rudyvdbrink/CitationDatabase huggingface dataset:
Underestimated Peripheral Effects Following Pharmacological and Conditional Genetic Microglial Depletion.
International journal of molecular sciences, 2020

Microglia, predominant parenchymal resident macrophages in the central nervous system (CNS), are crucial players in neurodevelopment and CNS homeostasis. In disease conditions, pro-inflammatory microglia predominate over their regulatory counterparts, and are thus a potential immunotherapeutic target. It has been well documented that microglia can be effectively depleted using both conditional genetic
Differential transcriptional response following glucocorticoid activation in cultured blood immune cells: a novel approach to PTSD biomarker development.
Translational psychiatry, 2019

Post-traumatic stress disorder (PTSD) is a condition of stress reactivity, whose clinical manifestations are evident when patients are triggered following exposure to a traumatic event. While baseline differences in gene expression of glucocorticoid signaling and inflammatory cytokines in peripheral blood mononuclear cells (PBMCs) have been associated with PTSD, these alterations do not fully recapitulate the molecular response to physiological triggers, such as stress hormones. Therefore, it is critical to develop new techniques that will capture the dynamic transcriptional response associated with stress-activated conditions relative to baseline conditions. To achieve this goal, cultured PBMCs from combat-exposed veterans with PTSD(+) (n = 10) and without PTSD(-) (n = 10) were incubated with increasing concentrations (vehicle, 2.5 nM, 5 nM, 50 nM) of dexamethasone (DEX). Across diagnosis and dosage, several genes and gene networks were reliable markers of glucocorticoid stimulation (FDR < 5%), including enhanced expression of FKPB5, VIPR1, NR1I3, and apoptosis-related pathways, and reduced expression of NR3C1, STAT1, IRF1, and related inflammatory and cellular stress-responsive pathways. Dose-dependent differential transcriptional changes in several genes were also identified between PTSD+ and PTSD-. Robust changes in expression were observed at 2.5 nM DEX in PTSD- but not PTSD+ participants; whereas, with increasing concentrations (5 nM and 50 nM), several genes were identified to be uniquely up-regulated in PTSD+ but not PTSD- participants. Collectively, these preliminary findings suggest that genome-wide gene expression profiling of DEX-stimulated PBMCs is a promising method for the exploration of the dynamic differential molecular responses to stress hormones in PTSD, and may identify novel markers of altered glucocorticoid signaling and responsivity in PTSD.
Reduced Proactive Control Processes Associated With Behavioral Response Inhibition Deficits in Autism Spectrum Disorder.
Autism research : official journal of the International Society for Autism Research, 2021

Impairments in inhibitory control are common in individuals with autism spectrum disorder (ASD) and associated with multiple clinical issues. Proactive (i.e., delaying response onset) and reactive control mechanisms (i.e., stopping quickly) contribute to successful inhibitory control in typically developing individuals and may be compromised in ASD. We assessed inhibitory control in 58 individuals with ASD and 63 typically developing controls aged 5-29 years using an oculomotor stop-signal task during which participants made rapid eye movements (i.e., saccades) toward peripheral targets (i.e., GO trials) or inhibited saccades (i.e., STOP trials). Individuals with ASD exhibited reduced ability to inhibit saccades, reduced reaction time slowing (GO RT slowing), and faster stop-signal reaction times (SSRT) compared to controls. Across participants, stopping accuracy was positively related to GO RT slowing, and increased age was associated with higher stopping accuracy and GO RT slowing. Our results indicate that failures to proactively delay prepotent responses in ASD underpin deficits of inhibitory control and may contribute to difficulties modifying their behavior according to changes in contextual demands. These findings implicate frontostriatal brain networks in inhibitory control and core symptoms of ASD. LAY SUMMARY: Difficulties stopping actions are common in individuals with autism spectrum disorder (ASD) and are related to repetitive behaviors. This study compared the ability to stop eye movements in individuals with ASD and healthy peers. We found that individuals with ASD were less able to stop eye movements and that this difficulty was related to a reduced ability to delay their eye movements before seeing the cue to stop, not their ability to react quickly to this cue.
[Brain and Artificial Intelligence].
Brain and nerve = Shinkei kenkyu no shinpo, 2019

The brain is an information machine equipped with mind and consciousness, acquired through a long history of evolution. Artificial intelligence (AI) aims at the development of intelligent functions in computers. We show mechanisms of deep learning in AI, and compare them with brain functions. In particular, we consider the function of consciousness in the brain, and its relation to AI. Mathematical neuroscience provides a powerful method to both AI and brain science. We conclude by emphasizing that further interactions are important for both AI and brain science.
Hyperbaric oxygen therapy increases telomere length and decreases immunosenescence in isolated blood cells: a prospective trial.
Aging, 2020

Aging is characterized by the progressive loss of physiological capacity. At the cellular level, two key hallmarks of the aging process include telomere length (TL) shortening and cellular senescence. Repeated intermittent hyperoxic exposures, using certain hyperbaric oxygen therapy (HBOT) protocols, can induce regenerative effects which normally occur during hypoxia. The aim of the current study was to evaluate whether HBOT affects TL and senescent cell concentrations in a normal, non-pathological, aging adult population.
DNA-labelled cytidine assay for the quantification of CAG repeats.
Journal of neuroscience methods, 2008

The sequencing procedure has been used to determine the size of the CAG repeat expansion for the diagnosis of genetic disorders. Likewise, standard polymerase chain reaction (PCR) and gel electrophoresis techniques are applied for screening large number of patients. The trinucleotide repeats (TNR) region amplification by means of the PCR procedure was initially performed using 32-P end-labelled primers and currently carried out with fluorescently end-labelled primers. The goal to obtain reliable TNR quantification assays, at low cost and short assay times, represents a challenge for the molecular diagnosis aimed at massive screening of affected populations. In the current work, we obtained preliminary results of a new methodology for the detection and size estimation of CAG expanded alleles. The assay was based on an indirect enzyme linked immunosorbent assay (ELISA) for quantifying the amount of labelled cytidines in DNA molecules. The label, 6-(p-bromobenzamido)caproyl radical, was introduced by the transamination and acylation reactions. A group of model sequences containing different numbers of CAG repeats, as well as the ATXN3 (ataxin 3) gene (from subjects suffering type 3 spinocerebellar ataxia SCA3) were used for assay standardization. The assay is simple, inexpensive, and easy to perform and differentiates distinct degrees of CAG expansions.
Artificial Intelligence Analysis of Magnetic Particle Imaging for Islet Transplantation in a Mouse Model.
Molecular imaging and biology, 2021

Current approaches to quantification of magnetic particle imaging (MPI) for cell-based therapy are thwarted by the lack of reliable, standardized methods of segmenting the signal from background in images. This calls for the development of artificial intelligence (AI) systems for MPI analysis.
Dynamics of manual skill: a computerized analysis of single peg movements and stochastic resonance hypothesis of cerebral laterality.
The International journal of neuroscience, 2008

Hand skill was analyzed using a computerized peg moving task. The durations of single hand movements (PMTs) were accurately measured in right-hand (RH) and left-hand (LH) writers. One trial consisted of 10 movements of the right hand and 10 movements of the left hand. Each participant performed five trials. Women showed significantly higher percentage than men in right-handedness; men showed higher percentage than women in left-handedness. This sex difference completely disappeared after taking the same height range in participants. The mean RH- and LH-PMTs decreased in 5 successive trials, even within a single trial during 10 successive hand movements, indicating a learning effect of repeated hand movements. The LH- minus RH-PMTs exhibited fluctuations within a single trial between positive (faster right hand) and negative (faster left hand) values. LH-RH PMTs were significantly greater than zero, in favor of right hand, in RH-writers, but not significantly different from zero in LH-writers, exhibiting a true fluctuating asymmetry. Participants with no familial sinistrality (FS-) were preponderantly right-handed (ca. 90%), those with left-handed mother and right-handed father (FS+1) showed stochastic distribution of hand preference (50:50). Participants with right-handed mother and left-hander father (FS+2) were not different from FS- individuals. LH-RH PMT was significantly greater than zero in FS- participants, almost equal to zero in FS+1 participants, and greater than zero in FS+2 participants exhibiting greater asymmetry than that in FS- participants. These results suggest a genetic inheritance of direction and degree of handedness, being a a X-linked trait originating from mother's genotype. It was suggested that fluctuating asymmetries may reflect interactions between stochastic resonance phenomena within right and left brains. This property of brain may genetically transmitted from mother's X chromosome; a net effect of stochastic interactions between hemispheres may result in right- or left-handedness, a predominantly unidirectional coupling creating right-handedness, in favor of left brain, and a stochastic bi-directional coupling between hemispheres would be a main trait of left-handers. This new "stochastic resonance hypothesis of cerebral laterality" concerns with stochastic fluctuations in hand-skill asymmetry and inter-hemispheric coupling through corpus callosum, and seems to be important for new developments in handedness research.
The analgesic effects of intrathecally pumped saline and artificial cerebrospinal fluid in a rat model of neuropathic pain.
Neuromodulation : journal of the International Neuromodulation Society, 2002

Objective. This experiment was performed to test the hypothesis that intrathecally pumped saline, but not artificial cerebrospinal fluid (CSF), would be analgesic in a rat model of neuropathic pain. Materials and Methods. Surgery for the chronic constriction injury (CCI) model of neuropathic pain and intrathecal catheter placement were performed on the rats, baseline pain testing and pump implantation were performed 7 days later, and pain tests were repeated on days 1, 4, 7, and 14 after pump implantation. Results. Intrathecally pumped saline and artificial CSF were analgesic for cold allodynia (p < 0.05), and intrathecally pumped saline but not CSF for heat nociception in the affected paw (p < 0.005) compared to rats with unattached subcutaneous pumps. No analgesia was observed on tests of spontaneous pain or pressure hyperalgesia (p > 0.1). Conclusions. Intrathecally pumped saline and artificial CSF have analgesic effects on some neuropathic and normal, nociceptive pain signs in CCI rats.
Schema therapy versus cognitive behavioral therapy versus individual supportive therapy for depression in an inpatient and day clinic setting: study protocol of the OPTIMA-RCT.
BMC psychiatry, 2020

Major depressive disorder represents (MDD) a major cause of disability and disease burden. Beside antidepressant medication, psychotherapy is a key approach of treatment. Schema therapy has been shown to be effective in the treatment of psychiatric disorders, especially personality disorders, in a variety of settings and patient groups. Nevertheless, there is no evidence on its effectiveness for MDD in an inpatient nor day clinic setting and little is known about the factors that drive treatment response in such a target group.
Successful Management of Natalizumab-Associated Primary Central Nervous System Lymphoma through Autologous Stem Cell Transplant.
Current oncology (Toronto, Ont.), 2020

Natalizumab is used as a second-line treatment for multiple sclerosis (MS). Some reports have linked natalizumab to primary central nervous system lymphoma (PCNSL), although few have described its management. A 45-year-old woman with Balo's Concentric Sclerosis presented dizziness, vertigo accompanied by dysarthria, weakness on the left side and blurred vision to the right eye after the fourth dose of natalizumab. Magnetic resonance imaging (MRI) and a brain biopsy confirmed the diagnosis of PCNSL. The patient received modified PCNSL chemotherapy (MATRix protocol) followed by high-dose chemotherapy (HDC) supported by an autologous hematopoietic stem cell transplant (ASCT) as a consolidation therapy. Thirty months later, she is still in complete remission of her PCNSL and MS. In this case, whole brain radiotherapy was excluded because it may be associated with an increased risk of neurotoxicity in MS. ASCT was preferred because it has been shown to prevent disability progression in less advanced MS stages. Our patient is the second to receive an ASCT in this context and this option of treatment should be the preferred if the patient is eligible.
Health behaviours as a predictor of quitting hazardous alcohol use in the Stockholm Public Health Cohort.
European journal of public health, 2018

Adopting healthy behaviours may facilitate the transition from hazardous to non-hazardous use of alcohol, yet, longitudinal studies of health behaviours in relation to the cessation of hazardous alcohol use are rare. We addressed this question using data from a large population-based cohort of adults in Sweden (Stockholm Public Health Cohort).
Cognitive impairment and its neuroimaging correlates in spinocerebellar ataxia 2.
Parkinsonism & related disorders, 2021

Cognitive impairment (CI) is reported but is poorly explored in spinocerebellar ataxia 2 (SCA2). This study was undertaken to evaluate and classify cognitive impairment in patients with SCA2 and to identify their grey matter (GM) correlates.
Cerebellar volume loss in radiologically isolated syndrome.
Multiple sclerosis (Houndmills, Basingstoke, England), 2021

Radiologically isolated syndrome (RIS), in which asymptomatic demyelinating-appearing lesions are detected incidentally on MRI, can be a pre-clinical form of multiple sclerosis (MS). In this study, we measured cerebellar volumes on 3D T1-weighted 3T MR images in 21 individuals with RIS and 38 age- and sex-matched healthy controls (HC). Normalized cerebellar white matter volume and the anterior cerebellar gray matter volume were significantly decreased in RIS compared to HC (
Infections and Chlamydia pneumoniae antibodies influence the functional outcome in thrombolysed strokes.
Journal of the neurological sciences, 2017

Thrombolysis is effective in ischemic stroke patients, but some factors influence its benefit. Previous infections could increase the risk of ischemic stroke by an activation of systemic inflammation. We analysed the influence of previous infections and Chlamydia pneumoniae serology on functional outcome in thrombolysed stroke patients.
Lipophilic dye-compatible brain clearing technique allowing correlative magnetic resonance/high-resolution fluorescence imaging in rat models of glioblastoma.
Scientific reports, 2020

In this work we optimized a novel approach for combining in vivo MRI and ex vivo high-resolution fluorescence microscopy that involves: (i) a method for slicing rat brain tissue into sections with the same thickness and spatial orientation as in in vivo MRI, to better correlate in vivo MRI analyses with ex-vivo imaging via scanning confocal microscope and (ii) an improved clearing protocol compatible with lipophilic dyes that highlight the neurovascular network, to obtain high tissue transparency while preserving tissue staining and morphology with no significant tissue shrinkage or expansion. We applied this methodology in two rat models of glioblastoma (GBM; U87 human glioma cells and patient-derived human glioblastoma cancer stem cells) to demonstrate how vital the information retrieved from the correlation between MRI and confocal images is and to highlight how the increased invasiveness of xenografts derived from cancer stem cells may not be clearly detected by standard in vivo MRI approaches. The protocol studied in this work could be implemented in pre-clinical GBM research to further the development and validation of more predictive and translatable MR imaging protocols that can be used as critical diagnostic and prognostic tools. The development of this protocol is part of the quest for more efficacious treatment approaches for this devastating and still uncurable disease. In particular, this approach could be instrumental in validating novel MRI-based techniques to assess cellular infiltration beyond the macroscopic tumor margins and to quantify neo-angiogenesis.
Changes in Striatal Medium Spiny Neuron Morphology Resulting from Dopamine Depletion Are Reversible.
Cells, 2020

The classical motor symptoms of Parkinson's disease (PD) are caused by degeneration of dopaminergic neurons in the substantia nigra, which is followed by secondary dendritic pruning and spine loss at striatal medium spiny neurons (MSN). We hypothesize that these morphological changes at MSN underlie at least in part long-term motor complications in PD patients. In order to define the potential benefits and limitations of dopamine substitution, we tested in a mouse model whether dendritic pruning and spine loss can be reversible when dopaminergic axon terminals regenerate. In order to induce degeneration of nigrostriatal dopaminergic neurons we used the toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in C57BL/6J mice; 30 mg/kg MPTP was applied i.p. on five consecutive days. In order to assess the consequences of dopamine depletion, mice were analyzed 21 days after the last injection. In order to test reversibility of MSN changes we exploited the property of this model that striatal axon terminals regenerate by sprouting within 90 days and analyzed a second cohort 90 days after MPTP. Degeneration of dopaminergic neurons was confirmed by counting TH-positive neurons in the substantia nigra and by analyzing striatal catecholamines. Striatal catecholamine recovered 90 days after MPTP. MSN morphology was visualized by Golgi staining and quantified as total dendritic length, number of dendritic branch points, and density of dendritic spines. All morphological parameters of striatal MSN were reduced 21 days after MPTP. Statistical analysis indicated that dendritic pruning and the reduction of spine density represent two distinct responses to dopamine depletion. Ninety days after MPTP, all morphological changes recovered. Our findings demonstrate that morphological changes in striatal MSN resulting from dopamine depletion are reversible. They suggest that under optimal conditions, symptomatic dopaminergic therapy might be able to prevent maladaptive plasticity and long-term motor complications in PD patients.
Layers II/III of Prefrontal Cortex in Df(h22q11)/+ Mouse Model of the 22q11.2 Deletion Display Loss of Parvalbumin Interneurons and Modulation of Neuronal Morphology and Excitability.
Molecular neurobiology, 2020

The 22q11.2 deletion has been identified as a risk factor for multiple neurodevelopmental disorders. Behavioral and cognitive impairments are common among carriers of the 22q11.2 deletion. Parvalbumin expressing (PV
Generalizable brain network markers of major depressive disorder across multiple imaging sites.
PLoS biology, 2020

Many studies have highlighted the difficulty inherent to the clinical application of fundamental neuroscience knowledge based on machine learning techniques. It is difficult to generalize machine learning brain markers to the data acquired from independent imaging sites, mainly due to large site differences in functional magnetic resonance imaging. We address the difficulty of finding a generalizable marker of major depressive disorder (MDD) that would distinguish patients from healthy controls based on resting-state functional connectivity patterns. For the discovery dataset with 713 participants from 4 imaging sites, we removed site differences using our recently developed harmonization method and developed a machine learning MDD classifier. The classifier achieved an approximately 70% generalization accuracy for an independent validation dataset with 521 participants from 5 different imaging sites. The successful generalization to a perfectly independent dataset acquired from multiple imaging sites is novel and ensures scientific reproducibility and clinical applicability.
xGAP: a python based efficient, modular, extensible and fault tolerant genomic analysis pipeline for variant discovery.
Bioinformatics (Oxford, England), 2021

Since the first human genome was sequenced in 2001, there has been a rapid growth in the number of bioinformatic methods to process and analyze next-generation sequencing (NGS) data for research and clinical studies that aim to identify genetic variants influencing diseases and traits. To achieve this goal, one first needs to call genetic variants from NGS data, which requires multiple computationally intensive analysis steps. Unfortunately, there is a lack of an open-source pipeline that can perform all these steps on NGS data in a manner, which is fully automated, efficient, rapid, scalable, modular, user-friendly and fault tolerant. To address this, we introduce xGAP, an extensible Genome Analysis Pipeline, which implements modified GATK best practice to analyze DNA-seq data with the aforementioned functionalities.
CYP2J2 Molecular Recognition: A New Axis for Therapeutic Design.
Pharmacology & therapeutics, 2020

Cytochrome P450 (CYP) epoxygenases are a special subset of heme-containing CYP enzymes capable of performing the epoxidation of polyunsaturated fatty acids (PUFA) and the metabolism of xenobiotics. This dual functionality positions epoxygenases along a metabolic crossroad. Therefore, structure-function studies are critical for understanding their role in bioactive oxy-lipid synthesis, drug-PUFA interactions, and for designing therapeutics that directly target the epoxygenases. To better exploit CYP epoxygenases as therapeutic targets, there is a need for improved understanding of epoxygenase structure-function. Of the characterized epoxygenases, human CYP2J2 stands out as a potential target because of its role in cardiovascular physiology. In this review, the early research on the discovery and activity of epoxygenases is contextualized to more recent advances in CYP epoxygenase enzymology with respect to PUFA and drug metabolism. Additionally, this review employs CYP2J2 epoxygenase as a model system to highlight both the seminal works and recent advances in epoxygenase enzymology. Herein we cover CYP2J2's interactions with PUFAs and xenobiotics, its tissue-specific physiological roles in diseased states, and its structural features that enable epoxygenase function. Additionally, the enumeration of research on CYP2J2 identifies the future needs for the molecular characterization of CYP2J2 to enable a new axis of therapeutic design.