rudyvdbrink/CitationDatabase huggingface dataset:
Gene therapy for inherited metabolic diseases.
Journal of mother and child, 2020

Over the last two decades, gene therapy has been successfully translated to many rare diseases. The number of clinical trials is rapidly expanding and some gene therapy products have now received market authorisation in the western world. Inherited metabolic diseases (IMD) are orphan diseases frequently associated with a severe debilitating phenotype with limited therapeutic perspective. Gene therapy is progressively becoming a disease-changing therapeutic option for these patients. In this review, we aim to summarise the development of this emerging field detailing the main gene therapy strategies, routes of administration, viral and non-viral vectors and gene editing tools. We discuss the respective advantages and pitfalls of these gene therapy strategies and review their application in IMD, providing examples of clinical trials with lentiviral or adeno-associated viral gene therapy vectors in rare diseases. The rapid development of the field and implementation of gene therapy as a realistic therapeutic option for various IMD in a short term also require a good knowledge and understanding of these technologies from physicians to counsel the patients at best.
Microsleep is associated with brain activity patterns unperturbed by auditory inputs.
Journal of neurophysiology, 2019

Microsleeps are brief episodes of arousal level decrease manifested through behavioral signs. Brain activity during microsleep in the presence of external stimulus remains poorly understood. In this study, we sought to understand neural responses to auditory stimulation during microsleep. We gave participants the simple task of listening to audios of different pitches and amplitude modulation frequencies during early afternoon functional MRI scans. We found the following:
An integrated approach to unravel a putative crosstalk network in Alzheimer's disease and Parkinson's disease.
Neuropeptides, 2020

Integration of multiple profiling data and construction of functional regulatory networks provide a powerful approach to uncover functional relationships and significant molecular entities from transcriptomic data, highlighting the molecular mechanisms of complex diseases. Despite having an overlap in the neuropathologies of AD and PD, the molecular entities overlapped and mechanisms behind them are less known. Here we used an integrated strategy to analyze miRNA and gene transcriptomic data to understand the role of miRNAs and genes in regulatory activities taking place in cells, and find transcriptomic signatures linking AD and PD. We preprocessed and analyzed publicly available microarray datasets and identified 97 DEGs and 21 DEmiRs that may be involved in the overlapped mechanisms between these two disorders. Among the DEGs, we found HSPA9, PGK1, SDHC, FH, DLD, YWHAZ and ACLY as the major protein-coding genes involved in the crosstalk for AD-PD pathogenesis. Further we integrated these DEGs and DEmiRs with regulatory TFs to construct an overlapped dysregulated network of AD and PD. In the network, miR-27a-3p, miR-148a-3p and miR-15a-5p were found to be the most relevant with maximum interactions, describing their significance in the potential crosstalk. We also looked into the dysregulated biological processes and pathways overlapped in AD and PD. In conclusion, we highlighted the DEGs, DEmiRs, their interactions and related pathways overlapped in AD and PD pathogenesis, also describing a potential crosstalk at molecular level. Besides, our findings can further be used for molecular studies to reveal an assured AD-PD crosstalk.
The safety of dopamine agonists in the treatment of Parkinson's disease.
Expert opinion on drug safety, 2008

Dopamine agonists are highly effective as adjunctive therapy to levodopa in advanced Parkinson's disease. These drugs have rapidly gained popularity as a monotherapy in the early stages of Parkinson's disease for patients < 65-70 years old, because they are about as effective as levodopa, but patients demonstrate a lower tendency to develop motor complications. However, dopamine agonists could have peripheral and central side effects, which are often the reason for the discontinuation of the treatment. This review focuses on the potential negative effects related to the use of dopamine agonists in the treatment of Parkinson's disease.
Intravenous self-administration of delta-9-THC in adolescent rats produces long-lasting alterations in behavior and receptor protein expression.
Psychopharmacology, 2021

Initial exposure to cannabinoids, including Δ-9-tetrahydrocannabinol (THC), often occurs during adolescence. Considerable neurodevelopmental alterations occur throughout adolescence, and the environmental insult posed by exogenous cannabinoid exposure may alter natural developmental trajectories. Multiple studies suggest that long-lasting deficits in cognitive function occur as a result of adolescent cannabis use, but considerable variability exists in the magnitude of these effects.
Exposure to different early-life stress experiences results in differentially altered DNA methylation in the brain and immune system.
Neurobiology of stress, 2020

The existence of a proportional relationship between the number of early-life stress (ELS) events experienced and the impoverishment of child mental health has been hypothesized. However, different types of ELS experiences may be associated with different neuro-psycho-biological impacts, due to differences in the intrinsic nature of the stress. DNA methylation is one of the molecular mechanisms that have been implicated in the "translation" of ELS exposure into neurobiological and behavioral abnormalities during adulthood. Here, we investigated whether different ELS experiences resulted in differential impacts on global DNA methylation levels in the brain and blood samples from mice and humans. ELS exposure in mice resulted in observable changes in adulthood, with exposure to social isolation inducing more dramatic alterations in global DNA methylation levels in several brain structures compared with exposure to a social threatening environment. Moreover, these two types of stress resulted in differential impacts on the epigenetic programming of different brain regions and cellular populations, namely microglia. In a pilot clinical study, blood global DNA methylation levels and exposure to childhood neglect or abuse were investigated in patients presenting with major depressive disorder or substance use disorder. A significant effect of the mental health diagnosis on global methylation levels was observed, but no effect of either childhood abuse or neglect was detected. These findings demonstrate that different types of ELS have differential impacts on epigenetic programming, through DNA methylation in specific brain regions, and that these differential impacts are associated with the different behavioral outcomes observed after ELS experiences.
Sparse representation of DWI images for fully automated brain tissue segmentation.
Journal of neuroscience methods, 2020

Brain tissue segmentation plays an important role in biomedical research and clinical applications. Traditional segmentation is performed on T1-weighted and/or T2-weighted MRI images. Recently, brain segmentation based on diffusion weighted imaging (DWI) has attracted research interest due to its advantage in diffusion MRI image processing and anatomically-constrained tractography.
Pinpointing the optimal spatial frequency range for automatic neural facial fear processing.
NeuroImage, 2020

Faces convey an assortment of emotional information via low and high spatial frequencies (LSFs and HSFs). However, there is no consensus on the role of particular spatial frequency (SF) information during facial fear processing. Comparison across studies is hampered by the high variability in cut-off values for demarcating the SF spectrum and by differences in task demands. We investigated which SF information is minimally required to rapidly detect briefly presented fearful faces in an implicit and automatic manner, by sweeping through an entire SF range without constraints of predefined cut-offs for LSFs and HSFs. We combined fast periodic visual stimulation with electroencephalography. We presented neutral faces at 6 ​Hz, periodically interleaved every 5th image with a fearful face, allowing us to quantify an objective neural index of fear discrimination at exactly 1.2 ​Hz. We started from a stimulus containing either only very low or very high SFs and gradually increased the SF content by adding higher or lower SF information, respectively, to reach the full SF spectrum over the course of 70 ​s. We found that faces require at least SF information higher than 5.93 cycles per image (cpi) to implicitly differentiate fearful from neutral faces. However, exclusive HSF faces, even in a restricted SF range between 94.82 and 189.63 cpi already carry the critical information to extract the emotional expression of the faces.
Structured event complexes are the primary representation in the human prefrontal cortex.
The Behavioral and brain sciences, 2020

Instead of endorsing an all-encompassing view about the influence of abstractions in predictive processing, I suggest that most deliberative thought including complex abstractions, agent actions, and/or perceived environmental sequences are stored in the human prefrontal cortex in the form of structured event complexes.
The closed-head impact model of engineered rotational acceleration (CHIMERA) as an application for traumatic brain injury pre-clinical research: A status report.
Experimental neurology, 2020

Closed-head traumatic brain injury (TBI) is a worldwide concern with increasing prevalence and cost to society. Rotational acceleration is a primary mechanism in TBI that results from tissue strains that give rise to diffuse axonal injury. The Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA) was recently introduced as a method for the study of impact acceleration effects in pre-clinical TBI research. This review provides a survey of the published literature implementing the CHIMERA device and describes pathological, imaging, neurophysiological, and behavioral findings. Findings show CHIMERA inflicts damage in white matter tracts as a key area of injury. Behaviorally, repeated studies have shown motor deficits and more chronic cognitive effects after CHIMERA injury. Good progress with model application has been accomplished by investigators attending to what is required for model validation. However, the majority of CHIMERA studies only utilize adult male mice. To further establish this model, more work with female animals and various age groups need to be performed, as well as studies to further establish and standardize methodologies for validation of the models for clinical relevance. Common data elements to standardize the reporting methodology for the CHIMERA literature are suggested.
Circadian rhythms and obesity: Timekeeping governs lipid metabolism.
Journal of pineal research, 2020

Almost all living organisms have evolved autoregulatory transcriptional-translational feedback loops that produce oscillations with a period of approximately 24-h. These endogenous time keeping mechanisms are called circadian clocks. The main function of these circadian clocks is to drive overt circadian rhythms in the physiology of the organisms to ensure that main physiological functions are in synchrony with the external environment. Disruption of circadian rhythms caused by genetic or environmental factors has long-term consequences for metabolic health. Of relevance, host circadian rhythmicity and lipid metabolism are increasingly recognized to cross-regulate and the circadian clock-lipid metabolism interplay may involve in the development of obesity. Multiple systemic and molecular mechanisms, such as hormones (ie, melatonin, leptin, and glucocorticoid), the gut microbiome, and energy metabolism, link the circadian clock and lipid metabolism, and predictably, the deregulation of circadian clock-lipid metabolism interplay can increase the risk of obesity, which in turn may exacerbate circadian disorganization. Feeding time and dietary nutrients are two of key environmental Zeitgebers affecting the circadian rhythm-lipid metabolism interplay, and the influencing mechanisms in obesity development are highlighted in this review. Together, the characterization of the clock machinery in lipid metabolism aimed at producing a healthy circadian lifestyle may improve obesity care.
Differences in Sociodemographic and Alcohol-Related Clinical Characteristics Between Treatment Seekers and Nontreatment Seekers and Their Role in Predicting Outcomes in the COMBINE Study for Alcohol Use Disorder.
Alcoholism, clinical and experimental research, 2020

One of the challenges in early-stage clinical research aimed at developing novel treatments for alcohol use disorder (AUD) is that the enrolled participants are heavy drinkers, but do not seek treatment for AUD.
The documentation of consent and disclosure of neurogenetic testing outside clinical genetics.
Neurogenetics, 2014

Neurogenetic tests are increasingly requested by clinical neurologists without any formal training in clinical genetics. The aim of our study was to assess the documentation of consent and disclosure of genetic test results in a large regional clinical neuroscience centre. Documentation of some form of consent was evident in only 26/132 (20 %) of tests. However, the higher proportion of both positive and negative results disclosed (50/132, 38 %) suggest that the former figure may underestimate actual rates of undocumented consent within the clinical setting. Our findings highlight the need for a review of established practices surrounding consent in clinical neurology.
TAVI imaging: over the echocardiography.
La Radiologia medica, 2020

Aortic valve stenosis (AS) is a common valvular heart disease. Recently, transcatheter aortic valve implantation (TAVI) has changed the treatment of severe AS in elderly patients with contraindications to traditional surgical replacement. Echocardiography is conventionally used as the first imaging modality to assess the presence and severity of AS and to provide anatomical and functional information. Nowadays, imaging techniques play a crucial role in the planning of TAVI to define suitable candidates. Computed tomography (CT) is essential to display the anatomy of the aortic valve complex (including aortic annulus, Valsalva sinuses, coronary arteries ostia, sinotubular junction), thoracoabdominal aorta, and vascular access. Cardiac CT may also provide the evaluation of coronary arteries in alternative to conventional coronary angiography. Magnetic resonance imaging may be alternative or supplementary in selected cases, providing detailed information of cardiac function and myocardial wall characteristics. More recently, advanced computer modeling image-based techniques can be used to support the evaluation of the feasibility and safety of TAVI procedures.
Outcomes after carotid endarterectomy among elderly dual Medicare-Medicaid-eligible patients.
Neurology, 2018

To determine whether patients who are dual eligible for Medicare and Medicaid benefits have outcomes after carotid endarterectomy (CEA) that are comparable to the outcomes of those eligible for Medicare alone.
Autologous Hematopoietic Stem Cell Transplant in Multiple Sclerosis: Recommendations of the National Multiple Sclerosis Society.
JAMA neurology, 2021

Autologous hematopoietic stem cell transplant (AHSCT) for multiple sclerosis has gained increasing interest in recent years. Despite the availability of many US Food and Drug Administration-approved disease-modifying therapies, some patients do not respond adequately and others may have very early aggressive disease that prompts consideration of alternative, highly effective, long-lasting therapy. The National Medical Advisory Committee of the National Multiple Sclerosis Society has reviewed recent literature on AHSCT for the purpose of making recommendations about its use based on current knowledge, as well as pointing out areas of controversy and issues requiring further research.
Sex differences in COVID-19: the role of androgens in disease severity and progression.
Endocrine, 2021

Throughout the SARS-CoV2 pandemic, multiple reports show higher percentages of hospitalization, morbidity, and mortality among men than women, indicating that men are more affected by COVID-19. The pathophysiology of this difference is yet not established, but recent studies suggest that sex hormones may influence the viral infectivity process. Here, we review the current evidence of androgen sensitivity as a decisive factor for COVID-19 disease severity.
Normal pressure hydrocephalus and CSF tap test response: the gait phenotype matters.
Journal of neural transmission (Vienna, Austria : 1996), 2021

This study compared gait speed changes after CSF tap test in patients with idiopathic normal pressure hydrocephalus presenting with various gait phenotypes (frontal, parkinsonian, normal, or other). All patients improved, except those with parkinsonian gait.
White matter disturbances in major depressive disorder: a coordinated analysis across 20 international cohorts in the ENIGMA MDD working group.
Molecular psychiatry, 2020

Alterations in white matter (WM) microstructure have been implicated in the pathophysiology of major depressive disorder (MDD). However, previous findings have been inconsistent, partially due to low statistical power and the heterogeneity of depression. In the largest multi-site study to date, we examined WM anisotropy and diffusivity in 1305 MDD patients and 1602 healthy controls (age range 12-88 years) from 20 samples worldwide, which included both adults and adolescents, within the MDD Working Group of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium. Processing of diffusion tensor imaging (DTI) data and statistical analyses were harmonized across sites and effects were meta-analyzed across studies. We observed subtle, but widespread, lower fractional anisotropy (FA) in adult MDD patients compared with controls in 16 out of 25 WM tracts of interest (Cohen's d between 0.12 and 0.26). The largest differences were observed in the corpus callosum and corona radiata. Widespread higher radial diffusivity (RD) was also observed (all Cohen's d between 0.12 and 0.18). Findings appeared to be driven by patients with recurrent MDD and an adult age of onset of depression. White matter microstructural differences in a smaller sample of adolescent MDD patients and controls did not survive correction for multiple testing. In this coordinated and harmonized multisite DTI study, we showed subtle, but widespread differences in WM microstructure in adult MDD, which may suggest structural disconnectivity in MDD.
Pharmacological Augmentation in Unipolar Depression: A Guide to the Guidelines.
The international journal of neuropsychopharmacology, 2020

Pharmacological augmentation is a recommended strategy for patients with treatment-resistant depression. A range of guidelines provide advice on treatment selection, prescription, monitoring and discontinuation, but variation in the content and quality of guidelines may limit the provision of objective, evidence-based care. This is of importance given the side effect burden and poorer long-term outcomes associated with polypharmacy and treatment-resistant depression. This review provides a definitive overview of pharmacological augmentation recommendations by assessing the quality of guidelines for depression and comparing the recommendations made.
Neurofilament light as a biomarker in traumatic brain injury.
Neurology, 2020

To determine whether serum neurofilament light (NfL) correlates with CSF NfL, traumatic brain injury (TBI) diagnosis, injury severity, brain volume, and diffusion tensor imaging (DTI) estimates of traumatic axonal injury (TAI).
Version-vergence interactions during memory-guided binocular gaze shifts.
Investigative ophthalmology & visual science, 2013

Visual orientation toward remembered or visible visual targets requires binocular gaze shifts that are accurate in direction (version) and ocular distance (vergence). We determined the accuracy of combined version and vergence movements and the contribution of the abducting and adducting eye during gaze shifts toward memorized and visual targets in three-dimensional space.
The spatial logic of fear.
Cognition, 2020

Peripersonal space (PPS) refers to the space surrounding the body. PPS is characterised by distinctive patterns of multisensory integration and sensory-motor interaction. In addition, facial expressions have been shown to modulate PPS representation. In this study we tested whether fearful faces lead to a different distribution of spatial attention, compared to neutral and joyful faces. Participants responded to tactile stimuli on the cheeks, while watching looming neutral, joyful (Experiment 1) or fearful (Experiment 2) faces of an avatar, appearing in far or near space. To probe spatial attention, when the tactile stimulus was delivered, a static ball briefly appeared central or peripheral in participant's vision, respectively ≈1° or ≈10° to the left or right of the face. With neutral and joyful faces, simple reactions to tactile stimuli were facilitated in near rather than in far space, replicating classic PPS effects, and in the presence of central rather than peripheral ball, suggesting that attention may be focused in the immediate surrounding of the face. However, when the face was fearful, response to tactile stimuli was modulated not only by the distance of the face from the participant, but also by the position of the ball. Specifically, in near space only, response to tactile stimuli was additionally facilitated by the peripheral compared to the central ball. These results suggest that as fearful faces come closer to the body, they promote a redirection of attention towards the periphery. Given the sensory-motor functions of PPS, this fear-evoked redirection of attention would enhance the defensive function of PPS specifically when it is most needed, i.e. when the source of threat is nearby, but its location has not yet been identified.
Load effect on background rhythms during motor execution: A magnetoencephalographic study.
Neuroscience research, 2016

We investigated the effect of load against self-paced movement on cortical involvement for motor execution. Ten right-handed healthy volunteers were requested to perform brisk extension of the right index finger at self-paced intervals exceeding 10s for three load conditions: 0g, 50g and 100g. Movement-related magnetic fields were recorded using an MEG system. The signals were band-pass-filtered through 18-23Hz and rectified before averaging with respect to EMG onset. We analyzed the time course and %change of peak amplitude with reference to the baseline amplitude in event-related desynchronization (ERD) or synchronization (ERS) in each hemisphere. Maximum response was observed around the left somatomotor area for all conditions. ERD did not show any significant difference before the movement onset among the three load conditions. For %change, ERS in the post-movement period was significantly larger for the 100g load condition than for the 0g load condition, and that was significantly greater over the left than over the right hemisphere. These findings indicate that the load has little effect on pre-movement desynchronization, whereas it affects the post-movement synchronization on background rhythms.