rudyvdbrink/CitationDatabase huggingface dataset:
Diagnostic performance and prediction of clinical progression of plasma phospho-tau181 in the Alzheimer's Disease Neuroimaging Initiative.
Molecular psychiatry, 2021

Whilst cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers for amyloid-β (Aβ) and tau pathologies are accurate for the diagnosis of Alzheimer's disease (AD), their broad implementation in clinical and trial settings are restricted by high cost and limited accessibility. Plasma phosphorylated-tau181 (p-tau181) is a promising blood-based biomarker that is specific for AD, correlates with cerebral Aβ and tau pathology, and predicts future cognitive decline. In this study, we report the performance of p-tau181 in >1000 individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI), including cognitively unimpaired (CU), mild cognitive impairment (MCI) and AD dementia patients characterized by Aβ PET. We confirmed that plasma p-tau181 is increased at the preclinical stage of Alzheimer and further increases in MCI and AD dementia. Individuals clinically classified as AD dementia but having negative Aβ PET scans show little increase but plasma p-tau181 is increased if CSF Aβ has already changed prior to Aβ PET changes. Despite being a multicenter study, plasma p-tau181 demonstrated high diagnostic accuracy to identify AD dementia (AUC = 85.3%; 95% CI, 81.4-89.2%), as well as to distinguish between Aβ- and Aβ+ individuals along the Alzheimer's continuum (AUC = 76.9%; 95% CI, 74.0-79.8%). Higher baseline concentrations of plasma p-tau181 accurately predicted future dementia and performed comparably to the baseline prediction of CSF p-tau181. Longitudinal measurements of plasma p-tau181 revealed low intra-individual variability, which could be of potential benefit in disease-modifying trials seeking a measurable response to a therapeutic target. This study adds significant weight to the growing body of evidence in the use of plasma p-tau181 as a non-invasive diagnostic and prognostic tool for AD, regardless of clinical stage, which would be of great benefit in clinical practice and a large cost-saving in clinical trial recruitment.
Up-regulation of NSP3 by Oligomeric Aβ Accelerates Neuronal Death Through Cas-independent Rap1A Activation.
Neuroscience, 2018

β-Amyloid (Aβ) plays an important role in the early pathogenesis of Alzheimer's disease (AD). In vitro studies have demonstrated that Aβ oligomers induce hippocampal and neocortical neuronal death. However the neurotoxic mechanisms by which soluble Aβ oligomers cause neuronal damage and death remain to be fully elucidated. To this end, we analyzed the gene expression profile of rat cerebral cortical neurons treated with Aβ oligomers in vitro. Aβ treatment induced the expression of novel SH2-containing protein 3 (NSP3), an adaptor molecule interacting with Cas family proteins. NSP3 expression was upregulated not only in oligomeric-Aβ-treated cultured neurons but also in the neocortex of aged Tg2576 mice. NSP3 overexpression in cultured cortical neurons accelerated neuronal death. The C-terminal region of NSP3 unbound to a Cas protein was necessary for the NSP3-induced acceleration of neuronal death, as was Cas-independent Rap1A activation downstream of NSP3. Moreover, NSP3 RNAi knockdown partially rescued Aβ-oligomer-treated neurons. These results indicate that NSP3 upregulation by soluble Aβ oligomers may accelerate neuronal death via Cas-independent Rap1A activation, implicating NSP3 in the pathogenesis of AD.
Psychophysical characterisation of burning mouth syndrome-A systematic review and meta-analysis.
Journal of oral rehabilitation, 2020

Primary burning mouth syndrome (BMS) is an oro-facial disease with neuropathic characteristics. Psychophysics, such as quantitative sensory testing (QST), is used to sub-classify neuropathic pain syndromes, but their usefulness in characterising BMS is not yet clear.
A Note on the Depth-from-Defocus Mechanism of Jumping Spiders.
Biomimetics (Basel, Switzerland), 2017

Jumping spiders are capable of estimating the distance to their prey relying only on the information from one of their main eyes. Recently, it has been shown that jumping spiders perform this estimation based on image defocus cues. In order to gain insight into the mechanisms involved in this blur-to-distance mapping as performed by the spider and to judge whether inspirations can be drawn from spider vision for depth-from-defocus computer vision algorithms, we constructed a three-dimensional (3D) model of the anterior median eye of the
Evaluating the Impact of Spinal Osteotomy on Surgical Outcomes of Thoracolumbar Deformity Correction.
World neurosurgery, 2020

In cases of adult spinal deformity (ASD) with severe sagittal malalignment, the use of osteotomies may be necessary in addition to posterior fusion. However, few data exist describing the impact of osteotomies on complications and quality outcomes during ASD surgery.
The clinical spectrum of primary lateral sclerosis.
Amyotrophic lateral sclerosis & frontotemporal degeneration, 2020

Primary lateral sclerosis is a distinct entity that has recently been classified as a "restricted phenotype" of ALS. It is characterized by a pattern of isolated upper motor neuron involvement that often begins in the legs and spreads diffusely. Distinction from other conditions requires careful consideration of clinical presentation and time course of disease. Mills' Syndrome is a rare unilateral variant of primary lateral sclerosis. Cognitive and behavioral involvement may occur.
The associations of the BDNF and APOE polymorphisms, hippocampal subfield volumes, and episodic memory performance across the lifespan.
Hippocampus, 2020

In this study, we explored the associations between the brain derived neurotrophic factor (BDNF) and the apolipoprotein E (APOE) polymorphisms and hippocampal subfields in 127 healthy participants (18-85 years). MRI datasets were collected on a 4.7 T system. Participants were administered the Wechsler Memory Scale to evaluate episodic memory function. Significant associations of both polymorphisms were present only in older adults (≥50 years). BDNF polymorphism was associated with larger dentate gyrus volumes within the anterior hippocampus (head) in Met-carriers compared to Val/Val homozygotes. We found that in Met-carriers total hippocampal volume predicted performance on visuospatial memory tasks. APOE polymorphism was associated with larger total hippocampal volume, especially in cornu ammonis 1-3 and subiculum in APOE ɛ2 carriers compared to both ɛ4 and ɛ3 carriers, while APOE ɛ3 and ɛ4 carriers did not differ from each other. APOE polymorphism was associated with better performance on visuospatial memory tasks in APOE ε2 carriers in comparison to ε4 carriers.
Oculo-auriculo-vertebral spectrum with craniosynostosis and osteo-cartilagineous multiple defects: a diffuse chondro-membranous-osteo-dysplasia.
La Pediatria medica e chirurgica : Medical and surgical pediatrics, 2015

We report on a female with oculo-auriculo-vertebral spectrum, low height, and on X-ray lambdoid suture synostosis, cerebral cyst/mild holoprosencephalia and cholesteatoma, and multiple abnormalities of bones of chondral origin. On the right side, maxillary, mandibular bones, external auditory canal, middle ear were hypoplastic as well as semicircular canal, cranial base, bones vestibule. On the left side, coclea, timpanic cavity, mastoid antrum were hypoplastic, while stapes was misshapen. Limbs bones were slender with thin metaphyses and some carpal bones were absent. Hand second phalanx was hypoplastic and fifth finger presented clynodactily. Lambdoid synostosis expressed membranous ossification abnormality. We hypothesize that during the blastogenesis a mutation of a factor responsible for abnormal generalized endochondral and connectival ossification (possibly fibroblast growth factor receptor) occurs.
Familial aggregation of anxiety disorder subtypes and anxious temperament in the NIMH Family Study of Affective Spectrum Disorders.
Journal of affective disorders, 2021

Evidence from family and twin studies suggests that mood and anxiety disorders, and related temperamental factors may share common etiologic factors. We examine the familial aggregation and coaggregation of anxiety disorder subtypes and anxiety-related temperamental traits, and their association with mood disorders.
Comparative genome hybridization array analysis for sporadic Parkinson's disease.
The International journal of neuroscience, 2008

Parkinson disease (PD) is a common neurodegenerative disorder, characterized by the loss of midbrain dopamine neurons and Lewy body inclusions. We investigated array CGH to analyze gain or loss of genetic material from 30 patients with PD. We identified the frequent copy number variations in PD; gains in 1p21.1, 4p15.31, 5p15.33, 6q24.1, 7q35, 8q24.3, 10q26.3, 11p15.5-15.4, 12q21.2, 16p13.3, 18q12.3 and 22q13.31, and losses in 1p36.33, and 5q13.2. These findings enable a better description of genetic variations in PD, and could provide a foundation for understanding the critical regions of the genome that may be involved in the development of PD.
Use of 5-Aminolevulinic Acid for Confirmation of Lesional Biopsy Sample in Presumed High-Grade Glioma.
World neurosurgery, 2019

5-amniolevulinic acid (5-ALA) assists neurosurgeons in defining operative margins during resection of high-grade gliomas, leading to improved rates of complete resection of enhancing tumor and progression-free survival. Here, we propose the use of 5-ALA in stereotactic biopsy for confirmation that the sample obtained is from the targeted mass. To the knowledge of the authors, this is the first known record of 5-ALA use for confirmation of pathologic specimen in stereotactic brain biopsy in the United States. This technique could be pivotal for lesions in highly eloquent areas where it is important to take as little tissue as possible in an effort to decrease neurologic deficits while still obtaining a diagnostic biopsy sample.
Diazaspirononane Nonsaccharide Inhibitors of O-GlcNAcase (OGA) for the Treatment of Neurodegenerative Disorders.
Journal of medicinal chemistry, 2020

O-GlcNAcylation is a post-translational modification of tau understood to lower the speed and yield of its aggregation, a pathological hallmark of Alzheimer's disease (AD). O-GlcNAcase (OGA) is the only enzyme that removes O-linked
Can metacognitive interventions improve insight in schizophrenia spectrum disorders? A systematic review and meta-analysis.
Psychological medicine, 2020

Patients with schizophrenia spectrum disorders (SSD) tend to lack insight, which is linked to poor outcomes. The effect size of previous treatments on insight changes in SSD has been small. Metacognitive interventions may improve insight in SSD, although this remains unproved.
Clinical effectiveness of different natalizumab interval dosing schedules in a large Italian population of patients with multiple sclerosis.
Journal of neurology, neurosurgery, and psychiatry, 2020

Natalizumab (NTZ) is one of the most effective treatment options for multiple sclerosis (MS) treatment. Our study aimed to evaluate the effectiveness of NTZ when administered according to the extended dosing strategy compared with standard 4-weekly administration in a large Italian MS population.
The expanding LARS2 phenotypic spectrum: HLASA, Perrault syndrome with leukodystrophy, and mitochondrial myopathy.
Human mutation, 2020

LARS2 variants are associated with Perrault syndrome, characterized by premature ovarian failure and hearing loss, and with an infantile lethal multisystem disorder: Hydrops, lactic acidosis, sideroblastic anemia (HLASA) in one individual. Recently we reported LARS2 deafness with (ovario) leukodystrophy. Here we describe five patients with a range of phenotypes, in whom we identified biallelic LARS2 variants: three patients with a HLASA-like phenotype, an individual with Perrault syndrome whose affected siblings also had leukodystrophy, and an individual with a reversible mitochondrial myopathy, lactic acidosis, and developmental delay. Three HLASA cases from two unrelated families were identified. All were males with genital anomalies. Two survived multisystem disease in the neonatal period; both have developmental delay and hearing loss. A 55-year old male with deafness has not displayed neurological symptoms while his female siblings with Perrault syndrome developed leukodystrophy and died in their 30s. Analysis of muscle from a child with a reversible myopathy showed reduced LARS2 and mitochondrial complex I levels, and an unusual form of degeneration. Analysis of recombinant LARS2 variant proteins showed they had reduced aminoacylation efficiency, with HLASA-associated variants having the most severe effect. A broad phenotypic spectrum should be considered in association with LARS2 variants.
Peripancreatic adipose tissue protects against high-fat-diet-induced hepatic steatosis and insulin resistance in mice.
International journal of obesity (2005), 2020

Visceral adiposity is associated with increased diabetes risk, while expansion of subcutaneous adipose tissue may be protective. However, the visceral compartment contains different fat depots. Peripancreatic adipose tissue (PAT) is an understudied visceral fat depot. Here, we aimed to define PAT functionality in lean and high-fat-diet (HFD)-induced obese mice.
Visual Processing: Hungry Like the Mouse.
Neuron, 2016

In this issue of Neuron, Burgess et al. (2016) explore how motivational state interacts with visual processing, by examining hunger modulation of food-associated visual responses in postrhinal cortical neurons and their inputs from amygdala.
Novel antibodies detect additional α-synuclein pathology in synucleinopathies: potential development for immunotherapy.
Alzheimer's research & therapy, 2020

Alpha-synuclein (α-Syn) aggregation is the primary characteristic of synucleinopathies including Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). Immunotherapy targeting α-Syn has shown promising results in animal models of the disease. This study investigates the target specificity of three different active vaccines for pathological α-Syn aggregates found in human brain tissue from synucleinopathies.
The Duffy-null genotype and risk of infection.
Human molecular genetics, 2020

Many medical treatments, from oncology to psychiatry, can lower white blood cell counts and thus access to these treatments can be restricted to individuals with normal levels of white blood cells, principally in order to minimize risk of serious infection. This adversely affects individuals of African or Middle Eastern ancestries who have on average a reduced number of circulating white blood cells, because of the Duffy-null (CC) genotype at rs2814778 in the ACKR1 gene. Here, we investigate whether the Duffy-null genotype is associated with the risk of infection using the UK Biobank sample and the iPSYCH Danish case-cohort study, two population-based samples from different countries and age ranges. We found that a high proportion of those with the Duffy-null genotype (21%) had a neutrophil count below the threshold often used as a cut-off for access to relevant treatments, compared with 1% of those with the TC/TT genotype. In addition we found that despite its strong association with lower average neutrophil counts, the Duffy-null genotype was not associated with an increased risk of infection, viral or bacterial. These results have widespread implications for the clinical treatment of individuals of African ancestry and indicate that neutrophil thresholds to access treatments could be lowered in individuals with the Duffy-null genotype without an increased risk of infection.
Disentangling the visual, motor and representational effects of vestibular input.
Cortex; a journal devoted to the study of the nervous system and behavior, 2018

The body midline provides a basic reference for egocentric representation of external space. Clinical observations have suggested that vestibular information underpins egocentric representations. Here we aimed to clarify whether and how vestibular inputs contribute to egocentric representation in healthy volunteers. In a psychophysical task, participants were asked to judge whether visual stimuli were located to the left or to the right of their body midline. Artificial vestibular stimulation was applied to stimulate the vestibular organs. We found that artificial stimulation of the vestibular system biased body midline perception. Importantly, no effect was found on motor effector selection. We also ruled out additional explanations based on allocentric visual representations and on potential indirect effects caused by vestibular-driven movements of the eyes, head and body. Taken together our data suggest that vestibular information contributes to computation of egocentric representations by affecting the internal representation of the body midline.
Using Rescorla's truly random control condition to measure truly exogenous covert orienting.
Psychonomic bulletin & review, 2019

Studies of exogenous covert orienting use peripheral cues (stimuli) that are spatially uninformative about the locations of subsequent targets. When the time course of the cue's influence on performance is explored (by varying the cue target onset asynchrony; CTOA), a biphasic pattern is usually seen with better performance at the cued location when the CTOA is short (typically attributed to attentional capture) and worse performance at the cued location when the CTOA is long (attributed to inhibition of return). However, while spatially uninformative, these cues (even when a nonaging foreperiod is used) entail a temporal contingency with the subsequent target. Consequently, this so-called capture may reflect an unintended consequence of endogenous allocation of temporal attention. Following Lawrence and Klein (Journal of Experimental Psychology: General, 142(2), 560-572, 2013) we used Rescorla's (Psychological Review, 74, 71-80, 1967) truly random control condition to ensure that the spatially uninformative peripheral stimuli were temporally completely uninformative. Even such completely uninformative peripheral stimuli generated the prototypical biphasic pattern.
Generation of a Hutchinson-Gilford progeria syndrome monkey model by base editing.
Protein & cell, 2020

Many human genetic diseases, including Hutchinson-Gilford progeria syndrome (HGPS), are caused by single point mutations. HGPS is a rare disorder that causes premature aging and is usually caused by a de novo point mutation in the LMNA gene. Base editors (BEs) composed of a cytidine deaminase fused to CRISPR/Cas9 nickase are highly efficient at inducing C to T base conversions in a programmable manner and can be used to generate animal disease models with single amino-acid substitutions. Here, we generated the first HGPS monkey model by delivering a BE mRNA and guide RNA (gRNA) targeting the LMNA gene via microinjection into monkey zygotes. Five out of six newborn monkeys carried the mutation specifically at the target site. HGPS monkeys expressed the toxic form of lamin A, progerin, and recapitulated the typical HGPS phenotypes including growth retardation, bone alterations, and vascular abnormalities. Thus, this monkey model genetically and clinically mimics HGPS in humans, demonstrating that the BE system can efficiently and accurately generate patient-specific disease models in non-human primates.
Acute D-Serine Co-Agonism of β-Cell NMDA Receptors Potentiates Glucose-Stimulated Insulin Secretion and Excitatory β-Cell Membrane Activity.
Cells, 2021

Insulin-secreting pancreatic β-cells express proteins characteristic of D-serine regulated synapses, but the acute effect of D-serine co-agonism on its presumptive β-cell target, N-methyl D-aspartate receptors (NMDARs), is unclear. We used multiple models to evaluate glucose homeostasis and insulin secretion in mice with a systemic increase in D-serine (intraperitoneal injection or DAAO mutants without D-serine catabolism) or tissue-specific loss of Grin1-encoded GluN1, the D-serine binding NMDAR subunit. We also investigated the effects of D-serine ± NMDA on glucose-stimulated insulin secretion (GSIS) and β-cell depolarizing membrane oscillations, using perforated patch electrophysiology, in β-cell-containing primary isolated mouse islets. In vivo models of elevated D-serine correlated to improved blood glucose and insulin levels. In vitro, D-serine potentiated GSIS and β-cell membrane excitation, dependent on NMDAR activating conditions including GluN1 expression (co-agonist target), simultaneous NMDA (agonist), and elevated glucose (depolarization). Pancreatic GluN1-loss females were glucose intolerant and GSIS was depressed in islets from younger, but not older, βGrin1 KO mice. Thus, D-serine is capable of acute antidiabetic effects in mice and potentiates insulin secretion through excitatory β-cell NMDAR co-agonism but strain-dependent shifts in potency and age/sex-specific Grin1-loss phenotypes suggest that context is critical to the interpretation of data on the role of D-serine and NMDARs in β-cell function.
mGreenLantern: a bright monomeric fluorescent protein with rapid expression and cell filling properties for neuronal imaging.
Proceedings of the National Academy of Sciences of the United States of America, 2020

Although ubiquitous in biological studies, the enhanced green and yellow fluorescent proteins (EGFP and EYFP) were not specifically optimized for neuroscience, and their underwhelming brightness and slow expression in brain tissue limits the fidelity of dendritic spine analysis and other indispensable techniques for studying neurodevelopment and plasticity. We hypothesized that EGFP's low solubility in mammalian systems must limit the total fluorescence output of whole cells, and that improving folding efficiency could therefore translate into greater brightness of expressing neurons. By introducing rationally selected combinations of folding-enhancing mutations into GFP templates and screening for brightness and expression rate in human cells, we developed mGreenLantern, a fluorescent protein having up to sixfold greater brightness in cells than EGFP. mGreenLantern illuminates neurons in the mouse brain within 72 h, dramatically reducing lag time between viral transduction and imaging, while its high brightness improves detection of neuronal morphology using widefield, confocal, and two-photon microscopy. When virally expressed to projection neurons in vivo, mGreenLantern fluorescence developed four times faster than EYFP and highlighted long-range processes that were poorly detectable in EYFP-labeled cells. Additionally, mGreenLantern retains strong fluorescence after tissue clearing and expansion microscopy, thereby facilitating superresolution and whole-brain imaging without immunohistochemistry. mGreenLantern can directly replace EGFP/EYFP in diverse systems due to its compatibility with GFP filter sets, recognition by EGFP antibodies, and excellent performance in mouse, human, and bacterial cells. Our screening and rational engineering approach is broadly applicable and suggests that greater potential of fluorescent proteins, including biosensors, could be unlocked using a similar strategy.