rudyvdbrink/CitationDatabase huggingface dataset:
First participant diagnosed with Creutzfeldt-Jakob disease in the population-based Rotterdam Study was classified with mild cognitive impairment.
BMJ case reports, 2021

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare, fatal, neurodegenerative disease caused by accumulation of abnormally folded prion protein. sCJD can have a long asymptomatic incubation period, with little known about this period. We describe the first-ever participant within the population-based Rotterdam Study diagnosed with sCJD. We retrieved clinical data from both the population-based Rotterdam Study and the National Prion Disease Registry. In 2011, a female participant of the Rotterdam Study was diagnosed with probable sCJD and registered into the Registry. Four months earlier, she was classified as having mild cognitive impairment based on assessment in the Rotterdam Study. Clinical deterioration was rapid, with the patient dying 7 months after the research centre visit. Postmortem brain autopsy confirmed the diagnosis of sCJD. In conclusion, we describe the first case diagnosed with sCJD who during diagnostic workup for sCJD was classified as having mild cognitive impairment in a population-based cohort study.
Autologous Hematopoietic Stem Cell Transplantation (AHSCT): Standard of Care for Relapsing-Remitting Multiple Sclerosis Patients.
Neurology and therapy, 2020

Autologous hematopoietic stem cell transplantation (AHSCT) has been used in the treatment of highly active multiple sclerosis (MS) for over two decades. It has been demonstrated to be highly efficacious in relapsing-remitting (RR) MS patients failing to respond to disease-modifying drugs (DMDs). AHSCT guarantees higher rates of no evidence of disease activity (NEDA) than those achieved with any other DMDs, but it is also associated with greater short-term risks which have limited its use. In the 2019 updated EBMT and ASBMT guidelines, which review the clinical evidence of AHSCT in MS, AHSCT indication for highly active RRMS has changed from "clinical option" to "standard of care". On this basis, AHSCT must be proposed on equal footing with second-line DMDs to patients with highly active RRMS, instead of being considered as a last resort after failure of all available treatments. The decision-making process requires a close collaboration between transplant hematologists and neurologists and a full discussion of risk-benefit of AHSCT and alternative treatments. In this context, we propose a standardized protocol for decision-making and informed consent process.
Examining the effect of online advertisement cues on human responses using eye-tracking, EEG, and MRI.
Behavioural brain research, 2021

This study sought to emphasize how disciplines such as neuroscience and marketing can be applied in advertising and consumer behavior. The application of neuroscience methods in analyzing and understanding human behavior related to the Elaboration Likelihood Model (ELM) and brain activity has recently garnered attention. This study examines brain processes while participants attempted to elicit preferences for a product, and demonstrates factors that influence consumer behavior using eye-tracking, electroencephalography (EEG), and magnetic resonance imaging (MRI) from a neuroscience approach. We planned two conditions of online advertising, namely, peripheral cues without argument and central cues with argument strength. Thirty respondents participated in the experiment, consisting of eye-tracking, EEG, and MRI instruments to explore brain activity in central cue conditions. We investigated whether diffusion tensor imaging (DTI) analysis could detect regional brain changes. Using eye-tracking, we found that the responses were mainly in the mean fixation duration, number of fixations, mean saccade duration, and number of saccade durations for the central cue condition. Moreover, the findings show that the fusiform gyrus and frontal cortex are significantly associated with building a relationship by inferring central cues in the EEG assay. The MRI images show that the fusiform gyrus and frontal cortex are significantly active in the central cue condition. DTI analysis indicates that the corpus callosum has changed in the central cue condition. We used eye-tracking, EEG, MRI, and DTI to understand that these connections may apprehend responses when viewing advertisements, especially in the fusiform gyrus, frontal cortex, and corpus callosum.
Spatiotemporal analysis of soluble aggregates and autophagy markers in the R6/2 mouse model.
Scientific reports, 2021

Maintenance of cellular proteostasis is vital for post-mitotic cells like neurons to sustain normal physiological function and homeostasis, defects in which are established hallmarks of several age-related conditions like AD, PD, HD, and ALS. The Spatio-temporal accumulation of aggregated proteins in the form of inclusion bodies/plaques is one of the major characteristics of many neurodegenerative diseases, including Huntington's disease (HD). Toxic accumulation of HUNTINGTIN (HTT) aggregates in neurons bring about the aberrant phenotypes of HD, including severe motor dysfunction, dementia, and cognitive impairment at the organismal level, in an age-dependent manner. In several cellular and animal models, aggrephagy induction has been shown to clear aggregate-prone proteins like HTT and ameliorate disease pathology by conferring neuroprotection. In this study, we used the mouse model of HD, R6/2, to understand the pathogenicity of mHTT aggregates, primarily focusing on autophagy dysfunction. We report that basal autophagy is not altered in R6/2 mice, whilst being functional at a steady-state level in neurons. Moreover, we tested the efficacy of a known autophagy modulator, Nilotinib (Tasigna™), presently in clinical trials for PD, and HD, in curbing mHTT aggregate growth and their potential clearance, which was ineffective in both inducing autophagy and rescuing the pathological phenotypes in R6/2 mice.
Insights into microbiome research 3: Who's there versus what are they doing?
Multiple sclerosis (Houndmills, Basingstoke, England), 2018

The main two questions that large microbiome studies typically address are "who's there?" and "what are they doing?" The first question aims at screening what kind of organisms are present, and it provides a low-resolution, relative composition of the microbiome. The second question focuses on precisely characterizing microbial communities by sequencing their entire genome on and providing insights into their metabolic capabilities. While DNA sequencing has become relatively affordable, differences in cost still exist between targeted and shotgun approaches, thus making these strategies quite complementary and commonly used.
New Mechanisms, New Opportunities: Integrating Novel Antidepressants in the Treatment of Major Depressive Disorder.
The Journal of clinical psychiatry, 2019

Listen to experts and view their slides from a panel session at the American Society of Clinical Psychopharmacology (ASCP) meeting, held on May 29, 2019, in Scottsdale, Arizona. Dr Murrough described the current understanding of depression etiology and new insights into antidepressant development. Dr Goldberg shared his expertise about whether antidepressant drugs with novel mechanisms of action can improve outcomes in patients with major depressive disorder. Dr Gaynes reviewed the link between major depressive disorder and elevated mortality risk and whether recovery from depression can reverse patients' mortality risk. Dr Citrome discussed current best practices and new medications for the treatment of depression. Finally, Dr Ketter provided his thoughts on his colleagues' presentations.
Correlation between interictal cerebral glucose hypometabolism and IQ in children with epilepsy.
Epilepsy & behavior : E&B, 2014

The aim of this study was to understand the relationship between IQ and glucose metabolism in brain cells in a wide variety of subjects with epilepsy. The study participants were 78 children with epilepsy and 15 healthy children for comparison. All participants were administered the Chinese Wechsler Intelligence Scale for Children (C-WISC). The verbal intelligence quotient (VIQ), performance intelligence quotient (PIQ), and full-scale intelligence quotient (FIQ) were compared between children with epilepsy and typically developing children. Seventy-eight patients underwent interictal positron emission computed tomography (PET) using 2-deoxy-2[(18)F]fluoro-d-glucose (FDG) as the tracer for evaluating brain glucose metabolism. Verbal intelligence quotient, PIQ, and FIQ based on the C-WISC were significantly lower in children with epilepsy than those in the healthy comparison group (P<0.001, P=0.001, and P<0.001, respectively). The IQ of patients with normal metabolism, unifocal abnormal hypometabolism, and multifocal abnormal hypometabolism determined by PET differed significantly. The extent of the abnormal hypometabolism was negatively correlated with the FIQ (rs=-0.549, P<0.001). In patients with lateralized hypometabolism based on PET, the VIQ/PIQ discrepancy scores (|VIQ-PIQ|≥15 points) differed significantly between the left hemisphere abnormal hypometabolism and right hemisphere abnormal hypometabolism subgroups, with negative values in the left and positive values in the right subgroups (P=0.004). In conclusion, brain metabolic abnormalities are correlated with IQ, and performing interictal PET along with C-WISC can better assess the extent of severity of cognitive impairment and VIQ/PIQ discrepancy.
Dissociable effects of dietary sodium in early life upon somatic growth, fluid homeostasis, and spatial memory in mice of both sexes.
American journal of physiology. Regulatory, integrative and comparative physiology, 2021

Postnatal growth failure is a common morbidity for preterm infants and is associated with adverse neurodevelopmental outcomes. Although sodium (Na) deficiency early in life impairs somatic growth, its impact on neurocognitive functions has not been extensively studied. We hypothesized that Na deficiency during early life is sufficient to cause growth failure and program neurobehavioral impairments in later life. C57BL/6J mice were placed on low- (0.4), normal- (1.5), or high- (3 g/kg) Na chow at weaning (
Acute phase treatment in central retinal artery occlusion: thrombolysis, hyperbaric oxygen therapy or both?
Journal of thrombosis and thrombolysis, 2020

Central retinal artery occlusion (CRAO) is a neuro-ophthalmological emergency. There is a finite time window for acute interventions such as revascularization (e.g. intravenous thrombolysis-IVT) and retinal oxygenation (e.g. hyperbaric oxygen therapy-HBOT) therapies. Case 1: A 35-year-old female presented with CRAO in the right eye (OD) confirmed by fluorescein angiography (FA) and optical coherence tomography (OCT). She underwent 4 sessions of HBOT (100% O2 at 2.4 atmosphere absolute for 90 min). Afterwards, visual defect on the nasal field was kept but visual acuity (VA) improved from counting fingers to 1.0. Case 2: A 65-year-old male presented with CRAO in his left eye (OS) with 1.5 h of evolution. Orbital sonography and OCT confirmed the presence of an embolus and he underwent IVT with rTPA (0.9 mg/kg). VA improved from light perception to 0.1. Case 3: A 21-year-old male presented acute visual loss in his OD with 2.5 h of evolution. OCT and retinography identified CRAO. He was submitted to IVT (rTPA-0.9 mg/kg) followed by 12 sessions of HBOT. VA improved from hand motion to 1.0. Our case series depicts the approaches and possible outcomes in acute management of an infrequent, but highly morbid, cerebroretinovascular disorder. Future clinical trials are warranted to tackle current difficulties in CRAO treatment.
Direct Insertion of the Papillary Muscle into the Anterior Mitral Leaflet: Cadaveric Findings.
Cureus, 2017

Direct insertion of the anterior papillary muscle (DPM) into the mitral valve is uncommon. During the routine dissection of an adult female, a DPM into the mitral valve with abnormal chordae tendinae was observed. This abnormal papillary muscle was measured as 28.0 mm in length from myocardial to insertion, 14.8 mm in width, and 7.0 mm in depth. The embryology, symptoms, associated cardiac diseases, and surgical precautions of this congenital malformation in the heart are reviewed.
Partial and full deletion of nicotinic acetylcholine receptor α4 and β2 subunits reduces sensitivity to acute nicotine administration and development of tolerance following chronic nicotine administration.
Behavioural pharmacology, 2020

The diversity of nicotinic cholinergic receptor (nAChR) subunits underlies the complex responses to nicotine. Mice differing in the expression of α4 and β2 subunits, which are most widely expressed in brain, were evaluated for the responses to acute nicotine administration on Y-maze crossings and rears, open-field locomotion and body temperature following chronic treatment with nicotine (0, 0.25, 1.0 and 4.0 mg/kg/h). Deletion or partial deletion of the α4, β2 or both nAChR subunits reduced the sensitivity of mice to acute nicotine administration. This reduced sensitivity was gene dose-dependent. Modification of α4 subunit expression elicited a greater reduction in sensitivity than the modification of β2 subunit expression. No measurable tolerance was observed for mice of any genotype following chronic treatment with 0.25 mg/kg/h nicotine. Modest tolerance was noted following treatment with 1.0 mg/kg/h. Greater tolerance was observed following treatment with 4.0 mg/kg/h. The extent of tolerance differed among the mice depending on genotype: wild-type (α4 and β2) developed measurable tolerance for all four tests. Heterozygotes (α4, β2 and α4/β2) developed tolerance for only Y-maze crossings and body temperature. Null mutants (α4 and β2) did not become tolerant. However, following chronic treatment with 4.0 mg/kg/h nicotine, wild type, α4 and α4 mice displayed increased Y-maze crossings following acute administration of 0.5 mg/kg nicotine that may reflect the activity of α6β2*-nAChR. These results confirm the importance of the α4 and β2 nAChR subunits in mediating acute and chronic effects of nicotine on locomotion and body temperature in the mouse.
Online Reinforcement Learning Using a Probability Density Estimation.
Neural computation, 2017

Function approximation in online, incremental, reinforcement learning needs to deal with two fundamental problems: biased sampling and nonstationarity. In this kind of task, biased sampling occurs because samples are obtained from specific trajectories dictated by the dynamics of the environment and are usually concentrated in particular convergence regions, which in the long term tend to dominate the approximation in the less sampled regions. The nonstationarity comes from the recursive nature of the estimations typical of temporal difference methods. This nonstationarity has a local profile, varying not only along the learning process but also along different regions of the state space. We propose to deal with these problems using an estimation of the probability density of samples represented with a gaussian mixture model. To deal with the nonstationarity problem, we use the common approach of introducing a forgetting factor in the updating formula. However, instead of using the same forgetting factor for the whole domain, we make it dependent on the local density of samples, which we use to estimate the nonstationarity of the function at any given input point. To address the biased sampling problem, the forgetting factor applied to each mixture component is modulated according to the new information provided in the updating, rather than forgetting depending only on time, thus avoiding undesired distortions of the approximation in less sampled regions.
Reactive Oxygen Species and Oxidative Stress in the Pathogenesis and Progression of Genetic Diseases of the Connective Tissue.
Antioxidants (Basel, Switzerland), 2020

Connective tissue is known to provide structural and functional "glue" properties to other tissues. It contains cellular and molecular components that are arranged in several dynamic organizations. Connective tissue is the focus of numerous genetic and nongenetic diseases. Genetic diseases of the connective tissue are minority or rare, but no less important than the nongenetic diseases. Here we review the impact of reactive oxygen species (ROS) and oxidative stress on the onset and/or progression of diseases that directly affect connective tissue and have a genetic origin. It is important to consider that ROS and oxidative stress are not synonymous, although they are often closely linked. In a normal range, ROS have a relevant physiological role, whose levels result from a fine balance between ROS producers and ROS scavenge enzymatic systems. However, pathology arises or worsens when such balance is lost, like when ROS production is abnormally and constantly high and/or when ROS scavenge (enzymatic) systems are impaired. These concepts apply to numerous diseases, and connective tissue is no exception. We have organized this review around the two basic structural molecular components of connective tissue: The ground substance and fibers (collagen and elastic fibers).
Thermal and cardiovascular strain imposed by motorcycle protective clothing under Australian summer conditions.
Ergonomics, 2016

Motorcycle protective clothing can be uncomfortably hot during summer, and this experiment was designed to evaluate the physiological significance of that burden. Twelve males participated in four, 90-min trials (cycling 30 W) across three environments (25, 30, 35 °C [all 40% relative humidity]). Clothing was modified between full and minimal injury protection. Both ensembles were tested at 25 °C, with only the more protective ensemble investigated at 30 and 35 °C. At 35 °C, auditory canal temperature rose at 0.02 °C min(-1) (SD 0.005), deviating from all other trials (p < 0.05). The thresholds for moderate (>38.5 °C) and profound hyperthermia (>40.0 °C) were predicted to occur within 105 min (SD 20.6) and 180 min (SD 33.0), respectively. Profound hyperthermia might eventuate in ~10 h at 30 °C, but should not occur at 25 °C. These outcomes demonstrate a need to enhance the heat dissipation capabilities of motorcycle clothing designed for summer use in hot climates, but without compromising impact protection. Practitioner's Summary: Motorcycle protective clothing can be uncomfortably hot during summer. This experiment was designed to evaluate the physiological significance of this burden across climatic states. In the heat, moderate (>38.5 °C) and profound hyperthermia (>40.0 °C) were predicted to occur within 105 and 180 min, respectively.
Sleep-readiness signals in insomniacs and good sleepers.
Journal of health psychology, 2016

Sleep is preceded by physiological and behavioural events that inform the subject that it is time to sleep. Our hypothesis is that insomniacs do not adequately recognize such signals, thus missing the best time to go to bed. Eighty-seven chronic insomniac participants and 76 age-matched good sleeper controls were recruited. Semi-structured interviews focused on three aspects of nocturnal sleep: features, habitual activities and signals that they usually rely on in order to decide their readiness to sleep. The results showed that insomniacs relied more than good sleepers on external signals (time) than on bodily ones to decide to go to sleep.
Neuropilin-1 expression in GnRH neurons regulates prepubertal weight gain and sexual attraction.
The EMBO journal, 2020

Hypothalamic neurons expressing gonadotropin-releasing hormone (GnRH), the "master molecule" regulating reproduction and fertility, migrate from their birthplace in the nose to their destination using a system of guidance cues, which include the semaphorins and their receptors, the neuropilins and plexins, among others. Here, we show that selectively deleting neuropilin-1 in new GnRH neurons enhances their survival and migration, resulting in excess neurons in the hypothalamus and in their unusual accumulation in the accessory olfactory bulb, as well as an acceleration of mature patterns of activity. In female mice, these alterations result in early prepubertal weight gain, premature attraction to male odors, and precocious puberty. Our findings suggest that rather than being influenced by peripheral energy state, GnRH neurons themselves, through neuropilin-semaphorin signaling, might engineer the timing of puberty by regulating peripheral adiposity and behavioral switches, thus acting as a bridge between the reproductive and metabolic axes.
The maturational characteristics of the GABA input in the anterior piriform cortex may also contribute to the rapid learning of the maternal odor during the sensitive period.
Learning & memory (Cold Spring Harbor, N.Y.), 2020

During the first ten postnatal days (P), infant rodents can learn olfactory preferences for novel odors if they are paired with thermo-tactile stimuli that mimic components of maternal care. After P10, the thermo-tactile pairing becomes ineffective for conditioning. The current explanation for this change in associative learning is the alteration in the norepinephrine (NE) inputs from the locus coeruleus (LC) to the olfactory bulb (OB) and the anterior piriform cortex (aPC). By combining patch-clamp electrophysiology and computational simulations, we showed in a recent work that a transitory high responsiveness of the OB-aPC circuit to the maternal odor is an alternative mechanism that could also explain early olfactory preference learning and its cessation after P10. That result relied solely on the maturational properties of the aPC pyramidal cells. However, the GABAergic system undergoes important changes during the same period. To address the importance of the maturation of the GABAergic system for early olfactory learning, we incorporated data from the GABA inputs, obtained from in vitro patch-clamp experiment in the aPC of rat pups aged P5-P7 reported here, to the model proposed in our previous publication. In the younger than P10 OB-aPC circuit with GABA synaptic input, the number of responsive aPC pyramidal cells to the conditioned maternal odor was amplified in 30% compared to the circuit without GABAergic input. When compared with the circuit with other younger than P10 OB-aPC circuit with adult GABAergic input profile, this amplification was 88%. Together, our results suggest that during the olfactory preference learning in younger than P10, the GABAergic synaptic input presumably acts by depolarizing the aPC pyramidal neurons in such a way that it leads to the amplification of the pyramidal neurons response to the conditioned maternal odor. Furthermore, our results suggest that during this developmental period, the aPC pyramidal cells themselves seem to resolve the apparent lack of GABAergic synaptic inhibition by a strong firing adaptation in response to increased depolarizing inputs.
[Neuronal connections within the hand representation in areas 3b and 1 of the somatosensory cortex in primates].
Orvosi hetilap, 2016

The close functional relationship between areas 3b and 1 of the somatosensory cortex is based on their reciprocal connections indicating that tactile sensation depends on the interaction of these two areas.