rudyvdbrink/CitationDatabase huggingface dataset:
Baseline phenotype and 30-day outcomes of people tested for COVID-19: an international network cohort including >3.32 million people tested with real-time PCR and >219,000 tested positive for SARS-CoV-2 in South Korea, Spain and the United States.
medRxiv : the preprint server for health sciences, 2020

Early identification of symptoms and comorbidities most predictive of COVID-19 is critical to identify infection, guide policies to effectively contain the pandemic, and improve health systems' response. Here, we characterised socio-demographics and comorbidity in 3,316,107persons tested and 219,072 persons tested positive for SARS-CoV-2 since January 2020, and their key health outcomes in the month following the first positive test. Routine care data from primary care electronic health records (EHR) from Spain, hospital EHR from the United States (US), and claims data from South Korea and the US were used. The majority of study participants were women aged 18-65 years old. Positive/tested ratio varied greatly geographically (2.2:100 to 31.2:100) and over time (from 50:100 in February-April to 6.8:100 in May-June). Fever, cough and dyspnoea were the most common symptoms at presentation. Between 4%-38% required admission and 1-10.5% died within a month from their first positive test. Observed disparity in testing practices led to variable baseline characteristics and outcomes, both nationally (US) and internationally. Our findings highlight the importance of large scale characterization of COVID-19 international cohorts to inform planning and resource allocation including testing as countries face a second wave.
The effects of bone pâté on human osteoblasts cell cultures.
European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery, 2016

The aim of the present study was to evaluate the effect of bone pate on human osteoblast differentiation by measuring cell viability, alkaline phosphatase activity and expression of the transcription factors and of the major components of the extracellular matrix. Although bone paté has been used in ear surgery for many years and when placed in contact with mastoid and external auditory canal bone become viable, the cellular mechanisms that lead to its osteointegration have never been described. Bone paté taken from four patients subjected to mastoidectomy and affected by middle ear and mastoid cholesteatoma was placed in contact with osteoblast-like cell cultures. Four experimental conditions were obtained: cell cultures treated with bone patè, with bone paté mixed with fibrin glue, with fibrin glue and untreated. After 24 h, the viability of the cells was evaluated; after 1 week, alkaline phosphatase activity and the expression of transcription factors and bone matrix proteins were assessed by quantitative polymerase chain reaction. After 24 h osteoblasts showed increased viability when treated with bone paté (19 % increase) and bone pate mixed with fibrin glue (34 % increase). After 1 week, the number of alkaline phosphatase positive cells increased by 97 and 94 % in cultures treated with bone paté alone and bone pate mixed with fibrin glue. Treatment with bone patè upregulated transcription factors and components of the extracellular matrix. The present data show that bone paté has a high osteoinductive potential on human osteoblasts, enhancing their activity.
Affective Game Planning for Health Applications: Quantitative Extension of Gerontoludic Design Based on the Appraisal Theory of Stress and Coping.
JMIR serious games, 2019

User retention is the first challenge in introducing any information and communication technologies (ICT) for health applications, particularly for seniors who are increasingly targeted as beneficiaries of such technologies. Interaction with digital technologies may be too stressful to older adults to guarantee their adoption in their routine selfcare. The second challenge, which also relates to adoption, is to supply empirical evidence that support the expectations of their beneficial outcomes. To address the first challenge, persuasive technologies such as serious games (SGs) are increasingly promoted as ludic approaches to deliver assistive care to older adults. However, there are no standards yet to assess the efficacy of different genres of games across populations, or compare and contrast variations in health outcomes arising from user interface design and user experience. For the past 3 decades, research has focused either on qualitative assessment of the appeal of digital games for seniors (by game designers) or on the quantitative evaluation of their clinical efficacy (by clinical researchers). The consensus is that interindividual differences play a key role in whether games can be useful or not for different individuals. Our challenge is to design SGs that retain their users long enough to sustain beneficial transfer effects. We propose to add a neuropsychological experimental framework (based on the appraisal theory of stress and coping) to a Gerontoludic design framework (that emphasizes designing positive and meaningful gaming experience over benefit-centric ones) in order to capture data to guide SG game development. Affective Game Planning for Health Applications (AGPHA) adds a model-driven mixed-methods experimental stage to a user-centered mechanics-dynamics-aesthetics game-design cycle. This intersectoral framework is inspired by latest trends in the fields of neuroimaging and neuroinformatics that grapple with similar challenges related to the psychobiological context of an individual's behaviors. AGPHA aims to bring users, designers, clinicians, and researchers together to generate a common data repository that consists of 4 components to define, design, evaluate, and document SGs. By unifying efforts under a standard approach, we will accelerate innovations in persuasive and efficacious ICTs for the aging population.
Altered baseline and amphetamine-mediated behavioral profiles in dopamine transporter Cre (DAT-Ires-Cre) mice compared to tyrosine hydroxylase Cre (TH-Cre) mice.
Psychopharmacology, 2020

Transgenic mouse lines expressing Cre-recombinase under the regulation of either dopamine transporter (DAT) or tyrosine hydroxylase (TH) promoters are commonly used to study the dopamine (DA) system. While use of the TH promoter appears to have less liability to changes in native gene expression, transgene insertion in the DAT locus results in reduced DAT expression and function. This confound is sometimes overlooked in genetically targeted behavioral experiments.
Location and functions of Inebriated in the 
Biology open, 2018

Histamine (HA) is a neurotransmitter in arthropod photoreceptors. It is recycled via conjugation to β-alanine to form β-alanylhistamine (carcinine). Conjugation occurs in epithelial glia that surround photoreceptor terminals in the first optic neuropil, and carcinine (CA) is then transported back to photoreceptors and cleaved to liberate HA and β-alanine. The gene
Alexithymia and pain experience among patients using methadone-maintenance therapy.
Drug and alcohol dependence, 2021

Alexithymia, difficulty identifying and describing one's emotions coupled with a tendency to externalize, is a potentially important yet understudied treatment target for patients with opioid use disorder. The aim of this study was to examine the role of alexithymia in pain experience among individuals with opioid use disorder.
Chemical mutagenesis of a GPCR ligand: Detoxifying "inflammo-attraction" to direct therapeutic stem cell migration.
Proceedings of the National Academy of Sciences of the United States of America, 2020

A transplanted stem cell's engagement with a pathologic niche is the first step in its restoring homeostasis to that site. Inflammatory chemokines are constitutively produced in such a niche; their binding to receptors on the stem cell helps direct that cell's "pathotropism." Neural stem cells (NSCs), which express CXCR4, migrate to sites of CNS injury or degeneration in part because astrocytes and vasculature produce the inflammatory chemokine CXCL12. Binding of CXCL12 to CXCR4 (a G protein-coupled receptor, GPCR) triggers repair processes within the NSC. Although a tool directing NSCs to where needed has been long-sought, one would not inject this chemokine in vivo because undesirable inflammation also follows CXCL12-CXCR4 coupling. Alternatively, we chemically "mutated" CXCL12, creating a CXCR4 agonist that contained a strong pure binding motif linked to a signaling motif devoid of sequences responsible for synthetic functions. This synthetic dual-moity CXCR4 agonist not only elicited more extensive and persistent human NSC migration and distribution than did native CXCL 12, but induced no host inflammation (or other adverse effects); rather, there was predominantly reparative gene expression. When co-administered with transplanted human induced pluripotent stem cell-derived hNSCs in a mouse model of a prototypical neurodegenerative disease, the agonist enhanced migration, dissemination, and integration of donor-derived cells into the diseased cerebral cortex (including as electrophysiologically-active cortical neurons) where their secreted cross-corrective enzyme mediated a therapeutic impact unachieved by cells alone. Such a "designer" cytokine receptor-agonist peptide illustrates that treatments can be controlled and optimized by exploiting fundamental stem cell properties (e.g., "inflammo-attraction").
Convergence between clinician-rated and patient-reported PTSD symptoms in a specialized outpatient service: The moderator role of gender.
Perspectives in psychiatric care, 2021

Posttraumatic stress disorder (PTSD) includes different symptoms: re-experiencing, avoidance of reminders and numbing, and hyperarousal. Although questionnaires are widely used, clinician-administered interviews provide a more comprehensive exploration of symptoms. Few studies examined the convergence between clinician-rated and patient-reported general severity and symptoms, with mixed findings. We explored the association between clinician-rated and patient-reported general severity and symptoms and the moderator role of gender in PTSD patients referred to a specialized outpatient service.
Reason for optimism: How a shifting focus on neural population codes is moving cognitive neuroscience beyond phrenology.
The Behavioral and brain sciences, 2016

Multivariate pattern analysis can address many of the challenges for cognitive neuroscience highlighted in After Phrenology (Anderson 2014) by illuminating the information content of brain regions and by providing insight into whether functional overlap reflects the recruitment of common or distinct computational mechanisms. Further, failing to consider submaximal but reliable population responses can lead to an overly modular account of brain function.
Individual magnitudes of neural variability quenching are associated with motion perception abilities.
Journal of neurophysiology, 2021

Remarkable trial-by-trial variability is apparent in cortical responses to repeating stimulus presentations. This neural variability across trials is relatively high before stimulus presentation and then reduced (i.e., quenched) ∼0.2 s after stimulus presentation. Individual subjects exhibit different magnitudes of variability quenching, and previous work from our lab has revealed that individuals with larger variability quenching exhibit lower (i.e., better) perceptual thresholds in a contrast discrimination task. Here, we examined whether similar findings were also apparent in a motion detection task, which is processed by distinct neural populations in the visual system. We recorded EEG data from 35 adult subjects as they detected the direction of coherent motion in random dot kinematograms. The results demonstrated that individual magnitudes of variability quenching were significantly correlated with coherent motion thresholds, particularly when presenting stimuli with low dot densities, where coherent motion was more difficult to detect. These findings provide consistent support for the hypothesis that larger magnitudes of neural variability quenching are associated with better perceptual abilities in multiple visual domain tasks.
Immune profiling of plasma-derived extracellular vesicles identifies Parkinson disease.
Neurology(R) neuroimmunology & neuroinflammation, 2020

To develop a diagnostic model based on plasma-derived extracellular vesicle (EV) subpopulations in Parkinson disease (PD) and atypical parkinsonism (AP), we applied an innovative flow cytometric multiplex bead-based platform.
Non-convulsive seizure clustering misdiagnosed as vertebrobasilar insufficiency.
Heliyon, 2020

Diagnosing non-convulsive seizures (NCSs) is a great challenge for most clinicians due to a wide spectrum of clinical presentations. The complexity of the disease course usually results in a delayed diagnosis or misdiagnosis so that timely and appropriate treatment is not given. Herein, we report a case with NCSs misdiagnosed as vertebrobasilar insufficiency (VBI), in which the patient suffered from episodes of prominent dizziness, vertigo, becoming transfixed, and worsening response within a day. Brain magnetic resonance image findings were unremarkable, however electroencephalography (EEG) showed rhythmic epileptiform discharges that appeared to originate from the right frontal area with ipsilateral hemispheric involvement. We prescribed intravenous valproate and the seizures ceased. Few studies have reported a patient with NCS misdiagnosed with VBI, a very different entity. It is thus important that clinicians should be aware of the trivial symptoms of NCSs, and to consider implementing early EEG studies and anti-epileptic drug therapy.
Acute intracerebral haemorrhage: diagnosis and management.
Practical neurology, 2020

Intracerebral haemorrhage (ICH) accounts for half of the disability-adjusted life years lost due to stroke worldwide. Care pathways for acute stroke result in the rapid identification of ICH, but its acute management can prove challenging because no individual treatment has been shown definitively to improve its outcome. Nonetheless, acute stroke unit care improves outcome after ICH, patients benefit from interventions to prevent complications, acute blood pressure lowering appears safe and might have a modest benefit, and implementing a bundle of high-quality acute care is associated with a greater chance of survival. In this article, we address the important questions that neurologists face in the diagnosis and acute management of ICH, and focus on the supporting evidence and practical delivery for the main acute interventions.
Differential mechanisms of tolerance induced by NMDA and 3,5-dihydroxyphenylglycine (DHPG) preconditioning.
Journal of neurochemistry, 2020

We investigated the molecular events triggered by NMDA and 3,5-dihydroxyphenylglycine (DHPG) preconditioning, that lead to neuroprotection against excitotoxic insults (AMPA or oxygen and glucose deprivation) in rat organotypic hippocampal slices, with particular attention on glutamate receptors and on cannabinoid system. We firstly evaluated the protein expression of NMDA and AMPA receptor subunits after preconditioning using western blot analysis performed in post-synaptic densities. We observed that following NMDA, but not DHPG preconditioning, the expression of GluA1 was significantly reduced and this reduction appeared to be associated with the internalization of AMPA receptors. Whole-cell voltage clamp recordings on CA1 pyramidal neurons of organotypic slices show that 24 hr after exposure to NMDA and DHPG preconditioning, AMPA-induced currents were significantly reduced. To clarify the mechanisms induced by DHPG preconditioning, we then investigated the involvement of the endocannabinoid system. Exposure of slices to the CB1 antagonist AM251 prevented the development of tolerance to AMPA toxicity induced by DHPG but not NMDA. Accordingly, the MAG-lipase inhibitor URB602, that increases arachidonoylglycerol (2-AG) content, but not the FAAH inhibitor URB597, that limits the degradation of anandamide, was also able to induce tolerance versus AMPA and OGD toxicity, suggesting that 2-AG is responsible for the DHPG-induced tolerance. In conclusion, preconditioning with NMDA or DHPG promotes differential neuroprotective mechanisms: NMDA by internalization of GluA1-AMPA receptors, DHPG by producing the endocannabinoid 2-AG.
Separate motor memories are formed when controlling different implicitly specified locations on a tool.
Journal of neurophysiology, 2019

Skillful manipulation requires forming and recalling memories of the dynamics of objects linking applied force to motion. It has been assumed that such memories are associated with entire objects. However, we often control different locations on an object, and these locations may be associated with different dynamics. We have previously demonstrated that multiple memories can be formed when participants are explicitly instructed to control different visual points marked on an object. A key question is whether this novel finding generalizes to more natural situations in which control points are implicitly defined by the task. To answer this question, we used objects with no explicit control points and tasks designed to encourage the use of distinct implicit control points. Participants moved a handle, attached to a robotic interface, to control the position of a rectangular object ("eraser") in the horizontal plane. Participants were required to move the eraser straight ahead to wipe away a column of dots ("dust"), located to either the left or right. We found that participants adapted to opposing dynamics when linked to the left and right dust locations, even though the movements required for these two contexts were the same. Control conditions showed this learning could not be accounted for by contextual cues or the fact that the task goal required moving in a straight line. These results suggest that people naturally control different locations on manipulated objects depending on the task context and that doing so affords the formation of separate motor memories. NEW & NOTEWORTHY Skilled manipulation requires forming motor memories of object dynamics, which have been assumed to be associated with entire objects. However, we recently demonstrated that people can form multiple memories when explicitly instructed to control different visual points on an object. In this article we show that this novel finding generalizes to more natural situations in which control points are implicitly defined by the task.
Mutant alleles of HD improve the life span of p53(-/-) mice.
Mechanisms of ageing and development, 2008

Loss of function mutations in the p53 tumor suppressor gene predispose mice and humans to cancer, resulting in abbreviated life spans. A dominant mutation in the murine HD gene, similar to mutations that cause Huntington's disease in humans, reverses some of the effects of p53 mutations on longevity. We attribute this to the enhanced apoptotic effect of the expanded polyglutamine region in the HD protein on proliferating cells lacking p53.
The impact of bone cancer on the peripheral encoding of mechanical pressure stimuli.
Pain, 2020

Skeletal metastases are frequently accompanied by chronic pain that is mechanoceptive in nature. Mechanistically, cancer-induced bone pain (CIBP) is mediated by peripheral sensory neurons innervating the cancerous site, the cell bodies of which are housed in the dorsal root ganglia (DRG). How these somatosensory neurons encode sensory information in CIBP remains only partly explained. Using a validated rat model, we first confirmed cortical bone destruction in CIBP but not sham-operated rats (day 14 after surgery, designated "late"-stage bone cancer). This occurred with behavioural mechanical hypersensitivity (Kruskal-Wallis H for independent samples; CIBP vs sham-operated, day 14; P < 0.0001). Next, hypothesising that the proportion and phenotype of primary afferents would be altered in the disease state, dorsal root ganglia in vivo imaging of genetically encoded calcium indicators and Markov Cluster Analysis were used to analyse 1748 late-stage CIBP (n = 10) and 757 sham-operated (n = 9), neurons. Distinct clusters of responses to peripheral stimuli were revealed. In CIBP rats, upon knee compression of the leg ipsilateral to the tumour, (1) 3 times as many sensory afferents responded (repeated-measures analysis of variance: P < 0.0001 [vs sham]); (2) there were significantly more small neurons responding (Kruskal-Wallis for independent samples (vs sham): P < 0.0001); and (3) approximately 13% of traced tibial cavity afferents responded (no difference observed between CIBP and sham-operated animals). We conclude that an increased sensory afferent response is present in CIBP rats, and this is likely to reflect afferent recruitment from outside of the bone rather than increased intraosseous afferent activity.
A change of mind: Globus pallidus activity and effective connectivity during changes in choice selections.
The European journal of neuroscience, 2021

The basal ganglia are a group of interconnected subcortical nuclei that plays a key role in multiple motor and cognitive processes, in a close interplay with several cortical regions. Two conflicting theories postulate that the basal ganglia pathways can either foster or suppress the cortico-striatal output or, alternatively, they can stabilize or destabilize the cortico-striatal circuit dynamics. These different approaches significantly impact the understanding of observable behaviours and cognitive processes in healthy, as well as clinical populations. We investigated the predictions of these models in healthy participants (N = 28), using dynamic causal modeling of fMRI BOLD activity to estimate time- and context-dependent changes in the indirect pathway effective connectivity, in association with repetitions or changes of choice selections. We used two multi-option tasks that required the participants to adapt to uncontrollable environmental changes, by performing sequential choice selections, with and without value-based feedbacks. We found that, irrespective of the task, the trials that were characterized by changes in choice selections (switch trials) were associated with a neural response that mostly overlapped with a network commonly described for the encoding of uncertainty. More interestingly, dynamic causal modeling and family-wise model comparison identified with high likelihood a directed causal relation from the external to the internal part of the globus pallidus (i.e., the short indirect pathway in the basal ganglia), in association with the switch trials. This finding supports the hypothesis that the short indirect pathway in the basal ganglia drives instability in the network dynamics, resulting in changes in choice selection.
Duplication of the odontoid process with other congenital defects of the craniocervical Junction: case report and review of the literature.
Anatomy & cell biology, 2020

Duplication of the odontoid process remains a rare developmental pathology that is underrepresented in the current literature. As the pivot point for the craniovertebral junction, the odontoid process is vital for the integrity of the atlanto-axial joint and the ability of the head and cervical spine to rotate correctly. The pathogenesis being incompletely understood, it has been proposed that odontoid process duplication involves faulty sclerotome migration and disruption of the axis ossification center. Patients presenting with this pathology usually have associated structural abnormalities. A detailed anatomical and embryological understanding of the odontoid process is necessary for successful management and treatment of patients presenting with odontoid process duplication. We present a rare case of a patient with a duplicated odontoid process in association with C2-C3 fusion, incomplete anterior arch of C1, variant inferior bony process of the transverse process of C1, and enlarged right jugular foramen.