rudyvdbrink/CitationDatabase huggingface dataset:
Double-Binding Botulinum Molecule with Reduced Muscle Paralysis: Evaluation in In Vitro and In Vivo Models of Migraine.
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2021

With a prevalence of 15%, migraine is the most common neurological disorder and among the most disabling diseases, taking into account years lived with disability. Current oral medications for migraine show variable effects and are frequently associated with intolerable side effects, leading to the dissatisfaction of both patients and doctors. Injectable therapeutics, which include calcitonin gene-related peptide-targeting monoclonal antibodies and botulinum neurotoxin A (BoNT/A), provide a new paradigm for treatment of chronic migraine but are effective only in approximately 50% of subjects. Here, we investigated a novel engineered botulinum molecule with markedly reduced muscle paralyzing properties which could be beneficial for the treatment of migraine. This stapled botulinum molecule with duplicated binding domain-binary toxin-AA (BiTox/AA)-cleaves synaptosomal-associated protein 25 with a similar efficacy to BoNT/A in neurons; however, the paralyzing effect of BiTox/AA was 100 times less when compared to native BoNT/A following muscle injection. The performance of BiTox/AA was evaluated in cellular and animal models of migraine. BiTox/AA inhibited electrical nerve fiber activity in rat meningeal preparations while, in the trigeminovascular model, BiTox/AA raised electrical and mechanical stimulation thresholds in Aδ- and C-fiber nociceptors. In the rat glyceryl trinitrate (GTN) model, BiTox/AA proved effective in inhibiting GTN-induced hyperalgesia in the orofacial formalin test. We conclude that the engineered botulinum molecule provides a useful prototype for designing advanced future therapeutics for an improved efficacy in the treatment of migraine.
Combination of Augmented Reality Based Brain- Computer Interface and Computer Vision for High-Level Control of a Robotic Arm.
IEEE transactions on neural systems and rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society, 2020

Recent advances in robotics, neuroscience, and signal processing make it possible to operate a robot through electroencephalography (EEG)-based brain-computer interface (BCI). Although some successful attempts have been made in recent years, the practicality of the entire system still has much room for improvement. The present study designed and realized a robotic arm control system by combing augmented reality (AR), computer vision, and steady-state visual evoked potential (SSVEP)-BCI. AR environment was implemented by a Microsoft HoloLens. Flickering stimuli for eliciting SSVEPs were presented on the HoloLens, which allowed users to see both the robotic arm and the user interface of the BCI. Thus users did not need to switch attention between the visual stimulator and the robotic arm. A four-command SSVEP-BCI was built for users to choose the specific object to be operated by the robotic arm. Once an object was selected, the computer vision would provide the location and color of the object in the workspace. Subsequently, the object was autonomously picked up and placed by the robotic arm. According to the online results obtained from twelve participants, the mean classification accuracy of the proposed system was 93.96 ± 5.05%. Moreover, all subjects could utilize the proposed system to successfully pick and place objects in a specific order. These results demonstrated the potential of combining AR-BCI and computer vision to control robotic arms, which is expected to further promote the practicality of BCI-controlled robots.
Antidepressant treatment, not depression, leads to reductions in behavioral and neural responses to pain empathy.
Translational psychiatry, 2019

Major depressive disorder (MDD) has been hypothesized to lead to impairments in empathy. Previous cross-sectional studies did not disentangle effects of MDD itself and antidepressant treatment. In this first longitudinal neuroimaging study on empathy in depression, 29 patients with MDD participated in two functional magnetic resonance imaging (fMRI) sessions before and after 3 months of antidepressant therapy. We compared their responses to an empathy for pain task to a group of healthy controls (N = 35). All participants provided self-report ratings targeting cognitive (perspective taking) and affective (unpleasant affect) aspects of empathy. To control for general effects on processing of negative affective states, participants additionally underwent an electrical pain task. Before treatment, we found no differences in empathic responses between controls and patients with MDD. After treatment, patients showed significant decreases in both affective empathy and activity of three a priori selected brain regions associated with empathy for pain. Decreases in affective empathy were moreover correlated with symptom improvement. Moreover, functional connectivity during the empathy task between areas associated with affective (anterior insula) and cognitive (precuneus) empathy decreased between sessions in the MDD group. Neither cognitive empathy nor responses to painful electrical shocks were changed after treatment. These findings contradict previous cross-sectional reports of empathy deficits in acute MDD. Rather, they suggest that antidepressant treatment reduces the aversive responses triggered by exposure to the suffering of others. Importantly, this cannot be explained by a general blunting of negative affect, as treatment did not change self-experienced pain.
Exposure to prolonged unpredictable light impairs spatial memory via induction of oxidative stress and tumor necrosis factor-alpha in rats.
Journal of basic and clinical physiology and pharmacology, 2021

The human body physiology rapidly changes and adapt to several environmental stimuli, including light. Abnormal artificial light exposures have been shown to affect sleep cycle, cognition, and mood. Although studies have reported inconsistent effects of short-term or constant long-term light exposures, human exposures to artificial lights occur at varying, unpredictable times and duration daily. Here, we studied the effects of long-term unpredictable light exposure on learning, memory, oxidative status, and associated cytokines in rats.
Migraine with aura is associated with impaired colour vision: Results from the cross-sectional German DMKG headache study.
Cephalalgia : an international journal of headache, 2015

Hypersensitivity to light, noise and odour are pivotal clinical characteristics of migraine associated with enhanced cortical excitability and dysfunctional habituation. However, little is known about the integrity of basic sensory functioning in migraine on a population-based level.
Cerebellar-limbic neurocircuit is the novel biosignature of physio-cognitive decline syndrome.
Aging, 2020

Both physical and cognitive deficits occur in the aging process. We operationally defined the phenomenon as physio-cognitive decline syndrome (PCDS) and aimed to decipher its corresponding neuroanatomy patterns and neurocircuit. High resolution 3T brain magnetic resonance imaging (MRI) images from a community-dwelling longitudinal aging cohort were analysed. PCDS was defined as weakness (handgrip strength) and/or slowness (gait speed) concomitant with impairment in any cognitive domain (defined by 1.5 standard deviation below age, sex-matched norms), but without dementia or disability. Among 1196 eligible ≥ 50-year-old (62±9 years, 47.6%men) subjects, 15.9% had PCDS. Compared to the other participants, individuals with PCDS had significantly lower gray-matter volume (GMV) in the bilateral amygdala and thalamus, right hippocampus, right temporo-occipital cortex, and left cerebellum VI and V regions. The regions of reduced GMV in people with PCDS were similar between the middle-aged and older adults; whereas larger clusters with more extensive GMV-depleted regions were observed in ≥65-year-olds with PCDS. Diffusion-weighted tractography showed disrupted hippocampus-amygdala-cerebellum connections in subjects with PCDS. The neuroanatomic characteristics revealed by this study provide evidence for pathophysiological processes associated with concomitant physio-cognitive decline in the elderly. This neurocircuit might constitute a target for future preventive interventions.
Selegiline (L-Deprenyl) Mitigated Oxidative Stress, Cognitive Abnormalities, and Histopathological Change in Rats: Alternative Therapy in Transient Global Ischemia.
Journal of molecular neuroscience : MN, 2020

Selegiline (L-deprenyl) is the major drug which is used in the treatment of Parkinson's disease because of its neurotrophic and antiapoptotic properties. Previous studies suggested that low dose of L-methamphetamine (L-METH) caused lower mortality rate in patients with severe traumatic brain injury. As L-methamphetamine is one of the metabolites of selegiline, the present study aims to examine whether L-deprenyl can improve cognitive, biochemical, and histopathological injury in animal model of transient global ischemia. The animals were randomized in ten groups orally gavaged three times a week for 28 days. Then, novel object recognition (NOR) was conducted to assess their behavioral abnormality. After scarification of the rats, their brains were divided into two sections to measure oxidative stress parameters and perform pathological evaluations in rats. Our data revealed the involvement of oxidative stress, behavioral despair, and pathological data in transient global ischemia rats. Significant recovery in cognitive behavior, oxidative stress biomarker, and number of dead cell in histopathological assay was observed in rats treated with 1,2 and 4 mg/kg of selegiline. So, selegiline appears to be useful in alternative therapy of transient global ischemia.
Statins role in preventing contrast-induced acute kidney injury: a scoping review.
Hong Kong medical journal = Xianggang yi xue za zhi, 2019

Acute renal failure secondary to contrast-induced acute kidney injury (CI-AKI) is one of the most commonly encountered problems in hospitalised patients. The CI-AKI may lead to the development of persistent renal disease, causing significant morbidity and mortality in high-risk patients. Statins are increasingly recognised as effective in preventing CI-AKI. In this review, we reviewed the literature on statin use for prophylaxis of CI-AKI, its potential benefits, and adverse effects. The aim of the present review was to reveal gaps and discrepancies in the available literature, and to identify areas for future research.
H258R mutation in KCNAB3 gene in a family with genetic epilepsy and febrile seizures plus.
Brain and behavior, 2020

The aim of this was to discover disease-causing gene mutations linked to genetic epilepsy with febrile seizures plus (GEFS+) in a family in the Southern Chinese Han population. Of a three-generation pedigree of 18 members in this family, 4 were affected with GEFS+.
[Cytomegalovirus myositis complicated with hemophagocytic lymphohistiocytosis, acute renal failure, and colitis].
Rinsho shinkeigaku = Clinical neurology, 2018

A 60-years-old previously healthy man presented with acute renal failure and hemophagocytic lymphohistiocytosis (HLH). Both conditions improved after immunotherapies, but severe limb weakness with elevation of serum CK developed. Needle EMG showed myogenic changes with spontaneous activities and muscle weakness thereafter improved without adding further immunotherapies, suggesting that our patient had viral myositis. After the stabilization of limb weakness, cecal perforation occurred due to cytomegalovirus (CMV) enteritis and temporal significant change of anti-CMV IgG antibody titer was confirmed using paired serum samples. Upregulation of MHC-class I molecule and numerous regenerative muscle fibers were observed in muscle biopsy, but no evidence of direct CMV infection in muscle fibers were seen. Although CMV infection may cause either myositis, acute renal failure, HLH or colitis in individual patient, this is the first case which had been complicated by all these conditions subsequent to CMV infection.
Synthesis and carbonic anhydrase activating properties of a series of 2-amino-imidazolines structurally related to clonidine
Journal of enzyme inhibition and medicinal chemistry, 2020

The Carbonic Anhydrase (CA, EC 4.2.1.1) activating properties of histamine have been known for a long time. This compound has been extensively modified but only in few instances the imidazole ring has been replaced with other heterocycles. It was envisaged that the imidazoline ring could be a bioisoster of the imidazole moiety. Indeed, we report that clonidine, a 2-aminoimidazoline derivative, was found able to activate several human CA isoforms (hCA I, IV, VA, VII, IX, XII and XIII), with potency in the micromolar range, while it was inactive on hCA II. A series of 2-aminoimidazoline, structurally related to clonidine, was then synthesised and tested on selected hCA isoforms. The compounds were inactive on hCA II while displayed activating properties on hCA I, VA, VII and XIII, with K
A blended cognitive behavioral intervention for patients with adjustment disorder with anxiety: A randomized controlled trial.
Internet interventions, 2020

Adjustment disorder with anxiety (ADA) is a common psychiatric pathology worldwide, but it is often undertreated. Cognitive behavioral therapy (CBT) is the first-line treatment, but very few studies have been carried out for the treatment of ADA. Internet-delivered CBT (iCBT) appears to be an effective treatment option, with the potential to reach a larger proportion of individuals suffering from ADA. Guidance is a beneficial feature of iCBT, provided in most studies by email or telephone (traditional guided iCBT). Blended CBT, which combines an online intervention and therapeutic guidance provided in person (face-to-face), could be a way to benefit from both the advantages of face-to-face CBT regarding human interactional quality and the advantages of internet-based CBT in terms of improved access to treatment. In this randomized controlled trial, the effectiveness of two forms of administration of
Identifying neural signatures mediating behavioral symptoms and psychosis onset: High-dimensional whole brain functional mediation analysis.
NeuroImage, 2021

Along the pathway from behavioral symptoms to the development of psychotic disorders sits the multivariate mediating brain. The functional organization and structural topography of large-scale multivariate neural mediators among patients with brain disorders, however, are not well understood. Here, we design a high-dimensional brain-wide functional mediation framework to investigate brain regions that intermediate between baseline behavioral symptoms and future conversion to full psychosis among individuals at clinical high risk (CHR). Using resting-state functional magnetic resonance imaging (fMRI) data from 263 CHR subjects, we extract an α brain atlas and a β brain atlas: the former underlines brain areas associated with prodromal symptoms and the latter highlights brain areas associated with disease onset. In parallel, we identify and separate mediators that potentially positively and negatively mediate symptoms and psychosis, respectively, and quantify the effect of each neural mediator on disease development. Taken together, these results paint a brain-wide picture of neural markers that are potentially mediating behavioral symptoms and the development of psychotic disorders; additionally, they underscore a statistical framework that is useful to uncover large-scale intermediating variables in a regulatory biological system.
Associations of endogenous 17-β-estradiol with theta amplitude and performance in semantic categorization in young women.
Neuroscience, 2015

In semantic categorization processes, individuals form a relation between perceived or imagined objects and knowledge about these objects. In the present semantic categorization study, we correlated endogenous 17-β-estradiol levels (E2) with performance as well as amplitude of theta oscillations in young women (age 23.1±3.4 years). The semantic categorization task consisted of nouns representing either living or non-living items. Each item was characterized either by many or by few features. We identified parameters associated or not associated with menstrual cycle phases. Irrespective of the menstrual cycle phase, women (1) responded faster to living items as well as to nouns characterized by many features compared to non-living items and items characterized by few features, (2) showed higher accuracy to non-living items and items having many features, and (3) showed negative correlation between response time (RT) and theta amplitude. RT, accuracy and post-stimulus theta amplitude were not statistically significantly different among early follicular, late follicular or luteal women. In early follicular but not in late follicular or luteal women, we observed (1) a positive correlation between E2 and latency in RT, (2) a negative correlation between E2 and accuracy, and (3) a negative correlation between E2 and post-stimulus theta amplitude. A mosaic of menstrual cycle phase-dependent and -independent associations may indicate that a similar performance in each menstrual cycle phase is related to different modulation of synaptic activity by hormones.
Emerging Evidence for Putative Neural Networks and Antecedents of Pediatric Anxiety in the Fetal, Neonatal, and Infant Periods.
Biological psychiatry, 2021

Anxiety disorders are the most prevalent psychiatric disorders in youth and are associated with profound individual impairment and public health costs. Research shows that clinically significant anxiety symptoms manifest in preschool-aged children, and correlates of anxiety symptoms are observable in infancy. Yet, predicting who is at risk for developing anxiety remains an enduring challenge. Predictive biomarkers of anxiety are needed before school age when anxiety symptoms typically consolidate into diagnostic profiles. Increasing evidence indicates that early neural measures implicated in anxiety and anxious temperament may be incorporated with traditional measures of behavioral risk (i.e., behavioral inhibition) to provide more robust classification of pediatric anxiety problems. This review examines the phenomenology of anxiety disorders in early life, highlighting developmental research that interrogates the putative neurocircuitry of pediatric anxiety. First, we discuss enduring challenges in identifying and predicting risk for pediatric anxiety. Second, we summarize emerging evidence for putative neural antecedents and networks underlying risk for pediatric anxiety in the fetal, neonatal, and infant periods that represent novel potential avenues for risk identification and prediction. We focus on evidence examining the importance of early amygdala and extended amygdala circuitry development to the emergence of anxiety. Finally, we discuss the utility of integrating developmental psychopathology and neuroscience to facilitate future research and clinical work.
A Novel In Vitro Device to Deliver Induced Electromagnetic Fields to Cell and Tissue Cultures.
Biophysical journal, 2020

We have developed a novel, to our knowledge, in vitro instrument that can deliver intermediate-frequency (100-400 kHz), moderate-intensity (up to and exceeding 6.5 V/cm pk-pk) electric fields (EFs) to cell and tissue cultures generated using induced electromagnetic fields (EMFs) in an air-core solenoid coil. A major application of these EFs is as an emerging cancer treatment modality. In vitro studies by Novocure reported that intermediate-frequency (100-300 kHz), low-amplitude (1-3 V/cm) EFs, which they called "tumor-treating fields (TTFields)," had an antimitotic effect on glioblastoma multiforme (GBM) cells. The effect was found to increase with increasing EF amplitude. Despite continued theoretical, preclinical, and clinical study, the mechanism of action remains incompletely understood. All previous in vitro studies of "TTFields" have used attached, capacitively coupled electrodes to deliver alternating EFs to cell and tissue cultures. This contacting delivery method suffers from a poorly characterized EF profile and conductive heating that limits the duration and amplitude of the applied EFs. In contrast, our device delivers EFs with a well-characterized radial profile in a noncontacting manner, eliminating conductive heating and enabling thermally regulated EF delivery. To test and demonstrate our system, we generated continuous, 200-kHz EMF with an EF amplitude profile spanning 0-6.5 V/cm pk-pk and applied them to exemplar human thyroid cell cultures for 72 h. We observed moderate reduction in cell density (<10%) at low EF amplitudes (<4 V/cm) and a greater reduction in cell density of up to 25% at higher amplitudes (4-6.5 V/cm). Our device can be readily extended to other EF frequency and amplitude regimes. Future studies with this device should contribute to the ongoing debate about the efficacy and mechanism(s) of action of "TTFields" by better isolating the effects of EFs and providing access to previously inaccessible EF regimes.
Cortical mediation of relationships between dopamine receptor D2 and cognition is absent in youth at risk of bipolar disorder.
Psychiatry research. Neuroimaging, 2021

Bipolar disorder is associated with cognitive deficits and cortical changes for which the developmental dynamics are not well understood. The dopamine D2 receptor (DRD2) gene has been associated with both psychiatric disorders and cognitive variability. Here we examined the mediating role of brain structure in the relationship between DRD2 genomic variation and cognitive performance, with target cortical regions selected based on evidence of association with DRD2, bipolar disorder and/or cognition from prior literature. Participants (n = 143) were aged 12-30 years and comprised 62 first-degree relatives of bipolar patients (deemed 'at-risk'), 55 controls, and 26 patients with established bipolar disorder; all were unrelated Caucasian individuals with complete data across the three required modalities (structural magnetic resonance imaging, neuropsychological and genetic data). A DRD2 haplotype was derived from three functional polymorphisms (rs1800497, rs1076560, rs2283265) associated with alternative splicing (i.e., D2-short/-long isoforms). Moderated mediation analyses explored group differences in relationships between this DRD2 haplotype, three structural brain networks which subsume the identified cortical regions of interest (frontoparietal, dorsal-attention, and ventral-attention), and three cognitive indices (intelligence, attention, and immediate memory). Controls who were homozygous for the DRD2 major haplotype demonstrated greater cognitive performance as a result of dorsal-attention network mediation. However, this association was absent in the 'at-risk' group. This study provides the first evidence of a functional DRD2-brain-cognition pathway. The absence of typical brain-cognition relationships in young 'at-risk' individuals may reflect biological differences that precede illness onset. Further insight into early pathogenic processes may facilitate targeted early interventions.
Safety of Anticoagulation in Patients Treated With Urgent Reperfusion for Ischemic Stroke Related to Atrial Fibrillation.
Stroke, 2020

The optimal timing for starting oral anticoagulant after an ischemic stroke related to atrial fibrillation remains a challenge, mainly in patients treated with systemic thrombolysis or mechanical thrombectomy. We aimed at assessing the incidence of early recurrence and major bleeding in patients with acute ischemic stroke and atrial fibrillation treated with thrombolytic therapy and/or thrombectomy, who then received oral anticoagulants for secondary prevention.