rudyvdbrink/CitationDatabase huggingface dataset:
Cyclic transitions between higher order motifs underlie sustained asynchronous spiking in sparse recurrent networks.
PLoS computational biology, 2020

A basic-yet nontrivial-function which neocortical circuitry must satisfy is the ability to maintain stable spiking activity over time. Stable neocortical activity is asynchronous, critical, and low rate, and these features of spiking dynamics contribute to efficient computation and optimal information propagation. However, it remains unclear how neocortex maintains this asynchronous spiking regime. Here we algorithmically construct spiking neural network models, each composed of 5000 neurons. Network construction synthesized topological statistics from neocortex with a set of objective functions identifying naturalistic low-rate, asynchronous, and critical activity. We find that simulations run on the same topology exhibit sustained asynchronous activity under certain sets of initial membrane voltages but truncated activity under others. Synchrony, rate, and criticality do not provide a full explanation of this dichotomy. Consequently, in order to achieve mechanistic understanding of sustained asynchronous activity, we summarized activity as functional graphs where edges between units are defined by pairwise spike dependencies. We then analyzed the intersection between functional edges and synaptic connectivity- i.e. recruitment networks. Higher-order patterns, such as triplet or triangle motifs, have been tied to cooperativity and integration. We find, over time in each sustained simulation, low-variance periodic transitions between isomorphic triangle motifs in the recruitment networks. We quantify the phenomenon as a Markov process and discover that if the network fails to engage this stereotyped regime of motif dominance "cycling", spiking activity truncates early. Cycling of motif dominance generalized across manipulations of synaptic weights and topologies, demonstrating the robustness of this regime for maintenance of network activity. Our results point to the crucial role of excitatory higher-order patterns in sustaining asynchronous activity in sparse recurrent networks. They also provide a possible explanation why such connectivity and activity patterns have been prominently reported in neocortex.
Abscess Formation in Metastatic Brain Tumor with History of Immune Checkpoint Inhibitor: A Case Report.
NMC case report journal, 2019

We present the case of a 68-year-old man with brain metastasis from lung cancer and a history of immune checkpoint inhibitor administration, with overlapping abscess within the metastatic lesion. He initially received antibiotic treatment under a diagnosis of brain abscess because of a hyper-intense area on diffusion-weighted imaging inside the gadolinium-enhanced wall. The size of the enhanced lesion did not change much, but the extent of perifocal edema decreased after antibiotic treatment. After 2-4 months, the lesion gradually enlarged, and imaging characteristics changed from single cyst to multiple cysts. Surgical resection was performed and pathological examination revealed the lesion as metastasis from the lung tumor. Smear preparation of the tumor contents detected Gram-positive bacilli, confirming the dual pathology of metastasis and brain abscess. Discussing the pathogenesis, we speculated that therapy with durvalumab (MEDI4736), an anti-PD-L1 antibody, induced immune status modification including immunosuppressive regulation, which might have promoted abscess formation.
Matrix Metalloprotease-7 Mediates Nucleolar Assembly and Intra-nucleolar Cleaving p53 in Gefitinib-Resistant Cancer Stem Cells.
iScience, 2020

The enlarged distinct bulky-ball-like nucleolus matrix assembly is observed in most cancer stem cells (CSCs); however, the underlying mechanism is largely unknown. We show that matrix metalloproteinase-7 (MMP-7) shedding MUC-1 SEA domain releases MUC-1 C-ter, facilitating the nucleolus trafficking of p53 in gefitinib-resistant lung CSCs. The nucleolus colocalizations of p53, MUC-1 C-ter, MMP-7 and nucleolin were observed in the CD34
Central processing of leg proprioception in 
eLife, 2020

Proprioception, the sense of self-movement and position, is mediated by mechanosensory neurons that detect diverse features of body kinematics. Although proprioceptive feedback is crucial for accurate motor control, little is known about how downstream circuits transform limb sensory information to guide motor output. Here we investigate neural circuits in
Preventive role of regular low-intensity exercise during adolescence in schizophrenia model mice with abnormal behaviors.
Biochemical and biophysical research communications, 2021

Schizophrenia is probably ascribed to perinatal neurodevelopmental deficits, and its onset might be affected by environmental factors. Hypofrontality with glutamatergic and dopaminergic neuronal dysfunction are known factors, but a way to mitigate abnormalities remains unfound. An early enriched environment such as a wheel running in rodents may contribute to the prevention, but its clinical applicability is very limited. From our studies, low-intensity exercise training (LET) based on physiological indices, such as lactate threshold, easily translates to humans and positively affects the brains. Hence, LET during adolescence may ameliorate abnormalities in neurodevelopment and prevent the development of schizophrenia. In the current study, LET prevented sensitization to phencyclidine (PCP) treatment, impairment of cognition, and affective behavioral abnormalities in an animal model of schizophrenia induced by prenatal PCP treatment. Further, LET increased dopamine turnover and attenuated the impairment of phosphorylation of ERK1/2 after exposure to a novel object in the prenatal PCP-treated mice. These results suggest that LET during adolescence completely improves schizophrenia-like abnormal behaviors associated with improved glutamate uptake and the dopamine-induced ERK1/2 signaling pathway in the PFC.
Eukaryotic initiation factor 5B (eIF5B) regulates temozolomide-mediated apoptosis in brain tumour stem cells (BTSCs).
Biochemistry and cell biology = Biochimie et biologie cellulaire, 2020

Glioblastoma multiforme (GBM) is among the deadliest cancers, owing in part to complex inter- and intra-tumor heterogeneity and the presence of a population of stem-like cells called brain tumour stem cells (BTSCs/BTICs). These cancer stem cells survive treatment and confer resistance to the current therapies - namely, radiation and the chemotherapeutic, temozolomide (TMZ). TMZ induces cell death by alkylating DNA, and BTSCs resist this mechanism via a robust DNA damage response. Hence, recent studies aimed to sensitize BTSCs to TMZ using combination therapy, such as inhibition of DNA repair machinery. We have previously demonstrated in established GBM cell lines that eukaryotic initiation factor 5B (eIF5B) promotes the translation of pro-survival and anti-apoptotic proteins. Consequently, silencing eIF5B sensitizes these cells to TRAIL-induced apoptosis. However, established cell lines do not always recapitulate the features of human glioma. Therefore, we investigated this mechanism in patient-derived BTSCs. We show that silencing eIF5B leads to increased TMZ sensitivity in two BTSC lines: BT25 and BT48. Depletion of eIF5B decreases the levels of anti-apoptotic proteins in BT48 and sensitizes these cells to TMZ-induced activation of caspase-3, cleavage of PARP, and apoptosis. We suggest that eIF5B represents a rational target to sensitize GBM tumors to the current standard-of-care.
Stroke: Carotid stenosis--surgery or stenting to prevent stroke?
Nature reviews. Neurology, 2010

Thromboembolism resulting from complex atheromatous plaque formation at the origin of the internal carotid artery is a common cause of ischemic stroke. In appropriately selected patients, plaque removal by carotid endarterectomy is of substantial net benefit. Endovascular stenting appears less "invasive" than endarterectomy,but is the former as safe and effective as the latter?
Essential omega-3 fatty acids tune microglial phagocytosis of synaptic elements in the mouse developing brain.
Nature communications, 2020

Omega-3 fatty acids (n-3 PUFAs) are essential for the functional maturation of the brain. Westernization of dietary habits in both developed and developing countries is accompanied by a progressive reduction in dietary intake of n-3 PUFAs. Low maternal intake of n-3 PUFAs has been linked to neurodevelopmental diseases in Humans. However, the n-3 PUFAs deficiency-mediated mechanisms affecting the development of the central nervous system are poorly understood. Active microglial engulfment of synapses regulates brain development. Impaired synaptic pruning is associated with several neurodevelopmental disorders. Here, we identify a molecular mechanism for detrimental effects of low maternal n-3 PUFA intake on hippocampal development in mice. Our results show that maternal dietary n-3 PUFA deficiency increases microglia-mediated phagocytosis of synaptic elements in the rodent developing hippocampus, partly through the activation of 12/15-lipoxygenase (LOX)/12-HETE signaling, altering neuronal morphology and affecting cognitive performance of the offspring. These findings provide a mechanistic insight into neurodevelopmental defects caused by maternal n-3 PUFAs dietary deficiency.
Cell specific quantitative iron mapping on brain slices by immuno-µPIXE in healthy elderly and Parkinson's disease.
Acta neuropathologica communications, 2021

Iron is essential for neurons and glial cells, playing key roles in neurotransmitter synthesis, energy production and myelination. In contrast, high concentrations of free iron can be detrimental and contribute to neurodegeneration, through promotion of oxidative stress. Particularly in Parkinson's disease (PD) changes in iron concentrations in the substantia nigra (SN) was suggested to play a key role in degeneration of dopaminergic neurons in nigrosome 1. However, the cellular iron pathways and the mechanisms of the pathogenic role of iron in PD are not well understood, mainly due to the lack of quantitative analytical techniques for iron quantification with subcellular resolution. Here, we quantified cellular iron concentrations and subcellular iron distributions in dopaminergic neurons and different types of glial cells in the SN both in brains of PD patients and in non-neurodegenerative control brains (Co). To this end, we combined spatially resolved quantitative element mapping using micro particle induced X-ray emission (µPIXE) with nickel-enhanced immunocytochemical detection of cell type-specific antigens allowing to allocate element-related signals to specific cell types. Distinct patterns of iron accumulation were observed across different cell populations. In the control (Co) SNc, oligodendroglial and astroglial cells hold the highest cellular iron concentration whereas in PD, the iron concentration was increased in most cell types in the substantia nigra except for astroglial cells and ferritin-positive oligodendroglial cells. While iron levels in astroglial cells remain unchanged, ferritin in oligodendroglial cells seems to be depleted by almost half in PD. The highest cellular iron levels in neurons were located in the cytoplasm, which might increase the source of non-chelated Fe
Device-measured physical activity and sedentary behaviour in relation to mental wellbeing: An analysis of the 1970 British cohort study.
Preventive medicine, 2021

Although physical activity and sedentary behaviour have established associations with mental illness, the extent to which they impact on mental wellbeing is not well understood. We examined associations between moderate to vigorous physical activity (MVPA), sitting time (ST) and mental wellbeing in 4526 participants from the 1970 British Cohort Study (UK) in the age 46 survey (2016-18). MVPA and ST were measured using a thigh mounted accelerometer device (activPAL 3 micro) worn continuously for 7 days and participants completed the 14-item Warwick-Edinburg Mental Wellbeing Scale (WEMWBS) to assess mental wellbeing. In linear regression models MVPA (per hr) was associated with an additional 0.57 points on the WEMWBS (95% CI 0.03-1.12) regardless of gender, wear time, education, socioeconomic status, smoking, body mass index, disability and psychological distress. ST was not associated with WEMWBS in the adjusted models (B = -0.11, -0.23, 0.02). In MVPA stratified analyses, ST showed a linear trend with WEMBS in participants with low levels of MVPA but not in medium and high MVPA categories. In this large, nationally representative cohort, device-measured MVPA showed an association with higher mental wellbeing whilst ST was only associated with reduced mental wellbeing in participants with low levels of MVPA. Our main limitation was the cross-sectional design which precludes any inference of direction of association or causality. Nevertheless, interventions to promote MVPA may be an effective public health policy to promote mental wellbeing. Further investigation of the effect different sitting behaviours has on mental wellbeing is warranted.
First episode rapid early intervention for eating disorders (FREED): From research to routine clinical practice.
Early intervention in psychiatry, 2020

Eating disorders are serious psychiatric disorders with high rates of morbidity and mortality. Early intervention can improve treatment outcomes and reduce disruption to psychosocial development. However, early intervention is not well established in the eating disorder field. First episode rapid early intervention for eating disorders (FREED) was developed to address barriers to early, effective eating disorder treatment in emerging adults aged 16 to 25 years. Since 2014, FREED has progressed from a single-site research project to an evidence-based care approach in nine eating disorder services. This paper aims to summarize key learning from the scaling of FREED to date, with attention to how this learning may generalizes to other models of care.
Examining changes in rodent temperament following repetitive mild traumatic brain injury in adolescence.
Behavioral neuroscience, 2020

Mild traumatic brain injuries are known to cause a host of symptoms, including headaches, nausea, and depression, that when persistent, are known as postconcussive syndrome. In addition to these overt symptomologies, individuals may experience changes in day-to-day behavior or temperament, which although not meeting criteria for postconcussive diagnosis, does cause distress to the individual. The aim of this study was to determine whether we could measure temperament in a rat and, if so, determine whether temperament is altered in response to repetitive mild traumatic brain injuries (RmTBI). Forty male and female adolescent Sprague-Dawley rats were same-sex pair housed and subjected to RmTBIs or sham injuries. The rats were recorded at 6 different time points throughout the study for the temperament assessment protocol, a measure of the complex behavioral profile of each rat within its dyadic home cage environment. The temperaments were quantified via a novel behavioral scoring algorithm. The rats were also tested on a battery of tests that were designed to measure symptoms of postconcussion syndrome. We determined that rodent temperament is quantifiable, is sex dependent, changes with age, and is modifiable in response to experiential factors such as RmTBI. Rats that received the RmTBIs were significantly less active and showed decreased levels of social interaction compared with their sham-injury counterparts. Moreover, both task switching and recovery patterns for RmTBI rats were dependent on the injury status of their cage mates. Future studies are now required to determine the mechanisms underlying these important changes in temperament. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
Myopathy secondary to intravascular large B-cell lymphoma.
Neuromuscular disorders : NMD, 2009

We report a case of a 78-year-old woman presenting with progressive proximal muscle weakness mainly to lower limbs and myopathic EMG associated with intravascular large B-cell lymphoma. Muscle biopsy showed myopathic changes, intravascular large B-cell lymphoma but no inflammation or fibre necrosis; the patient's serum cross-reacted with an unidentified nuclear antigen of approximately 45 kDa present in muscle and lymphoma cells. Our case illustrates a myopathy associated with intravascular large B-cell lymphoma probably mediated by antibodies cross-reacting with a nuclear protein expressed by neoplastic cells and normal muscle. The nature of this nuclear antigen remains unidentified.
Perception of successive brief objects as a function of stimulus onset asynchrony: model experiments based on two-stage synchronization of neuronal oscillators.
Cognitive neurodynamics, 2013

Recently we introduced a new version of the perceptual retouch model incorporating two interactive binding operations-binding features for objects and binding the bound feature-objects with a large scale oscillatory system that acts as a mediary for the perceptual information to reach consciousness-level representation. The relative level of synchronized firing of the neurons representing the features of an object obtained after the second-stage synchronizing modulation is used as the equivalent of conscious perception of the corresponding object. Here, this model is used for simulating interaction of two successive featured objects as a function of stimulus onset asynchrony (SOA). Model output reproduces typical results of mutual masking-with shortest and longest SOAs first and second object correct perception rate is comparable while with intermediate SOAs second object dominates over the first one. Additionally, with shortest SOAs misbinding of features to form illusory objects is simulated by the model.
Thioredoxin-Interacting Protein (TXNIP) with Focus on Brain and Neurodegenerative Diseases.
International journal of molecular sciences, 2020

The development of new therapeutic approaches to diseases relies on the identification of key molecular targets involved in amplifying disease processes. One such molecule is thioredoxin-interacting protein (TXNIP), also designated thioredoxin-binding protein-2 (TBP-2), a member of the α-arrestin family of proteins and a central regulator of glucose and lipid metabolism, involved in diabetes-associated vascular endothelial dysfunction and inflammation. TXNIP sequesters reduced thioredoxin (TRX), inhibiting its function, resulting in increased oxidative stress. Many different cellular stress factors regulate TXNIP expression, including high glucose, endoplasmic reticulum stress, free radicals, hypoxia, nitric oxide, insulin, and adenosine-containing molecules. TXNIP is also directly involved in inflammatory activation through its interaction with the nucleotide-binding domain, leucine-rich-containing family, and pyrin domain-containing-3 (NLRP3) inflammasome complex. Neurodegenerative diseases such as Alzheimer's disease have significant pathologies associated with increased oxidative stress, inflammation, and vascular dysfunctions. In addition, as dysfunctions in glucose and cellular metabolism have been associated with such brain diseases, a role for TXNIP in neurodegeneration has actively been investigated. In this review, we will focus on the current state of the understanding of possible normal and pathological functions of TXNIP in the central nervous system from studies of in vitro neural cells and the brains of humans and experimental animals with reference to other studies. As TXNIP can be expressed by neurons, microglia, astrocytes, and endothelial cells, a complex pattern of regulation and function in the brain is suggested. We will examine data suggesting TXNIP as a therapeutic target for neurodegenerative diseases where further research is needed.
The orexin receptors in the ventral tegmental area are involved in the development of sensitization to expression of morphine-induced preference in rats.
Behavioural pharmacology, 2020

Recent studies have shown that orexin neurons in the lateral hypothalamus send a compelling project to the ventral tegmental area (VTA). Besides, orexin-1 (OX1) and orexin-2 (OX2) in the VTA are necessary for the development of morphine-induced place preference. Also, sensitivity to morphine can reinforce the rewarding effects of morphine. The current study aims to determine the role of VTAs orexin receptors in morphine sensitization in rats. In 84 adult male albino Wistar rats, two separate cannulae bilaterally implanted into the VTA. They received intra-VTA infusions of SB334867 (0.1, 1 and 10 nM) and TCS OX2 29 (1, 7 and 20 nM) as OX1 and OX2 receptor antagonists, respectively, 10 min before subcutaneous administration of morphine (5 mg/kg) during 3-day sensitization period. After a 5-day drug-free period, the conditioned place preference (CPP) paradigm induced by subthreshold doses of morphine (0.5 mg/kg), and CPP scores were measured by EthoVision software. The results revealed that the blockade of both OX1 and OX2 receptors within the VTA reduced the expression of morphine-induced CPP in the sensitized rats. It is plausible that VTAs orexin receptors are involved in the development/acquisition of sensitization to morphine-induced CPP in the rats.
Brain Neurodegeneration in the Chronic Stage of the Survivors from Severe Non-Missile Traumatic Brain Injury: A Voxel-Based Morphometry Within-Group at One versus Nine Years from a Head Injury.
Journal of neurotrauma, 2021

The long-term time course of neuropathological changes occurring in survivors from severe traumatic brain injury (TBI) remains uncertain. We investigated the brain morphometry and memory performance modifications within the same group of severe non-missile traumatic brain injury patients (nmTBI) after about ∼one year and at ∼ nine years from injury. Brain magnetic resonance imaging (MRI) measurements were performed with voxel-based morphometry (VBM) to determine specific changes in the gray matter (GM) and white matter (WM) and the overall gray matter volume modifications (GMV) and white matter volume modifications (WMV). Contemporarily, memory-tests were also administered. In comparison with healthy control subjects (HC), those with nmTBI showed a significant change and volume reduction in the GM and WM and also in the GMV and WMV after ∼one year; conversely, ∼nine years after injury, neurodegenerative changes spared the GM and GMV, but a prominent loss was detected in WMV and in WM sites, such as the superior longitudinal fasciculi, the body of the corpus callosum, the optic radiation, and the uncinate fasciculus. Memory performance at ∼one year in comparison with ∼nine years was stable with a subtle but significant trend toward recovery. These data demonstrate that patients with nmTBI undergo neurodegenerative processes during the chronic stage affecting mainly the cerebral WM rather than GM. Despite these anatomical brain parenchyma losses, memory performance tends to be stable or even slightly recovered. These results suggest possible correlations between progressive demyelinization and/or neuropsychiatric changes other than memory performance, and support possible treatments to prevent long-term WM degeneration of the examined nmTBI.
[Use of the PELICAN software for the creation and export of standardized pathology reports in central nervous system tumors: Example of meningiomas].
Annales de pathologie, 2019

PELICAN ("Partager Efficacement en Laboratoire les Informations des Comptes rendus ANatomopathologiques") is a software, which generates standardized reports, and allows to automatically create a database. It has been used in central nervous system tumor pathology at the University Hospital of Nancy since 2014. The purpose of this article was to illustrate the use of this application for meningiomas, with a first statistical evaluation.