rudyvdbrink/CitationDatabase huggingface dataset:
Lysosome-targeted stress reveals increased stability of lipofuscin-containing lysosomes.
Age (Dordrecht, Netherlands), 2008

Cellular ageing is associated with accumulation of undegradable intralysosomal material, called lipofuscin. In order to accelerate the lipofuscin accumulation, confluent, growth-arrested human fibroblasts were cultured under hyperoxic conditions. To provide a better insight into the effects of lipofuscin on cellular functions, we compared lysosomal stability in control and lipofuscin-loaded human fibroblasts under conditions of lysosome-targeted stress induced by exposure to either the lysosomotropic detergent MSDH or the redox-cycling quinone naphthazarin. We show that lysosomal damage, assessed by acridine-orange relocation, translocation of cathepsin D to the cytosol, and alkalinization of lysosomes, is more pronounced in control than in lipofuscin-loaded fibroblasts. Finding that lysosomal integrity was less affected or even preserved in case of lipofuscin-loaded cells enables us to suggest that lipofuscin exerts lysosome-stabilizing properties.
High neural activity accelerates the decline of cognitive plasticity with age in 
eLife, 2020

The ability to learn progressively declines with age. Neural hyperactivity has been implicated in impairing cognitive plasticity with age, but the molecular mechanisms remain elusive. Here, we show that chronic excitation of the
Neuron-based high-content assay and screen for CNS active mitotherapeutics.
Science advances, 2020

Impaired mitochondrial dynamics and function are hallmarks of many neurological and psychiatric disorders, but direct screens for mitotherapeutics using neurons have not been reported. We developed a multiplexed and high-content screening assay using primary neurons and identified 67 small-molecule modulators of neuronal mitostasis (MnMs). Most MnMs that increased mitochondrial content, length, and/or health also increased mitochondrial function without altering neurite outgrowth. A subset of MnMs protected mitochondria in primary neurons from Aβ(1-42) toxicity, glutamate toxicity, and increased oxidative stress. Some MnMs were shown to directly target mitochondria. The top MnM also increased the synaptic activity of hippocampal neurons and proved to be potent in vivo, increasing the respiration rate of brain mitochondria after administering the compound to mice. Our results offer a platform that directly queries mitostasis processes in neurons, a collection of small-molecule modulators of mitochondrial dynamics and function, and candidate molecules for mitotherapeutics.
Application of the Audio Recorded Cognitive Screen and its relation to functioning in schizophrenia.
Acta neuropsychiatrica, 2015

This study investigated the ability of the Audio Recorded Cognitive Screen (ARCS) to detect cognitive deficit in individuals with schizophrenia, relative to the Mini Mental State Examination (MMSE) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and explored the associations between the ARCS and functional outcomes. We hypothesised that the ARCS would be able to better discriminate between individuals with schizophrenia and healthy controls than the MMSE, and that ARCS performance would be correlated with measures of social and vocational functioning.
Asymmetric interlateral transfer of motor learning in unipedal dynamic balance.
Experimental brain research, 2020

Interlateral transfer of learning between the legs in body balance training is a topic of theoretical and practical interest, but it has been left untouched in previous research. In this investigation, we aimed to evaluate the magnitude and asymmetry of interlateral transfer of balance stability following the practice of a challenging task of unipedal support on an unstable base. Thirty participants (18-30 years old) were assigned to two groups practicing either with the right or the left leg. Training consisted of a single practice session of unipedal balance on a platform free to sway in the anteroposterior direction. Balance time (off ground) of either leg in 10-s trials was compared across pre-test, post-test, and 7-day retention. Post-test indicated that both groups had similar performance gains with the trained leg, and equivalent transfer to the transfer leg. Analysis of retention indicated further balance improvement with both transfer legs, while practice with the right leg led to the superior transfer to the untrained leg as compared to the opposite transfer direction. These results suggest that persistent transfer of learning effects for unipedal dynamic balance is bilateral but more prominent in the right-to-left direction.
Sex differences in health and disease: A review of biological sex differences relevant to cancer with a spotlight on glioma.
Cancer letters, 2021

The influence of biological sex differences on human health and disease, while being increasingly recognized, has long been underappreciated and underexplored. While humans of all sexes are more alike than different, there is evidence for sex differences in the most basic aspects of human biology and these differences have consequences for the etiology and pathophysiology of many diseases. In a disease like cancer, these consequences manifest in the sex biases in incidence and outcome of many cancer types. The ability to deliver precise, targeted therapies to complex cancer cases is limited by our current understanding of the underlying sex differences. Gaining a better understanding of the implications and interplay of sex differences in diseases like cancer will thus be informative for clinical practice and biological research. Here we review the evidence for a broad array of biological sex differences in humans and discuss how these differences may relate to observed sex differences in various diseases, including many cancers and specifically glioblastoma. We focus on areas of human biology that play vital roles in healthy and disease states, including metabolism, development, hormones, and the immune system, and emphasize that the intersection of sex differences in these areas should not go overlooked. We further propose that mathematical approaches can be useful for exploring the extent to which sex differences affect disease outcomes and accounting for those in the development of therapeutic strategies.
Deep brain stimulation of the subthalamic nucleus in obsessive-compulsives disorders: long-term follow-up of an open, prospective, observational cohort.
Journal of neurology, neurosurgery, and psychiatry, 2020

Obsessive-compulsive disorder (OCD) is a major cause of disability in western country and responsible for severe impairment of quality of life. About 10% of patients present with severe OCD symptoms and require innovative treatment such as deep brain stimulation (DBS). Among possible targets, the non-motor subthalamic nucleus (STN) is a key node of the basal ganglia circuitry, strongly connected to limbic cortical areas known to be involved in OCD.
Time course and diagnostic utility of NfL, tau, GFAP, and UCH-L1 in subacute and chronic TBI.
Neurology, 2020

To determine whether neurofilament light (NfL), glial fibrillary acidic protein (GFAP), tau, and ubiquitin C-terminal hydrolase-L1 (UCH-L1) measured in serum relate to traumatic brain injury (TBI) diagnosis, injury severity, brain volume, and diffusion tensor imaging (DTI) measures of traumatic axonal injury (TAI) in patients with TBI.
A Machine Learning Approach to Identifying Changes in Suicidal Language.
Suicide & life-threatening behavior, 2020

With early identification and intervention, many suicidal deaths are preventable. Tools that include machine learning methods have been able to identify suicidal language. This paper examines the persistence of this suicidal language up to 30 days after discharge from care.
Motor signs in Alzheimer's disease and vascular dementia: Detection through natural language processing, co-morbid features and relationship to adverse outcomes.
Experimental gerontology, 2021

Motor signs in patients with dementia are associated with a higher risk of cognitive decline, institutionalisation, death and increased health care costs, but prevalences differ between studies. The aims of this study were to employ a natural language processing pipeline to detect motor signs in a patient cohort in routine care; to explore which other difficulties occur co-morbid to motor signs; and whether these, as a group and individually, predict adverse outcomes.
Rosuvastatin and thapsigargin modulate γ-secretase gene expression and APP processing in a human neuroglioma model.
Journal of molecular neuroscience : MN, 2011

Alzheimer's disease (AD) is a progressive neurodegenerative disorder leading to slow neuronal loss in several brain regions. It is characterised by the presence of cerebral senile plaques comprised of aggregated amyloid-β peptides. Transcriptional regulation of the γ-secretase complex, which cleaves the β-amyloid precursor protein to produce Aβ-peptides, could modulate the pathological phenotype of AD patients. This study investigates whether rosuvastatin, an HMG-CoA reductase inhibitor, modulates the expression of genes involved in the function of the γ-secretase complex, in a human cellular model for Aβ peptide accumulation. In particular, we analysed the effect of the statin combined with apoptotic induction. Experimental apoptosis was induced by thapsigargin treatment, a drug that depletes intracellular calcium stores via inhibition of the calcium ATPase pump. Notably, systemic calcium dysregulation accompanies almost all of the brain pathology processes observed in AD. We found differential transcriptional regulation of some γ-secretase cofactors relative to rosuvastatin treatment, in cells expressing Swedish mutant APP. Interestingly, this statin down-regulated the transcription of some enzyme cofactors, similar to treatment with thapsigargin. However, rosuvastatin neither affected the basal Aβ levels nor counteracted APP processing or Aβ over-production triggered by the thapsigargin. Our results provide evidence that rosuvastatin alters gene expression of the γ-secretase complex without affecting enzyme activity.
Direct Delivery of Antisense Oligonucleotides to the Middle and Inner Ear Improves Hearing and Balance in Usher Mice.
Molecular therapy : the journal of the American Society of Gene Therapy, 2020

Usher syndrome is a syndromic form of hereditary hearing impairment that includes sensorineural hearing loss and delayed-onset retinitis pigmentosa (RP). Type 1 Usher syndrome (USH1) is characterized by congenital profound sensorineural hearing impairment and vestibular areflexia, with adolescent-onset RP. Systemic treatment with antisense oligonucleotides (ASOs) targeting the human USH1C c.216G>A splicing mutation in a knockin mouse model of USH1 restores hearing and balance. Herein, we explore the effect of delivering ASOs locally to the ear to treat hearing and vestibular dysfunction associated with Usher syndrome. Three localized delivery strategies were investigated in USH1C mice: inner ear injection, trans-tympanic membrane injection, and topical tympanic membrane application. We demonstrate, for the first time, that ASOs delivered directly to the ear correct Ush1c expression in inner ear tissue, improve cochlear hair cell transduction currents, restore vestibular afferent irregularity, spontaneous firing rate, and sensitivity to head rotation, and successfully recover hearing thresholds and balance behaviors in USH1C mice. We conclude that local delivery of ASOs to the middle and inner ear reach hair cells and can rescue both hearing and balance. These results also demonstrate the therapeutic potential of ASOs to treat hearing and balance deficits associated with Usher syndrome and other ear diseases.
Cannabidiol induces antidepressant and anxiolytic-like effects in experimental type-1 diabetic animals by multiple sites of action.
Metabolic brain disease, 2021

Cannabidiol (CBD), a phytocannabinoid compound, presents antidepressant and anxiolytic-like effects in the type-1 diabetes mellitus(DM1) animal model. Although the underlying mechanism remains unknown, the type-1A serotonin receptor (5-HT1A) and cannabinoids type-1 (CB1) and type-2 (CB2) receptors seem to play a central role in mediating the beneficial effects on emotional responses. We aimed to study the involvement of these receptors on an antidepressant- and anxiolytic-like effects of CBD and on some parameters of the diabetic condition itself. After 2 weeks of the DM1 induction in male Wistar rats by streptozotocin (60 mg/kg; i.p.), animals were treated continuously for 2-weeks with the 5-HT1A receptor antagonist WAY100635 (0.1 mg/kg, i.p.), CB1 antagonist AM251 (1 mg/kg i.p.) or CB2 antagonist AM630 (1 mg/kg i.p.) before the injection of CBD (30 mg/kg, i.p.) or vehicle (VEH, i.p.) and then, they were submitted to the elevated plus-maze and forced swimming tests. Our findings show the continuous treatment with CBD improved all parameters evaluated in these diabetic animals. The previous treatment with the antagonists - 5-HT1A, CB1, or CB2 - blocked the CBD-induced antidepressant-like effect whereas only the blockade of 5-HT1A or CB1 receptors was able to inhibit the CBD-induced anxiolytic-like effect. Regarding glycemic control, only the blockade of CB2 was able to inhibit the beneficial effect of CBD in reducing the glycemia of diabetic animals. These findings indicated a therapeutic potential for CBD in the treatment of depression/anxiety associated with diabetes pointing out a complex intrinsic mechanism in which 5-HT1A, CB1, and/or CB2 receptors are differently recruited.
Study on the applicability of instrumental measures for black-box evaluation of static feedback control in hearing aids.
The Journal of the Acoustical Society of America, 2011

Presented is a report on black-box evaluation of feedback control systems for commercial hearing aids. The aim of the study is to examine the ability of existing instrumental measures to quantify the performance of the feedback control system in black-box settings and on realistic signals, when more than one element of the signal processing chain may be active (compression, noise suppression, microphone directionality, etc.). The evaluation is carried out on 6 different hearing aids and for 10 measures. Thereby it is possible to see which measure is best suited to measuring which specific characteristic of the feedback control system, and serves as a beginning for conducting perceptual tests. The study uses static (but variable) feedback paths and is based on signals recorded from the in-ear microphone of an artificial head, on which the hearing instruments are mounted.
Feasibility and implementation of a healthy lifestyles program in a community setting in Ontario, Canada: protocol for a pragmatic mixed methods pilot study.
BMJ open, 2019

Rates of chronic conditions, such as diabetes, cardiovascular disease and obesity are increasing in Canada and internationally. There are effective lifestyle interventions that are known to improve chronic conditions. However, there is often a gap in 'how to' make lifestyle changes. Mental health and other determinants of health play a role in the development and progression of chronic conditions. Changing habits takes time and requires the use of multiple techniques, including mental health and behavioural change strategies, based on a person's needs. A new, multidisciplinary, person-centred and evidence-based and practice-based programme has been created to address these needs. This proposal aims to evaluate the feasibility and implementation of this programme and to determine changes in participant-directed and clinical outcomes through a pilot study.
Improving our understanding of the most important items of the Multiple Sclerosis Walking Scale-12 indicating mobility dysfunction: Secondary results from a RIMS multicenter study.
Multiple sclerosis and related disorders, 2020

The 12-item Multiple Sclerosis Walking Scale (MSWS-12) is currently the most widely validated, patient-reported outcome measure assessing patients' perception of the impact of multiple sclerosis (MS) on walking ability. To date, the majority of previous studies investigating the MSWS-12 have focused on the total score despite individual items being potentially informative. Therefore, our objective was to examine the associations between the individual items of the MSWS-12 and mobility and whether these associations depend on disability level.
Pre- and Postsynaptic Effects of Glutamate in the Frog Labyrinth.
Neuroscience, 2018

The role of glutamate in quantal release at the cytoneural junction was examined by measuring mEPSPs and afferent spikes at the posterior canal in the intact frog labyrinth. Release was enhanced by exogenous glutamate, or dl-TBOA, a blocker of glutamate reuptake. Conversely, drugs acting on ionotropic glutamate receptors did not affect release; the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA-R) blocker CNQX decreased mEPSP size in a dose-dependent manner; the NMDA-R blocker d-AP5 at concentrations <200 µM did not affect mEPSP size, either in the presence or absence of Mg and glycine. In isolated hair cells, glutamate did not modify Ca currents. Instead, it systematically reduced the compound delayed potassium current, IKD, whereas the metabotropic glutamate receptor (mGluR)-II inverse agonist, (2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl)propanoic acid (LY341495), increased it. Given mGluR-II decrease cAMP production, these finding are consistent with the reported sensitivity of IKD to protein kinase A (PKA)-mediated phosphorylation. LY341495 also enhanced transmitter release, presumably through phosphorylation-mediated facilitation of the release machinery. The observed enhancement of release by glutamate confirms previous literature data, and can be attributed to activation of mGluR-I that promotes Ca release from intracellular stores. Glutamate-induced reduction in the repolarizing IKD may contribute to facilitation of release. Overall, glutamate exerts both a positive feedback action on mGluR-I, through activation of the phospholipase C (PLC)/IP
Sleep Induction by Mechanosensory Stimulation in Drosophila.
Cell reports, 2020

People tend to fall asleep when gently rocked or vibrated. Experimental studies have shown that rocking promotes sleep in humans and mice. However, the mechanisms underlying the phenomenon are not well understood. A habituation model proposes that habituation, a form of non-associative learning, mediates sleep induction by monotonous stimulation. Here, we show that gentle vibration promotes sleep in Drosophila in part through habituation. Vibration-induced sleep (VIS) leads to increased homeostatic sleep credit and reduced arousability, and can be suppressed by heightened arousal or reduced GABA signaling. Multiple mechanosensory organs mediate VIS, and the magnitude of VIS depends on vibration frequency and genetic background. Sleep induction improves over successive blocks of vibration. Furthermore, training with continuous vibration does not generalize to intermittent vibration, demonstrating stimulus specificity, a characteristic of habituation. Our findings suggest that habituation plays a significant role in sleep induction by vibration.
The Psychiatric Assessment and Brief Intervention Program: Partnering With Primary Care Providers.
The primary care companion for CNS disorders, 2018

To present the structure and outcomes to date for the Psychiatric Assessment and Brief Intervention (PABI), a pilot program developed at University of California, San Francisco, to improve access of primary care patients to mental health services. PABI offers diagnostic evaluations and brief (up to 3 months) evidence-based treatment, including pharmacologic management and psychotherapy, to medical patients 18 years of age and older. Core PABI features are ensuring prompt access, actively partnering with patients and referring providers, and coordinating seamless transitions of care.
The burden of unintentional drowning: global, regional and national estimates of mortality from the Global Burden of Disease 2017 Study.
Injury prevention : journal of the International Society for Child and Adolescent Injury Prevention, 2020

Drowning is a leading cause of injury-related mortality globally. Unintentional drowning (International Classification of Diseases (ICD) 10 codes W65-74 and ICD9 E910) is one of the 30 mutually exclusive and collectively exhaustive causes of injury-related mortality in the Global Burden of Disease (GBD) study. This study's objective is to describe unintentional drowning using GBD estimates from 1990 to 2017.
A MAC2-positive progenitor-like microglial population is resistant to CSF1R inhibition in adult mouse brain.
eLife, 2020

Microglia are the resident myeloid cells in the central nervous system (CNS). The majority of microglia rely on CSF1R signaling for survival. However, a small subset of microglia in mouse brains can survive without CSF1R signaling and reestablish the microglial homeostatic population after CSF1R signaling returns. Using single-cell transcriptomic analysis, we characterized the heterogeneous microglial populations under CSF1R inhibition, including microglia with reduced homeostatic markers and elevated markers of inflammatory chemokines and proliferation. Importantly, MAC2/
Preventive effect of morning light exposure on relapse into depressive episode in bipolar disorder.
Acta psychiatrica Scandinavica, 2021

Light therapy has been suggested to have a curative effect on bipolar depression; however, preventive effects of light exposure on depressive episodes remain unclear. This study evaluated whether daytime light exposure in real-life situations was associated with a preventive effect on relapse into depressive episodes in patients with bipolar disorder.
Dendritic Inhibitory Synapses Punch above Their Weight.
Neuron, 2015

Müllner et al. (2015) show that single inhibitory synapses placed in the right location on the dendritic tree can exert a powerful impact on backpropagating action potentials in hippocampal pyramidal neurons by controlling local Ca(2+) influx with μm and ms precision.
Shorter-lived neural taste representations in obese compared to lean individuals.
Scientific reports, 2018

Previous attempts to uncover a relation between taste processing and weight status have yielded inconclusive results leaving it unclear whether lean and obese individuals process taste differently, and whether group differences reflect differential sensory encoding or evaluative and reward processing. Here, we present the first comparison of dynamic neural processing as assessed by gustatory evoked potentials in obese and lean individuals. Two supra-threshold concentrations of sweet and salty tastants as well as two sizes of blue and green squares were presented to 30 lean (BMI 18.5-25) and 25 obese (BMI > 30) individuals while recording head-surface electroencephalogram (EEG). Multivariate pattern analyses (MVPA) revealed differential taste quality representations from 130 ms until after stimulus offset. Notably, taste representations faded earlier and exhibited a reduced strength in the obese compared to the lean group; temporal generalization analysis indicated otherwise similar taste processing. Differences in later gustatory response patterns even allowed decoding of group membership. Importantly, group differences were absent for visual processing thereby excluding confounding effects from anatomy or signal-to-noise ratio alone. The latency of observed effects is consistent with memory maintenance rather than sensory encoding of taste, thereby suggesting that later evaluative aspects of taste processing are altered in obesity.