rudyvdbrink/CitationDatabase huggingface dataset:
Line scan-based rapid magnetic resonance imaging of repetitive motion.
Scientific reports, 2021

Two-dimensional (2D) line scan-based dynamic magnetic resonance imaging (MRI) is examined as a means to capture the interior of objects under repetitive motion with high spatiotemporal resolutions. The method was demonstrated in a 9.4-T animal MRI scanner where line-by-line segmented k-space acquisition enabled recording movements of an agarose phantom and quail eggs in different conditions-raw and cooked. A custom MR-compatible actuator which utilized the Lorentz force on its wire loops in the scanner's main magnetic field effectively induced the required periodic movements of the objects inside the magnet. The line-by-line k-space segmentation was achieved by acquiring a single k-space line for every frame in a motion period before acquisition of another line with a different phase-encode gradient in the succeeding motion period. The reconstructed time-course images accurately represented the objects' displacements with temporal resolutions up to 5.5 ms. The proposed method can drastically increase the temporal resolution of MRI for imaging rapid periodic motion of objects while preserving adequate spatial resolution for internal details when their movements are driven by a reliable motion-inducing mechanism.
Impact of Glatiramer Acetate on B Cell-Mediated Pathogenesis of Multiple Sclerosis.
CNS drugs, 2018

Growing evidence indicates that B cells play a key role in the pathogenesis of multiple sclerosis (MS). B cells occupy distinct central nervous system (CNS) compartments in MS, including the cerebrospinal fluid and white matter lesions. Also, it is now known that, in addition to entering the CNS, B cells can circulate into the periphery via a functional lymphatic system. Data suggest that the role of B cells in MS mainly involves their in situ activation in demyelinating lesions, leading to altered pro- and anti-inflammatory cytokine secretion, and a highly effective antigen-presenting cell function, resulting in activation of memory or naïve T cells. Clinically, B cell-depleting agents show significant efficacy in MS. In addition, many disease-modifying therapies (DMTs) traditionally understood to target T cells are now known to influence B cell number and function. One of the earliest DMTs to be developed, glatiramer acetate (GA), has been shown to reduce the total frequency of B cells, plasmablasts, and memory B cells. It also appears to promote a shift toward reduced inflammation by increasing anti-inflammatory cytokine release and/or reducing pro-inflammatory cytokine release by B cells. In the authors' opinion, this may be mediated by cross-reactivity of B cell receptors for GA with antigen (possibly myelin basic protein) expressed in the MS lesion. More research is required to further characterize the role of B cells and their bidirectional trafficking in the pathogenesis of MS. This may uncover novel targets for MS treatments and facilitate the development of B cell biomarkers of drug response.
The expression of long noncoding RNA NEAT1 is reduced in schizophrenia and modulates oligodendrocytes transcription.
NPJ schizophrenia, 2019

Oligodendrocyte (OLG)-related abnormalities have been broadly observed in schizophrenia (SZ); however, the etiology of these abnormalities remains unknown. As SZ is broadly believed to be a developmental disorder, the etiology of the myelin abnormalities in SZ may be related to OLG fate specification during development. Noncoding RNAs (ncRNAs) are an important part of multifaceted transcriptional complexes participating in neurogenic commitment and regulation of postmitotic cell function. The long ncRNA, NEAT1, is a structural component of paraspeckles (subnuclear bodies in interchromatin regions) that may control activity of developmental enhancers of OLG fate specification. Gene expression studies of multiple cortical regions from individuals with SZ showed strong downregulation of NEAT1 levels relative to controls. NEAT1-deficient mice show significant decreases in the numbers of OLG-lineage cells in the frontal cortex. To gain further insight into biological processes affected by NEAT1 deficiency, we analyzed RNA-seq data from frontal cortex of NEAT1
A probabilistic atlas of the human inner ear's bony labyrinth enables reliable atlas-based segmentation of the total fluid space.
Journal of neurology, 2019

Intravenous contrast agent-enhanced magnetic resonance imaging of the endolymphatic space (ELS) of the inner ear permits direct, in-vivo, non-invasive visualization of labyrinthine structures and thus verification of endolymphatic hydrops (ELH). However, current volumetric assessment approaches lack normalization. The aim of this study was to develop a probabilistic atlas of the inner ear's bony labyrinth as a first step towards an automated and reproducible volume-based quantification of the ELS. The study included three different datasets: a source dataset (D1) to build the probabilistic atlas and two testing sets (D2, D3). D1 included 24 right-handed patients (12 females; mean age 51.5 ± 3.9 years) and D2 5 patients (3 female; mean age 48.8 ± 5.01 years) with vestibular migraine without ELH or any measurable vestibular deficits. D3 consisted of five patients (one female; mean age 46 ± 5.2 years) suffering from unilateral Menière's disease and ELH. Data processing comprised three steps: preprocessing using an affine and deformable fusion registration pipeline, computation of an atlas for the left and right inner ear using a label-assisted approach, and validation of the atlas based on localizing and segmenting previously unseen ears. The three-dimensional probabilistic atlas of the inner ear's bony labyrinth consisted of the internal acoustic meatus and inner ears (including cochlea, otoliths, and semicircular canals) for both sides separately. The analyses showed a high level of agreement between the atlas-based segmentation and the manual gold standard with an overlap of 89% for the right ear and 86% for the left ear (measured by dice scores). This probabilistic in vivo atlas of the human inner ear's bony labyrinth and thus of the inner ear's total fluid space for both ears represents a necessary step towards a normalized, easily reproducible and reliable volumetric quantification of the perilymphatic and endolymphatic space in view of MR volumetric assessment of ELH. The proposed atlas lays the groundwork for state-of-the-art approaches (e.g., deep learning) and will be provided to the scientific community.
Multimodal stimuli modulate rapid visual responses during reaching.
Journal of neurophysiology, 2019

The reticulospinal tract plays an important role in primate upper limb function, but methods for assessing its activity are limited. One promising approach is to measure rapid visual responses (RVRs) in arm muscle activity during a visually cued reaching task; these may arise from a tecto-reticulospinal pathway. We investigated whether changes in reticulospinal excitability can be assessed noninvasively using RVRs, by pairing the visual stimuli of the reaching task with electrical stimulation of the median nerve, galvanic vestibular stimulation, or loud sounds, all of which are known to activate the reticular formation. Surface electromyogram (EMG) recordings were made from the right deltoid of healthy human subjects as they performed fast reaching movements toward visual targets. Stimuli were delivered up to 200 ms before target appearance, and RVR was quantified as the EMG amplitude in a window 75-125 ms after visual target onset. Median nerve, vestibular, and auditory stimuli all consistently facilitated the RVRs, as well as reducing the latency of responses. We propose that this facilitation reflects modulation of tecto-reticulospinal excitability, which is consistent with the idea that the amplitude of RVRs can be used to assess changes in brain stem excitability noninvasively in humans.
AMN082, an allosteric mGluR7 agonist that inhibits afferent glutamatergic transmission in rat basolateral amygdala.
Neuropharmacology, 2008

Glutamatergic neurotransmission has been implicated in the pathophysiology of psychiatric disorders, such as anxiety and depression. The possible contribution of group III metabotropic glutamate receptors has been poorly investigated, due to the lack of selective pharmacological tools. However, a selective agonist of mGLUR7, AMN082 has been identified recently, and shown to act through an allosteric mechanism in recombinant cells expressing the receptor. Thus, using AMN082, we examined the role of mGLUR7 in modulating synaptic transmission in the rat basolateral amygdala (BLA), a brain region known to be important for the genesis of anxious states. We found that bath application of AMN082 (1-10microM) produced a concentration-dependent inhibition of synaptic transmission evoked at 2Hz, but had no effect on transmission evoked at 0.05Hz. However, at this lower frequency, AMN082 (10microM) significantly increased the synaptic inhibition produced by a group III mGLUR agonist, L-AP4 (100microM). This effect was blocked by pre-application of CPPG (500microM), a group III mGLUR-preferring antagonist, consistent with the involvement of mGLUR7. Thus, we have shown that AMN082 can modulate high frequency synaptic transmission in the BLA, in vitro, and appears to act on the receptor via an allosteric mechanism. These results suggest that mGLUR7 has a unique role in regulating neuronal activity in the BLA and may be a target for novel drugs for the treatment of anxiety.
Age-related changes in the temporal focus and self-referential content of spontaneous cognition during periods of low cognitive demand.
Psychological research, 2019

An intriguing aspect of human cognition is the unique capacity to mentally retreat from our immediate surroundings to consider perspectives distinct from the here and now. Despite increasing interest in this phenomenon, relatively little is known regarding age-related changes in off-task, self-generated thought (often referred to as "mind-wandering"), particularly under conditions of low cognitive demand. While a number of studies have investigated the temporal orientation of mind-wandering with increasing age, findings have been largely inconsistent. Here, we explored the frequency, temporal focus, and self-referential/social content of spontaneous task-unrelated, perceptually decoupled thought in 30 young and 33 healthy older adults using the Shape Expectations task, a validated experimental paradigm in which discrete facets of inner mentation are quantified along a conceptual continuum using open-ended report. Participants also completed the daydreaming subscale of the Imaginal Process Inventory (IPI) as a trait measure of mind-wandering propensity. Significant group differences emerged on the Shape Expectations task, with reduced instances of mind-wandering in the context of elevated task-related thoughts relative to younger adults. In terms of temporal focus, a preponderance of present/atemporal off-task thoughts was evident irrespective of group; however, significantly higher levels of future-oriented thoughts were provided by younger adults, contrasting with significantly higher instances of retrospection in the older group. In addition, older adults displayed significantly fewer incidences of self-referential cognition relative to their younger counterparts. Our findings indicate a distinct attenuation of off-task, self-generated thought processes with increasing age, with evidence for a shift in temporal focus and self-referential quality, during periods of low cognitive demand.
On the Policy of the Italian Government in the Discovery, Development, and Access to Medicines.
Clinical therapeutics, 2018

This commentary outlines how discovery, development, and access to medicines are regulated and promoted in Italy by the government through the Ministry of University and Research, the Ministry of Health, and the Italian Medicines Agency. We describe and comment on the existing research programs stimulating preclinical, translational, and clinical research and how access to medicines and their pricing is regulated by Italy's National Health Service both at the national and regional levels. Finally, we describe the current scenario of industrial research and medicines manufacturing. The resulting picture shows a country in which high-level competitive research on medicines is promoted alongside an excellent national health system working toward fairness of access to health care services for all citizens and fiscal solidarity as a fundamental form of system financing. Critical challenges still exist, including the relative scarcity of public funding for research and the non-uniform access to the benefits of the National Health Service across Italian regions.
Hydrophilic interaction liquid chromatography-tandem mass spectrometric approach for simultaneous determination of safingol and D-erythro-sphinganine in human plasma.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 2019

A simple and specific hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) method was developed for the simultaneous determination of C18-L-threo-sphinganine (safingol, an anti-neoplastic in phase I trials) and its diastereomer, C18-D-erythro-sphinganine (sphinganine), in human plasma. Sample pretreatment involved a protein precipitation with methanol using 25 μL aliquots of plasma. Chromatographic separation of the diastereomers and C17-D-erythro-sphinganine, an internal standard, was achieved on a Xbridge HILIC (3.5 μm, 100 × 2.1 mm) using isocratic elution with the mobile phase of 2 mM ammonium bicarbonate in water (pH 8.3) and acetonitrile at a flow rate of 0.3 mL/min. Electrospray ionization (ESI) mass spectrometry was operated in the positive ion mode with multiple reaction monitoring (MRM). The calibration curves obtained were linear over the concentration range of 0.2-100 ng/mL with a lower limit of quantification of 0.2 ng/mL. The relative standard deviation of intra-day and inter-day precision was below 8.27%, and the accuracy ranged from 92.23 to 110.06%. The extraction recoveries were found to be higher than 93.22% and IS-normalized matrix effect was higher than 90.92%. The analytes were stable for the durations of the stability studies. The validated method was successfully applied to the analyses of pharmacokinetic samples from patients treated with safingol and all-trans-N-(4-hydroxyphenyl)retinamide; (fenretinide, 4-HPR) in a current phase I clinical trial (SPOC-2010-002, ClinicalTrials.gov Identifier: NCT01553071).
Disease reactivation after switching from natalizumab to daclizumab.
Journal of neurology, 2017

Discontinuation of natalizumab can lead to severe rebound of disease activity in patients with relapsing-remitting multiple sclerosis (RRMS); nevertheless, the treatment regimen in this clinical situation remains controversial. We report the case of a 25-year-old male patient with RRMS who was clinically stable under 3 years of natalizumab before treatment was stopped due to progressive multifocal leucencephalopathy (PML) safety concerns. After initiation of daclizumab, the patient suffered from disease reactivation, which was ultimately controlled by intravenous methylprednisolone and alemtuzumab treatment. Therefore, in some patients, daclizumab might not be sufficient to control disease activity after discontinuing natalizumab treatment.
Foundational numerical capacities and the origins of dyscalculia.
Trends in cognitive sciences, 2010

One important cause of very low attainment in arithmetic (dyscalculia) seems to be a core deficit in an inherited foundational capacity for numbers. According to one set of hypotheses, arithmetic ability is built on an inherited system responsible for representing approximate numerosity. One account holds that this is supported by a system for representing exactly a small number (less than or equal to four4) of individual objects. In these approaches, the core deficit in dyscalculia lies in either of these systems. An alternative proposal holds that the deficit lies in an inherited system for sets of objects and operations on them (numerosity coding) on which arithmetic is built. I argue that a deficit in numerosity coding, not in the approximate number system or the small number system, is responsible for dyscalculia. Nevertheless, critical tests should involve both longitudinal studies and intervention, and these have yet to be carried out.
Up-regulation of spinal microglial Iba-1 expression persists after resolution of neuropathic pain hypersensitivity.
Neuroscience letters, 2013

Spinal microglial activation plays a major role in the development of neuropathic pain following peripheral nerve injury. We here provide evidence for an elevated expression of the microglial marker Iba-1 in the lumbar dorsal horn ipsilateral to L5 spinal nerve transection that persists for at least 14 weeks, a time at which mechanical hypersensitivity had fully resolved. Iba-1 expression was, however; significantly lower than at 4 weeks. We therefore conclude that microglia remain partly activated beyond the phase of pain hypersensitivity. Thus, the relation between microglial cells and neuropathic pain outcome is subject to change over time after nerve injury.
Adrenomedullin, a Novel Target for Neurodegenerative Diseases.
Molecular neurobiology, 2018

Neurodegenerative diseases represent a heterogeneous group of disorders whose common characteristic is the progressive degeneration of neuronal structure and function. Although much knowledge has been accumulated on the pathophysiology of neurodegenerative diseases over the years, more efforts are needed to understand the processes that underlie these diseases and hence to propose new treatments. Adrenomedullin (AM) is a multifunctional peptide involved in vasodilation, hormone secretion, antimicrobial defense, cellular growth, and angiogenesis. In neurons, AM and related peptides are associated with some structural and functional cytoskeletal proteins that interfere with microtubule dynamics. Furthermore, AM may intervene in neuronal dysfunction through other mechanisms such as immune and inflammatory response, apoptosis, or calcium dyshomeostasis. Alterations in AM expression have been described in neurodegenerative processes such as Alzheimer's disease or vascular dementia. This review addresses the current state of knowledge on AM and its possible implication in neurodegenerative diseases.
The influence of averageness on children's judgments of facial attractiveness.
Journal of experimental child psychology, 2013

We examined developmental changes in the influence of averageness on judgments of facial attractiveness by showing adults and children pairs of individual faces in which one face was transformed 50% toward its group average, whereas the other face was transformed 50% away from that average. In one comparison, adults and 5-year-olds rated the more average faces as more attractive whether the faces were of adult females, 5-year-old boys, or 5-year-old girls. The influence of averageness, however, was weaker in 5-year-olds than in adults. In another comparison, a new group of adults and 9-year-olds rated the more average faces as more attractive for male and female faces of adults, 9-year-olds, and 5-year-olds. The influence of averageness was again weaker for children than for adults, although the strength of 9-year-olds' preference was greater than that of 5-year-olds. Developmental changes may reflect the refinement of an average face prototype as children are exposed to more faces, increased sensitivity as visual perception develops, and/or the greater salience of attractiveness after puberty.
Evidence that the nucleus accumbens shell, ventral pallidum, and lateral hypothalamus are components of a lateralized feeding circuit.
Behavioural brain research, 2012

Pronounced feeding can be elicited by injections of the GABA(A) agonist muscimol into the medial shell region of the nucleus accumbens (AcbSh). This region of AcbSh has been shown to project to both the lateral hypothalamus (LH) and the medial ventral pallidum (VPm). The current study examined the effects of unilateral LH or VPm lesions on the ingestive responses induced by injections of muscimol into the AcbSh on either the same or the opposite side of the brain. We found that lesions of either of these structures drastically attenuated feeding induced from the ipsilateral, as compared to the contralateral, AcbSh. The "ipsilateral/contralateral disruption design" employed here virtually rules out the possibility that the suppressive effects of the lesions were nonspecific and suggests that the VPm and LH play essential roles in mediating the ingestive effects of inactivation of the AcbSh.
Communication behaviors associated with successful conversation in semantic variant primary progressive aphasia.
International psychogeriatrics, 2017

Primary progressive aphasia (PPA) affects a range of language and cognitive domains that impact on conversation. Little is known about conversation breakdown in the semantic variant of PPA (svPPA, also known as semantic dementia). This study investigates conversation of people with svPPA.
Translatable mitochondria-targeted protection against programmed cardiovascular dysfunction.
Science advances, 2020

The prenatal origins of heart disease in offspring have been established. However, research in species with developmental milestones comparable to humans is lacking, preventing translation of this knowledge to clinical contexts. Using sheep and chickens, two species with similar cardiovascular developmental milestones to humans, we combined in vivo experiments with in vitro studies at organ, cellular, mitochondrial, and molecular levels. We tested mitochondria-targeted antioxidant intervention with MitoQ against cardiovascular dysfunction programmed by developmental hypoxia, a common complication in human pregnancy. Experiments in sheep determined in vivo fetal and adult cardiovascular function through surgical techniques not possible in humans, while those in chicken embryos isolated effects independent of maternal or placental influences. We show that hypoxia generates mitochondria-derived oxidative stress during cardiovascular development, programming endothelial dysfunction and hypertension in adult offspring. MitoQ treatment during hypoxic development protects against this cardiovascular risk via enhanced nitric oxide signaling, offering a plausible intervention strategy.
Early cortical metabolic rearrangement related to clinical data in idiopathic sudden sensorineural hearing loss.
Hearing research, 2017

Results in studies concerning cortical changes in idiopathic sudden sensorineural hearing loss (ISSNHL) are not homogeneous, in particular due to the different neuroimaging techniques implemented and the diverse stages of ISSNHL studied. Considering the recent advances in state-of-the-art positron emission tomography (PET) cameras, the aim of this study was to gain more insight into the neuroanatomical differences associated with the earliest stages of unilateral ISSNHL and clinical-perceptual performance changes. After an audiological examination including the mean auditory threshold (mean AT), mean speech discrimination score (mean SDS) and Tinnitus Handicap Inventory (THI), 14 right-handed ISSNHL patients underwent brain [