rudyvdbrink/CitationDatabase huggingface dataset:
Restoration of motor learning in a mouse model of Rett syndrome following long-term treatment with a novel small-molecule activator of TrkB.
Disease models & mechanisms, 2020

Reduced expression of brain-derived neurotrophic factor (BDNF) and impaired activation of the BDNF receptor, tropomyosin receptor kinase B (TrkB; also known as Ntrk2), are thought to contribute significantly to the pathophysiology of Rett syndrome (RTT), a severe neurodevelopmental disorder caused by loss-of-function mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2). Previous studies from this and other laboratories have shown that enhancing BDNF expression and/or TrkB activation in
Selective inhibition of mitochondrial respiratory complexes controls the transition of microglia into a neurotoxic phenotype in situ.
Brain, behavior, and immunity, 2020

Microglia are tissue resident macrophages (innate immunity) and universal sensors of alterations in CNS physiology. In response to pathogen or damage signals, microglia feature rapid activation and can acquire different phenotypes exerting neuroprotection or neurotoxicity. Although transcriptional aspects of microglial phenotypic transitions have been described, the underlying metabolic reprogramming is widely unknown. Employing postnatal organotypic hippocampal slice cultures, we describe that microglia transformed into a mild reactive phenotype by single TLR4 stimulation with lipopolysaccharide (LPS), which was boosted into a severe neurotoxic phenotype by IFN-γ (LPS + INF-γ). The two reactive phenotypes associated with reduction of microglial homeostatic "surveillance" markers, increase of cytokine release (IL-6, TNF-α) as well as enhancement of tissue energy demand and lactate production. These reactive phenotypes differed in the pattern of inhibition of the respiratory chain in mitochondria, however. TLR4 stimulation induced succinate dehydrogenase (complex II) inhibition by the metabolite itaconate. By contrast, TLR4 + IFN-γ receptor stimulation mainly resulted in complex IV inhibition by nitric oxide (NO) that also associated with severe oxidative stress, neuronal dysfunction and death. Notably, pharmacological depletion of microglia or treatment with itaconate resulted in effective neuroprotection reflected by well-preserved cytoarchitecture and electrical network activity, i.e., neuronal gamma oscillations (30-70 Hz) that underlie higher cognitive functions in vivo. Our findings provide in situ evidence that (i) proinflammatory microglia can substantially alter brain energy metabolism and (ii) fine-tuning of itaconate and NO metabolism determines microglial reactivity, impairment of neural network function and neurodegeneration. These data add mechanistic insights into microglial activation, with relevance to disorders featuring neuroinflammation and to drug discovery.
Development and validation of the Mandarin disyllable recognition test.
Acta oto-laryngologica, 2012

Given the phonetic balancing across lists and the validation with spectrally degraded speech, the present Mandarin disyllable recognition test (DRT) materials may be useful for assessing speech performance of Mandarin-speaking cochlear implant (CI) users. If combined with the previously developed sentence materials, these materials would help to establish standardized speech perception tests for Mandarin-speaking hearing-impaired (HI) and CI patients.
Variability and heritability of mouse brain structure: Microscopic MRI atlases and connectomes for diverse strains.
NeuroImage, 2020

Genome-wide association studies have demonstrated significant links between human brain structure and common DNA variants. Similar studies with rodents have been challenging because of smaller brain volumes. Using high field MRI (9.4 T) and compressed sensing, we have achieved microscopic resolution and sufficiently high throughput for rodent population studies. We generated whole brain structural MRI and diffusion connectomes for four diverse isogenic lines of mice (C57BL/6J, DBA/2J, CAST/EiJ, and BTBR) at spatial resolution 20,000 times higher than human connectomes. We measured narrow sense heritability (h
An individually randomised controlled multi-centre pragmatic trial with embedded economic and process evaluations of early vocational rehabilitation compared with usual care for stroke survivors: study protocol for the RETurn to work After stroKE (RETAKE) trial.
Trials, 2020

Return to work (RTW) is achieved by less than 50% of stroke survivors. The rising incidence of stroke among younger people, the UK economic forecast, and clinical drivers highlight the need for stroke survivors to receive support with RTW. However, evidence for this type of support is lacking. This randomised controlled trial (RCT) will investigate whether Early Stroke Specialist Vocational Rehabilitation (ESSVR) plus usual care (UC) (i.e. usual NHS rehabilitation) is more clinically and cost-effective for supporting post-stroke RTW, than UC alone.
Safety and Tolerability of SRX246, a Vasopressin 1a Antagonist, in Irritable Huntington's Disease Patients-A Randomized Phase 2 Clinical Trial.
Journal of clinical medicine, 2020

SRX246 is a vasopressin (AVP) 1a receptor antagonist that crosses the blood-brain barrier. It reduced impulsive aggression, fear, depression and anxiety in animal models, blocked the actions of intranasal AVP on aggression/fear circuits in an experimental medicine fMRI study and demonstrated excellent safety in Phase 1 multiple-ascending dose clinical trials. The present study was a 3-arm, multicenter, randomized, placebo-controlled, double-blind, 12-week, dose escalation study of SRX246 in early symptomatic Huntington's disease (HD) patients with irritability. Our goal was to determine whether SRX246 was safe and well tolerated in these HD patients given its potential use for the treatment of problematic neuropsychiatric symptoms. Participants were randomized to receive placebo or to escalate to 120 mg twice daily or 160 mg twice daily doses of SRX246. Assessments included standard safety tests, the Unified Huntington's Disease Rating Scale (UHDRS), and exploratory measures of problem behaviors. The groups had comparable demographics, features of HD and baseline irritability. Eighty-two out of 106 subjects randomized completed the trial on their assigned dose of drug. One-sided exact-method confidence interval tests were used to reject the null hypothesis of inferior tolerability or safety for each dose group vs. placebo. Apathy and suicidality were not affected by SRX246. Most adverse events in the active arms were considered unlikely to be related to SRX246. The compound was safe and well tolerated in HD patients and can be moved forward as a candidate to treat irritability and aggression.
The role of sleep in the formation and updating of abstract mental representations.
The Behavioral and brain sciences, 2020

According to Gilead and colleagues, to be efficient abstraction requires a hierarchical organization of information into long-term memory. But, how and when are abstract representations consolidated into long-term memory and how are they integrated with pre-existing abstracta are questions not discussed by Gilead and colleagues. Here, we propose that these processes occur preferentially during offline periods such as sleep.
An approach to using pharmacokinetics and electroencephalography for propofol anesthesia for surgery in infants.
Paediatric anaesthesia, 2020

Safe and effective techniques for propofol total intravenous anesthesia (TIVA) in infants are not well imbedded into clinical practice, resulting in practitioner unfamiliarity and potential for over- and under-dosing. In this education article, we describe our approach to TIVA dosing in infants and toddlers (birth to 36 months) which combines the use of pharmacokinetic models with EEG multi-parameter analysis. Pharmacokinetic models describe propofol and remifentanil effect site concentrations (Ce) over time in different age groups for a given dosing regimen. These models display substantial biological variability between individuals within age groups, impeding their application to clinical practice. Nevertheless, they reveal that younger infants require a higher propofol loading dose, a lower propofol maintenance dose, and a higher remifentanil dose compared with older infants. Proprietary EEG indices (eg, Bispectral Index) can serve as a biomarker of propofol Ce in adults and children to guide dosing to the individual patient; however, they are not recommended for infants as their validity remains uncertain this population. In our experience, EEG waveforms and processed parameters can reflect propofol Ce in infants, reflected by spectral edge frequency (SEF), density spectral array (DSA), and waveform patterns. In our practice, we use a "lookup table" of age-based dosing regimens or target-controlled infusion (TCI) based on the pharmacokinetic models to deliver a target propofol Ce and co-administer remifentanil and/or regional technique for analgesia. We analyze Electroencephalogram (EEG) waveforms, SEF, and DSA to adjust the propofol dose or TCI target concentration to the individual infant. EEG analysis mitigates against biological variability inherent in the pharmacokinetic models and has improved our experience with TIVA for infants.
Integrative analyses prioritize GNL3 as a risk gene for bipolar disorder.
Molecular psychiatry, 2020

Genome-wide association studies (GWASs) have identified numerous single nucleotide polymorphisms (SNPs) associated with bipolar disorder (BD), but what the causal variants are and how they contribute to BD is largely unknown. In this study, we used FUMA, a GWAS annotation tool, to pinpoint potential causal variants and genes from the latest BD GWAS findings, and performed integrative analyses, including brain expression quantitative trait loci (eQTL), gene coexpression network, differential gene expression, protein-protein interaction, and brain intermediate phenotype association analysis to identify the functions of a prioritized gene and its connection to BD. Convergent lines of evidence prioritized protein-coding gene G Protein Nucleolar 3 (GNL3) as a BD risk gene, with integrative analyses revealing GNL3's roles in cell proliferation, neuronal functions, and brain phenotypes. We experimentally revealed that BD-related eQTL SNPs rs10865973, rs12635140, and rs4687644 regulate GNL3 expression using dual luciferase reporter assay and CRISPR interference experiment in human neural progenitor cells. We further identified that GNL3 knockdown and overexpression led to aberrant neuronal proliferation and differentiation, using two-dimensional human neural cell cultures and three-dimensional forebrain organoid model. This study gathers evidence that BD-related genetic variants regulate GNL3 expression which subsequently affects neuronal proliferation and differentiation.
Subgroup-specific prognostic signaling and metabolic pathways in pediatric medulloblastoma.
BMC cancer, 2019

Using a pathway-focused approach, we aimed to provide a subgroup-specific basis for finding novel therapeutic strategies and further refinement of the risk stratification in pediatric medulloblastoma.
Guidelines to Study and Develop Soft Electrode Systems for Neural Stimulation.
Neuron, 2020

Electrical stimulation of nervous structures is a widely used experimental and clinical method to probe neural circuits, perform diagnostics, or treat neurological disorders. The recent introduction of soft materials to design electrodes that conform to and mimic neural tissue led to neural interfaces with improved functionality and biointegration. The shift from stiff to soft electrode materials requires adaptation of the models and characterization methods to understand and predict electrode performance. This guideline aims at providing (1) an overview of the most common techniques to test soft electrodes in vitro and in vivo; (2) a step-by-step design of a complete study protocol, from the lab bench to in vivo experiments; (3) a case study illustrating the characterization of soft spinal electrodes in rodents; and (4) examples of how interpreting characterization data can inform experimental decisions. Comprehensive characterization is paramount to advancing soft neurotechnology that meets the requisites for long-term functionality in vivo.
Award for Distinguished Scientific Early Career Contributions to Psychology: Katherine B. Ehrlich.
The American psychologist, 2020

The Early Career Awards, given for the first time in 1974, recognize the large number of excellent early career psychologists. Recipients of this award may not have held a doctoral degree for more than nine years. For purposes of this award, psychology has been divided into 10 areas: animal learning and behavior, comparative; developmental; health; cognition/human learning; psychopathology; behavioral and cognitive neuroscience; perception/motor performance; social; applied research; and individual differences. Five areas are considered each year, with areas rotated in two-year cycles. The areas considered in 2020 were animal learning and behavior, comparative; developmental; health; cognition/ human learning; and psychopathology. Each year, panels are selected for the areas under consideration, and these panels recommend nominees to the Committee on Scientific Awards. The 2020 recipients of the APA Scientific Contribution Awards were recognized by the 2019 Board of Scientific Affairs and selected by the 2019 Committee on Scientific Awards. For outstanding research that elucidates how children's social relationships affect their physical health. Katherine B. Ehrlich's innovative research brings together insights from multiple subareas of psychology, including health, developmental, and social, to address questions of great importance for public health and human development. Her studies are characterized by sophisticated theory, rigorous methodology, and impressive creativity. Her theoretical and empirical work is already leaving a substantial mark on the field and paving the way for an integrative biosocial science of human development. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
Cognitive diagnostic assessment with different weight for attribute: based on the Dina model.
Psychological reports, 2014

An attribute weight calculation method which used a Bayesian network and the least squares distance method was proposed to assign different weights to different attributes in cognitive diagnosis. This method is independent of any specific cognitive diagnostic models, so it is practicable to consider attribute weight not only in the models with explicit expression but also in item response theory-based cognitive diagnostic methods. Simulation studies showed that the data fit for the least squares distance method was excellent and the weighted status can yield higher correct classification rates than the unweighted status. The weighted status had a promising performance in recognizing the knowledge states of examinees for various slippage probabilities under different attribute hierarchies. The numbers of items and attributes could also affect the examinees' classification accuracy.
DCC regulates astroglial development essential for telencephalic morphogenesis and corpus callosum formation.
eLife, 2021

The forebrain hemispheres are predominantly separated during embryogenesis by the interhemispheric fissure (IHF). Radial astroglia remodel the IHF to form a continuous substrate between the hemispheres for midline crossing of the corpus callosum (CC) and hippocampal commissure (HC). Deleted in colorectal carcinoma (DCC) and netrin 1 (NTN1) are molecules that have an evolutionarily conserved function in commissural axon guidance. The CC and HC are absent in
Monitoring caffeine intake in children with a questionnaire and urine collection: a cross-sectional study in a convenience sample in Switzerland.
European journal of nutrition, 2020

The objectives of this study were (1) to estimate caffeine intake and identify the main sources of intake using a dietary questionnaire, (2) to assess 24-h urinary excretion of caffeine and its metabolites, and (3) to assess how self-reported intake estimates correlates with urinary excretion among children in Switzerland.
47-year-old man with left leg numbness.
Brain pathology (Zurich, Switzerland), 2013

A 47-year-old white male with a history of uveitis, hypercalcemia and nephrolithiasis presented with acute onset partial seizure. On exam he had decreased sensation to light touch on his left lower extremity. A Brain MRI revealed a right frontal mass, which was initially thought to be a metastatic lesion or a primary brain tumor. However, biopsy of the lesion revealed it to be a non-caseating granulomatous lesion consistent with neurosarcoidosis.
Restricting ankle dorsiflexion does not mitigate the benefits of external focus of attention on landing biomechanics in healthy females.
Human movement science, 2020

Restricted ankle dorsiflexion can promote aberrant biomechanics associated with risk for knee injury during dynamic activities. Attentionally focused instructions have been used to improve high-risk knee biomechanics during landing tasks. Yet, it is unknown whether attentionally focused instruction can effectively improve landing patterns in the presence of a mechanical restriction on the ankle. Therefore, our purpose was to determine whether restricting ankle dorsiflexion by use of bracing mitigated the effects of attentional foci on landing biomechanics in healthy females.
How complete is the information on preadmission psychotropic medications in inpatients with dementia? A comparison of hospital medical records with dispensing data.
International journal of methods in psychiatric research, 2018

Reliable information on preadmission medications is essential for inpatients with dementia, but its quality has hardly been evaluated. We assessed the completeness of information and factors associated with incomplete recording.
[Spinal Cord Sarcoidosis].
Brain and nerve = Shinkei kenkyu no shinpo, 2020

Spinal cord sarcoidosis is rare, but often appears as a diagnostic challenge in myelopathy of unknown origin. Although definite diagnosis requires histological confirmation of non-caseating epithelioid granuloma in the spinal cord, it is hardly obtained due to the invasiveness of the biopsy procedure. Hence, extensive searches for involvement of other organs involvement should be prompted, including biopsy of the most "promising" and "easy touch" lesions identified in individual patients. Spinal sarcoidosis is generally treated with high-dose corticosteroids, immunosuppressants, or both, but it is often refractory to treatment and requires a long treatment period. Therefore, extensive examinations to evaluate the likelihood of sarcoidosis should be carried out before the initiation of immunotherapy, especially in cases without histological confirmation.
Timing Rewarding Movements.
Neuron, 2019

Preparatory activity is found across the motor network. In this issue of Neuron, Chabrol et al. (2019) show that preparatory activity in the anterior lateral motor cortex (ALM) and cerebellum is related to the prediction of reward delivery and that the cerebellum provides a learned timing signal to the ALM.
The suprachiasmatic nucleus and sleep-wake regulation.
Postgraduate medicine, 2004

Human behavior is organized into 24-hour cycles that are typically composed of about 16 hours of wakefulness and about 8 hours of sleep. Sleep is an essential behavior and is critical for maintaining normal adaptive waking behavior. Both sleep and wake are initiated and maintained by separate and specific neural systems. The sleep-wake cycle is a function of 2 processes--a homeostatic drive for sleep that increases throughout the waking day and an opposing circadian influence that promotes wakefulness centered in the suprachiasmatic nucleus (SCN). A better understanding of the basis for sleep can help treatment and direct research about sleep.
Can mHealth interventions improve quality of life of cancer patients? A systematic review and meta-analysis.
Critical reviews in oncology/hematology, 2021

mHealth can be used to deliver interventions to optimize Health-related quality of life (HRQoL) of cancer patients. In this systematic-review and meta-analysis, we explored the possible impact of health interventions delivered via mHealth tools on HRQoL of cancer patients. The systematic literature search was performed on July 20, 2019, to identify studies that evaluated the impact of mHealth intervention on HRQoL of cancer patients. We identified 25 studies (17 randomized controlled trials and 8 pre-post design studies; 957 patients) that evaluated mHealth interventions. The most commonly studied mHealth interventions included physical activity/ fitness interventions (9 studies), cognitive behavioral therapy (6 studies), mindfulness/ stress management (3 studies). In the majority of studies, mHealth interventions were associated with an improved HRQoL of cancer patients. The meta-analysis of the identified studies supported the positive effect of mHealth interventions for HRQoL of cancer patients. mHealth interventions are promising for improving HRQoL of cancer patients.
Stress reduces both model-based and model-free neural computations during flexible learning.
NeuroImage, 2021

Stressful events are thought to impair the flexible adaptation to changing environments, yet the underlying mechanisms are largely unknown. Here, we combined computational modeling and functional magnetic resonance imaging (fMRI) to elucidate the neurocomputational mechanisms underlying stress-induced deficits in flexible learning. Healthy participants underwent a stress or control manipulation before they completed, in the MRI scanner, a Markov decision task, frequently used to dissociate model-based and model-free contributions to choice, with repeated reversals of reward contingencies. Our results showed that stress attenuated the behavioral sensitivity to reversals in reward contingencies. Computational modeling further indicated that stress specifically affected the use of value computations for subsequent action selection. This reduced application of learned information on subsequent behavior was paralleled by a stress-induced reduction in inferolateral prefrontal cortex activity during model-free computations. For model-based learning, stress decreased specifically posterior, but not anterior, hippocampal activity, pointing to a functional segregation of model-based processing and its modulation by stress along the hippocampal longitudinal axis. Our findings shed light on the mechanisms underlying deficits in flexible learning under stress and indicate that, in highly dynamic environments, stress may hamper both model-based and model-free contributions to adaptive behavior.