rudyvdbrink/CitationDatabase huggingface dataset:
Exploratory neuroimmune profiling identifies CNS-specific alterations in COVID-19 patients with neurological involvement.
bioRxiv : the preprint server for biology, 2020

One third of COVID-19 patients develop significant neurological symptoms, yet SARS-CoV-2 is rarely detected in central nervous system (CNS) tissue, suggesting a potential role for parainfectious processes, including neuroimmune responses. We therefore examined immune parameters in cerebrospinal fluid (CSF) and blood samples from a cohort of patients with COVID-19 and significant neurological complications. We found divergent immunological responses in the CNS compartment, including increased levels of IL-12 and IL-12-associated innate and adaptive immune cell activation. Moreover, we found increased proportions of B cells in the CSF relative to the periphery and evidence of clonal expansion of CSF B cells, suggesting a divergent intrathecal humoral response to SARS-CoV-2. Indeed, all COVID-19 cases examined had anti-SARS-CoV-2 IgG antibodies in the CSF whose target epitopes diverged from serum antibodies. We directly examined whether CSF resident antibodies target self-antigens and found a significant burden of CNS autoimmunity, with the CSF from most patients recognizing neural self-antigens. Finally, we produced a panel of monoclonal antibodies from patients' CSF and show that these target both anti-viral and anti-neural antigens-including one mAb specific for the spike protein that also recognizes neural tissue. This exploratory immune survey reveals evidence of a compartmentalized and self-reactive immune response in the CNS meriting a more systematic evaluation of neurologically impaired COVID-19 patients.
Equivalence class formation when responding is separated from sample and comparison stimuli: Working memory, priming, and sorting.
Journal of the experimental analysis of behavior, 2020

The experiment determined whether equivalence class formation required overlap of comparison stimuli and responding. Each trial contained a sample first, a single, nonoverlapping comparison second, and a nonoverlapping response-window (RW) third, during which the participant made one of two responses (2R). All 11 participants formed two 3-member ABC equivalence classes using these "trace-stimulus-pairing two-response with response window" (TSP-2R-RW) trials. After adding a fourth stimulus (D) by CD training, ABCD tests showed immediate expansion to 4-member ABCD classes. When 4-member probes (AD, DA, BD, DB, CD, DC) were administered without 3-member probes, many participants showed decrements in class-indicative responding that then resurged to mastery with test repetition. Thus, 3-member probes enhanced class expansion. Class formation occurred for all participants when responding was temporally dissociated from the comparisons. In a matched, contemporaneously published experiment, where responding occurred during comparisons, only 54% of participants formed the classes. Thus, the comparison-response-separation nearly doubled class formation. Additionally, a special post-class-formation sorting test documented the emergence of two explicit equivalence classes. Finally, we noted a 1:1 correspondence for TSP-2R-RW and priming trials. Since priming measures neural substrates of equivalence classes, TSP-2R-RW trials should do the same.
A model of listening engagement (MoLE).
Hearing research, 2020

Hearing impairment in older adulthood puts people at risk of communication difficulties, disengagement from listening, and social withdrawal. Here, we develop a model of listening engagement (MoLE) that provides a conceptual foundation to understand when people engage in listening and why some people disengage. We use the term "listening engagement" to describe the recruitment of executive and other cognitive resources in the service of a valued communication goal. Listening engagement, listening motivation, and listening experiences are closely interconnected: motivation and other factors determine the degree to which resources are recruited during listening, which in turn influences subjective listening experiences such as enjoyment, effort, frustration, and boredom. We anticipate that this model will help researchers assess more accurately whether a person with hearing difficulties is at risk of disengagement and social withdrawal. It is further useful to more comprehensively characterize a person's listening experiences in laboratory settings when rich, engaging stimulus materials, such as spoken stories, are used. We hope this model will allow new questions in applied and basic hearing science and auditory cognitive neuroscience to be asked and answered.
Smoking is a negative predictor of arteriovenous malformation posttreatment obliteration: analysis of vascular risk factors in 774 patients.
Neurosurgical focus, 2014

Cigarette smoking has been well established as a risk factor in vascular pathology, such as cerebral aneurysms. However, tobacco's implications for patients with cerebral arteriovenous malformations (AVMs) are controversial. The object of this study was to identify predictors of AVM obliteration and risk factors for complications.
3D printing of silk microparticle reinforced polycaprolactone scaffolds for tissue engineering applications.
Materials science & engineering. C, Materials for biological applications, 2021

Polycaprolactone (PCL) scaffolds have been widely investigated for tissue engineering applications, however, they exhibit poor cell adhesion and mechanical properties. Subsequently, PCL composites have been produced to improve the material properties. This study utilises a natural material, Bombyx mori silk microparticles (SMP) prepared by milling silk fibre, to produce a composite to enhance the scaffolds properties. Silk is biocompatible and biodegradable with excellent mechanical properties. However, there are no studies using SMPs as a reinforcing agent in a 3D printed thermoplastic polymer scaffold. PCL/SMP (10, 20, 30 wt%) composites were prepared by melt blending. Rheological analysis showed that SMP loading increased the shear thinning and storage modulus of the material. Scaffolds were fabricated using a screw-assisted extrusion-based additive manufacturing system. Scanning electron microscopy and X-ray microtomography was used to determine scaffold morphology. The scaffolds had high interconnectivity with regular printed fibres and pore morphologies within the designed parameters. Compressive mechanical testing showed that the addition of SMP significantly improved the compressive Young's modulus of the scaffolds. The scaffolds were more hydrophobic with the inclusion of SMP which was linked to a decrease in total protein adsorption. Cell behaviour was assessed using human adipose derived mesenchymal stem cells. A cytotoxic effect was observed at higher particle loading (30 wt%) after 7 days of culture. By day 21, 10 wt% loading showed significantly higher cell metabolic activity and proliferation, high cell viability, and cell migration throughout the scaffold. Calcium mineral deposition was observed on the scaffolds during cell culture. Large calcium mineral deposits were observed at 30 wt% and smaller calcium deposits were observed at 10 wt%. This study demonstrates that SMPs incorporated into a PCL scaffold provided effective mechanical reinforcement, improved the rate of degradation, and increased cell proliferation, demonstrating potential suitability for bone tissue engineering applications.
[Pericytes of the Nervous System: Physiological and Pathological Role].
Brain and nerve = Shinkei kenkyu no shinpo, 2020

Pericytes stabilize microvessels by wrapping them with their processes. They are located within the neurovascular unit between endothelial cells, astrocytes, and neurons, and interact with neighboring cells to generate diverse functional responses that are critical for central nerve system (CNS) function in health and disease. Recent evidence suggests that brain pericytes play crucial roles in regulating microvascular functions, such as blood-brain barrier properties, capillary blood flow, angiogenesis, and the entry of leukocytes into the brain. Pericytes also take part in tissue repair after CNS injury and may have stem cell-like properties. In addition, recent reports suggest that peripheral nerve pericytes, forming the blood-nerve barrier (BNB), regulate BNB function and basement membrane maintenance. Microvascular dysfunction due to pericyte degeneration initiates secondary neurodegenerative changes in the nervous system. In this review, we will first describe the origin, heterogeneity, and the physiological characteristics of pericytes. We next review possible pathological mechanisms and consequences of pericyte impairment in nervous system diseases including Alzheimer's diseases, diabetes, vascular dementia, and stroke. Finally, we will discuss how pericytes can be targeted for developing novel therapeutic approaches for treating patients with neurological disorders.
Ccny knockout mice display an enhanced susceptibility to kainic acid-induced epilepsy.
Pharmacological research, 2020

Cyclin Y (CCNY) is a member of cyclin superfamily proteins involved in the regulation of the cell cycle in proliferating cells. Intriguingly, CCNY is highly expressed in terminally differentiated neuronal cells of multiple brain regions and acts as a postsynaptic protein, which plays an inhibitory role in long-term potentiation. However, the pathophysiological significance of CCNY in the nervous system remains largely unexplored. In this study, we revisited our RNA-sequencing (RNA-seq) data obtained from cultured hippocampal neurons virally overexpressing or depleting CCNY. Using RNA-seq-based bioinformatic disease analysis and synaptic gene ontology analysis, we identified that numerous genes associated with epilepsy (e.g. Chrna4, Gabrd, Nhlrc1, Reln, Samd12, Slc6a1, etc.) or neurodegenerative diseases (e.g. Psen1, Pdyn, Ndrg1, etc.) are affected by the level of CCNY expression. In agreement with the RNA-seq-based disease analysis, we found that Ccny knockout (KO) mice are more susceptible to kainic acid-induced epilepsy than wild-type mice. In addition, some epilepsy-associated genes that are regulated by CCNY levels were further validated in the brain of Ccny KO mice at the mRNA and protein levels. Collectively, our findings indicate that CCNY shifts the expression profile of epilepsy-associated genes and exerts a protective effect against kainic acid-induced epilepsy, suggesting CCNY as a potential pharmaceutical candidate for the treatment of epilepsy.
Intraglottal Aerodynamics at Vocal Fold Vibration Onset.
Journal of voice : official journal of the Voice Foundation, 2021

The most frequently observed type of voice onset in spontaneous speech in normal subjects is the soft onset, and it may be considered as the "physiological" onset. It starts from an immobile narrow glottal slit crossed by a continuous airflow, and then a few oscillations (even a single one in some cases) precede the first glottal closure. It is a transient event, during which the acting forces, lung pressure, intraglottal pressure, myoelastic tension of the vocal fold (VF) oscillator and inertance of the supraglottal vocal tract, interact to progressively reach the steady state of a sustained oscillation. Combined measurements of flow, area, and pressure provide a detailed qualitative and quantitative analysis of the intraglottal mechanical events at the precise moment of starting oscillation in a physiological (soft or soft/breathy) onset. Our in vivo measurements of airflow and glottal area show that the very first oscillation occurs exactly at the time when turbulence appears at the level of the glottal narrowing, ie, when the Reynolds number reaches its critical value. The turbulence may be assumed to trigger an oscillator consisting in the ensemble of the VFs and the air of the vocal tract, which is known to be weakly damped. Turbulence can act here as an aspecific flick, triggering the oscillator, the frequency of oscillation being determined by its mechanical properties. Furthermore, the first noticeable glottal oscillations are sinusoidal: the VFs are neither steeply sucked together by a negative Bernoulli pressure, nor burst apart by the lung pressure. Our measurements show that, at the critical time, the rising positive lung pressure is balanced by the rising negative Bernoulli pressure generated by the transglottal flow.
Early Interaction of Alternaria infectoria Conidia with Macrophages.
Mycopathologia, 2019

Fungi of the genus Alternaria are ubiquitous indoor and outdoor airborne agents, and individuals are daily exposed to their spores. Although its importance in human infections and, particularly in respiratory allergies, there are no studies of how Alternaria spp. spores interact with host cells. Our aim was to study the early interaction of Alternaria infectoria spores with macrophages, the first line of immune defense. RAW 264.7 macrophages were infected with A. infectoria conidia, and the internalization and viability of conidia once inside the macrophages were quantified during the first 6 h of interaction. Live cell imaging was used to study the dynamics of this interaction. TNF-α production was quantified by relative gene expression, and the concentration of other cytokines (IL-1α, IL-1β, IL-6, IL-4, IL-10, IL-17, GM-CSF and INF-γ) and a chemokine, MIP-1α, was quantified by ELISA. Conidia were rapidly internalized by macrophages, with approximately half internalized after 30 min of interaction. During the first 6 h of interaction, macrophages retained the ability to mitotically divide while containing internalized conidia. The classical macrophage-activated morphology was absent in macrophages infected with conidia, and TNF-α and other cytokines and chemokines failed to be produced. Thus, macrophages are able to efficiently phagocyte A. infectoria conidia, but, during the first 6 h, no effective antifungal response is triggered, therefore promoting the residence of these fungal conidia inside the macrophages.
Train the brain with music (TBM): brain plasticity and cognitive benefits induced by musical training in elderly people in Germany and Switzerland, a study protocol for an RCT comparing musical instrumental practice to sensitization to music.
BMC geriatrics, 2020

Recent data suggest that musical practice prevents age-related cognitive decline. But experimental evidence remains sparse and no concise information on the neurophysiological bases exists, although cognitive decline represents a major impediment to healthy aging. A challenge in the field of aging is developing training regimens that stimulate neuroplasticity and delay or reverse symptoms of cognitive and cerebral decline. To be successful, these regimens should be easily integrated in daily life and intrinsically motivating. This study combines for the first-time protocolled music practice in elderly with cutting-edge neuroimaging and behavioral approaches, comparing two types of musical education.
How individuals make choices explains addiction's distinctive, non-eliminable features.
Behavioural brain research, 2021

In keeping with the goals of this Special Issue, this paper poses the following questions: What are addiction's non-eliminable features and can they be explained by one or more general principles? I have added the qualifier "distinctive" to these goals, as in "distinctive non-eliminable features." The result is a highly heterogeneous list, which includes features of addiction's natural history, such as its high remission rates, its unique idioms (e.g., "kicking the habit"), and its patented interventions, such as Alcoholics Anonymous. I show that each of these distinctive features reflects how individuals make choices. In particular, they reflect the competing claims of two basic choice processes: global maximizing of the sort assumed in introductory economics textbooks and Herrnstein's matching law, which has empirical rather than theoretical roots. These are basic choice processes, which apply to all decision making, not just drugs and not just addicts. Nevertheless, they can result in addiction when one of the options has the capacity to undermine the value of competing interests and undermine global maximizing. Conversely, the analyses also show that the two basic choice processes combine so as to predict that addiction is a semi-stable state that is biased to resolve in favor of remission. These predictions are supported by the high rates of addiction, by the high rates of remission from addiction, and by the fact that remission is often unassisted or "spontaneous." The analyses fail to support the idea that pathological psychological processes lead to addiction. Rather they show that addiction emerges from the interactions of normal choice processes and the behaviorally toxic effects of drugs.
Anti-depressant effect of Zhi-zi-chi decoction on CUMS mice and elucidation of its signaling pathway.
Journal of ethnopharmacology, 2021

Zhi-zi-chi decoction (ZZCD) is used for treating depression as an effectively traditional Chinese medicine. Until now, studies on pharmacological research of ZZCD have mostly been centered in pharmacokinetic level. Little was known about its pharmacological mechanism of relieving depression.
The neural substrates of subliminal attentional bias and reduced inhibition in individuals with a higher BMI: A VBM and resting state connectivity study.
NeuroImage, 2021

Previous studies have shown that individuals with overweight and obesity may experience attentional biases and reduced inhibition toward food stimuli. However, evidence is scarce as to whether the attentional bias is present even before stimuli are consciously recognized. Moreover, it is not known whether or not differences in the underlying brain morphometry and connectivity may co-occur with attentional bias and impulsivity towards food in individuals with different BMIs. To address these questions, we asked fifty-three participants (age M = 23.2, SD = 2.9, 13 males) to perform a breaking Continuous Flash Suppression (bCFS) task to measure the speed of subliminal processing, and a Go/No-Go task to measure inhibition, using food and nonfood stimuli. We collected whole-brain structural magnetic resonance images and functional resting-state activity. A higher BMI predicted slower subliminal processing of images independently of the type of stimulus (food or nonfood, p = 0.001, ε
The Non-Motor Symptoms Scale in Parkinson's disease: Validation and use.
Acta neurologica Scandinavica, 2021

The Non-Motor Symptoms Scale (NMSS) was developed and validated in 2007 as the first instrument for the comprehensive assessment of a range of non-motor symptoms in Parkinson's disease (PD). Thirteen years have elapsed since its introduction and extensive international validation with good psychometric attributes has been carried out. Here, we review the validation data of the NMSS and its cross-validity with other scales, and describe the key evidence derived from use of the NMSS in clinical studies. To date, over 100 clinical studies and trials have made use of it as an outcome measure, showing consistent and strong correlations between NMSS burden and health-related quality of life measures. Moreover, the scale has shown to be capable of detecting longitudinal changes in non-motor symptoms, where studies have shown differential changes over time of several of the NMSS domains. The scale has become a key outcome in several randomized clinical trials. Highlighting the prevalence and importance of non-motor symptoms to quality of life in patients with PD, the development of NMSS has also been useful in signposting clinical and biomarker based research addressing non-motor symptoms in PD.
HIV and Proteomics: What We Have Learned from High Throughput Studies.
Proteomics. Clinical applications, 2021

The accelerated development of technology over the last three decades has driven biological sciences to high-throughput profiling experiments, now broadly referred to as systems biology. The unprecedented improvement of analytical instrumentation has opened new avenues for more complex experimental designs and expands the knowledge in genomics, proteomics, and other omics fields. Despite the collective efforts of hundreds of researchers, gleaning all the expected information from omics experiments is still quite far. This paper summarizes what has been learned from high-throughput proteomics studies thus far, and what is believed should be done to reveal even more valuable information from such studies. It is drawn from the background in using proteomics to study human immunodeficiency virus 1 infection of macrophages and/or T cells, but it is believed that some conclusions will be more broadly applicable.
8-Nitro-cGMP attenuates context-dependent fear memory in mice.
Biochemical and biophysical research communications, 2019

We previously reported that 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) is endogenously produced via nitric oxide/reactive oxygen species signaling pathways and it reacts with protein thiol residues to add cGMP structure to proteins through S-guanylation. S-Guanylation occurs on synaptosomal-associated protein 25 (SNAP-25), which is a part of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex that regulates exocytosis. However, the biological relevance of 8-nitro-cGMP in the nervous system remains unclear. Here, we investigated the effects of intracerebroventricular (icv) infusion of 8-nitro-cGMP on mouse brain functions. The results of an open-field test and fear-conditioning task revealed that icv infusion of 8-nitro-cGMP decreased the vertical activity and context-dependent fear memory of mice, which are both associated with the hippocampus. Immunohistochemical analysis revealed increased c-Fos-positive cells in the dentate gyrus in 8-nitro-cGMP-infused mice. Further, biochemical analyses showed that icv infusion of 8-nitro-cGMP increased S-guanylated proteins including SNAP-25 and SNARE complex formation as well as decreased complexes containing complexin, which regulates exocytosis by binding to the SNARE complex, in the hippocampus. These findings suggest that accumulation of 8-nitro-cGMP in the hippocampus affects its functions, including memory, via S-guanylation of hippocampal proteins such as SNAP-25.
Bilateral polymicrogyria associated with dystonia: A new neurogenetic syndrome?
American journal of medical genetics. Part A, 2020

The clinical presentation of bilateral perisylvian polymicrogyria (PMG) is highly variable, including oromotor dysfunction, epilepsy, intellectual disability, and pyramidal signs. Extrapyramidal features are extremely rare. We present four apparently unrelated patients with a unique association of PMG with dystonia. The clinical, genetic, and radiologic features are described and possible mechanisms of dystonia are discussed. All patients were female and two were born to consanguineous families. All presented with early childhood onset dystonia. Other neurologic symptoms and signs classically seen in bilateral perisylvian PMG were observed, including oromotor dysfunction and speech abnormalities ranging from dysarthria to anarthria (4/4), pyramidal signs (3/4), hypotonia (3/4), postnatal microcephaly (1/4), and seizures (1/4). Neuroimaging showed a unique pattern of bilateral PMG with an infolded cortex originating primarily from the perisylvian region in three out of four patients. Whole exome sequencing was performed in two out of four patients and did not reveal pathogenic variants in known genes for cortical malformations or movement disorders. The dystonia seen in our patients is not described in bilateral PMG and suggests an underlying mechanism of impaired connectivity within the motor network or compromised cortical inhibition. The association of bilateral PMG with dystonia in our patients may represent a new neurogenetic disorder.