rudyvdbrink/CitationDatabase huggingface dataset:
Prophylactic TLR9 stimulation reduces brain metastasis through microglia activation.
PLoS biology, 2019

Brain metastases are prevalent in various types of cancer and are often terminal, given the low efficacy of available therapies. Therefore, preventing them is of utmost clinical relevance, and prophylactic treatments are perhaps the most efficient strategy. Here, we show that systemic prophylactic administration of a toll-like receptor (TLR) 9 agonist, CpG-C, is effective against brain metastases. Acute and chronic systemic administration of CpG-C reduced tumor cell seeding and growth in the brain in three tumor models in mice, including metastasis of human and mouse lung cancer, and spontaneous melanoma-derived brain metastasis. Studying mechanisms underlying the therapeutic effects of CpG-C, we found that in the brain, unlike in the periphery, natural killer (NK) cells and monocytes are not involved in controlling metastasis. Next, we demonstrated that the systemically administered CpG-C is taken up by endothelial cells, astrocytes, and microglia, without affecting blood-brain barrier (BBB) integrity and tumor brain extravasation. In vitro assays pointed to microglia, but not astrocytes, as mediators of CpG- C effects through increased tumor killing and phagocytosis, mediated by direct microglia-tumor contact. In vivo, CpG-C-activated microglia displayed elevated mRNA expression levels of apoptosis-inducing and phagocytosis-related genes. Intravital imaging showed that CpG-C-activated microglia cells contact, kill, and phagocytize tumor cells in the early stages of tumor brain invasion more than nonactivated microglia. Blocking in vivo activation of microglia with minocycline, and depletion of microglia with a colony-stimulating factor 1 inhibitor, indicated that microglia mediate the antitumor effects of CpG-C. Overall, the results suggest prophylactic CpG-C treatment as a new intervention against brain metastasis, through an essential activation of microglia.
Effects of Carvedilol Versus Metoprolol on Platelet Aggregation in Patients With Acute Coronary Syndrome: The PLATE-BLOCK Study.
The American journal of cardiology, 2018

Platelet aggregation plays a pivotal role in acute coronary syndrome (ACS). In this setting, β-blockers (BBs) are used to counteract the effects of catecholamines on heart. Circulating catecholamines can also potentiate platelet reactivity, mainly through α
Dramatically decreased cocaine self-administration in dopamine but not serotonin transporter knock-out mice.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009

There has been much interest in the relative importance of dopamine and serotonin transporters in the abuse-related-effects of cocaine. We tested the hypotheses that mice lacking the dopamine transporter (DAT(-/-)), the serotonin transporter (SERT(-/-)), or both (DAT(-/-)SERT(-/-)) exhibit decreased reinforcing effects of cocaine. We also assessed whether observed effects on self-administration are specific to cocaine or if operant behavior maintained by food or a direct dopamine agonist are similarly affected. We used a broad range of experimental conditions that included acquisition without previous training, behavior established with food training and subsequent testing with food, cocaine or a direct dopamine agonist as reinforcers, fixed ratio and progressive ratio schedules of reinforcement, and a reversal procedure. Wild-type mice readily acquired cocaine self-administration and showed dose-response curves characteristic of the schedule of reinforcement that was used. While some DAT(-/-) mice appeared to acquire cocaine self-administration transiently, almost all DAT(-/-) mice failed to self-administer cocaine reliably. Food-maintained behaviors were not decreased by the DAT mutation, and IV self-administration of a direct dopamine agonist was robust in the DAT(-/-) mice. In contrast to those mice, cocaine's reinforcing effects were not diminished in SERT(-/-) mice under any of the conditions tested, except for impaired initial acquisition of both food- and cocaine-maintained behavior. These findings support the notion that the DAT, but not the SERT, is critical in mediating the reinforcing effects of cocaine.
The impact of statin discontinuation and restarting rates on the optimal time to initiate statins and on the number of cardiovascular events prevented.
Pharmacoepidemiology and drug safety, 2020

A patient is eligible for statins in England if they have a 10-year risk of cardiovascular disease >10%. We hypothesize that if statin discontinuation rates are high it may be better to delay statin initiation until patients are at a higher risk, to maximize the benefit of the drug.
Elevation of Hippocampal Neurogenesis Induces a Temporally Graded Pattern of Forgetting of Contextual Fear Memories.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2018

Throughout life neurons are continuously generated in the subgranular zone of the hippocampus. The subsequent integration of newly generated neurons alters patterns of dentate gyrus input and output connectivity, potentially rendering memories already stored in those circuits harder to access. Consistent with this prediction, we previously showed that increasing hippocampal neurogenesis after training induces forgetting of hippocampus-dependent memories, including contextual fear memory. However, the brain regions supporting contextual fear memories change with time, and this time-dependent memory reorganization might regulate the sensitivity of contextual fear memories to fluctuations in hippocampal neurogenesis. By virally expressing the inhibitory designer receptor exclusively activated by designer drugs, hM4Di, we first confirmed that chemogenetic inhibition of dorsal hippocampal neurons impairs retrieval of recent (day-old) but not remote (month-old) contextual fear memories in male mice. We then contrasted the effects of increasing hippocampal neurogenesis at recent versus remote time points after contextual fear conditioning in male and female mice. Increasing hippocampal neurogenesis immediately following training reduced conditioned freezing when mice were replaced in the context 1 month later. In contrast, when hippocampal neurogenesis was increased time points remote to training, conditioned freezing levels were unaltered when mice were subsequently tested. These temporally graded forgetting effects were observed using both environmental and genetic interventions to increase hippocampal neurogenesis. Our experiments identify memory age as a boundary condition for neurogenesis-mediated forgetting and suggest that, as contextual fear memories mature, they become less sensitive to changes in hippocampal neurogenesis levels because they no longer depend on the hippocampus for their expression.
Functional Architecture of the Rat Parasubiculum.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2016

The parasubiculum is a major input structure of layer 2 of medial entorhinal cortex, where most grid cells are found. Here we investigated parasubicular circuits of the rat by anatomical analysis combined with juxtacellular recording/labeling and tetrode recordings during spatial exploration. In tangential sections, the parasubiculum appears as a linear structure flanking the medial entorhinal cortex mediodorsally. With a length of ∼5.2 mm and a width of only ∼0.3 mm (approximately one dendritic tree diameter), the parasubiculum is both one of the longest and narrowest cortical structures. Parasubicular neurons span the height of cortical layers 2 and 3, and we observed no obvious association of deep layers to this structure. The "superficial parasubiculum" (layers 2 and 1) divides into ∼15 patches, whereas deeper parasubicular sections (layer 3) form a continuous band of neurons. Anterograde tracing experiments show that parasubicular neurons extend long "circumcurrent" axons establishing a "global" internal connectivity. The parasubiculum is a prime target of GABAergic and cholinergic medial septal inputs. Other input structures include the subiculum, presubiculum, and anterior thalamus. Functional analysis of identified and unidentified parasubicular neurons shows strong theta rhythmicity of spiking, a large fraction of head-direction selectivity (50%, 34 of 68), and spatial responses (grid, border and irregular spatial cells, 57%, 39 of 68). Parasubicular output preferentially targets patches of calbindin-positive pyramidal neurons in layer 2 of medial entorhinal cortex, which might be relevant for grid cell function. These findings suggest the parasubiculum might shape entorhinal theta rhythmicity and the (dorsoventral) integration of information across grid scales.
Electrophysiological Activity Prior to Self-initiated Movements is Related to Impulsive Personality Traits.
Neuroscience, 2018

Electrophysiological and neuroimaging studies suggest that our actions are initiated by unconscious mental processes long before awareness of intention to act. The time window between the awareness of the intention to move and the movement onset, which normally permits to exert a conscious "veto" on the impending action, is modulated by individual differences in trait impulsivity. In particular, trait impulsive people show a delayed awareness of the intention to act, probably exceeding the "point of no return", after which the action can no longer be inhibited. In order to investigate if individual differences in the "veto" interval might be explained by differences in the readiness potential (RP) dynamics, nineteen healthy participants underwent an impulsivity trait assessment using the Barratt Impulsiveness Scale (BIS-11) and performed a task based on Libet's clock paradigm, during EEG recordings of pre-movement neural activity. We observed a positive relationship between impulsive personality trait and motor system excitability during the preparation of self-initiated movements. In particular, the RP showed an earlier negative rising phase and a greater amplitude, with the increasing of BIS-11 scores. Based on present results, we conclude hypothesizing that trait impulsivity might be characterized by less effective preparatory inhibition mechanisms, which have a fundamental role in the control of behavior.
Influence of intranasal exposure of MPTP in multiple doses on liver functions and transition from non-motor to motor symptoms in a rat PD model.
Naunyn-Schmiedeberg's archives of pharmacology, 2020

Besides the effects on the striatum, the impairment of visceral organs including liver functions has been reported in Parkinson's disease (PD) patients. However, it is yet unclear if liver functions are affected in the early stage of the disease before the motor phase has appeared. The aim of our present study was thus to assess the effect of intranasal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in different doses on striatum and liver functions. Deterioration of non-motor activities appeared on single exposure to MPTP along with rise in striatum oxidative stress and decline in antioxidant levels. Decreases in dopamine, noradrenaline, and GABA and increase in serotonin were detected in striatum. Motor coordination was impaired with a single dose of MPTP, and with repeated MPTP exposure, there was further significant impairment. Locomotor activity was affected from second exposure of MPTP, and the impairment increased with third MPTP exposure. Impairment of liver function through increase in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels was observed after first MPTP insult, and it worsened with second and third administrations. First administration of MPTP triggered systemic inflammation showing significant increase in inflammatory markers in the liver. Our data shows for the first time that an intranasal route of entry of MPTP affects liver from the non-motor phase of PD itself, occurring concomitantly with the reduction of striatal dopamine. It also suggests that a single dose is not enough to bring about progression of the disease from non-motor to locomotor deficiency, and a repeated dose is needed to establish the motor severity phase in the rat intranasal MPTP model.
Chemically Modified, α-Amino-3-hydroxy-5-methyl-4-isoxazole (AMPA) Receptor RNA Aptamers Designed for in Vivo Use.
ACS chemical neuroscience, 2017

Glutamate ion channels have three subtypes, that is, α-amino-3-hydroxy-5-methyl-4-isoxazole (AMPA), kainate, and N-methyl-d-aspartate (NMDA) receptors. Excessive activity of these receptor subtypes either individually or collectively is involved in various neurological disorders. RNA aptamers as antagonists of these receptors are potential therapeutics. For developing aptamer therapeutics, the RNA aptamers must be chemically modified to become ribonuclease-resistant or stable in biological fluids. Using systematic evolution of ligands by exponential enrichment (SELEX) and a chemically modified library, prepared enzymatically (i.e., the library contains RNAs with 2'-fluoro modified nucleoside triphosphates or ATPs, CTPs and UTPs, but regular GTPs), we have isolated an aptamer. The short aptamer (69 nucleotides) FN1040s selectively inhibits the GluA1 and GluA2Q
A cortical network for the encoding of object change.
Cerebral cortex (New York, N.Y. : 1991), 2015

Understanding events often requires recognizing unique stimuli as alternative, mutually exclusive states of the same persisting object. Using fMRI, we examined the neural mechanisms underlying the representation of object states and object-state changes. We found that subjective ratings of visual dissimilarity between a depicted object and an unseen alternative state of that object predicted the corresponding multivoxel pattern dissimilarity in early visual cortex during an imagery task, while late visual cortex patterns tracked dissimilarity among distinct objects. Early visual cortex pattern dissimilarity for object states in turn predicted the level of activation in an area of left posterior ventrolateral prefrontal cortex (pVLPFC) most responsive to conflict in a separate Stroop color-word interference task, and an area of left ventral posterior parietal cortex (vPPC) implicated in the relational binding of semantic features. We suggest that when visualizing object states, representational content instantiated across early and late visual cortex is modulated by processes in left pVLPFC and left vPPC that support selection and binding, and ultimately event comprehension.
Abnormal cognitive network interactions in Lennox-Gastaut syndrome: A potential mechanism of epileptic encephalopathy.
Epilepsia, 2016

In patients with Lennox-Gastaut syndrome (LGS), recurrent epileptic activity is thought to contribute to impaired cognition (epileptic encephalopathy). Using concurrent electroencephalography-functional magnetic resonance imaging (EEG-fMRI), we recently showed that epileptiform discharges in LGS recruit large-scale networks that normally support key cognitive processes. In LGS, given that epileptic activity engages cognitive networks, and cognition is pervasively impaired, we hypothesized that cognitive network interactions in LGS are persistently abnormal.
Structure of RC1339/APRc from Rickettsia conorii, a retropepsin-like aspartic protease.
Acta crystallographica. Section D, Biological crystallography, 2015

The crystal structures of two constructs of RC1339/APRc from Rickettsia conorii, consisting of either residues 105-231 or 110-231 followed by a His tag, have been determined in three different crystal forms. As predicted, the fold of a monomer of APRc resembles one-half of the mandatory homodimer of retroviral pepsin-like aspartic proteases (retropepsins), but the quaternary structure of the dimer of APRc differs from that of the canonical retropepsins. The observed dimer is most likely an artifact of the expression and/or crystallization conditions since it cannot support the previously reported enzymatic activity of this bacterial aspartic protease. However, the fold of the core of each monomer is very closely related to the fold of retropepsins from a variety of retroviruses and to a single domain of pepsin-like eukaryotic enzymes, and may represent a putative common ancestor of monomeric and dimeric aspartic proteases.
Peripheral facial paralysis as presenting symptom of COVID-19 in a pregnant woman.
BMJ case reports, 2020

Acute facial nerve disease leading to peripheral facial paralysis is commonly associated with viral infections. COVID-19 may be a potential cause of peripheral facial paralysis and neurological symptoms could be the first and only manifestation of the disease. We report a case of a term pregnancy diagnosed with COVID-19 after presenting with isolated peripheral facial palsy.
How and why do T cells and their derived cytokines affect the injured and healthy brain?
Nature reviews. Neuroscience, 2017

The evolution of adaptive immunity provides enhanced defence against specific pathogens, as well as homeostatic immune surveillance of all tissues. Despite being 'immune privileged', the CNS uses the assistance of the immune system in physiological and pathological states. In this Opinion article, we discuss the influence of adaptive immunity on recovery after CNS injury and on cognitive and social brain function. We further extend a hypothesis that the pro-social effects of interferon-regulated genes were initially exploited by pathogens to increase host-host transmission, and that these genes were later recycled by the host to form part of an immune defence programme. In this way, the evolution of adaptive immunity may reflect a host-pathogen 'arms race'.
Sixth Kraepelin Symposium-Understanding and Treating Cognitive Impairment and Depression in Schizophrenia and Affective Disorders.
Schizophrenia bulletin, 2019

The Sixth Kraepelin Symposium was held at the Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich in October 2018, covering reports from 12 working groups (Keith H. Nuechterlein, Ph.D., University of California, Los Angeles; Kim T. Mueser, Ph.D., Center for Psychiatric Rehabilitation, Boston University, U.S.A.; Dominic Dwyer, Ph.D, Hospital LMU, Munich; David Fowler, Ph.D. University of Sussex, Brighton, U.K.; Martin Hautzinger, Ph.D., University of Tübingen; Nikolaos Koutsouleris, M.D., Hospital LMU, Munich; Stephan Leucht, M.D., Technical University Munich, Munich; David Miklowitz, Ph.D., UCLA School of Medicine, Los Angeles. U.S.A.; Cornelius Schüle, M.D., Hospital LMU, Munich; Florian Seemüller. M.D., kbo-Lech-Mangfall Clinics for Psychiatry and Psychotherapy, Garmisch Partenkirchen; Carla Torrent, Ph.D., Institute of Neuroscience, University of Barcelona, Barcelona, Spain.) from the United States and Europe on understanding and treating cognitive impairment and depression in schizophrenia and affective disorders. Current psychological interventions to improve outcome in schizophrenia and affective disorder such as cognitive remediation, illness management, psychoeducational and cognitive therapy were focused on, as were evidence-based psychological and pharmacological treatment options, guidelines for treating cognitive deficits and depression in schizophrenia, Cochrane-meta-analysis of acute therapies, relapse prevention as well as supported withdrawal from medication. Prevention of cognitive dysfunction and symptom exacerbation was approached in terms of machine learning methods to revisit Kraepelin's illness distinctions, application of new strategies in order to increase the rate of social recovery in patients with first-episode psychosis as well as in terms of state of the art psychosocial interventions for bipolar disorder in adolescents. Finally, the dissemination of information to consumers and the contribution to the reduction of stereotypes in psychiatry was also part of the symposiums aims.
O-GlcNAcylation Reduces Ischemia-Reperfusion-Induced Brain Injury.
Scientific reports, 2017

O-GlcNAcylation is a common posttranslational modification of nucleocytoplasmic proteins with β-N-acetylglucosamine (GlcNAc) and regulates numerous biological processes. By using mouse models of cerebral ischemia induced by permanent and transient middle cerebral artery occlusion (MCAO), we observed an initial elevation (~1.7-fold, 1-4 hours after ischemia) and then decline of O-GlcNAcylation during cerebral ischemia. We found that moderate increase (<3-fold) of brain O-GlcNAcylation by pharmacological means ameliorated cerebral ischemia-reperfusion injury and the consequent motor and neurological deficits. Interference of the transient elevation of O-GlcNAcylation pharmacologically or genetically aggravates the ischemia-induced brain damage, motor deficits and mortality. The alteration of O-GlcNAcylation was also seen in the ischemic areas of postmortem human brains. This study reveals an important regulation of cerebral ischemia-reperfusion injury by O-GlcNAcylation and also provides a possible therapeutic strategy, i.e., by increasing O-GlcNAcylation, to reduce the cerebral damage and improve the clinical outcome of ischemic stroke.
Apolipoprotein E polymorphisms in frontotemporal lobar degeneration: a meta-analysis.
Alzheimer's & dementia : the journal of the Alzheimer's Association, 2013

Case-control studies have not been consistent in showing association between apolipoprotein E (APOE) polymorphisms and frontotemporal lobar degeneration (FTLD), producing contradictory findings. The study objective was to define and quantify further the disease risk associated with the carriage of different APOE alleles to determine whether APOE gene polymorphism is a risk factor for FTLD.
Vessel Wall Enhancement and Blood-Cerebrospinal Fluid Barrier Disruption After Mechanical Thrombectomy in Acute Ischemic Stroke.
Stroke, 2017

Less than half of acute ischemic stroke patients treated with mechanical thrombectomy obtain permanent clinical benefits. Consequently, there is an urgent need to identify mechanisms implicated in the limited efficacy of early reperfusion. We evaluated the predictors and prognostic significance of vessel wall permeability impairment and its association with blood-cerebrospinal fluid barrier (BCSFB) disruption after acute stroke treated with thrombectomy.
A Novel Mobile Tool (Somatomap) to Assess Body Image Perception Pilot Tested With Fashion Models and Nonmodels: Cross-Sectional Study.
JMIR mental health, 2019

Distorted perception of one's body and appearance, in general, is a core feature of several psychiatric disorders including anorexia nervosa and body dysmorphic disorder and is operative to varying degrees in nonclinical populations. Yet, body image perception is challenging to assess, given its subjective nature and variety of manifestations. The currently available methods have several limitations including restricted ability to assess perceptions of specific body areas. To address these limitations, we created Somatomap, a mobile tool that enables individuals to visually represent their perception of body-part sizes and shapes as well as areas of body concerns and record the emotional valence of concerns.
Misuse of buprenorphine maintenance treatment since introduction of its generic forms: OPPIDUM survey.
Pharmacoepidemiology and drug safety, 2012

The purpose of the study was to compare, using data from Observation of Illicit Psychotropic Substances or Non-medical Used Medications (OPPIDUM) surveys, first, the profile of buprenorphine users and their modalities of buprenorphine use from 2006 to 2008 and, second, two subgroups: brand-name and generic buprenorphine users in 2008.