The current experiments examined the effects of cannabinoids in an animal model of AUD.
Long-term outcomes of two patients with progressive myoclonic epilepsy treated with vagus nerve stimulation therapy.
Heliyon, 2020

Long-term outcomes associated with vagus nerve stimulation (VNS) therapy for progressive myoclonic epilepsy (PME) have not been studied. The purpose of this study was to report long-term outcomes of VNS therapy in two patients with PME.
Positive Germline Selection in Pedigrees With Multiple Endocrine Neoplasia Type 2 Carrying V804M Mutation in the RET Gene.
World journal of oncology, 2016

Multiple endocrine neoplasia (MEN) type 2 is an autosomal dominant cancer syndrome associated with the development of thyroid cancer and tumors or hyperplasia in other endocrine organs. It is caused by mutations in the RET gene and can be phenotypically classified into MEN types 2A and 2B. MEN2B is often sporadic resulting from a spontaneous mutation, M981T. A positive paternal germline selection has been reported for this mutation.
Choriocarcinoma Presenting as Recurrent Intracranial Hemorrhage in an Adolescent Patient.
Journal of pediatric and adolescent gynecology, 2021

Due to its highly metastatic and invasive nature, choriocarcinoma may affect other organ systems and mimic conditions not typical of gynecologic cancers. Recurrent intracranial hemorrhage secondary to rupture of multiple oncotic aneurysms is one of its rare initial presentations.
Up-regulation of the p75 neurotrophin receptor is an essential mechanism for HIV-gp120 mediated synaptic loss in the striatum.
Brain, behavior, and immunity, 2020

Reduced synaptodendritic complexity appears to be a key feature in human immunodeficiency virus (HIV)-associated neurological disorder (HAND). Viral proteins, and in particular the envelope protein gp120, play a role in the pathology of synapses. Gp120 has been shown to increase both in vitro and in vivo the proneurotrophin brain-derived neurotrophic factor, which promotes synaptic simplification through the activation of the p75 neurotrophin receptor (p75NTR). To provide evidence that p75NTR plays a role in gp120-mediated loss of synapses in vivo, we intercrossed gp120tg mice with p75NTR null mice and used molecular, histological and behavioral analyses to establish a link between p75NTR and gp120-mediated synaptic simplification. Synaptosomes obtained from the striatum of gp120tg mice exhibited a significant increase in p75NTR levels concomitantly to a decrease in synaptic markers such as TrkB and PSD95. Analysis of striatal dendritic spines by Golgi staining revealed that gp120tg mice display a reduced proportion of mushroom-type spines in addition to fewer spines overall, when compared to wild type or gp120tg lacking one or two p75NTR alleles. Moreover, removal of one p75NTR allele in gp120 transgenic mice abolished the gp120-driven impairment on a task of striatal-dependent motor learning. These data indicate that p75NTR could be a key player in HIV-mediated synaptic simplification in the striatum.
Predicates: External description or neural reality?
The Behavioral and brain sciences, 2003

Hurford argues that propositions of the form PREDICATE(x) represent conceptual structures that predate language and that can be explicated in terms of neural structure. I disagree, arguing that such predicates are descriptions of limited aspects of brain function, not available as representations in the brain to be exploited in the frog or monkey brain and turned into language in the human.
Tumor Excision as a Metastatic Russian Roulette: Perioperative Interventions to Improve Long-Term Survival of Cancer Patients.
Trends in cancer, 2020

Uncertainty regarding the development of postoperative metastatic disease is highly prevalent. Here we assert that numerous processes that occur during the immediate perioperative period (IPP) markedly affect the probability of postoperative metastatic disease and that these processes can be manipulated to improve cancer survival. Specifically, tumor excision facilitates both prometastatic and antimetastatic processes, which, within each domain, are often synergistic and self-propagating. Consequently, minor perioperative dominance of either prometastatic or antimetastatic processes can trigger a 'snowball-like effect' leading to either accelerated progression of minimal residual disease (MRD) or its dormancy/elimination, establishing the 'surgical metastatic roulette'. Thus, the IPP should become a significant antimetastatic therapeutic arena, exploiting feasible approaches including immunotherapies and manipulations/modifications of inflammatory-stress responses, surgical procedures, and hormonal status.
Mouse TRPA1 function and membrane localization are modulated by direct interactions with cholesterol.
eLife, 2019

The cation channel TRPA1 transduces a myriad of noxious chemical stimuli into nociceptor electrical excitation and neuropeptide release, leading to pain and neurogenic inflammation. Despite emergent evidence that TRPA1 is regulated by the membrane environment, it remains unknown whether this channel localizes in membrane microdomains or whether it interacts with cholesterol. Using total internal reflection fluorescence microscopy and density gradient centrifugation we found that mouse TRPA1 localizes preferably into cholesterol-rich domains and functional experiments revealed that cholesterol depletion decreases channel sensitivity to chemical agonists. Moreover, we identified two structural motifs in transmembrane segments 2 and 4 involved in mTRPA1-cholesterol interactions that are necessary for normal agonist sensitivity and plasma membrane localization. We discuss the impact of such interactions on TRPA1 gating mechanisms, regulation by the lipid environment, and role of this channel in sensory membrane microdomains, all of which helps to understand the puzzling pharmacology and pathophysiology of this channel.
Carbamazepine Restores Neuronal Signaling, Protein Synthesis, and Cognitive Function in a Mouse Model of Fragile X Syndrome.
International journal of molecular sciences, 2020

Fragile X syndrome (FXS) is a leading genetic disorder of intellectual disability caused by the loss of the functional fragile X mental retardation protein (FMRP). To date, there is no efficacious mechanism-based medication for FXS. With regard to potential disease mechanisms in FXS, it is widely accepted that the lack of FMRP causes elevated protein synthesis and deregulation of neuronal signaling. Abnormal enhancement of the ERK½ (extracellular signal-regulated kinase ½) and PI3K-Akt (Phosphoinositide 3 kinase-protein kinase B) signaling pathways has been identified in both FXS patients and FXS mouse models. In this study, we show that carbamazepine, which is an FDA-approved drug and has been mainly used to treat seizure and neuropathic pain, corrects cognitive deficits including passive avoidance and object location memory in FXS mice. Carbamazepine also rescues hyper locomotion and social deficits. At the cellular level, carbamazepine dampens the elevated level of ERK½ and Akt signaling as well as protein synthesis in FXS mouse neurons. Together, these results advocate repurposing carbamazepine for FXS treatment.
Diabetes Mellitus, Glycemic Traits, and Cerebrovascular Disease: A Mendelian Randomization Study.
Neurology, 2021

We employed Mendelian randomization to explore the effects of genetic predisposition to type 2 diabetes (T2D), hyperglycemia, insulin resistance, and pancreatic β-cell dysfunction on risk of stroke subtypes and related cerebrovascular phenotypes.
Efficacy of spaced learning in adaptation of optokinetic response.
Brain and behavior, 2021

The superiority of spaced training, in which repeated training sessions are given with resting intervals, over massed training in learning efficacy has been well established. However, longer duration of total training time has been required for spaced training than massed training because spacing intervals intervene between training sessions in spaced training. Thus, the learning efficacy may not be simply compared between spaced and massed training in terms of "time efficiency." The aim of the present study was to investigate the efficacy of spaced and massed training using adaptation of horizontal optokinetic reflex (hOKR) in mice.
A genome-wide methylation study reveals X chromosome and childhood trauma methylation alterations associated with borderline personality disorder.
Translational psychiatry, 2021

Borderline personality disorder (BPD) is a severe and highly prevalent psychiatric disorder, more common in females than in males and with notable differences in presentation between genders. Recent studies have shown that epigenetic modifications such as DNA methylation may modulate gene × environment interactions and impact on neurodevelopment. We conducted an epigenome wide study (Illumina Infinium HumanMethylation450k beadchip) in a group of BPD patients with (N = 49) and without (N = 47) childhood traumas and in a control group (N = 44). Results were confirmed in a replication cohort (N = 293 BPD patients and N = 114 controls) using EpiTYPER assays. Differentially methylated CpG sites were observed in several genes and intragenic regions in the X chromosome (PQBP1, ZNF41, RPL10, cg07810091 and cg24395855) and in chromosome 6 (TAP2). BPD patients showed significantly lower methylation levels in these CpG sites than healthy controls. These differences seemed to be increased by the existence of childhood trauma. Comparisons between BPD patients with childhood trauma and patients and controls without revealed significant differences in four genes (POU5F1, GGT6, TNFRSF13C and FAM113B), none of them in the X chromosome. Gene set enrichment analyses revealed that epigenetic alterations were more frequently found in genes controlling oestrogen regulation, neurogenesis and cell differentiation. These results suggest that epigenetic alterations in the X chromosome and oestrogen-regulation genes may contribute to the development of BPD and explain the differences in presentation between genders. Furthermore, childhood trauma events may modulate the magnitude of the epigenetic alterations contributing to BPD.
Progress in the Management of Paediatric-Onset Multiple Sclerosis.
Children (Basel, Switzerland), 2020

Considerable progress has been made in the understanding and treatment of paediatric-onset multiple sclerosis (POMS); how this has translated into more effective care is less well understood. Here, we evaluate how recent advances have affected patient management and outcomes with a retrospective review of POMS patients managed at two paediatric neuroimmunology centres. Two cohorts, seen within a decade, were compared to investigate associations between management approaches and outcomes. Demographic, clinical and neurocognitive data were extracted from case notes and analysed. Of 51 patients, 24 were seen during the period 2007-2010 and 27 during the period 2015-2016. Median age at onset was 13.7 years; time from symptom onset to diagnosis was 9 months. Disease-modifying therapies were commenced in 19 earlier-cohort and 24 later-cohort patients. Median time from diagnosis to treatment was 9 months for earlier vs. 3.5 months in later patients (
Emotion anticipation induces emotion effects in neutral words during sentence reading: Evidence from event-related potentials.
Cognitive, affective & behavioral neuroscience, 2020

This study examined whether emotion responses during reading are co-constituted by lexical items and the preceding context. Event-related potentials to coherent emotion and neutral words finishing sentences with or without strong constraint for the incoming valence were analyzed. Typical frontal P200 and posterior late positive component (LPC) emotion responses were seen to emotion words relative to neutral words in the neutral context, indicating heightened attention allocation and further valence analysis induced by word-level emotionality. With emotional bias in the context, words elicited reduced N400 responses, indicating facilitated semantic processing. Critically, we obtained evidence for contextualized emotion responses during coherent sentence comprehension. With active anticipation of the incoming emotionality (evidenced by the frontal positivity to plausible emotionally unpredicted words), enhanced P200 and LPC responses were seen to neutral words in emotional contexts. These findings demonstrated that, like word emotionality, emotion-constraining contexts could similarly engage motivational circuits and attention resources, affecting early perception and later further affective evaluation of the incoming information, even for emotionally neutral words. Despite the seeming similarity, multiple routes may be involved for giving rise to these neurophysiological reactions during emotion processing - while lexically driven LPCs were significantly correlated with empathy, contextually driven LPCs were not. Together, these findings provide support for contextualized emotion responses during congruent sentence reading when explicit emotional judgment on the materials is not required. These findings also provide an initial understanding about how these responses are mediated by empathy - an important aspect of human ability to perceive emotion.
[The Last Lecture of Professor Masao Ito: The Cerebellum and Cerebrum].
Brain and nerve = Shinkei kenkyu no shinpo, 2019

Comment Professor Masao Ito's last lecture, delivered at the University of Tokyo Faculty of Medicine on March 7, 1989, is reproduced here in an abridged form. Its original title was "the Cerebellum and Cerebrum," and this lecture was a real masterpiece, full of insights and suggestions on brain functions, together with humorous phrases here and there. When I tried to reproduce this lecture by using all figures at that time, just one week after Professor Ito passed away, I was struck by his foresight even after thirty years. I deeply appreciate his family's permission for the reproduction.
Validation of PET/MRI attenuation correction methodology in the study of brain tumours.
BMC medical imaging, 2020

This study aims to compare proton density weighted magnetic resonance imaging (MRI) zero echo time (ZTE) and head atlas attenuation correction (AC) to the reference standard computed tomography (CT) based AC for
Applications of predictive control in neuroscience.
The Behavioral and brain sciences, 2013

The sensory cortex has been interpreted as coding information rather than stimulus properties since Sokolov in 1960 showed increased response to an unexpected stimulus decrement. The motor cortex is also organized around expectation, coding the goal of an act rather than a set of muscle movements. Expectation drives not only immediate responses but also the very structure of the cortex, as demonstrated by development of receptive fields that mirror the structure of the visual world.
The human cerebellum has almost 80% of the surface area of the neocortex.
Proceedings of the National Academy of Sciences of the United States of America, 2020

The surface of the human cerebellar cortex is much more tightly folded than the cerebral cortex. It was computationally reconstructed for the first time to the level of all individual folia from multicontrast high-resolution postmortem MRI scans. Its total shrinkage-corrected surface area (1,590 cm
EEG spindles in the rat: evidence for a synchronous network phenomenon.
Epilepsy research, 2010

Whether physiological and pathological electroencephalographic (EEG) spindling phenomena are generated by similar mechanisms remains unknown. We studied four different types of spindling events analysing the behaviour of 19 brain regions during these events in the intact brain of freely behaving rats hypothesising similar generation with a leading role of thalamus or cortex for the dominant rhythm of the spindles with a hierarchy of time delays for propagation throughout the brain led by these structures. Autoregressive analysis revealed that all structures studied were capable of leading a spindle, although some did so infrequently. The highest incidence of significant leadership was shown by hindlimb cortex with a proportion of 0.38 during picrotoxin spindles. Contralateral time delays within bilateral structures were extremely small demonstrating synchronous activity with no dominant hemisphere for any of the spindling activities (range: 0.1+/-0.4 ms for frontal cortex to 10.0+/-1.6 ms for piriform cortex). Between different structures, time delays demonstrated that spindling activity occurred in all structures almost simultaneously (range: 0.2+/-1.4 ms between frontal cortex and piriform cortex to 12.3+/-1.2 ms between hindlimb cortex and amygdala). We conclude that different spindle types appear to be subtle alterations of a single phenomenon, during which many brain regions briefly synchronise.
The role of lateral inhibition in binocular motion rivalry.
Journal of vision, 2013

It is generally believed that percept alternations in binocular rivalry result from the interplay between mutual inhibition and slow adaptation of the competing percepts. This view is supported by growing evidence that dynamic changes in adaptation indeed support percept alternations in binocular rivalry. Empirical evidence for the involvement of mutual inhibition, however, is still scarce. To fill this gap, we presented human subjects with dichoptic random-dot motion stimuli and manipulated the angle between the monocular directions of motion from pure opponent horizontal motion to pure vertical motion in the same direction. We hypothesized that this decrease in motion-direction disparity increases the cross-inhibition gain due to lateral inhibition between neurons in the brain that are coarsely tuned to adjacent directions of visual motion, which predicts the largest changes in dominance at the smallest instead of the largest motion-direction disparities. We found that decreasing the angle between the two monocular directions of motion indeed systematically increased the predominance and mean dominance durations of the motion pattern presented to the ocular dominant eye (as identified by the hole-in-card test). Moreover, this effect was stronger if the contrast of the stimuli was lowered. Simulations showed that these features are indeed hallmark of weighted lateral inhibition between populations of directionally tuned motion-sensitive neurons. Our findings thus suggest dominance and suppression in binocular rivalry arises naturally from this fundamental principle in sensory processing. Interestingly, if the two monocular directions of motion differed <60°, the percept alternations also included transitions to in-between (vertical) motion percepts. We speculate that this behavior might result from positive feedback arising from adapting disinhibitory circuits in the network.
Promoting attachment between parents and neonates despite the COVID-19 pandemic.
Acta paediatrica (Oslo, Norway : 1992), 2020

Social distancing is the only option available during the COVID-19 pandemic until a vaccine is developed. However, this is having a major impact on human relationships and bonding between parents and neonates is a major concern. Separation during this health emergency could have lifelong consequences for offspring, and there are even greater concerns if newborn infants are sick or vulnerable and need intensive care. We look at how bonding can be safely supported and maintained without risking infecting neonates, by comparing the international guidelines and proposing safe actions within those frameworks.
Low-spatial-frequency information facilitates threat detection in a response-specific manner.
Journal of vision, 2021

The role of different spatial frequency bands in threat detection has been explored extensively. However, most studies use manual responses and the results are mixed. Here, we aimed to investigate the contribution of spatial frequency information to threat detection by using three response types, including manual responses, eye movements, and reaching movements, together with a priming paradigm. The results showed that both saccade and reaching responses were significantly faster to threatening stimuli than to nonthreatening stimuli when primed by low-spatial-frequency gratings rather than by high-spatial-frequency gratings. However, the manual response times to threatening stimuli were comparable to nonthreatening stimuli, irrespective of the spatial frequency content of the primes. The findings provide clear evidence that low-spatial-frequency information can facilitate threat detection in a response-specific manner, possibly through the subcortical magnocellular pathway dedicated to processing threat-related signals, which is automatically prioritized in the oculomotor system and biases behavior.
Widespread cortical dyslamination in epilepsy patients with malformations of cortical development.
Neuroradiology, 2021

Recent research in epilepsy patients confirms our understanding of epilepsy as a network disorder with widespread cortical compromise. Here, we aimed to investigate the neocortical laminar architecture in patients with focal cortical dysplasia (FCD) and periventricular nodular heterotopia (PNH) using clinically feasible 3 T MRI.