rudyvdbrink/CitationDatabase huggingface dataset:
Signaling endosomes trigger synapse assembly.
Neuron, 2010

In this issue of Neuron, Sharma et al. report that target-derived NGF exerts long-distance control of postsynaptic assembly. A major advance is the discovery that TrkA signaling endosomes are retrogradely transported to neuronal dendrites and directly trigger the clustering of postsynaptic density proteins.
Expansion of the GRIA2 phenotypic representation: a novel de novo loss of function mutation in a case with childhood onset schizophrenia.
Journal of human genetics, 2021

Childhood-onset schizophrenia (COS) is a rare form of schizophrenia with an onset before 13 years of age. There is rising evidence that genetic factors play a major role in COS etiology, yet, only a few single gene mutations have been discovered. Here we present a diagnostic whole-exome sequencing (WES) in an Israeli Jewish female with COS and additional neuropsychiatric conditions such as obsessive-compulsive disorder (OCD), anxiety, and aggressive behavior. Variant analysis revealed a de novo novel stop gained variant in GRIA2 gene (NM_000826.4: c.1522 G > T (p.Glu508Ter)). GRIA2 encodes for a subunit of the AMPA sensitive glutamate receptor (GluA2) that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. GluA2 subunit mutations are known to cause variable neurodevelopmental phenotypes including intellectual disability, autism spectrum disorder, epilepsy, and OCD. Our findings support the potential diagnostic role of WES in COS, identify GRIA2 as possible cause to a broad psychiatric phenotype that includes COS as a major manifestation and expand the previously reported GRIA2 loss of function phenotypes.
Extension of Public Smoking Ban Was Not Associated with Any Immediate Effect on Stroke Occurrence in Finland.
Journal of clinical medicine, 2021

We investigated the association between the widening of a nationwide restaurant smoking ban, enacted on 1 June 2007, and stroke admissions. All acute stroke admissions between 1 May 2005 and 30 June 2009 were retrieved from a mandatory registry covering mainland Finland. Patients aged ≥18 years were included. One annual admission per patient was included. Negative binomial regression accounting for the at-risk population was applied. We found no difference in stroke occurrence before and after the smoking ban within 7 days (
Young adults are more vulnerable to chronic sleep deficiency and recurrent circadian disruption than older adults.
Scientific reports, 2018

More than a third of US adults report fewer than 6 hours of sleep a night, making chronic sleep restriction a growing public health concern. Sleep curtailment is associated with an increase in industrial accidents, motor vehicle accidents, medical and other occupational errors. Young adults are more vulnerable to acute sleep deprivation than older adults, but less is known about how young vs. older adults respond to the more commonly experienced chronic sleep restriction. To test the hypothesis that young adults are more vulnerable to chronic sleep loss than older adults, we compared data from young and older adults who underwent three weeks of chronic sleep restriction (equivalent to 5.6 hours/24 hours) combined with recurrent circadian disruption in an experiment that enabled us to separate the influences of the sleep-wake homeostatic process, the circadian timing system, and the chronic sleep deficit. We found that while young and older adults reported similar levels of subjective sleepiness, objective measures of sleepiness revealed that young adults were more vulnerable and had more attentional failures than the older adults. These results have important public health implications, particularly related to prevention of sleep-related motor vehicle crashes in young drivers. Further research is needed to understand the neurobiological basis of these age-related differences.
Academic Productivity of Neurosurgeons Practicing in Joint Residency Advisory and Accreditation Committee Accredited Programs.
World neurosurgery, 2020

Bibliometric indexes are often used to evaluate and compare neurosurgeons and departments, and they have been shown to correlate with academic rank and department reputation. We evaluated academic productivity of neurosurgeons practicing in departments accredited by the Joint Residency Advisory and Accreditation Committee and European Association of Neurological Surgeons.
Novel culture system via wirelessly controllable optical stimulation of the FGF signaling pathway for human and pig pluripotency.
Biomaterials, 2021

Stem cell fate is largely determined by cellular signaling networks and is heavily dependent on the supplementation of exogenous recombinant proteins into culture media; however, uneven distribution and inconsistent stability of recombinant proteins are closely associated with the spontaneous differentiation of pluripotent stem cells (PSCs) and result in significant costs in large-scale manufacturing. Here, we report a novel PSC culture system via wirelessly controllable optical activation of the fibroblast growth factor (FGF) signaling pathway without the need for supplementation of recombinant FGF2 protein, a key molecule for maintaining pluripotency of PSCs. Using a fusion protein between the cytoplasmic region of the FGF receptor-1 and a light-oxygen-voltage domain, we achieved tunable, blue light-dependent activation of FGF signaling in human and porcine PSCs. Our data demonstrate that a highly controllable optical stimulation of the FGF signaling pathway is sufficient for long-term maintenance of PSCs, without the loss of differentiation potential into three germ layers. This culture system will be a cost-effective platform for a large-scale stem cell culture.
Persistent treatment resistance in genetic generalized epilepsy: A long-term outcome study in a tertiary epilepsy center.
Epilepsia, 2020

To assess prognostic patterns and investigate clinical and electroencephalography (EEG) variables associated with persistent treatment resistance in a population of genetic generalized epilepsy (GGE) patients with a long-term follow-up.
Gestational Exposure to Benzodiazepines, 1: The Risk of Spontaneous Abortion Examined Through the Prism of Research Design.
The Journal of clinical psychiatry, 2019

A recent, large, case-control study found that, after adjusting for measured confounds, early gestational exposure to benzodiazepines was associated with a nearly doubled odds of spontaneous abortion. The risks differed little between pregnancies exposed to short- and long-acting benzodiazepines. The risks were elevated for all benzodiazepines for which data were adequate for analysis. The risks were higher with higher daily doses. These findings indicate that early gestational exposure to benzodiazepines is a marker for the risk of spontaneous abortion. These findings are not evidence for a cause-effect relationship because analyses in studies such as this can adjust for only measured confounds; therefore, unmeasured, inadequately measured, and unknown confounds will continue to contaminate the interpretation of findings. It follows, therefore, that replication of the study with the same study design using data extracted from other databases will serve no purpose. So, innovative research designs should be considered, such as the examination of risk associated with benzodiazepine exposure in the year before pregnancy, examination of risk in previously unexposed pregnancies, examination of risk in discordant sibling pairs, and examination of risk associated with paternal exposure. Such research designs have the potential to indirectly partially address unmeasured and unknown confounds, including those related to genetics and the family environment.
Computed Tomography Radiomics for Residual Positron Emission Tomography-Computed Tomography Uptake in Lymph Nodes after Treatment.
Cancers, 2020

Although a substantial decrease in 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) uptake on positron emission tomography-computed tomography (PET-CT) indicates a promising metabolic response to treatment, predicting the pathologic status of lymph nodes (LN) remains challenging. We investigated the potential of a CT radiomics approach to predict the pathologic complete response of LNs showing residual uptake after neoadjuvant concurrent chemoradiotherapy (NeoCCRT) in patients with non-small cell lung cancer (NSCLC). Two hundred and thirty-seven patients who underwent NeoCCRT for stage IIIa NSCLC were included. Two hundred fifty-two CT radiomics features were extracted from LNs showing remaining positive FDG uptake upon restaging PET-CT. A multivariable logistic regression analysis of radiomics features and clinicopathologic characteristics was used to develop a prediction model. Of the 237 patients, 135 patients (185 nodes) met our inclusion criteria. Eighty-seven LNs were proven to be malignant (47.0%, 87/185). Upon multivariable analysis, metastatic LNs were significantly prevalent in females and patients with adenocarcinoma (odds ratio (OR) = 2.02, 95% confidence interval (CI) = 0.88-4.62 and OR = 0.39, 95% CI = 0.19-0.77 each). Metastatic LNs also had a larger maximal 3D diameter and higher cluster tendency (OR = 9.92, 95% CI = 3.15-31.17 and OR = 2.36, 95% CI = 1.22-4.55 each). The predictive model for metastasis showed a discrimination performance with an area under the receiver operating characteristic curve of 0.728 (95% CI = 0.654-0.801,
Association of Markers of Microvascular Dysfunction With Prevalent and Incident Depressive Symptoms: The Maastricht Study.
Hypertension (Dallas, Tex. : 1979), 2020

The etiology of late-life depression (LLD) is still poorly understood. Microvascular dysfunction (MVD) has been suggested to play a role in the etiology of LLD, but direct evidence of this association is scarce. The aim of this study was to investigate whether direct and indirect markers of early microvascular dysfunction are associated with prevalent and incident LLD in the population-based Maastricht Study cohort. We measured microvascular dysfunction at baseline by use of flicker light-induced retinal vessel dilation response (Dynamic Vessel Analyzer), heat-induced skin hyperemic response (laser- Doppler flowmetry), and plasma markers of endothelial dysfunction (endothelial dysfunction; sICAM-1 [soluble intercellular adhesion molecule-1], sVCAM-1 [soluble vascular adhesion molecule-1], sE-selectin [soluble E-selectin], and vWF [Von Willebrand Factor]). Depressive symptoms were assessed with the 9-item Patient Health Questionnaire (PHQ-9) at baseline and annually over 4 years of follow-up (n=3029; mean age 59.6±8.2 years, 49.5% were women, n=132 and n=251 with prevalent and incident depressive symptoms [PHQ-9≥10]). We used logistic, negative binominal and Cox regression analyses, and adjusted for demographic, cardiovascular, and lifestyle factors. Retinal venular dilatation and plasma markers of endothelial dysfunction were associated with the more prevalent depressive symptoms after full adjustment (PHQ-9 score, RR, 1.05 [1.00-1.11] and RR 1.06 [1.01-1.11], respectively). Retinal venular dilatation was also associated with prevalent depressive symptoms (PHQ-9≥10; odds ratio, 1.42 [1.09-1.84]), after full adjustment. Retinal arteriolar dilatation and plasma markers of endothelial dysfunction were associated with incident depressive symptoms (PHQ-9≥10; HR, 1.23 [1.04-1.46] and HR, 1.19 [1.05-1.35]), after full adjustment. These findings support the concept that microvascular dysfunction in the retina, and plasma markers of endothelial dysfunction is involved in the etiology of LLD and might help in finding additional targets for the prevention and treatment of LLD.
Problem drinking alters gray matter volume and food cue responses of the lateral orbitofrontal cortex.
Addiction biology, 2021

Alcohol misuse is associated with significant energy deficits. As feeding involves multiple sensory, cognitive, and affective processes, low food intake in problem drinkers likely reflects alterations in both regional and inter-regional responses. To investigate the effects of problem drinking on feeding-related neural activities and connectivities, we examined functional magnetic resonance imaging (fMRI) data in 82 drinkers who viewed palatable food and nonfood images in alternating blocks. Drinking severity was assessed with the Alcohol Use Disorders Identification Test (AUDIT). A whole-brain multiple regression with AUDIT scores as the predictor showed a negative correlation between drinking severity and activation to food vs nonfood cues in the lateral orbitofrontal cortex (lOFC). AUDIT scores were also negatively correlated with the gray matter volume (GMV) of the lOFC and regions that responded preferentially to food stimuli, including the left middle frontal gyrus, bilateral middle insula, and occipital cortices. Connectivity strength between the lOFC and these regions was negatively modulated by drinking severity. In contrast, there was no relationship between AUDIT scores and lOFC connectivity with regions that did not show either selectivity to food images or GMV loss. A mediation analysis further suggested that alcohol misuse may have compromised lOFC's structural integrity, which in turn disrupted lOFC interactions with regions that support the processing of visual food cues. Overall, the findings provide evidence for the effects of problem drinking on the brain substrates of feeding, potentially shedding light on the neural mechanisms underlying energy deficits in at-risk drinkers.
Hierarchical control of coherent gene clusters defines the molecular mechanisms of glioblastoma.
Molecular bioSystems, 2015

Glioblastoma is a highly-aggressive and rapidly-lethal tumor characterized by resistance to therapy. Although data on multiple genes, proteins, and pathways are available, the key challenge is deciphering this information and identifying central molecular targets. Therapeutically targeting individual molecules is often unsuccessful due to the presence of compensatory and redundant pathways, and crosstalk. A systems biology approach that involves a hierarchical gene group networks analysis can delineate the coherent functions of different disease mediators. Here, we report an integrative networks-based analysis to identify a system of coherent gene modules in primary and secondary glioblastoma. Our study revealed a hierarchical transcriptional control of genes in these modules. We elucidated those modules responsible for conversion of the glioma-associated microglia/macrophages into glioma-supportive, immunosuppressive cells. Further, we identified clusters comprising mediators of angiogenesis, proliferation, and cell death for both primary and secondary glioblastomas. Data obtained for these clusters point to a possible role of transcription regulators that function as the gene modules mediators in glioblastoma pathogenesis. We elucidated a set of possible transcription regulators that can be targeted to affect the selected gene clusters at specific levels for glioblastoma. Our innovative approach to construct informative disease models may hold the key to successful management of complex diseases including glioblastoma and other cancers.
Discoveries: an innovative platform for publishing cutting-edge research discoveries in medicine, biology and chemistry.
Discoveries (Craiova, Romania), 2013

Discoveries is a new peer-reviewed, open access, online multidisciplinary and integrative journal publishing high impact reviews, experimental articles, perspective articles, and editorials from all areas related to medicine, biology, and chemistry, including but not limited to: Molecular and Cellular Biology, Biochemistry, Biophysics, Genomics, Proteomics, Biotechnology, Synthetic Biology, Bioengineering, Systems Biology, Bioinformatics, Translational Medicine, Medicine/ Clinical findings, Cognitive Science, Epidemiology, Global Medicine, Family Medicine, Organic/ Inorganic/ Physical Chemistry and Ethics in Science. Discoveries brings to the research community an outstanding editorial board that aims to address several of the innovations proposed above: there is no need to format the manuscript before submission, we have a rapid and efficient submission process, there is no need for a Cover Letter and we support the need for rules for validation of critical reagents, such as antibodies. Discoveries will aim to support high quality research on human subjects materials to provide relevance for non-human studies along with mechanistic insights into human biology and chemistry. We also aim to avoid requesting unnecessary experiments during the review process, without affecting the quality and conclusions of published manuscripts. In addition, we recognize the need of adopting the recommendations made by NCCD and other similar scientific guiding entities.
Intercellular communication and ion channels in neuropathic pain chronicization.
Inflammation research : official journal of the European Histamine Research Society ... [et al.], 2020

Neuropathic pain is caused by primary lesion or dysfunction of either peripheral or central nervous system. Due to its complex pathogenesis, often related to a number of comorbidities, such as cancer, neurodegenerative and neurovascular diseases, neuropathic pain still represents an unmet clinical need, lacking long-term effective treatment and complex case-by-case approach.
Anxiety in Children with Selective Mutism: A Meta-analysis.
Child psychiatry and human development, 2020

This study evaluates the current conceptualization of selective mutism (SM) as an anxiety disorder in the DSM-5 using a meta-analytic approach. In the absence of any systematic assessment of anxiety in the field of SM, we pooled prevalence data of comorbid anxiety disorders in a random-effects meta-analysis. On the basis of 22 eligible studies (N = 837), we found that 80% of the children with SM were diagnosed with an additional anxiety disorder, notably social phobia (69%). However, considerable heterogeneity was present, which remained unexplained by a priori specified moderators. The finding that SM is often diagnosed in combination with anxiety disorders, indicates that these disorders are not discrete, separable categories. Moreover, this finding does not help to elucidate the relation between SM and anxiety as an etiological mechanism or symptomatic feature. Broadening our research strategies regarding the assessment of anxiety is paramount to clarify the role of anxiety in SM, and allow for proper classification.
Mitigation of B1+ inhomogeneity using spatially selective excitation with jointly designed quadratic spatial encoding magnetic fields and RF shimming.
Magnetic resonance in medicine, 2017

The inhomogeneity of flip angle distribution is a major challenge impeding the application of high-field MRI. We report a method combining spatially selective excitation using generalized spatial encoding magnetic fields (SAGS) with radiofrequency (RF) shimming to achieve homogeneous excitation. This method can be an alternative approach to address the challenge of B1+ inhomogeneity using nonlinear gradients.
Understanding motor difficulties in children with ADHD: A fixel-based analysis of the corticospinal tract.
Progress in neuro-psychopharmacology & biological psychiatry, 2021

Children with attention deficit hyperactivity disorder (ADHD) often present with deficits in fine motor control. The cortico-spinal tract (CST) is critical for voluntary motor control. Although neuroimaging work has identified anomalous microstructural properties in the CST in ADHD, no study to date has attempted to investigate the link between deficits in fine motor performance and microstructural properties of the CST in children with ADHD. This study aimed to address this gap using a novel fixel-based analysis (FBA).
Depression: a new enzyme AT play.
EMBO reports, 2020

Neuronal activity is the main contributor to the high-energy demand of the human brain. ATP is needed for the maintenance of ionic gradients, neurotransmitter transport, and release, as well as the signaling pathways that follow activation of post-synaptic receptors. The inability to maintain a high supply of ATP through tight regulatory mechanisms can, therefore, have severe consequences for brain function. In this issue of EMBO Reports, Cui et al [1] show that pharmacological inhibition or genetic inactivation of CD39, an ectonucleotide tri(di)phosphohydrolase responsible for converting ATP into AMP, has antidepressant-like effects by maintaining high extracellular ATP levels in the presence of stress.
Effects of increasing Ca2+ channel-vesicle separation on facilitation at the crayfish inhibitory neuromuscular junction.
Neuroscience, 2008

We investigated the mechanism of facilitation at the crayfish inhibitory neuromuscular junction before and after blocking P-type Ca(2+) channels. P-type channels have been shown to be closer to releasable synaptic vesicles than non-P-type channels at this synapse. Prior to the block of P-type channels, facilitation evoked by a train of 10 action potentials at 100 Hz was increased by application of 40 mM [Mg(2+)](o), but decreased by pressure-injected EGTA. Blocking P-type channels with 5 nM omega-Aga IVA, which reduced total Ca(2+) influx and release to levels comparable to that recorded in 40 mM [Mg(2+)](o), did not change the magnitude of facilitation. We explored whether this observation could be attributed to the buffer saturation model of facilitation, since increasing the Ca(2+) channel-vesicle separation could potentially enhance the role of endogenous buffers. The characteristics of facilitation in synapses treated with omega-Aga IVA were probed with broad action potentials in the presence of K(+) channel blockers. After Ca(2+) channel-vesicle separation was increased by omega-Aga IVA, facilitation probed with broad action potential was still decreased by EGTA injection and increased by 40 mM [Mg(2+)](o). EGTA-AM perfusion was used to test the impact of EGTA over a range of concentration in omega-Aga IVA-poisoned preparations. The results showed a concentration dependent decrease in facilitation as EGTA concentration rose. Thus, probing facilitation with EGTA and reduced Ca(2+) influx showed that characteristics of facilitation are not changed after the role of endogenous buffer is enhanced by increasing Ca(2+) channel-vesicle separation. There is no clear indication that buffer saturation has become the dominant mechanism for facilitation after omega-Aga IVA poisoning. Finally, we sought correlation between residual Ca(2+) and the magnitude of facilitation. Using fluorescence transients of a low affinity Ca(2+) indicator, we calculated the ratio of fluorescence amplitude measured immediately before test pulse (residual Ca(2+)) to that evoked during action potential (local Ca(2+)). This ratio provides an estimate of relative changes between residual Ca(2+) and local Ca(2+) important for release. There is a significant increase in the ratio when Ca(2+) influx is reduced by 40 mM [Mg(2+)](o). The magnitude of facilitation exhibited a clear and positive correlation with the ratio, regardless of separation between Ca(2+) channels and releasable vesicles. This correlation suggests the importance of relative changes between residual and local Ca(2+) and lends support to the residual Ca(2+) hypothesis of facilitation.
A postpartum separation induces c-Fos expression in the supramammillary nucleus of lactating rats.
Reproductive medicine and biology, 2009

Elucidation of the neural mechanism of maternal behaviors is a medically and biologically important research task. The rat is the laboratory animal most extensively analyzed for maternal behaviors. However, the neural mechanism that maintains the motivation of postpartum rats for maternal behaviors has not yet been elucidated. In this study, we aimed to identify brain regions involved in the maintenance of motivation for maternal behaviors by detecting brain regions that exhibit changes in nerve activity when the mother rat is separated from her pups.