rudyvdbrink/CitationDatabase huggingface dataset:
Reconsidering Systems-Based Practice: Advancing Structural Competency, Health Equity, and Social Responsibility in Graduate Medical Education.
Academic medicine : journal of the Association of American Medical Colleges, 2020

Health inequities stem from systematic, pervasive social and structural forces. These forces marginalize populations and create the circumstances that disadvantage these groups, as reflected in differences in outcomes like life expectancy and infant mortality and in inequitable access to and delivery of health care resources. To help eradicate these inequities, physicians must understand racism, sexism, oppression, historical marginalization, power, privilege, and other sociopolitical and economic forces that sustain and create inequities. A new educational paradigm emphasizing the knowledge, skills, and attitudes to achieve health equity is needed.Systems-based practice is the graduate medical education core competency that focuses on complex systems and physicians' roles within them; it includes topics like multidisciplinary team-based care, patient safety, cost containment, end-of-life goals, and quality improvement. This competency, however, is largely health care centric and does not train physicians to engage with the complexities of the social and structural determinants of health or to partner with systems and communities that are outside health care.The authors propose a new core competency centered on health equity, social responsibility, and structural competency to address this gap in graduate medical education. For the development of this new competency, the authors draw on existing, innovative undergraduate and graduate medical pedagogy and public health, health services research, and social medicine frameworks. They describe how this new competency would inform graduate medical education and clinical care and encourage future physicians to engage in the work of health equity.
Transactivation of EGF receptors in chicken Müller cells by α2A-adrenergic receptors stimulated by brimonidine.
Investigative ophthalmology & visual science, 2014

Alpha2-adrenergic receptor agonists are used in glaucoma treatment and have been shown to have some neuroprotective effects. We performed this study to test the hypothesis that epidermal growth factor receptors on chicken Müller cells are transactivated by α2-adrenergic receptors and we focused on the extracellular signal-activated kinases 1/2 (ERK) pathway.
Gamma oscillations in a nonlinear regime: a minimal model approach using heterogeneous integrate-and-fire networks.
Neural computation, 2008

Fast oscillations and in particular gamma-band oscillation (20-80 Hz) are commonly observed during brain function and are at the center of several neural processing theories. In many cases, mathematical analysis of fast oscillations in neural networks has been focused on the transition between irregular and oscillatory firing viewed as an instability of the asynchronous activity. But in fact, brain slice experiments as well as detailed simulations of biological neural networks have produced a large corpus of results concerning the properties of fully developed oscillations that are far from this transition point. We propose here a mathematical approach to deal with nonlinear oscillations in a network of heterogeneous or noisy integrate-and-fire neurons connected by strong inhibition. This approach involves limited mathematical complexity and gives a good sense of the oscillation mechanism, making it an interesting tool to understand fast rhythmic activity in simulated or biological neural networks. A surprising result of our approach is that under some conditions, a change of the strength of inhibition only weakly influences the period of the oscillation. This is in contrast to standard theoretical and experimental models of interneuron network gamma oscillations (ING), where frequency tightly depends on inhibition strength, but it is similar to observations made in some in vitro preparations in the hippocampus and the olfactory bulb and in some detailed network models. This result is explained by the phenomenon of suppression that is known to occur in strongly coupled oscillating inhibitory networks but had not yet been related to the behavior of oscillation frequency.
Outcome Trajectories and Prognostic Factors for Suicide and Self-Harm Behaviors in Patients With Borderline Personality Disorder Following One Year of Outpatient Psychotherapy.
Journal of personality disorders, 2018

This study examined suicide and self-harm trajectories in 180 individuals with BPD receiving dialectical behavior therapy or general psychiatric management in a randomized controlled trial. Suicide and self-harm behaviors were assessed at baseline, every four months throughout treatment, and every 6 months over 2 years of follow-up. Latent class growth mixture modeling identified suicide and self-harm trajectories. Multinomial logistic regression analyses examined baseline patient characteristics. Three latent subgroups were identified. The largest responded rapidly to treatment and sustained a favorable response post-discharge. The second progressed slowly during treatment but achieved and maintained a favorable response. A third subgroup showed a rapid favorable response during treatment, however symptoms returned to near baseline levels post-discharge. This third subgroup had higher baseline depression, emergency department visits, and unemployment. BPD patients with high baseline health care utilization, depression, and unemployment may benefit from modifications to treatment specifically targeting these issues.
Mislocalization of stationary and flashed bars after saccadic inward and outward adaptation of reactive saccades.
Journal of neurophysiology, 2012

Recent studies have shown that saccadic inward adaptation (i.e., the shortening of saccade amplitude) and saccadic outward adaptation (i.e., the lengthening of saccade amplitude) rely on partially different neuronal mechanisms. There is increasing evidence that these differences are based on differences at the target registration or planning stages since outward but not inward adaptation transfers to hand-pointing and perceptual localization of flashed targets. Furthermore, the transfer of reactive saccade adaptation to long-duration overlap and scanning saccades is stronger after saccadic outward adaptation than that after saccadic inward adaptation, suggesting that modulated target registration stages during outward adaptation are increasingly used in the execution of saccades when the saccade target is visually available for a longer time. The difference in target presentation duration between reactive and scanning saccades is also linked to a difference in perceptual localization of different targets. Flashed targets are mislocalized after inward adaptation of reactive and scanning saccades but targets that are presented for a longer time (stationary targets) are mislocalized stronger after scanning than after reactive saccades. This link between perceptual localization and adaptation specificity suggests that mislocalization of stationary bars should be higher after outward than that after inward adaptation of reactive saccades. In the present study we test this prediction. We show that the relative amount of mislocalization of stationary versus flashed bars is higher after outward than that after inward adaptation of reactive saccades. Furthermore, during fixation stationary and flashed bars were mislocalized after outward but not after inward adaptation. Thus, our results give further evidence for different adaptation mechanisms between inward and outward adaptation and harmonize some recent research.
Timing of Direct Enteral Tube Placement and Outcomes after Acute Stroke.
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association, 2019

Direct enteral feeding tube (DET) placement for dysphagia after stroke is associated with poor outcomes. However, the relationship between timing of DET placement and poststroke mortality and disability is unknown. We sought to determine the risk of mortality and severe disability in patients who receive DET at different times after stroke.
Machine learning approaches reveal subtle differences in breathing and sleep fragmentation in 
Journal of neurophysiology, 2021

Modern neurophysiology research requires the interrogation of high-dimensionality data sets. Machine learning and artificial intelligence (ML/AI) workflows have permeated into nearly all aspects of daily life in the developed world but have not been implemented routinely in neurophysiological analyses. The power of these workflows includes the speed at which they can be deployed, their availability of open-source programming languages, and the objectivity permitted in their data analysis. We used classification-based algorithms, including random forest, gradient boosted machines, support vector machines, and neural networks, to test the hypothesis that the animal genotypes could be separated into their genotype based on interpretation of neurophysiological recordings. We then interrogate the models to identify what were the major features utilized by the algorithms to designate genotype classification. By using raw EEG and respiratory plethysmography data, we were able to predict which recordings came from genotype class with accuracies that were significantly improved relative to the no information rate, although EEG analyses showed more overlap between groups than respiratory plethysmography. In comparison, conventional methods where single features between animal classes were analyzed, differences between the genotypes tested using baseline neurophysiology measurements showed no statistical difference. However, ML/AI workflows successfully were capable of providing successful classification, indicating that interactions between features were different in these genotypes. ML/AI workflows provide new methodologies to interrogate neurophysiology data. However, their implementation must be done with care so as to provide high rigor and reproducibility between laboratories. We provide a series of recommendations on how to report the utilization of ML/AI workflows for the neurophysiology community.
A crucial role for primary cilia in cortical morphogenesis.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008

Primary cilia are important sites of signal transduction involved in a wide range of developmental and postnatal functions. Proteolytic processing of the transcription factor Gli3, for example, occurs in primary cilia, and defects in intraflagellar transport (IFT), which is crucial for the maintenance of primary cilia, can lead to severe developmental defects and diseases. Here we report an essential role of primary cilia in forebrain development. Uncovered by N-ethyl-N-nitrosourea-mutagenesis, cobblestone is a hypomorphic allele of the IFT gene Ift88, in which Ift88 mRNA and protein levels are reduced by 70-80%. cobblestone mutants are distinguished by subpial heterotopias in the forebrain. Mutants show both severe defects in the formation of dorsomedial telencephalic structures, such as the choroid plexus, cortical hem and hippocampus, and also a relaxation of both dorsal-ventral and rostral-caudal compartmental boundaries. These defects phenocopy many of the abnormalities seen in the Gli3 mutant forebrain, and we show that Gli3 proteolytic processing is reduced, leading to an accumulation of the full-length activator isoform. In addition, we observe an upregulation of canonical Wnt signaling in the neocortex and in the caudal forebrain. Interestingly, the ultrastructure and morphology of ventricular cilia in the cobblestone mutants remains intact. Together, these results indicate a critical role for ciliary function in the developing forebrain.
Musical training modulates encoding of higher-order regularities in the auditory cortex.
The European journal of neuroscience, 2011

We investigated the effect of long-term musical training on the time course of development of neuronal representations within the auditory cortex by means of magnetoencephalography. In musicians but not in nonmusicians, pre-attentive encoding of a complex regularity within a tone sequence was evident by a constant increase of the pattern mismatch negativity within < 10 min. The group difference was more pronounced in the left hemisphere, indicating stronger plastic changes in its structures supporting temporal analysis and sound pattern encoding. The results suggest an effect of long-term musical training on short-term auditory learning processes. This has implications not only for cognitive neuroscience in showing how short-term and long-term neuronal plasticity can interact within the auditory cortex, but also for educational and clinical applications of implicit auditory learning where beneficial effects of (musical) experience might be exploited.
Affiliative behavior requires juvenile, but not adult neurogenesis.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011

The capacity to interact with conspecifics is essential for stable social networks, reproduction, and survival in mammals. In rodents, social exploration and play behavior increase during the juvenile period, suggesting that this timeframe represents an important window for socialization. However, the cellular and molecular mechanisms necessary to support this developmental process have not been elucidated. Neurogenesis during the juvenile period, like that in adults, is mainly confined to the subgranular and subventricular zones. Nevertheless, the levels of neurogenesis are significantly higher during the juvenile period, suggesting unique functions not shared with adult neurogenesis. Here we use a transgenic mouse approach that allows for ablation of neurogenesis during different developmental phases. We find that ablating neurogenesis during either juvenile or adult phases altered anxiety and memory in adult female mice, demonstrating an age-independent function of new neurons for certain behaviors. Blocking neurogenesis during the juvenile period resulted in a profound impairment in the ability of these mice to interact with other adult females or to retrieve pups, without causing gross olfactory deficits. Interestingly, ablating neurogenesis in adult females had no effect on these social behaviors. This work defines a novel role for juvenile neurogenesis in establishing brain circuits necessary for socialization, and demonstrates that juvenile and adult neurogenesis make different contributions to social competency in adult female mice. Additional work is needed to determine whether ablation of juvenile neurogenesis in the subgranular zone and/or the subventricular zone is responsible for the social abnormalities seen after global elimination of juvenile neurogenesis.
Acute Stress and Anxiety in Medical Residents on the Emergency Department Duty.
International journal of environmental research and public health, 2018

The objectives of this longitudinal study were to compare salivary cortisol release patterns in medical residents and their self-perceived anxiety levels between a regular working day and a day when on call in the emergency department (ED-duty day) and to determine any differences in cortisol release pattern as a function of years of residency or sex. The study included 35 residents (physicians-in-training) of the Granada University Hospital, Granada, Spain. Acute stress was measured on a regular working day and an ED-duty day, evaluating anxiety-state with the Spanish version of the State-Trait Anxiety Inventory. Physiological stress assessment was based on salivary cortisol levels. Cortisol release concentrations were higher on an ED-duty day than on a regular working day, with a significantly increased area under the curve (AUC) (
Unitary response of mouse olfactory receptor neurons.
Proceedings of the National Academy of Sciences of the United States of America, 2011

The sense of smell begins with odorant molecules binding to membrane receptors on the cilia of olfactory receptor neurons (ORNs), thereby activating a G protein, G(olf), and the downstream effector enzyme, an adenylyl cyclase (ACIII). Recently, we have found in amphibian ORNs that an odorant-binding event has a low probability of activating sensory transduction at all; even when successful, the resulting unitary response apparently involves a single active Gα(olf)-ACIII molecular complex. This low amplification is in contrast to rod phototransduction in vision, the best-quantified G-protein signaling pathway, where each photoisomerized rhodopsin molecule is well known to produce substantial amplification by activating many G-protein, and hence effector-enzyme, molecules. We have now carried out similar experiments on mouse ORNs, which offer, additionally, the advantage of genetics. Indeed, we found the same low probability of transduction, based on the unitary olfactory response having a fairly constant amplitude and similar kinetics across different odorants and randomly encountered ORNs. Also, consistent with our picture, the unitary response of Gα(olf)(+/-) ORNs was similar to WT in amplitude, although their Gα(olf)-protein expression was only half of normal. Finally, from the action potential firing, we estimated that ≤19 odorant-binding events successfully triggering transduction in a WT mouse ORN will lead to signaling to the brain.
Overexpression of Protein Kinase Mζ in the Hippocampus Enhances Long-Term Potentiation and Long-Term Contextual But Not Cued Fear Memory in Rats.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2016

The persistently active protein kinase Mζ (PKMζ) has been found to be involved in the formation and maintenance of long-term memory. Most of the studies investigating PKMζ, however, have used either putatively unselective inhibitors or conventional knock-out animal models in which compensatory mechanisms may occur. Here, we overexpressed an active form of PKMζ in rat hippocampus, a structure highly involved in memory formation, and embedded in several neural networks. We investigated PKMζ's influence on synaptic plasticity using electrophysiological recordings of basal transmission, paired pulse facilitation, and LTP and combined this with behavioral cognitive experiments addressing formation and retention of both contextual memory during aversive conditioning and spatial memory during spontaneous exploration. We demonstrate that hippocampal slices overexpressing PKMζ show enhanced basal transmission, suggesting a potential role of PKMζ in postsynaptic AMPAR trafficking. Moreover, the PKMζ-overexpressing slices augmented LTP and this effect was not abolished by protein-synthesis blockers, indicating that PKMζ induces enhanced LTP formation in a protein-synthesis-independent manner. In addition, we found selectively enhanced long-term memory for contextual but not cued fear memory, underlining the theory of the hippocampus' involvement in the contextual aspect of aversive reinforced tasks. Memory for spatial orientation during spontaneous exploration remained unaltered, suggesting that PKMζ may not affect the neural circuits underlying spontaneous tasks that are different from aversive tasks. In this study, using an overexpression strategy as opposed to an inhibitor-based approach, we demonstrate an important modulatory role of PKMζ in synaptic plasticity and selective memory processing.
A solid majority remit following evidence-based OCD treatments: a 3-year naturalistic outcome study in pediatric OCD.
European child & adolescent psychiatry, 2018

This study reports follow-up 2 and 3 years after the initial assessment of a sample of youth with a primary diagnosis of OCD. Participants were 109 children and adolescents, aged 5-17 years, recruited from a specialized, outpatient OCD clinic in Sweden. Patients were treated with cognitive behavioral therapy (CBT), augmented when indicated by selective serotonin reuptake inhibitor (SSRI). In cases where SSRIs were insufficient, augmentation with a second-generation antipsychotic (SGA) was applied. Participants were assessed with the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS), Children's OCD Impact Scale (COIS), and Children's Depressive Inventory (CDI) at follow-ups 2 and 3 years after baseline assessment. Treatment response was defined as CY-BOCS total score ≤ 15, and remission was defined as CY-BOCS total score ≤ 10. Analyzing the outcomes with linear mixed-effects models (LME) showed a decrease in OCD symptom load from 23 to 6.9 at the 3-year follow-up. Moreover, two of three (66.1%) participants were in remission, and another 19.2% had responded to treatment at the 3-year follow-up. Thus, 85.3% of participants responded to treatment. Moreover, during the follow-up period, participants' psychosocial functioning had significantly improved, and depressive symptoms had significantly decreased. The results suggest that evidence-based treatment for pediatric OCD, following expert consensus guidelines, has long-term positive effects for most children and adolescents diagnosed with OCD. The results also indicate that improvements are maintained over a 3-year period, at least, and that improvement is also found with regard to psychosocial functioning and depressive symptoms.
Substrate recognition mechanism of atypical protein kinase Cs revealed by the structure of PKCι in complex with a substrate peptide from Par-3.
Structure (London, England : 1993), 2012

Protein kinase C (PKC) play critical roles in many cellular functions including differentiation, proliferation, growth, and survival. However, the molecular bases governing PKC's substrate recognitions remain poorly understood. Here we determined the structure of PKCι in complex with a peptide from Par-3 at 2.4 Å. PKCι in the complex adopts catalytically competent, closed conformation without phosphorylation of Thr402 in the activation loop. The Par-3 peptide binds to an elongated groove formed by the N- and C-lobes of the kinase domain. The PKCι/Par-3 complex structure, together with extensive biochemical studies, reveals a set of substrate recognition sites common to all PKC isozymes as well as a hydrophobic pocket unique to aPKC. A consensus aPKC's substrate recognition sequence pattern can be readily identified based on the complex structure. Finally, we demonstrate that the pseudosubstrate sequence of PKCι resembles its substrate sequence, directly binds to and inhibits the activity of the kinase.
Electrophysiological correlates of visual binding errors after bilateral parietal damage.
Neuroscience, 2016

Illusory conjunctions (e.g. the confusion between the shape of one stimulus with the color of another stimulus) are the most dramatic expression of binding failures in vision. Under brief exposure or when attention is diverted illusory conjunctions may be observed in healthy participants, but they only represent a real-life problem for patients with parietal damage. However, it is unclear whether such failures reflect the impairment of early or late stages of visual processing. Here, we examined the time-course of visual processing using evoked potential measures in a patient with bilateral damage to the posterior parietal cortex presenting prominent binding failures. The patient was asked to identify colored letters that were briefly flashed to the left or right hemifield. When only one item was presented she adequately identified color or shape of left and right letters. In contrast, when presentation was bilateral she either identified the correct right shape-color combination and missed the item in the left hemifield (extinction) or combined incorrectly the right shape with the left color (illusory conjunction). Evoked potential analyses revealed a specific electrophysiological signature of illusory conjunctions, starting ∼105ms after stimulus onset over the right frontal cortex. These findings indicate that binding errors reflect failures of early stages of attentional filtering relying on the integrity of the posterior parietal cortex.