rudyvdbrink/CitationDatabase huggingface dataset:
Decreased Serum Levels of Interleukin-4 and Interleukin-21 in New Pemphigus Vulgaris Patients, but Not Chronic Patients With Inactive Disease Compared to Healthy Controls.
Dermatology practical & conceptual, 2021

Pemphigus is a rare group of autoimmune blistering diseases with unknown etiology and unclear pathogenesis. Pemphigus vulgaris (PV) is the most common subtype, and is characterized by ulcerations or flaccid blisters on mucous membranes and on the skin. It is accepted that cytokines have a critical role in the pathogenesis of PV, while their exact roles remain to be elucidated.
When the first seizure can be the last: ventricular fibrillation following a new-onset seizure.
Epileptic disorders : international epilepsy journal with videotape, 2020

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related mortality. Its mechanisms remain incompletely understood. Post-ictal arrhythmias rather than ictal arrhythmias appear to be associated with an increased risk of SUDEP. Only a handful of individuals with epilepsy who have survived ventricular arrhythmias post seizure (near-SUDEP) are reported in the literature. We report a case of ventricular fibrillation following a first-ever unprovoked seizure in a patient without epilepsy, in whom a sinus rhythm was restored following cardioversion. A defibrillator was subsequently implanted. Our case suggests that even first seizures might account for some of the many cases of unexplained ventricular fibrillation or sudden cardiac death.
Association of time to surgery with leg pain after lumbar discectomy: is delayed surgery detrimental?
Journal of neurosurgery. Spine, 2020

While it has been established that lumbar discectomy should only be performed after a certain waiting period unless neurological deficits are present, little is known about the association of late surgery with outcome. Using data from a prospective registry, the authors aimed to quantify the association of time to surgery (TTS) with leg pain outcome after lumbar discectomy and to identify a maximum TTS cutoff anchored to the minimum clinically important difference (MCID).
Measuring change in health-related quality of life: the impact of different analytical methods on the interpretation of treatment effects in glioma patients.
Neuro-oncology practice, 2020

Different analytical methods may lead to different conclusions about the impact of treatment on health-related quality of life (HRQoL). This study aimed to examine 3 different methods to evaluate change in HRQoL and to study whether these methods result in different conclusions.
Reprint of: Recent Updates on Obesity Treatments: Available Drugs and Future Directions.
Neuroscience, 2020

In the last thirty years, obesity has reached epidemic proportions and is now regarded as a major health issue in contemporary society trending to serious economic and social burdens. The latest projections of the World Health Organization are alarming. By 2030, nearly 60% of the worldwide population could be either obese or overweight, highlighting the needs to find innovative treatments. Currently, bariatric surgery is the most effective way to efficiently lower body mass. Although great improvements in terms of recovery and patient care were made in these surgical procedures, bariatric surgery remains an option for extreme forms of obesity and seems unable to tackle obesity pandemic expansion. Throughout the last century, numerous pharmacological strategies targeting either peripheral or central components of the energy balance regulatory system were designed to reduce body mass, some of them reaching sufficient levels of efficiency and safety. Nevertheless, obesity drug therapy remains quite limited on its effectiveness to actually overcome the obesogenic environment. Thus, innovative unimolecular polypharmacology strategies, able to simultaneously target multiple actors involved in the obesity initiation and expansion, were developed during the last ten years opening a new promising avenue in the pharmacological management of obesity. In this review, we first describe the clinical features of obesity-associated conditions and then focus on the outcomes of currently approved drug therapies for obesity as well as new ones expecting to reach the clinic in the near future.
Evaluation of discrete orthogonal versus polar Stockwell Transform for local multi-resolution texture analysis using brain MRI of multiple sclerosis patients.
Magnetic resonance imaging, 2020

The Stockwell Transform has the potential to perform multi-resolution texture analysis in magnetic resonance imaging (MRI). However, it is computationally intensive and memory demanding. The polar Stockwell Transform (PST) is rotation-invariant and relatively memory efficient, but still computationally demanding. The new Discrete Orthogonal Stockwell Transform (DOST) appears to have addressed both the computation and storage challenges; however, its utility in localized texture analysis remains unclear. Our goal was to investigate the theory and texture analysis ability of the DOST versus PST using both synthetic and MR images, and explore the relative importance of the associated texture features using a simple classification example based on clinical brain MRI of six multiple sclerosis patients. MRI texture analysis focused on FLAIR images, and the classification used a machine learning algorithm, random forest, that differentiated regions of interest (ROIs) into 2 classes: white matter lesions, and the contralateral normal-appearing white matter (control). Our results showed that the PST features had a greater ability in detecting subtle changes in image structure than the DOST and polar-index DOST (PDOST). Quantitatively, based on 187 lesion and 187 control ROIs, both the PST and the rotation-invariant radial PST performed better in the classification than the DOST and PDOST, where the latter were no better than guessing (p = 0.65 and 0.98). Further analysis using a hierarchical random forest showed that combining MRI signal intensity with the PST or DOST predictions increased the classification performance, with the accuracy, sensitivity, and specificity all improved to >85% in the tests. Collectively, the DOST is less competitive than the PST in localized image texture analysis. The PST features may help with texture-based lesion classification in MS based on clinical brain MRI scans following further verification.
High-Spatial-Resolution Multi-Omics Sequencing via Deterministic Barcoding in Tissue.
Cell, 2020

We present deterministic barcoding in tissue for spatial omics sequencing (DBiT-seq) for co-mapping of mRNAs and proteins in a formaldehyde-fixed tissue slide via next-generation sequencing (NGS). Parallel microfluidic channels were used to deliver DNA barcodes to the surface of a tissue slide, and crossflow of two sets of barcodes, A1-50 and B1-50, followed by ligation in situ, yielded a 2D mosaic of tissue pixels, each containing a unique full barcode AB. Application to mouse embryos revealed major tissue types in early organogenesis as well as fine features like microvasculature in a brain and pigmented epithelium in an eye field. Gene expression profiles in 10-μm pixels conformed into the clusters of single-cell transcriptomes, allowing for rapid identification of cell types and spatial distributions. DBiT-seq can be adopted by researchers with no experience in microfluidics and may find applications in a range of fields including developmental biology, cancer biology, neuroscience, and clinical pathology.
Traumatic Events Are Associated with Diverse Psychological Symptoms in Typically-Developing Children.
Journal of child & adolescent trauma, 2020

Childhood traumatic events are significant risk factors for psychopathology according to adult retrospective research; however, few studies examine trauma exposure and psychological symptoms in pre-adolescent children. Typically-developing children, aged 9-12 years (
Contrast enhanced magnetic resonance imaging highlights neurovasculature changes following experimental traumatic brain injury in the rat.
Scientific reports, 2020

Neurovascular injury has been proposed as a universal pathological hallmark of traumatic brain injury (TBI) with molecular markers of angiogenesis and endothelial function associated with injury severity and morbidity. Sex differences in the neurovasculature response post-TBI may contribute to the differences seen in how males and females respond to injury. Steady-state contrast enhanced magnetic resonance imaging (SSCE-MRI) can be used to non-invasively assess the neurovasculature and may be a useful tool in understanding and predicting outcomes post-TBI. Here we used SSCE-MRI to investigate the neurovasculature of male and female rats at 48 h after an experimental TBI, and how these changes related to neuromotor function at 1-week post-TBI. In addition to TBI induced changes, we found that female rats had greater vessel density, greater cerebral blood volumes and performed better on a neuromotor task than their male counterparts. These results suggest that acute post-TBI cerebrovascular function is worse in males, and that this may contribute to the greater functional deficits observed post-injury. Furthermore, these results highlight the potential of SSCE-MRI to provide insights into the cerebral microvasculature post-TBI. Future studies, incorporating both males and females, are warranted to investigate the evolution of these changes and the underlying mechanisms.
Investigating the role of exogenous cueing on selection history formation.
Psychonomic bulletin & review, 2019

An abundance of recent empirical data suggest that repeatedly allocating visual attention to task-relevant and/or reward-predicting features in the visual world engenders an attentional bias for these frequently attended stimuli, even when they become task irrelevant and no longer predict reward. In short, attentional selection in the past hinders voluntary control of attention in the present. But do such enduring attentional biases rely on a history of voluntary, goal-directed attentional selection, or can they be generated through involuntary, effortless attentional allocation? An abrupt visual onset triggers such a reflexive allocation of covert spatial attention to its location in the visual field, automatically modulating numerous aspects of visual perception. In this Registered Report, we asked whether a selection history that has been reflexively and involuntarily derived (i.e., through abrupt-onset cueing) also interferes with goal-directed attentional control, even in the complete absence of exogenous cues. To build spatially distinct histories of exogenous selection, we presented abrupt-onset cues twice as often at one of two task locations, and as expected, these cues reflexively modulated visual processing: task accuracy increased, and response times (RTs) decreased, when the cue appeared near the target's location, relative to that of the distractor. Upon removal of these cues, however, we found no evidence that exogenous selection history modulated task performance: task accuracy and RTs at the previously most-cued and previously least-cued sides were statistically indistinguishable. Thus, unlike voluntarily directed attention, involuntary attentional allocation may not be sufficient to engender historically contingent selection biases.
Phosphoprotein-based biomarkers as predictors for cancer therapy.
Proceedings of the National Academy of Sciences of the United States of America, 2020

Disparities in cancer patient responses have prompted widespread searches to identify differences in sensitive vs. nonsensitive populations and form the basis of personalized medicine. This customized approach is dependent upon the development of pathway-specific therapeutics in conjunction with biomarkers that predict patient responses. Here, we show that Cdk5 drives growth in subgroups of patients with multiple types of neuroendocrine neoplasms. Phosphoproteomics and high throughput screening identified phosphorylation sites downstream of Cdk5. These phosphorylation events serve as biomarkers and effectively pinpoint Cdk5-driven tumors. Toward achieving targeted therapy, we demonstrate that mouse models of neuroendocrine cancer are responsive to selective Cdk5 inhibitors and biomimetic nanoparticles are effective vehicles for enhanced tumor targeting and reduction of drug toxicity. Finally, we show that biomarkers of Cdk5-dependent tumors effectively predict response to anti-Cdk5 therapy in patient-derived xenografts. Thus, a phosphoprotein-based diagnostic assay combined with Cdk5-targeted therapy is a rational treatment approach for neuroendocrine malignancies.
How functional network connectivity changes as a result of lesion and recovery: An investigation of the network phenotype of stroke.
Cortex; a journal devoted to the study of the nervous system and behavior, 2020

This study, through a series of univariate and multivariate (classification) analyses, investigated fMRI task-based functional connectivity (FC) at pre- and post-treatment time-points in 18 individuals with chronic post-stroke dysgraphia. The investigation examined the effects of lesion and treatment-based recovery on functional organization, focusing on both inter-hemispheric (homotopic) and intra-hemispheric connectivity. The work confirmed, in the chronic stage, the "network phenotype of stroke injury" proposed by Siegel et al. (2016) consisting of abnormally low inter-hemispheric connectivity as well as abnormally high intra-hemispheric (ipsilesional) connectivity. In terms of recovery-based changes in FC, this study found overall hyper-normalization of these abnormal inter and intra-hemispheric connectivity patterns, suggestive of over-correction. Specifically, treatment-related homotopic FC increases were observed between left and right dorsal frontal-parietal regions. With regard to intra-hemispheric connections, recovery was dominated by increased ipsilateral connectivity between frontal and parietal regions along with decreased connectivity between the frontal regions and posterior parietal-occipital-temporal areas. Both inter and intra-hemispheric changes were associated with treatment-driven improvements in spelling performance. We suggest an interpretation according to which, with treatment, as posterior orthographic processing areas become more effective, executive control from frontal-parietal networks becomes less necessary.
Oxidative Stress and Alterations in the Antioxidative Defense System in Neuronal Cells Derived from NPC1 Patient-Specific Induced Pluripotent Stem Cells.
International journal of molecular sciences, 2020

Oxidative stress (OS) represents a state of an imbalanced amount of reactive oxygen species (ROS) and/or a hampered efficacy of the antioxidative defense system. Cells of the central nervous system are particularly sensitive to OS, as they have a massive need of oxygen to maintain proper function. Consequently, OS represents a common pathophysiological hallmark of neurodegenerative diseases and is discussed to contribute to the neurodegeneration observed amongst others in Alzheimer's disease and Parkinson's disease. In this context, accumulating evidence suggests that OS is involved in the pathophysiology of Niemann-Pick type C1 disease (NPC1). NPC1, a rare hereditary neurodegenerative disease, belongs to the family of lysosomal storage disorders. A major hallmark of the disease is the accumulation of cholesterol and other glycosphingolipids in lysosomes. Several studies describe OS both in murine in vivo and in vitro NPC1 models. However, studies based on human cells are limited to NPC1 patient-derived fibroblasts. Thus, we analyzed OS in a human neuronal model based on NPC1 patient-specific induced pluripotent stem cells (iPSCs). Higher ROS levels, as determined by DCF (dichlorodihydrofluorescein) fluorescence, indicated oxidative stress in all NPC1-deficient cell lines. This finding was further supported by reduced superoxide dismutase (SOD) activity. The analysis of mRNA and protein levels of SOD1 and SOD2 did not reveal any difference between control cells and NPC1-deficient cells. Interestingly, we observed a striking decrease in catalase mRNA and protein levels in all NPC1-deficient cell lines. As catalase is a key enzyme of the cellular antioxidative defense system, we concluded that the lack of catalase contributes to the elevated ROS levels observed in NPC1-deficient cells. Thus, a restitution of a physiological catalase level may pose an intervention strategy to rescue NPC1-deficient cells from the repercussions of oxidative stress contributing to the neurodegeneration observed in NPC1.
Exploring Social Biomarkers in High-Functioning Adults with Autism and Asperger's Versus Healthy Controls: A Cross-Sectional Analysis.
Journal of autism and developmental disorders, 2020

Biomarkers for autism spectrum disorder (ASD) are lacking but would facilitate drug development for the core deficits of the disorder. We evaluated markers proposed for characterization of differences in social communication and interaction in adults with ASD versus healthy controls (HC) for utility as biomarkers. Data pooled from an observational study and baseline data from a placebo-controlled study were analyzed. Between-group differences were observed in eye-tracking tasks for activity monitoring, biomotion, human activity preference, composite score (p = 0.0001-0.037) and pupillometry (various tasks, p = 0.017-0.05). Impaired olfaction was more common in the ASD sample versus HC (p = 0.018). Our preliminary results suggest the potential use for stratification and response sub-analyses outcome-prediction of specific eye-tracking tasks, pupillometry and olfaction tests in ASD trials.
The effects of acute serotonin challenge on executive planning in patients with obsessive-compulsive disorder (OCD), their first-degree relatives, and healthy controls.
Psychopharmacology, 2020

Obsessive-compulsive disorder (OCD) is characterized by executive function impairment and by clinical responsivity to selective serotonin reuptake inhibitors (SSRIs). Executive planning deficits constitute a candidate endophenotype for OCD. It is not known whether this endophenotype is responsive to acute serotonin manipulation.
Neural electrophysiological mechanism of joint hierarchical rule shifting: an event-related potential study.
Neuroreport, 2021

Although previous studies have explored the brain mechanism by which an individual independently accomplishes task switching or rule shifting with different hierarchical structures, electrophysiological evidence indicating that two actors cooperate to complete the hierarchical rule shift remains unclear. This study adopts a modified joint hierarchical rule shifting paradigm in which one actor judged the parity task and the other decided the magnitude task. Results demonstrated that cues in high- and low-shift conditions elicited larger P2 amplitudes and that low-shift had a larger P3 amplitude than high-shift. Results further indicated that participants required more attention resources to ascertain who would make a judgment for the current trial and that low hierarchical features were superior in reconfiguring changed rules. Regarding the target, the high-shift condition evoked smaller P2 and larger N2 amplitudes when compared to low-shift and repeat conditions, whereas when compared to high- and low-shifts, the repeat condition elicited a larger P3 amplitude. The findings revealed that participants required more control resources to process the varied features and that repeat condition required the least cognitive resources to update rules. Thus, participants had different process patterns between cues and targets when cooperating with their co-actors.
Auto-adaptive positive airway pressure improves lung function and arterial stiffness parameters in patients with severe obstructive sleep apnea syndrome over a 1 year follow-up.
Physiological measurement, 2020

Auto-adaptive positive airway pressure (APAP) is an emerging therapeutic modality for obstructive sleep apnea (OSA) patients. However, their associated physiological effects have not been well-defined. Therefore, we aimed to investigate the impact of a 1 year APAP treatment on lung function and arterial stiffness parameters.
An autopsy case of sporadic amyotrophic lateral sclerosis with 16-year survival without artificial ventilation.
Neuropathology : official journal of the Japanese Society of Neuropathology, 1999

An autopsy case of a 65-year-old male diagnosed as having classic amyotrophic lateral sclerosis (ALS) and who survived for 16 years without artificial ventilation is described. The progression of the disease was remarkably slow, and the bulbar and respiratory functions remained relatively well preserved. Pathologically, both upper and lower motor neurons were affected, the latter much more than the former. The volume of the spinal anterior horn of the fourth cervical cord (C4) was relatively well preserved compared to those of the thoracic cords, which were the most severely affected. This preservation of C4 may have been compatible with the relatively good preservation of respiratory muscle. Despite the long clinical course, the involvement was restricted to the motor and related systems, which was compatible with classic ALS. However, this case was distinctive in the lack of myelin pallor and the absence of macrophages in the pyramidal tracts, where large myelinated fibers were markedly decreased. Further-more, no identification was made of any Bunina bodies or skein-like inclusions despite a survey of almost the entire spinal cord. No abnormalities were found in superoxide dismutase 1 complementary DNA sequences. Among the previously reported long surviving cases, certain cases showed relatively uniform neuropathologic findings including the lack of Bunina bodies and macrophage activation in the pyramidal tracts. Such cases as well as ours may represent a form of ALS. Further study is required to determine the significance of these long sur-viving cases for understanding the pathomechanisms underlying motor neuron diseases.
Neuroprotective Activities of Long-Acting Granulocyte-Macrophage Colony-Stimulating Factor (mPDM608) in 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Intoxicated Mice.
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2020

Loss of dopaminergic neurons along the nigrostriatal axis, neuroinflammation, and peripheral immune dysfunction are the pathobiological hallmarks of Parkinson's disease (PD). Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been successfully tested for PD treatment. GM-CSF is a known immune modulator that induces regulatory T cells (Tregs) and serves as a neuronal protectant in a broad range of neurodegenerative diseases. Due to its short half-life, limited biodistribution, and potential adverse effects, alternative long-acting treatment schemes are of immediate need. A long-acting mouse GM-CSF (mPDM608) was developed through Calibr, a Division of Scripps Research. Following mPDM608 treatment, complete hematologic and chemistry profiles and T-cell phenotypes and functions were determined. Neuroprotective and anti-inflammatory capacities of mPDM608 were assessed in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mice that included transcriptomic immune profiles. Treatment with a single dose of mPDM608 resulted in dose-dependent spleen and white blood cell increases with parallel enhancements in Treg numbers and immunosuppressive function. A shift in CD4