rudyvdbrink/CitationDatabase huggingface dataset:
Ontology-based prediction of cancer driver genes.
Scientific reports, 2019

Identifying and distinguishing cancer driver genes among thousands of candidate mutations remains a major challenge. Accurate identification of driver genes and driver mutations is critical for advancing cancer research and personalizing treatment based on accurate stratification of patients. Due to inter-tumor genetic heterogeneity many driver mutations within a gene occur at low frequencies, which make it challenging to distinguish them from non-driver mutations. We have developed a novel method for identifying cancer driver genes. Our approach utilizes multiple complementary types of information, specifically cellular phenotypes, cellular locations, functions, and whole body physiological phenotypes as features. We demonstrate that our method can accurately identify known cancer driver genes and distinguish between their role in different types of cancer. In addition to confirming known driver genes, we identify several novel candidate driver genes. We demonstrate the utility of our method by validating its predictions in nasopharyngeal cancer and colorectal cancer using whole exome and whole genome sequencing.
CD38 deficiency alleviates Ang II-induced vascular remodeling by inhibiting small extracellular vesicle-mediated vascular smooth muscle cell senescence in mice.
Signal transduction and targeted therapy, 2021

CD38 is the main enzyme for nicotinamide adenine dinucleotide (NAD) degradation in mammalian cells. Decreased NAD levels are closely related to metabolic syndromes and aging-related diseases. Our study showed that CD38 deficiency significantly alleviated angiotensin II (Ang II)-induced vascular remodeling in mice, as shown by decreased blood pressures; reduced vascular media thickness, media-to-lumen ratio, and collagen deposition; and restored elastin expression. However, our bone marrow transplantation assay showed that CD38 deficiency in lymphocytes led to lack of protection against Ang II-induced vascular remodeling, suggesting that the effects of CD38 on Ang II-induced vascular remodeling might rely primarily on vascular smooth muscle cells (VSMCs), not lymphocytes. In addition, we observed that CD38 deficiency or NAD supplementation remarkably mitigated Ang II-induced vascular senescence by suppressing the biogenesis, secretion, and internalization of senescence-associated small extracellular vesicles (SA-sEVs), which facilitated the senescence of neighboring non-damaged VSMCs. Furthermore, we found that the protective effects of CD38 deficiency on VSMC senescence were related to restoration of lysosome dysfunction, particularly with respect to the maintenance of sirtuin-mediated mitochondrial homeostasis and activation of the mitochondria-lysosomal axis in VSMCs. In conclusion, our findings demonstrated that CD38 and its associated intracellular NAD decline are critical for Ang II-induced VSMC senescence and vascular remodeling.
Beyond perceptual symbols: a call for representational pluralism.
Cognition, 2009

Recent evidence from cognitive neuroscience suggests that certain cognitive processes employ perceptual representations. Inspired by this evidence, a few researchers have proposed that cognition is inherently perceptual. They have developed an innovative theoretical approach that rests on the notion of perceptual simulation and marshaled several general arguments supporting the centrality of perceptual representations to concepts. In this article, I identify a number of weaknesses in these arguments and defend a multiple semantic code approach that posits both perceptual and non-perceptual representations.
Crosslinked Hyaluronic Acid with Liposomes and Crocin Confers Cytoprotection in an Experimental Model of Dry Eye.
Molecules (Basel, Switzerland), 2021

Dry eye disease (DED) is a multifactorial condition caused by tear deficiency and accompanied by ocular surface damage. Recent data support a key role of oxidative and inflammatory processes in the pathogenesis of DED. Hyaluronic acid (HA) is widely used in artificial tears to treat DED by improving ocular hydration and reducing surface friction. Crocin (Cr), the main constituent of saffron, is a renowned compound that exhibits potent antioxidant and anti-inflammatory effects. The present study was undertaken to assess the viscosity and muco-adhesiveness of a photoactivated formulation with crosslinked HA (cHA), Cr, and liposomes (cHA-Cr-L). Our aim was also to evaluate whether cHA-Cr-L may exert cytoprotective effects against oxidative and inflammatory processes in human corneal epithelial cells (HCECs). Viscosity was measured using a rotational rheometer, and then the muco-adhesiveness was evaluated. Under hyperosmolarity (450 mOsm), the HCECs were treated with cHA-Cr-L. Interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα) were quantified by quantitative real-time polymerase chain reaction (RT-qPCR). The levels of reactive oxygen species (ROS) were measured using the DCF assay. The combined action of cHA-Cr-L produced a higher viscosity and muco-adhesiveness compared to the control. The anti-inflammatory effect of cHA-Cr-L was achieved through a significant reduction of IL-1β and TNFα (
Trigonometric regressive spectral analysis: an innovative tool for evaluating the autonomic nervous system.
Journal of neural transmission (Vienna, Austria : 1996), 2013

Biological rhythms, describing the temporal variation of biological processes, are a characteristic feature of complex systems. The analysis of biological rhythms can provide important insights into the pathophysiology of different diseases, especially, in cardiovascular medicine. In the field of the autonomic nervous system, heart rate variability (HRV) and baroreflex sensitivity (BRS) describe important fluctuations of blood pressure and heart rate which are often analyzed by Fourier transformation. However, these parameters are stochastic with overlaying rhythmical structures. R-R intervals as independent variables of time are not equidistant. That is why the trigonometric regressive spectral (TRS) analysis--reviewed in this paper--was introduced, considering both the statistical and rhythmical features of such time series. The data segments required for TRS analysis can be as short as 20 s allowing for dynamic evaluation of heart rate and blood pressure interaction over longer periods. Beyond HRV, TRS also estimates BRS based on linear regression analyses of coherent heart rate and blood pressure oscillations. An additional advantage is that all oscillations are analyzed by the same (maximal) number of R-R intervals thereby providing a high number of individual BRS values. This ensures a high confidence level of BRS determination which, along with short recording periods, may be of profound clinical relevance. The dynamic assessment of heart rate and blood pressure spectra by TRS allows a more precise evaluation of cardiovascular modulation under different settings as has already been demonstrated in different clinical studies.
ADHD subtypes and neuropsychological performance in an adult sample.
Research in developmental disabilities, 2016

The study investigated, with an adult sample, the hypothesis that differences between subtypes of ADHD on neuropsychological tests contribute to the poor separation of ADHD and healthy groups on tests of this kind. Groups of ADHD inattentive (n=16) and combined (n=16) subtypes were carefully identified using DSM-IV criteria, and their performance on 14 measures of attention, memory, and executive function (EF) was compared between subtypes and between the two subtypes combined and a group of healthy controls (n=30). Multivariate analyses showed statistically significant differences between the two subtypes, and between the two subtypes combined and the healthy controls. Importantly for the hypothesis, where differences for neuropsychological tests in terms of effect sizes between subtypes were largest, the differences in effect sizes between the two groups combined and controls were smallest (r=-0.64, 95% CI [-0.15, -0.87]).
Dual use of Diff-Quik-like stains for the simultaneous evaluation of human sperm morphology and chromatin status.
Human reproduction (Oxford, England), 2009

Sperm chromatin status and nuclear DNA damage can be detected using well-established assays. However, most techniques are time-consuming and/or involve elaborate protocols and equipment. We have recently developed a simple and fast method to monitor sperm chromatin status in field conditions using the Diff-Quik assay which is employed in fertility clinics to assess sperm morphology with standard bright field microscopy. In the present study, we demonstrate that any Diff-Quik-like stain can easily, reproducibly and routinely monitor human sperm chromatin status as well.
Cognitive behavioral therapy for menopausal symptoms.
Climacteric : the journal of the International Menopause Society, 2021

This article describes cognitive behavioral therapy (CBT) for women with problematic menopausal symptoms, and provides the evidence from clinical trials of women going through the menopause, women with breast cancer treatment-induced symptoms and women with problematic symptoms in a work context. The CBT focus is primarily on vasomotor symptoms (VMS) but it also targets stress, low mood and sleep problems. CBT is a brief therapy (four to six sessions) that is theory- and evidence-based; it is acceptable to women and effectively reduces the impact of VMS, improves sleep and has benefits to quality of life. VMS frequency is also reduced significantly in some trials but not others. CBT has been found to be consistently effective when delivered in groups, self-help book and on-line formats (with or without additional support). The MENOS 1 and MENOS 2 CBT protocols are recommended for the treatment of VMS by the North American Menopause Society (2015); CBT has been recommended for the treatment of anxiety and depression for women during the menopause transition and post menopause (NICE, 2015); and telephone CBT has been shown to be an effective treatment for insomnia.
Color-tuned neurons are spatially clustered according to color preference within alert macaque posterior inferior temporal cortex.
Proceedings of the National Academy of Sciences of the United States of America, 2009

Large islands of extrastriate cortex that are enriched for color-tuned neurons have recently been described in alert macaque using a combination of functional magnetic resonance imaging (fMRI) and single-unit recording. These millimeter-sized islands, dubbed "globs," are scattered throughout the posterior inferior temporal cortex (PIT), a swath of brain anterior to area V3, including areas V4, PITd, and posterior TEO. We investigated the micro-organization of neurons within the globs. We used fMRI to identify the globs and then used MRI-guided microelectrodes to test the color properties of single glob cells. We used color stimuli that sample the CIELUV perceptual color space at regular intervals to test the color tuning of single units, and make two observations. First, color-tuned neurons of various color preferences were found within single globs. Second, adjacent glob cells tended to have the same color tuning, demonstrating that glob cells are clustered by color preference and suggesting that they are arranged in color columns. Neurons separated by 50 microm, measured parallel to the cortical sheet, had more similar color tuning than neurons separated by 100 microm, suggesting that the scale of the color columns is <100 microm. These results show that color-tuned neurons in PIT are organized by color preference on a finer scale than the scale of single globs. Moreover, the color preferences of neurons recorded sequentially along a given electrode penetration shifted gradually in many penetrations, suggesting that the color columns are arranged according to a chromotopic map reflecting perceptual color space.
Optimization of graph construction can significantly increase the power of structural brain network studies.
NeuroImage, 2019

Structural brain networks derived from diffusion magnetic resonance imaging data have been used extensively to describe the human brain, and graph theory has allowed quantification of their network properties. Schemes used to construct the graphs that represent the structural brain networks differ in the metrics they use as edge weights and the algorithms they use to define the network topologies. In this work, twenty graph construction schemes were considered. The schemes use the number of streamlines, the fractional anisotropy, the mean diffusivity or other attributes of the tracts to define the edge weights, and either an absolute threshold or a data-driven algorithm to define the graph topology. The test-retest data of the Human Connectome Project were used to compare the reproducibility of the graphs and their various attributes (edges, topologies, graph theoretical metrics) derived through those schemes, for diffusion images acquired with three different diffusion weightings. The impact of the scheme on the statistical power of the study and on the number of participants required to detect a difference between populations or an effect of an intervention was also calculated. The reproducibility of the graphs and their attributes depended heavily on the graph construction scheme. Graph reproducibility was higher for schemes that used thresholding to define the graph topology, while data-driven schemes performed better at topology reproducibility (mean similarities of 0.962 and 0.984 respectively, for graphs derived from diffusion images with b=2000 s/mm
Metabolomic analysis reveals metabolic disturbances in the prefrontal cortex of the lipopolysaccharide-induced mouse model of depression.
Behavioural brain research, 2016

Major depressive disorder (MDD) is a debilitating illness. However, the underlying molecular mechanisms of depression remain largely unknown. Increasing evidence supports that inflammatory cytokine disturbances may be associated with the pathophysiology of depression in humans. Systemic administration of lipopolysaccharide (LPS) has been used to study inflammation-associated neurobehavioral changes in rodents, but no metabonomic study has been conducted to assess differential metabolites in the prefrontal cortex (PFC) of a LPS-induced mouse model of depression. Here, we employed a gas chromatography-mass spectrometry-based metabonomic approach in the LPS-induced mouse model of depression to investigate any significant metabolic changes in the PFC. Multivariate statistical analysis, including principal component analysis (PCA), partial least squares-discriminate analysis (PLS-DA), and pair-wise orthogonal projections to latent structures discriminant analysis (OPLS-DA), was implemented to identify differential PFC metabolites between LPS-induced depressed mice and healthy controls. A total of 20 differential metabolites were identified. Compared with control mice, LPS-treated mice were characterized by six lower level metabolites and 14 higher level metabolites. These molecular changes were closely related to perturbations in neurotransmitter metabolism, energy metabolism, oxidative stress, and lipid metabolism, which might be evolved in the pathogenesis of MDD. These findings provide insight into the pathophysiological mechanisms underlying MDD and could be of valuable assistance in the clinical diagnosis of MDD.
Activity patterns of serotonin neurons underlying cognitive flexibility.
eLife, 2017

Serotonin is implicated in mood and affective disorders. However, growing evidence suggests that a core endogenous role is to promote flexible adaptation to changes in the causal structure of the environment, through behavioral inhibition and enhanced plasticity. We used long-term photometric recordings in mice to study a population of dorsal raphe serotonin neurons, whose activity we could link to normal reversal learning using pharmacogenetics. We found that these neurons are activated by both positive and negative prediction errors, and thus report signals similar to those proposed to promote learning in conditions of uncertainty. Furthermore, by comparing the cue responses of serotonin and dopamine neurons, we found differences in learning rates that could explain the importance of serotonin in inhibiting perseverative responding. Our findings show how the activity patterns of serotonin neurons support a role in cognitive flexibility, and suggest a revised model of dopamine-serotonin opponency with potential clinical implications.
Memory of my victory and your defeat: Contributions of reward- and memory-related regions to the encoding of winning events in competitions with others.
Neuropsychologia, 2021

Social interactions enhance human memories, but little is known about how the neural mechanisms underlying episodic memories are modulated by rewarding outcomes in social interactions. To investigate this, fMRI data were recorded while healthy young adults encoded unfamiliar faces in either a competition or a control task. In the competition task, participants encoded opponents' faces in the rock-paper-scissors game, where trial-by-trial outcomes of Win, Draw, and Lose for participants were shown by facial expressions of opponents (Angry, Neutral, and Happy). In the control task, participants encoded faces by assessing facial expressions. After encoding, participants recognized faces previously learned. Behavioral data showed that emotional valence for opponents' Angry faces as the Win outcome was rated positively in the competition task, whereas the rating for Angry faces was rated negatively in the control task, and that Angry faces were remembered more accurately than Neutral or Happy faces in both tasks. fMRI data showed that activation in the medial orbitofrontal cortex (mOFC) paralleled the pattern of valence ratings, with greater activation for the Win than Draw or Lose conditions of the competition task, and the Angry condition of the control task. Moreover, functional connectivity between the mOFC and hippocampus was increased in Win compared to Angry, and the mOFC-hippocampus functional connectivity predicted individual differences in subsequent memory performance only in Win of the competition task, but not in any other conditions of the two tasks. These results demonstrate that the memory enhancement by context-dependent social rewards involves interactions between reward- and memory-related regions.
Microglial Remodeling of the Extracellular Matrix Promotes Synapse Plasticity.
Cell, 2020

Synapse remodeling is essential to encode experiences into neuronal circuits. Here, we define a molecular interaction between neurons and microglia that drives experience-dependent synapse remodeling in the hippocampus. We find that the cytokine interleukin-33 (IL-33) is expressed by adult hippocampal neurons in an experience-dependent manner and defines a neuronal subset primed for synaptic plasticity. Loss of neuronal IL-33 or the microglial IL-33 receptor leads to impaired spine plasticity, reduced newborn neuron integration, and diminished precision of remote fear memories. Memory precision and neuronal IL-33 are decreased in aged mice, and IL-33 gain of function mitigates age-related decreases in spine plasticity. We find that neuronal IL-33 instructs microglial engulfment of the extracellular matrix (ECM) and that its loss leads to impaired ECM engulfment and a concomitant accumulation of ECM proteins in contact with synapses. These data define a cellular mechanism through which microglia regulate experience-dependent synapse remodeling and promote memory consolidation.
Perceptual inference predicts contextual modulations of sensory responses.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012

Sensory receptive fields (RFs) vary as a function of stimulus properties and measurement methods. Previous stimuli or surrounding stimuli facilitate, suppress, or change the selectivity of sensory neurons' responses. Here, we propose that these spatiotemporal contextual dependencies are signatures of efficient perceptual inference and can be explained by a single neural mechanism, input targeted divisive inhibition. To respond both selectively and reliably, sensory neurons should behave as active predictors rather than passive filters. In particular, they should remove input they can predict ("explain away") from the synaptic inputs to all other neurons. This implies that RFs are constantly and dynamically reshaped by the spatial and temporal context, while the true selectivity of sensory neurons resides in their "predictive field." This approach motivates a reinvestigation of sensory representations and particularly the role and specificity of surround suppression and adaptation in sensory areas.
Neuroimaging: a scanner, colourfully.
Current biology : CB, 2012

Two recent studies report changes in human brain responses after exposure to psilocybin, the active ingredient of hallucinogenic mushrooms. Psilocybin increased sensory cortex responses during emotional recollection, but decreased resting-state blood flow in prefrontal cortex, with potential implications for treating depression.
MID-PREGNANCY CORTICOTROPIN-RELEASING HORMONE LEVELS IN ASSOCIATION WITH POSTPARTUM DEPRESSIVE SYMPTOMS.
Depression and anxiety, 2016

Peripartum depression is a common cause of pregnancy- and postpartum-related morbidity. The production of corticotropin-releasing hormone (CRH) from the placenta alters the profile of hypothalamus-pituitary-adrenal axis hormones and may be associated with postpartum depression. The purpose of this study was to assess, in nondepressed pregnant women, the possible association between CRH levels in pregnancy and depressive symptoms postpartum.
Are serum autoantibodies associated with brain changes in systemic lupus erythematosus? MRI data from the Leiden NP-SLE cohort.
Lupus, 2019

The effect of serum autoantibodies on the brain of systemic lupus erythematosus (SLE) patients remains unclear. We investigated whether serum autoantibodies, individually and assessed in groups, are associated with specific brain-MRI abnormalities or whether these structural changes are associated with other SLE-related or traditional cardiovascular disease risk factors.
Appraisals of psychotic experiences: an experimental investigation of symptomatic, remitted and non-need-for-care individuals.
Psychological medicine, 2016

Appraisals are suggested to play a determining role in the clinical outcome of psychotic experiences (PEs). We used experimental tasks that mimic PEs to investigate appraisals in individuals with PEs with and without a 'need-for-clinical-care', and psychosis patients whose symptoms have remitted. We predicted that patients would appraise the tasks as threatening regardless of current symptom level, while non-clinical and control groups would appraise them as non-threatening.