rudyvdbrink/CitationDatabase huggingface dataset:
Differential sensory and clinical phenotypes of patients with chronic widespread and regional musculoskeletal pain.
Pain, 2021

The differentiation of chronic primary pain syndromes into those with widespread vs regional musculoskeletal pain has been characterized by controversial discussions about common or distinct mechanisms and core clinical and sensory criteria. For example, the recent revision of fibromyalgia criteria has discarded sensory characteristics such as number of "tender points." This study examined empirical evidence related to this diagnostic shift and aimed to identify basic sensory-clinical pain phenotypes in patients with chronic local primary pain (chronic primary back pain [CBP]) and patients with chronic widespread primary pain (fibromyalgia syndrome). Combined sensory-clinical pain phenotypes of 185 patients with previous CBP and fibromyalgia syndrome diagnoses were derived by a stepwise data reduction through descriptive statistical, correlational, principal components and latent class analyses. Clusters were cross-validated by linear discriminant analysis. Four clusters of patients were identified, requiring 4 pressure pain sensitivity markers (number of sensitive tender and control points, pain intensity, and pressure pain threshold at the trapezius) and 2 clinical pain characteristics (pain regions and present pain intensity). Subsequent discriminant analysis revealed that 3 discriminant functions of pressure sensitivity markers sufficed to differentiate the clusters. These sensory-clinical phenotypes differed also in somatic symptoms and impairment but neither in psychopathology nor in psychosocial cofactors. The results highlight the relevance of sensory testing in combination with clinical pain assessment in chronic primary pain syndromes.
Neurointensive care of patients with severe community-acquired meningitis.
Acta anaesthesiologica Scandinavica, 2011

Reports about neurointensive care of severe community-acquired meningitis are few. The aims of this retrospective study were to review the acute clinical course, management and outcome in a series of bacterial meningitis patients receiving neurointensive care.
Is the pathology of corticobasal syndrome predictable in life?
Movement disorders : official journal of the Movement Disorder Society, 2009

Corticobasal syndrome (CBS) has been associated with a heterogeneous spectrum of pathologies with an increasing number of reports of Alzheimer's type pathology. There is, however, no means of predicting pathology of CBS in vivo at present. We compared the clinical features of patients presenting with CBS who have either pathologic changes of classic corticobasal degeneration (CBD) or Alzheimer's disease (AD) at post-mortem to identify predictors of the specific pathological processes in life. Twelve patients with CBS were followed prospectively; six had AD and six had classic CBD neuropathology. After review of the presenting clinical features, we identified nine potential predictor variables, compared their frequency in the two groups, and performed a discriminant function analysis. Initial episodic memory complaints and poor performance on the combined orientation-memory subtest of the Addenbrooke's Cognitive Examination (ACE) reliably predicted AD pathology while varying combinations of early frontal-lobe type behavioral symptoms, nonfluent language disturbance, orobuccal apraxia, and utilization behavior predicted CBD pathology ante-mortem. CBS is frequently associated with Alzheimer's disease pathology. Early episodic memory impairment versus early behavioral symptomatology appears to best predict AD or CBD pathology in life.
The role of hippocampal GABA
Molecular biology reports, 2020

Echium amoenum (EA), a popular medicinal plant in Persian medicine, has anxiolytic, antioxidant, sedative, and anti-inflammatory effects. This study examined whether GABA-ergic signaling is involved in the anxiolytic effects of EA in mice. Sixty BALB/c mice (25-30 g) were divided into six groups (n = 10) as follows: the (I) control group received 10 ml/kg normal saline (NS). In the stress groups, the animals underwent 14 consecutive days of restraint stress (RS), and received following treatments simultaneously; (II) RS + NS; (III) RS + Diaz (Diazepam); (IV) RS + EA; (V) RS + Flu (Flumazenil) + EA; (VI) RS + Flu + Diaz. Behavioral tests including the open field test (OFT) and elevated plus maze (EPM) were performed to evaluate anxiety-like behaviors and the effects of the regimens. The plasma level of corticosterone and the hippocampal protein expressions of IL-1β, TNF-α, CREB, and BDNF, as well as p-GABA
Between- and within-site variability of fMRI localizations.
Human brain mapping, 2016

This study provides first data about the spatial variability of fMRI sensorimotor localizations when investigating the same subjects at different fMRI sites. Results are comparable to a previous patient study. We found a median between-site variability of about 6 mm independent of task (motor or sensory) and experimental standardization (high or low). An intraclass correlation coefficient analysis using data quality measures indicated a major influence of the fMRI site on variability. In accordance with this, within-site localization variability was considerably lower (about 3 mm). We conclude that the fMRI site is a considerable confound for localization of brain activity. However, when performed by experienced clinical fMRI experts, brain pathology does not seem to have a relevant impact on the reliability of fMRI localizations. Hum Brain Mapp 37:2151-2160, 2016. © 2016 Wiley Periodicals, Inc.
Cellular changes underlying hyperoxia-induced delay of white matter development.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011

Impaired neurological development in premature infants frequently arises from periventricular white matter injury (PWMI), a condition associated with myelination abnormalities. Recently, exposure to hyperoxia was reported to disrupt myelin formation in neonatal rats. To identify the causes of hyperoxia-induced PWMI, we characterized cellular changes in the white matter (WM) using neonatal wild-type 2-3-cyclic nucleotide 3-phosphodiesterase-enhanced green fluorescent protein (EGFP) and glial fibrillary acidic protein (GFAP)-EGFP transgenic mice exposed to 48 h of 80% oxygen from postnatal day 6 (P6) to P8. Myelin basic protein expression and CC1(+) oligodendroglia decreased after hyperoxia at P8, but returned to control levels during recovery between P12 and P15. At P8, hyperoxia caused apoptosis of NG2(+)O4(-) progenitor cells and reduced NG2(+) cell proliferation. This was followed by restoration of the NG2(+) cell population and increased oligodendrogenesis in the WM after recovery. Despite apparent cellular recovery, diffusion tensor imaging revealed WM deficiencies at P30 and P60. Hyperoxia did not affect survival or proliferation of astrocytes in vivo, but modified GFAP and glutamate-aspartate transporter expression. The rate of [(3)H]-d-aspartic acid uptake in WM tissue was also decreased at P8 and P12. Furthermore, cultured astrocytes exposed to hyperoxia showed a reduced capacity to protect oligodendrocyte progenitor cells against the toxic effects of exogenous glutamate. This effect was prevented by 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide treatment. Our analysis reveals a role for altered glutamate homeostasis in hyperoxia-induced WM damage. Understanding the cellular dynamics and underlying mechanisms involved in hyperoxia-induced PWMI will allow for future targeted therapeutic intervention.
Nanoparticles Targeting STATs in Cancer Therapy.
Cells, 2019

Over the past decades, an increase in the incidence rate of cancer has been witnessed. Although many efforts have been made to manage and treat this life threatening condition, it is still one of the leading causes of death worldwide. Therefore, scientists have attempted to target molecular signaling pathways involved in cancer initiation and metastasis. It has been shown that signal transducers and activator of transcription (STAT) contributes to the progression of cancer cells. This important signaling pathway is associated with a number of biological processes including cell cycle, differentiation, proliferation and apoptosis. It appears that dysregulation of the STAT signaling pathway promotes the migration, viability and malignancy of various tumor cells. Hence, there have been many attempts to target the STAT signaling pathway. However, it seems that currently applied therapeutics may not be able to effectively modulate the STAT signaling pathway and suffer from a variety of drawbacks such as low bioavailability and lack of specific tumor targeting. In the present review, we demonstrate how nanocarriers can be successfully applied for encapsulation of STAT modulators in cancer therapy.
Corticostriatal functional connectivity predicts transition to chronic back pain.
Nature neuroscience, 2012

The mechanism of brain reorganization in pain chronification is unknown. In a longitudinal brain imaging study, subacute back pain (SBP) patients were followed over the course of 1 year. When pain persisted (SBPp, in contrast to recovering SBP and healthy controls), brain gray matter density decreased. Initially greater functional connectivity of nucleus accumbens with prefrontal cortex predicted pain persistence, implying that corticostriatal circuitry is causally involved in the transition from acute to chronic pain.
Smad Anchor for Receptor Activation and Phospho-Smad3 Were Upregulated in Patients with Temporal Lobe Epilepsy.
Journal of molecular neuroscience : MN, 2019

Smad anchor for receptor activation (SARA) is an important regulator of transforming growth factor β (TGF-β) signaling by recruiting Smad2/3 to TGF-β receptors. We recently demonstrated that the expressions of SARA and level of downstream phospho-Smad3 (p-Smad3) were upregulated in the brain in the epileptic rat model, but were never examined in patients with temporal lobe epilepsy (TLE). In this study, we examined the expressions of SARA and level of p-Smad3 in brain tissues of TLE patients using immunohistochemistry and western blot to demonstrate that SARA activation in neurons is sufficient to facilitate TGF- β pathway in patients to regulate epilepsy. We found that the expressions of SARA and level of p-Smad3 were significantly upregulated in neurons of the temporal cortex of TLE patients compared to controls. Moreover, SARA and p-Smad3 were strongly stained in the cytoplasm in the temporal cortex of TLE patients. Our results indicate that upregulation of SARA and p-Smad3 in cortex neurons might be involved in the development of intractable temporal lobe epilepsy.
Cdk5 suppresses the neuronal cell cycle by disrupting the E2F1-DP1 complex.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010

Neurons that reenter a cell cycle after maturation are at increased risk for death, yet the mechanisms by which a normal neuron suppresses the cycle remain mostly unknown. Our laboratory has shown that cyclin-dependent kinase 5 (Cdk5) is a potent cell cycle suppressor, and we report here on the molecular basis of this activity. Cell cycle suppression by Cdk5 requires its binding to the p35 activator protein. The related p39 and p25 proteins cannot serve as substitutes. Unexpectedly, Cdk5 enzymatic activity is not required to perform this function. Rather, the link to cell cycle regulation is made through the formation of a previously unknown complex consisting of the p35-Cdk5 dimer and E2F1. Formation of this complex excludes the E2F1 cofactor, DP1, thus inhibiting E2F1 binding to the promoters of various cell cycle genes. This anti-cell cycle activity is most likely a neuroprotective function of Cdk5.
Assessing individual performance and maintaining breath sample integrity in biomedical detection dogs.
Behavioural processes, 2018

In empirical tests of biomedical detection dogs, exhaled breath samples are often used because breath contains volatile organic compounds that can signal metabolic states, infection, or disease. However, in studies that present dogs with breath samples, results show a notable degree of variability both between and within studies. Differing protocols for the collection and storage of exhaled breath samples may contribute to this observed variability. The goal of the current study was therefore to test whether there was a difference in the detectability of breath samples collected using silicone-coated versus uncoated cotton balls. This was tested in two experiments. In the first experiment, breath samples were prepared using both silicone-coated and uncoated cotton balls, which were then left exposed to the surrounding air. Four dogs' detection of the samples was tested using a cued, three alternative forced choice (3AFC) procedure at regular intervals up to two hours after the samples were prepared. The results of Experiment 1 showed that the dogs' performance was above chance and there was no significant difference in the dogs' detection of the breath samples across conditions. In the second experiment, a series of breath samples were prepared and stored for one, two, three, and four week periods. The same four dogs' ability to detect the breath samples was tested each week using the same cued 3AFC procedure. The results of Experiment 2 showed that when silicone-coated cotton balls were used, all four dogs could detect the breath samples at above chance levels after the samples were stored for three weeks, and two dogs could detect the samples that were stored for four weeks. When the dogs were tested on their ability to detect the breath samples prepared using uncoated cotton, two dogs' performance fell to below chance levels at one week of storage time, while the other two dogs could detect the breath samples at above chance levels after the samples were stored for four weeks. Taken together, the results of the two experiments illustrate that silicone-coated cotton balls do not improve detectability of breath samples within two hours, but can greatly improve the detectability of breath samples stored over longer periods of time. Since the use of silicone-coated cotton balls only improved the detectability of the breath samples for two of the four dogs, these results highlight the importance of examining individual differences in dogs' performance. Furthermore, we argue that, given the inherent differences in olfactory ability across dogs, widespread use of silicone-coated cotton balls for the collection of breath samples would increase the pool of testable dogs for biomedical detection studies and would decrease the degree of variability both within and between studies.
The Effect of Locomotion on Early Visual Contrast Processing in Humans.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2018

Most of our knowledge about vision comes from experiments in which stimuli are presented to immobile human subjects or animals. In the case of human subjects, movement during psychophysical, electrophysiological, or neuroimaging experiments is considered to be a source of noise to be eliminated. Animals used in visual neuroscience experiments are typically restrained and, in many cases, anesthetized. In reality, however, vision is often used to guide the motion of awake, ambulating organisms. Recent work in mice has shown that locomotion elevates visual neuronal response amplitudes (Niell and Stryker, 2010; Erisken et al., 2014; Fu et al., 2014; Lee et al., 2014; Mineault et al., 2016) and reduces long-range gain control (Ayaz et al., 2013). Here, we used both psychophysics and steady-state electrophysiology to investigate whether similar effects of locomotion on early visual processing can be measured in humans. Our psychophysical results show that brisk walking has little effect on subjects' ability to detect briefly presented contrast changes and that co-oriented flankers are, if anything, more effective masks when subjects are walking. Our electrophysiological data were consistent with the psychophysics indicating no increase in stimulus-driven neuronal responses while walking and no reduction in surround suppression. In summary, we have found evidence that early contrast processing is altered by locomotion in humans but in a manner that differs from that reported in mice. The effects of locomotion on very low-level visual processing may differ on a species-by-species basis and may reflect important differences in the levels of arousal associated with locomotion.
The Role of Integrated Knowledge Translation in Intervention Research.
Prevention science : the official journal of the Society for Prevention Research, 2018

There is widespread recognition across the full range of applied research disciplines, including health and social services, about the challenges of integrating scientifically derived research evidence into policy and/or practice decisions. These "disconnects" or "knowledge-practice gaps" between research production and use have spawned a new research field, most commonly known as either "implementation science" or "knowledge translation." The present paper will review key concepts in this area, with a particular focus on "integrated knowledge translation" (IKT)-which focuses on researcher-knowledge user partnership-in the area of mental health and prevention of violence against women and children using case examples from completed and ongoing work. A key distinction is made between the practice of KT (disseminating, communicating, etc.), and the science of KT, i.e., research regarding effective KT approaches. We conclude with a discussion of the relevance of IKT for mental health intervention research with children and adolescents.
Set-shifting in children with autism spectrum disorders: reversal shifting deficits on the Intradimensional/Extradimensional Shift Test correlate with repetitive behaviors.
Autism : the international journal of research and practice, 2009

Research examining set-shifting has revealed significant difficulties for adults with autism spectrum disorders (ASDs). However, research with high-functioning children with ASDs has yielded mixed results. The current study tested 6- to 13-year-old high-functioning children with ASD and typically developing controls matched on age, gender, and IQ using the Intradimensional/Extradimensional (ID/ED) Shift Test from the Cambridge Neuropsychological Test Automated Battery. Children with ASDs completed as many ED shifts and reversal ED shifts as controls; however, they made significantly more errors than controls while completing the ED reversal shifts. Analyses on a subset of cases revealed a significant positive correlation between ED reversal errors and the number of repetitive behavior symptoms in the ASD group. These findings suggest that high-functioning children with ASDs require additional feedback to shift successfully. In addition, the relationship between set-shifting and non-social symptoms suggests its utility as a potentially informative intermediate phenotype in ASDs.
Altered signaling associated with chronic arsenic exposure in human skin keratinocytes.
Proteomics. Clinical applications, 2017

Modulation of signaling pathways upon chronic arsenic exposure remains poorly studied. Here, we carried out SILAC-based quantitative phosphoproteomics analysis to dissect the signaling induced upon chronic arsenic exposure in human skin keratinocyte cell line, HaCaT. We identified 4171 unique phosphosites derived from 2000 proteins. We observed differential phosphorylation of 406 phosphosites (twofold) corresponding to 305 proteins. Several pathways involved in cytoskeleton maintenance and organization were found to be significantly enriched (p<0.05). Our data revealed altered phosphorylation of proteins associated with adherens junction remodeling and actin polymerization. Kinases such as protein kinase C iota type (PRKCI), mitogen-activated protein kinase kinase kinase 1 (MAP3K1), tyrosine-protein kinase BAZ1B (BAZ1B) and STE20 like kinase (SLK) were found to be hyperphosphorylated. Our study provides novel insights into signaling perturbations associated with chronic arsenic exposure in human skin keratinocytes. All MS/MS data have been deposited to the ProteomeXchange with identifier PXD004868.
Building blocks of joint attention: Early sensitivity to having one's own gaze followed.
Developmental cognitive neuroscience, 2019

Detecting when one's own gaze has been followed is a critical component of joint attention, but little is known about its development. To address this issue, we used electroencephalography (EEG) to record infant neural responses at 6.5 and 9.5 months during observation of an adult either turning to look at the same object as the infant (congruent actor), or turning to look at a different object (incongruent actor). We also used a preferential looking paradigm to investigate whether infants would demonstrate a preference for the congruent versus incongruent actor. Greater suppression of alpha band activity in the congruent compared to incongruent condition was revealed at both ages in central and parietal regions. However, the effect of congruency on alpha suppression was stronger at 9.5 months, and only at this age did infants demonstrate a preference towards looking at the congruent actor. Together, these results suggest that although infants are sensitive to others' gaze following from early on, important neural and behavioural developments occur between 6.5 and 9.5 months.
Neural mechanisms of human perceptual choice under focused and divided attention.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015

Perceptual decisions occur after the evaluation and integration of momentary sensory inputs, and dividing attention between spatially disparate sources of information impairs decision performance. However, it remains unknown whether dividing attention degrades the precision of sensory signals, precludes their conversion into decision signals, or dampens the integration of decision information toward an appropriate response. Here we recorded human electroencephalographic (EEG) activity while participants categorized one of two simultaneous and independent streams of visual gratings according to their average tilt. By analyzing trial-by-trial correlations between EEG activity and the information offered by each sample, we obtained converging behavioral and neural evidence that dividing attention between left and right visual fields does not dampen the encoding of sensory or decision information. Under divided attention, momentary decision information from both visual streams was encoded in slow parietal signals without interference but was lost downstream during their integration as reflected in motor mu- and beta-band (10-30 Hz) signals, resulting in a "leaky" accumulation process that conferred greater behavioral influence to more recent samples. By contrast, sensory inputs that were explicitly cued as irrelevant were not converted into decision signals. These findings reveal that a late cognitive bottleneck on information integration limits decision performance under divided attention, and places new capacity constraints on decision-theoretic models of information integration under cognitive load.