rudyvdbrink/CitationDatabase huggingface dataset:
Real-world experience with direct brain-responsive neurostimulation for focal onset seizures.
Epilepsia, 2020

The RNS System is a direct brain-responsive neurostimulation system that is US Food and Drug Administration-approved for adults with medically intractable focal onset seizures based on safety and effectiveness data from controlled clinical trials. The purpose of this study was to retrospectively evaluate the real-world safety and effectiveness of the RNS System.
Is baseline routine renal ultrasound indicated for all MS patients?
Postgraduate medical journal, 2020

Most patients with multiple sclerosis (MS) develop multiple urological complaints due to hyperactive or hypoactive bladder, and may have detrusor-sphincter dyssynergia. Routine renal ultrasound (RUS) screening has been recommended for both symptomatic and asymptomatic MS patients; however, there is little data to support this practice.
Functional connectivity fingerprints of the human pulvinar: Decoding its role in cognition.
NeuroImage, 2020

The pulvinar is the largest thalamic nucleus in the brain and considered as a key structure in sensory processing and attention. Although its anatomy is well known, in particular thanks to studies in non-human primates, its role in perception and cognition remains poorly understood. Here, we used resting-state functional connectivity from a large sample of high-resolution data provided by the Human Connectome Project, combined with a large-scale meta-analysis approach to segregate and characterize the functional organization of the pulvinar nucleus. We identified five clusters per pulvinar with distinct connectivity profiles and determined their respective co-activation patterns. Using the Neurosynth database, we then investigated the functional significance of these co-activation networks. Our results confirm the functional heterogeneity of the pulvinar, revealing clearcut differences across clusters in terms of their connectivity patterns and associated cognitive domains. While the anterior and lateral clusters appear to be involved in action and attention domains, the ventromedial and dorsomedial clusters may preferentially subserve emotional processes and saliency detection. In contrast, the inferior cluster shows less specificity but correlates with perception and memory processes. Collectively, our results suggest that the pulvinar underwrites different components of cognition, supporting a central role in the coordination of cortico-subcortical processes mediated by distributed brain networks.
Blood-brain barrier genetic disruption leads to protective barrier formation at the Glia Limitans.
PLoS biology, 2020

Inflammation of the central nervous system (CNS) induces endothelial blood-brain barrier (BBB) opening as well as the formation of a tight junction barrier between reactive astrocytes at the Glia Limitans. We hypothesized that the CNS parenchyma may acquire protection from the reactive astrocytic Glia Limitans not only during neuroinflammation but also when BBB integrity is compromised in the resting state. Previous studies found that astrocyte-derived Sonic hedgehog (SHH) stabilizes the BBB during CNS inflammatory disease, while endothelial-derived desert hedgehog (DHH) is expressed at the BBB under resting conditions. Here, we investigated the effects of endothelial Dhh on the integrity of the BBB and Glia Limitans. We first characterized DHH expression within endothelial cells at the BBB, then demonstrated that DHH is down-regulated during experimental autoimmune encephalomyelitis (EAE). Using a mouse model in which endothelial Dhh is inducibly deleted, we found that endothelial Dhh both opens the BBB via the modulation of forkhead box O1 (FoxO1) transcriptional activity and induces a tight junctional barrier at the Glia Limitans. We confirmed the relevance of this glial barrier system in human multiple sclerosis active lesions. These results provide evidence for the novel concept of "chronic neuroinflammatory tolerance" in which BBB opening in the resting state is sufficient to stimulate a protective barrier at the Glia Limitans that limits the severity of subsequent neuroinflammatory disease. In summary, genetic disruption of the BBB generates endothelial signals that drive the formation under resting conditions of a secondary barrier at the Glia Limitans with protective effects against subsequent CNS inflammation. The concept of a reciprocally regulated CNS double barrier system has implications for treatment strategies in both the acute and chronic phases of multiple sclerosis pathophysiology.
Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer disease.
Alzheimer's research & therapy, 2020

We previously found temporoparietal-predominant atrophy patterns in the behavioral variant of Alzheimer's disease (bvAD), with relative sparing of frontal regions. Here, we aimed to understand the clinico-anatomical dissociation in bvAD based on alternative neuroimaging markers.
Expression pattern of cochlear microRNAs in the mammalian auditory hindbrain.
Cell and tissue research, 2021

The auditory system comprises the auditory periphery, engaged in sound transduction and the central auditory system, implicated in auditory information processing and perception. Recently, evidence mounted that the mammalian peripheral and central auditory systems share a number of genes critical for proper development and function. This bears implication for auditory rehabilitation and evolution of the auditory system. To analyze to which extent microRNAs (miRNAs) belong to genes shared between both systems, we characterize the expression pattern of 12 cochlea-abundant miRNAs in the central auditory system. Quantitative real-time PCR (qRT-PCR) demonstrated expression of all 12 genes in the cochlea, the auditory hindbrain and the non-auditory prefrontal cortex (PFC) at embryonic stage (E)16 and postnatal stages (P)0 and P30. Eleven of them showed differences in expression between tissues and nine between the developmental time points. Hierarchical cluster analysis revealed that the temporal expression pattern in the auditory hindbrain was more similar to the PFC than to the cochlea. Spatiotemporal expression analysis by RNA in situ hybridization demonstrated widespread expression throughout the cochlear nucleus complex (CNC) and the superior olivary complex (SOC) during postnatal development. Altogether, our data indicate that miRNAs represent a relevant class of genetic factors functioning across the auditory system. Given the importance of gene regulatory network (GRN) components for development, physiology and evolution, the 12 miRNAs provide promising entry points to gain insights into their molecular underpinnings in the auditory system.
Intracerebroventricular transplanted bone marrow stem cells survive and migrate into the brain of rats with Parkinson's disease.
Neural regeneration research, 2012

In this study, 6-hydroxydopamine was stereotaxically injected into the right substantia nigra compact and ventral tegmental area of rats to establish Parkinson's disease models. The rats then received a transplantation of bone marrow stromal cells that were previously isolated, cultured and labeled with 5-bromo-2'-deoxyuridine in vitro. Transplantation of the bone marrow stromal cells significantly decreased apomorphine-induced rotation time and the escape latency in the Morris water maze test as compared with rats with untreated Parkinson's disease. Immunohistochemical staining showed that, 5-bromo-2'-deoxyuridine-immunoreactive cells were present in the lateral ventricular wall and the choroid plexus 1 day after transplantation. These immunoreactive cells migrated to the surrounding areas of the lateral cerebral ventricle along the corpus callosum. The results indicated that bone marrow stromal cells could migrate to tissues surround the cerebral ventricle via the cerebrospinal fluid circulation and fuse with cells in the brain, thus altering the phenotype of cells or forming neuron-like cells or astrocytes capable of expressing neuron-specific proteins. Taken together, the present findings indicate that bone marrow stromal cells transplanted intracerebroventricularly could survive, migrate and significantly improve the rotational behavior and cognitive function of rats with experimentally induced Parkinson's disease.
Disruption of metabolic, sleep, and sensorimotor functional outcomes in a female transgenic mouse model of Alzheimer's disease.
Behavioural brain research, 2021

Alzheimer's Disease (AD) is the most prevalent form of dementia globally, and the number of individuals with AD diagnosis is expected to double by 2050. Numerous preclinical AD studies have shown that AD neuropathology accompanies alteration in learning and memory. However, less attention has been given to alterations in metabolism, sleep, and sensorimotor functional outcomes during AD pathogenesis. The objective of this study was to elucidate the extent to which metabolic activity, sleep-wake cycle, and sensorimotor function is impaired in APPSwDI/Nos2
Catching the imposter in the brain: The case of Capgras delusion.
Cortex; a journal devoted to the study of the nervous system and behavior, 2020

Here we describe a rare case of Capgras delusion - a misidentification syndrome characterized by the belief that a person has been replaced by an imposter - in a patient without evident neurological or psychiatric symptoms. Intriguingly, delusional belief was selective for both person and modality, as the patient believed that his son - not his daughter or other relatives - was substituted with an imposter only while being in presence of him and looking at his face, but not when merely listening to his voice. A neuroanatomical reconstruction obtained integrating morphological and functional patient's neuroimaging data highlighted two main peculiarities: a compression of the rostral portion of right temporal lobe due to a large arachnoid cyst, and a bilaterally reduced metabolism of frontal areas. Autonomic data obtained from thermal infra-red camera and skin conductance recordings showed that a higher sympathetic activation was evoked by the observation of daughter's face, relative to the observation of the son's face as well as of not-familiar faces; conversely, daughter and son voices elicited a similar sympathetic activation, higher relative to not-familiar voices, indicating a modality-dependent dissociation consistent with the delusional behavior. Our case supports the "two-hit hypothesis" about Capgras delusion etiopathogenesis: here, the first hit is represented by the right-temporal lesion impairing the association between familiar faces and emotional values, the second one is the frontal bilateral hypometabolism favoring delusional behavior. The selective occurrence of "imposter" delusion for a particular subject and for a specific perceptual modality suggests the involvement of modality-specific interactions in the retrieval of affective properties during familiar people recognition.
Precision prevention of Alzheimer's and other dementias: Anticipating future needs in the control of risk factors and implementation of disease-modifying therapies.
Alzheimer's & dementia : the journal of the Alzheimer's Association, 2020

Empirical evidence suggests that a fair proportion of dementia cases are preventable, that some preventive actions can be taken immediately, and others may soon be implemented. Primary prevention may target cognitively normal persons with modifiable risk factors through lifestyle and multiple domain interventions (including general cardiovascular health). While the effect on individuals may be modest, it might have a large societal impact by decreasing overall dementia incidence by up to 35%. Secondary prevention will target cognitively normal persons at high risk of dementia due to Alzheimer's disease pathology with future anti-amyloid, anti-tau, or other drugs. This approach is likely to have major benefits to both individuals and society. Memory clinics will need structural and functional changes to adapt to novel technologies and increased patients' demands, and brand-new services may need to be developed with specific skills on risk profiling, risk communication, and personalized risk reduction plans.
A Customizable Protocol for String Assembly gRNA Cloning (STAgR).
Journal of visualized experiments : JoVE, 2018

The bacterial CRISPR/Cas9 system has substantially increased methodological options for life scientists. Due to its utilization, genetic and genomic engineering became applicable to a large range of systems. Moreover, many transcriptional and epigenomic engineering approaches are now generally feasible for the first time. One reason for the broad applicability of CRISPR lies in its bipartite nature. Small gRNAs determine the genomic targets of the complex, variants of the protein Cas9, and the local molecular consequences. However, many CRISPR approaches depend on the simultaneous delivery of multiple gRNAs into individual cells. Here, we present a customizable protocol for string assembly gRNA cloning (STAgR), a method that allows the simple, fast and efficient generation of multiplexed gRNA expression vectors in a single cloning step. STAgR is cost-effective, since (in this protocol) the individual targeting sequences are introduced by short overhang primers while the long DNA templates of the gRNA expression cassettes can be re-used multiple times. Moreover, STAgR allows single step incorporation of a large number of gRNAs, as well as combinations of different gRNA variants, vectors and promoters.
Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders.
Nature communications, 2020

Most genes associated with neurodevelopmental disorders (NDDs) were identified with an excess of de novo mutations (DNMs) but the significance in case-control mutation burden analysis is unestablished. Here, we sequence 63 genes in 16,294 NDD cases and an additional 62 genes in 6,211 NDD cases. By combining these with published data, we assess a total of 125 genes in over 16,000 NDD cases and compare the mutation burden to nonpsychiatric controls from ExAC. We identify 48 genes (25 newly reported) showing significant burden of ultra-rare (MAF < 0.01%) gene-disruptive mutations (FDR 5%), six of which reach family-wise error rate (FWER) significance (p < 1.25E-06). Among these 125 targeted genes, we also reevaluate DNM excess in 17,426 NDD trios with 6,499 new autism trios. We identify 90 genes enriched for DNMs (FDR 5%; e.g., GABRG2 and UIMC1); of which, 61 reach FWER significance (p < 3.64E-07; e.g., CASZ1). In addition to doubling the number of patients for many NDD risk genes, we present phenotype-genotype correlations for seven risk genes (CTCF, HNRNPU, KCNQ3, ZBTB18, TCF12, SPEN, and LEO1) based on this large-scale targeted sequencing effort.
Neutral ceramidase is a marker for cognitive performance in rats and monkeys.
Pharmacological reports : PR, 2021

Ceramides are lipid molecules determining cell integrity and intercellular signaling, and thus, involved in the pathogenesis of several psychiatric and neurodegenerative disorders. However, little is known about the role of particular enzymes of the ceramide metabolism in the mechanisms of normal behavioral plasticity. Here, we studied the contribution of neutral ceramidase (NC), one of the main enzymes mediating ceramide degradation, in the mechanisms of learning and memory in rats and non-human primates.
Towards in vivo g-ratio mapping using MRI: Unifying myelin and diffusion imaging.
Journal of neuroscience methods, 2021

The g-ratio, quantifying the comparative thickness of the myelin sheath encasing an axon, is a geometrical invariant that has high functional relevance because of its importance in determining neuronal conduction velocity. Advances in MRI data acquisition and signal modelling have put in vivo mapping of the g-ratio, across the entire white matter, within our reach. This capacity would greatly increase our knowledge of the nervous system: how it functions, and how it is impacted by disease.
The Effect of Positively Framing Side-Effect Risk in Two Different Formats on Side-Effect Expectations, Informed Consent and Credibility: A Randomised Trial of 16- to 75-Year-Olds in England.
Drug safety, 2020

Reframing side-effect information in patient information leaflets (PILs) in terms of those who remain side-effect-free may reduce negative expectations and side-effects, although there are concerns this may impact informed consent. This study compared two versions of positively framed PILs with current practice to see which reduces side-effect expectations whilst maintaining informed consent and credibility.
[Adaptation and validation of a brief screening questionnaire of depressive disorders in patients with cancer: Q2i study].
Bulletin du cancer, 2016

Depression is a sustainable state of deep sadness and abatement. It is frequently identified in patients with cancer and often undervalued by oncologists. The reduced PRIME-MD questionnaire is a questionnaire of 2 items validated in French. However, it has been neither translated nor validated in French. The objective of our study is to translate the PRIME-MD and validate it into French.
PAIP 2019: Liver cancer segmentation challenge.
Medical image analysis, 2021

Pathology Artificial Intelligence Platform (PAIP) is a free research platform in support of pathological artificial intelligence (AI). The main goal of the platform is to construct a high-quality pathology learning data set that will allow greater accessibility. The PAIP Liver Cancer Segmentation Challenge, organized in conjunction with the Medical Image Computing and Computer Assisted Intervention Society (MICCAI 2019), is the first image analysis challenge to apply PAIP datasets. The goal of the challenge was to evaluate new and existing algorithms for automated detection of liver cancer in whole-slide images (WSIs). Additionally, the PAIP of this year attempted to address potential future problems of AI applicability in clinical settings. In the challenge, participants were asked to use analytical data and statistical metrics to evaluate the performance of automated algorithms in two different tasks. The participants were given the two different tasks: Task 1 involved investigating Liver Cancer Segmentation and Task 2 involved investigating Viable Tumor Burden Estimation. There was a strong correlation between high performance of teams on both tasks, in which teams that performed well on Task 1 also performed well on Task 2. After evaluation, we summarized the top 11 team's algorithms. We then gave pathological implications on the easily predicted images for cancer segmentation and the challenging images for viable tumor burden estimation. Out of the 231 participants of the PAIP challenge datasets, a total of 64 were submitted from 28 team participants. The submitted algorithms predicted the automatic segmentation on the liver cancer with WSIs to an accuracy of a score estimation of 0.78. The PAIP challenge was created in an effort to combat the lack of research that has been done to address Liver cancer using digital pathology. It remains unclear of how the applicability of AI algorithms created during the challenge can affect clinical diagnoses. However, the results of this dataset and evaluation metric provided has the potential to aid the development and benchmarking of cancer diagnosis and segmentation.
[Current therapy studies in atypical Parkinson syndromes].
Fortschritte der Neurologie-Psychiatrie, 2018

Atypical Parkinson syndromes are a heterogeneous group of neurodegenerative diseases which present with parkinsonism and other non-motor symptoms. On the basis of the underlying pathology, namely the abnormal aggregation of the proteins alpha-synuclein or tau, atypical Parkinson syndromes can be divided into synucleinopathies (multiple system atrophy, Lewy body dementia) and tauopathies (progressive supranuclear palsy, corticobasal degeneration). Currently there are no effective treatments to slow down disease progression available. Medications which help to manage the symptoms show only temporary and insufficient efficacy. In recent years, preclinical research identified essential steps in the pathogenesis of the diseases. Treatments which inhibit pathological protein aggregation and its spreading were developed and showed promising results in animal models. First clinical trials of causal treatments targeting the underlying pathomechanism have been finished; several trials are recruiting patients or being planned at the moment. In the following article we present the latest developments regarding the causal therapy of atypical Parkinson syndromes and the current clinical trials.
Glucocorticoids do not promote prosociality in a wild group-living fish.
Hormones and behavior, 2021

Individuals often respond to social disturbances by increasing prosociality, which can strengthen social bonds, buffer against stress, and promote overall group cohesion. Given their importance in mediating stress responses, glucocorticoids have received considerable attention as potential proximate regulators of prosocial behaviour during disturbances. However, previous investigations have largely focused on mammals and our understanding of the potential prosocial effects of glucocorticoids across vertebrates more broadly is still lacking. Here, we assessed whether experimentally elevated glucocorticoid levels (simulating endogenous cortisol responses mounted following disturbances) promote prosocial behaviours in wild groups of the cichlid fish, Neolamprologus pulcher. Using SCUBA in Lake Tanganyika, we observed how subordinate group members adjusted affiliation, helping, and submission (all forms of prosocial behaviour) following underwater injections of either cortisol or saline. Cortisol treatment reduced affiliative behaviours-but only in females-suggesting that glucocorticoids may reduce overall prosociality. Fish with elevated glucocorticoid levels did not increase performance of submission or helping behaviours. Taken together, our results do not support a role for glucocorticoids in promoting prosocial behaviour in this species and emphasize the complexity of the proximate mechanisms that underlie prosociality.
Is there bias in the treatment of degenerative spine disease? Analysis of anonymous voting via a multidisciplinary conference.
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia, 2020

Many institutions have developed shared decision-making conferences as a mechanism for reducing treatment costs and improving patient outcomes. Little is known about the process of shared decision-making that takes place in these conferences, and there is the possibility of bias among surgeons and nonsurgeons for treatment within their respective specialties. This study was conducted to determine who is contributing to the decision-making process in a multidisciplinary spine conference and to what extent treatment biases exist among the surgical and nonsurgical members of this conference. Voting data were collected during weekly multidisciplinary spine conferences. Descriptive statistics were calculated on the cases presented and the number and type of physicians voting for each case. The likelihood of a particular vote in the surgeon and nonsurgeon cohorts was evaluated using relative risk calculation and multinomial logistic regression. A total of 262 consecutive cases were analyzed. No significant differences in treatment recommendation were observed between surgery and nonsurgical management (relative risk, 1.1; 95% CI, 0.97-1.25) when comparing votes from the surgeon and nonsurgeon cohorts. Multinomial logistic regression showed the odds of nonsurgeons recommending nonsurgical management over surgery was 20% greater than receiving that recommendation from their surgeon colleagues. Individual surgeon and nonsurgeon voters were evenly distributed above and below the mean for treatment recommendation. Individual and group biases exist among surgeons and nonsurgeons treating degenerative spine diseases. Multidisciplinary conferences may or may not level these biases, depending on how they are conducted.