rudyvdbrink/CitationDatabase huggingface dataset:
A genotyping method combining primer competition PCR with HRM analysis to identify point mutations in Duchenne animal models.
Scientific reports, 2020

Dystrophin-null sapje zebrafish is an excellent model for better understanding the pathological mechanisms underlying Duchenne muscular dystrophy, and it has recently arisen as a powerful tool for high-throughput screening of therapeutic candidates for this disease. While dystrophic phenotype in sapje larvae can be easily detected by birefringence, zebrafish genotyping is necessary for drug screening experiments, where the potential rescue of larvae phenotype is the primary outcome. Genotyping is also desirable during colony husbandry since heterozygous progenitors need to be selected. Currently, sapje zebrafish are genotyped through techniques involving sequencing or multi-step PCR, which are often costly, tedious, or require special equipment. Here we report a simple, precise, cost-effective, and versatile PCR genotyping method based on primer competition. Genotypes can be resolved by standard agarose gel electrophoresis and high-resolution melt assay, the latter being especially useful for genotyping a large number of samples. Our approach has shown high sensitivity, specificity, and reproducibility in detecting the A/T point mutation in sapje zebrafish and the C/T mutation in the mdx mouse model of Duchenne. Hence, this method can be applied to other single nucleotide substitutions and may be further optimized to detect small insertions and deletions. Given its robust performance with crude DNA extracts, our strategy may be particularly well-suited for detecting single nucleotide variants in poor-quality samples such as ancient DNA or DNA from formalin-fixed, paraffin-embedded material.
A neuro-cognitive process model of emotional intelligence.
Biological psychology, 2018

The construct of emotional intelligence (EI) broadly reflects the idea that individuals differ in their disposition/ability to adaptively generate, recognize, understand, and regulate the emotions of self and others. However, while the neural processes underlying such differences have begun to receive investigation, no brain-based model of EI has yet been proposed to help guide the design and interpretation of neuroimaging research in this area. In this article, we propose a neural model of EI to fill this need. This model incorporates recent insights from emotion theory, computational neuroscience, and large-scale network models of brain function. It also highlights several domain general processes - including those underlying conceptualization, automatic attention, habit formation, and cognitive control - that offer plausible targets for improving EI with training. Our model offers considerable promise in advancing understanding of intelligent emotional functioning and in guiding future neuroscience research on EI.
A novel case of natural killer cell deficiency associated with Joubert syndrome.
The International journal of neuroscience, 2013

Joubert syndrome (JS) is a rare, complex autosomal recessive inherited disorder mostly characterized by partial or complete agenesis of the cerebellar vermis. There is a wide clinical and genetic heterogeneity in the syndrome. The main clinical features of JS are hypotonia, ataxia, developmental delay, oculomotor apraxia, breathing abnormalities and peculiar neuroimaging findings. A lot of additional features have been reported. Here, we first reported a case of the syndrome with natural killer (NK) cell deficiency. NK cell deficiency in JS might be not an incidental phenomenon. NK cell deficiency might be associated with JS when there are additional features such as recurrent infections and tumors. NK cell deficiency may be part of the clinical spectrum of JS. Reduced cellular immunity in association with NK cell deficiency may be a feature in a subset of JS patients, especially if there is a history of recurrent infections, tumors and autoimmune disorders.
Evaluation and comparison of histologic changes and implant survival in extraction sites immediately grafted with two different xenografts: A randomized clinical pilot study.
Clinical oral implants research, 2020

The purpose of this prospective, single-center randomized pilot study was to histologically evaluate and compare vital bone development in premolar and molar-extraction sites grafted with two different bovine-derived xenografts. The secondary outcome of interest was implant survival in the grafted sites.
The fate of the unexpected: Consequences of misprediction assessed using ERP repetition effects.
Brain research, 2021

Amid increasing interest in the role of prediction in language comprehension, there remains a gap in our understanding of what happens when predictions are disconfirmed. Are unexpected words harder to process and encode because of interference from the original prediction? Or, because of their relevance for learning, do expectation violations strengthen the representations of unexpected words? In two experiments, we used event-related potentials to probe the downstream consequences of prediction violations. Critical words were unexpected but plausible completions of either strongly constraining sentences, wherein they constituted a prediction violation, or weakly constraining sentences that did not afford a clear prediction. Three sentences later the critical word was repeated at the end of a different, weakly constraining sentence. In Experiment 1, repeated words elicited a reduced N400 and an enhanced late positive complex (LPC) compared to words seen for the first time. Critically, there was no effect of initial sentence constraint on the size of the repetition effect in either time window. Thus, prediction violations did not accrue either costs or benefits for later processing. Experiment 2 used the same critical items and added strongly constraining filler sentences with expected endings to further promote prediction. Again, there was no effect of initial sentence constraint on either the N400 or the LPC to repeated critical words. When taken with prior findings, the results suggest that prediction is both powerful and flexible: It can facilitate processing of predictable information by reducing encoding effort without causing processing difficulties for unexpected inputs.
Amplitude modulations of cortical sensory responses in pulsatile evidence accumulation.
eLife, 2020

How does the brain internally represent a sequence of sensory information that jointly drives a decision-making behavior? Studies of perceptual decision-making have often assumed that sensory cortices provide noisy but otherwise veridical sensory inputs to downstream processes that accumulate and drive decisions. However, sensory processing in even the earliest sensory cortices can be systematically modified by various external and internal contexts. We recorded from neuronal populations across posterior cortex as mice performed a navigational decision-making task based on accumulating randomly timed pulses of visual evidence. Even in V1, only a small fraction of active neurons had sensory-like responses time-locked to each pulse. Here, we focus on how these 'cue-locked' neurons exhibited a variety of amplitude modulations from sensory to cognitive, notably by choice and accumulated evidence. These task-related modulations affected a large fraction of cue-locked neurons across posterior cortex, suggesting that future models of behavior should account for such influences.
The blockade of D1- and D2-like dopamine receptors within the dentate gyrus attenuates food deprivation stress-induced reinstatement of morphine-extinguished conditioned place preference in rats.
Pharmacology, biochemistry, and behavior, 2020

The high rate of relapse to drug abuse is one of the main problems in the treatment of addiction. Stress plays an essential role in relapsing to drug abuse. The present study investigates the role of D1- and D2-like dopamine receptors in the dentate gyrus (DG) of the hippocampus on the reinstatement of morphine (5 mg/kg)-induced conditioned place preference (CPP) both by food deprivation stress (FDS) and a sub-threshold dose of morphine (0.5 mg/kg, s.c.). All the animals in this study experienced pre-test, conditioning, post-test (expression), extinction, and reinstatement phases. The CPP scores of the pre-test and post-test were compared between the groups, and a significant difference between the CPP scores of the pre- and post-test was the criterion for the induction of CPP. Extinction continued for each animal until the calculated score for two consecutive days became the same as the pre-test score. The animals received different doses of SCH-23390 or Sulpiride (0.25, 1 and 4 μg/0.5 μl vehicle), as D1- and D2-like dopamine receptor antagonists, into the DG. After the administration of the antagonists, the animals were deprived of food for 24 h. Then, on the reinstatement day, they received a sub-threshold dose of morphine and afterwards, the conditioning scores were measured. The results demonstrated that the effective doses 50% of SCH-23390 and Sulpiride on the reinstatement induced by FDS and morphine was 1.37 and 2.28 (μg/0.5 μl vehicle per side), respectively. The results also showed that both antagonists can lead to a decrease in morphine reinstatement, and this effect was in a dose-dependent manner. In conclusion, these results indicate that D1- and D2-like dopamine receptors in the DG may be a potential target for preventing relapse to drugs in stressful life conditions.
Lobar microbleeds are associated with cognitive impairment in patients with lacunar infarction.
Scientific reports, 2020

Associations between cognitive decline and cerebral microbleeds (CMBs) have received increasing attention. An association between CMB distribution (deep or lobar) and cognitive decline has been reported, but these findings are controversial. We investigated the association between magnetic resonance imaging (MRI) findings, including CMBs, and cognitive function in patients with first-ever lacunar infarction. We retrospectively included consecutive patients admitted with first-ever lacunar infarction identified by MRI from July 1, 2011, to December 31, 2018. We excluded patients diagnosed with dementia, including strategic single-infarct dementia, before or after the onset of stroke. The Mini-Mental State Examination (MMSE) was performed within 3 days of admission. We searched the records of 273 patients (age 72.0 ± 11.2 years, 95 females). The median MMSE score was 27 (interquartile range 25.5-29). In a univariate analysis, the MMSE score was associated with age, body mass index (BMI), education, dyslipidemia, chronic kidney disease (CKD), periventricular hyperintensity, medial temporal atrophy, lobar CMBs, and mixed CMBs (p < 0.20). The lacunar infarction location was not associated with the MMSE score. In a multivariate analysis of these factors, lobar CMBs (p < 0.001) and mixed CMBs (p = 0.008) were independently associated with the MMSE score. Lobar CMBs were associated with cognitive impairment.
Multimodal Neurophysiological and Neuroimaging Evidence of Genetic Influence on Motor Control: A Case Report of Monozygotic Twins.
Cognitive and behavioral neurology : official journal of the Society for Behavioral and Cognitive Neurology, 2021

Considering genetic influence on brain structure and function, including motor control, we report a case of right-handed monozygotic twins with atypical organization of fine motor movement control that might imply genetic influence. Structural and functional organization of the twins' motor function was assessed using transcranial magnetic stimulation (TMS), fMRI with a motor-task paradigm, and diffusion tensor imaging (DTI) tractography. TMS revealed that both twins presented the same unexpected activation and inhibition of both motor cortices during volitional unilateral fine hand movement. The right ipsilateral corticospinal tract was weaker than the left contralateral one. The motor-task fMRI identified activation in the left primary motor cortex and bilateral secondary motor areas during right-hand (dominant) movement and activation in the bilateral primary motor cortex and secondary motor areas during left-hand movement. Based on DTI tractography, both twins showed a significantly lower streamline count (number of fibers) in the right corticospinal tract compared with a control group, which was not the case for the left corticospinal tract. Neither twin reported any difficulty in conducting fine motor movements during their activities of daily living. The combination of TMS and advanced neuroimaging techniques identified an atypical motor control organization that might be influenced by genetic factors. This combination emphasizes that activation of the unilateral uncrossed pyramidal tract represents an alternative scheme to a "failure" of building a standard pattern but may not necessarily lead to disability.
Same path, different beginnings.
Nature neuroscience, 2018

An extensive single-cell transcriptomic collection of over 30,000 cells of the developing hippocampus shows that adult hippocampal neurogenesis follows the same differentiation path as embryonic neurogenesis, but the cell of origin differs. This work provides an invaluable resource with important implications for neuronal regeneration.
The relationship between semantic access and introspective awareness.
Brain and cognition, 2018

There have long been speculations about the relationship between consciousness and language. This study aimed to determine whether an individual's level of introspective awareness, based on self-report, relates to accessibility of their semantic system as evaluated by the N400. Thirty-five university students completed the study. All were right-handed, with normal or corrected-to-normal vision, without known neurological or psychological health issues. They first performed on a lexical decision task while their brain electrophysiological responses were recorded. Then, they provided assessment ratings about their levels of introspective awareness. Analysis revealed moderate to strong correlations (Pearson's rs = 0.49-0.62) between awareness self-ratings and ease of semantic access as indexed by the N400. Correlation between the self-report measure and the objective neurophysiological measure suggests that subjective assessment of awareness may deserve more credibility, which in addition to reflecting subjective perception and evaluation about one's own higher order mental functioning, may also interact with the neurophysiological processes contributive and subject to such awareness. Implications for future research on the role of semantic network in the mechanism of introspective awareness are discussed.
Sex differences in treatment, radiological features and outcome after intracerebral haemorrhage: Pooled analysis of Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage trials 1 and 2.
European stroke journal, 2020

Reports vary on how sex influences the management and outcome from acute intracerebral haemorrhage. We aimed to quantify sex disparities in clinical characteristics, management, including response to blood pressure lowering treatment, and outcomes in patients with acute intracerebral haemorrhage, through interrogation of two large clinical trial databases.
The association between incidence and mortality of brain cancer and human development index (HDI): an ecological study.
BMC public health, 2020

Brain cancer is a rare and deadly malignancy with a low survival rate. The present study aims to evaluate the epidemiology of brain cancer and its relationship with the human development index (HDI) worldwide.
Accumulation of amyloid precursor protein C-terminal fragments triggers mitochondrial structure, function, and mitophagy defects in Alzheimer's disease models and human brains.
Acta neuropathologica, 2021

Several lines of recent evidence indicate that the amyloid precursor protein-derived C-terminal fragments (APP-CTFs) could correspond to an etiological trigger of Alzheimer's disease (AD) pathology. Altered mitochondrial homeostasis is considered an early event in AD development. However, the specific contribution of APP-CTFs to mitochondrial structure, function, and mitophagy defects remains to be established. Here, we demonstrate in neuroblastoma SH-SY5Y cells expressing either APP Swedish mutations, or the β-secretase-derived APP-CTF fragment (C99) combined with β- and γ-secretase inhibition, that APP-CTFs accumulation independently of Aβ triggers excessive mitochondrial morphology alteration (i.e., size alteration and cristae disorganization) associated with enhanced mitochondrial reactive oxygen species production. APP-CTFs accumulation also elicit basal mitophagy failure illustrated by enhanced conversion of LC3, accumulation of LC3-I and/or LC3-II, non-degradation of SQSTM1/p62, inconsistent Parkin and PINK1 recruitment to mitochondria, enhanced levels of membrane and matrix mitochondrial proteins, and deficient fusion of mitochondria with lysosomes. We confirm the contribution of APP-CTFs accumulation to morphological mitochondria alteration and impaired basal mitophagy in vivo in young 3xTgAD transgenic mice treated with γ-secretase inhibitor as well as in adeno-associated-virus-C99 injected mice. Comparison of aged 2xTgAD and 3xTgAD mice indicates that, besides APP-CTFs, an additional contribution of Aβ to late-stage mitophagy activation occurs. Importantly, we report on mitochondrial accumulation of APP-CTFs in human post-mortem sporadic AD brains correlating with mitophagy failure molecular signature. Since defective mitochondria homeostasis plays a pivotal role in AD pathogenesis, targeting mitochondrial dysfunctions and/or mitophagy by counteracting early APP-CTFs accumulation may represent relevant therapeutic interventions in AD.
Relationship between Perceived Training Load, Well-Being Indices, Recovery State and Physical Enjoyment during Judo-Specific Training.
International journal of environmental research and public health, 2020

This study investigated the relationship between well-being indices and the session rating of perceived exertion (session-RPE), recovery (TQR), and physical enjoyment (PE) during intensified, tapering phases of judo training. Sixty-one judo athletes (37 males, ranges 14-17 years, 159-172 cm, 51-67 kg) were randomly assigned to three experimental (i.e., randori, uchi-komi, running) and control groups (regular training). Experimental groups trained four times per week for 4 weeks of intensified training followed by 12 days of tapering. Session-RPE, well-being indices (i.e., sleep, stress, fatigue, delayed onset of muscle soreness (DOMS), Hooper index (HI)), and TQR were measured every session, whereas PE was recorded after intensified, tapering periods. Recovery (TQR) was negatively correlated with sleep, stress, fatigue, DOMS, HI, session-RPE in intensified period and was negatively correlated with sleep, stress, fatigue, DOMS, HI in tapering. Session-RPE was positively correlated with sleep, fatigue, DOMS, HI in intensified period and positively correlated with fatigue, DOMS in tapering. PE was negatively correlated with stress in intensified training. Enjoyment could be partially predicted by sleep only in intensified periods. Session-RPE could be partially predicted by TQR, fatigue during intensified periods and by sleep, and HI during tapering. Sleep, recovery state, pre-fatigue states, and HI are signals contributing to the enjoyment and internal intensity variability during training. Coaches can use these simple tools to monitor judo training.
5-Fluorouracil degradation rate as a predictive biomarker of toxicity in breast cancer patients treated with capecitabine.
Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners, 2020

Capecitabine is an oral prodrug of 5-fluorouracil with a relevant role in the treatment of breast cancer. Severe and unexpected toxicities related to capecitabine are not rare, and the identification of biomarkers is challenging. We evaluate the relationship between dihydropyrimidine dehydrogenase, thymidylate synthase enhancer region and methylenetetrahydrofolate reductase polymorphisms, 5-fluorouracil degradation rate and the onset of G3-4 toxicities in breast cancer patients. Genetic polymorphisms and the 5-fluorouracil degradation rate of breast cancer patients treated with capecitabine were retrospectively studied. Genetic markers and the 5-fluorouracil degradation rate were correlated with the reported toxicities. Thirty-seven patients with a median age of 58 years old treated with capecitabine for stages II-IV breast cancer were included in this study. Overall, 34 (91.9%) patients suffered from at least an episode of any grade toxicity while nine patients had G3-4 toxicity. Homozygous methylenetetrahydrofolate reductase 677TT was found to be significantly related to haematological toxicity (OR = 6.5 [95% IC 1.1-37.5], P = 0.04). Three patients had a degradation rate less than 0.86 ng/mL/106 cells/min and three patients greater than 2.1 ng/mL/106 cells/min. At a univariate logistic regression analysis, an altered value of 5-fluorouracil degradation rate (values < 0.86 or >2.10 ng/mL/106 cells/min) increased the risk of G3-4 adverse events (OR = 10.40 [95% IC: 1.48-7.99], P = 0.02). A multivariate logistic regression analysis, adjusted for age, comorbidity and CAPE-regimen, confirmed the role of 5-fluorouracil degradation rate as a predictor of G3-4 toxicity occurrence (OR = 10.9 [95% IC 1.2-96.2], P = 0.03). The pre-treatment evaluation of 5-fluorouracil degradation rate allows to identify breast cancer patients at high risk for severe 5-FU toxicity.
The role of DNA damage response in amyotrophic lateral sclerosis.
Essays in biochemistry, 2020

Amyotrophic lateral sclerosis (ALS) is a rapidly disabling and fatal neurodegenerative disease. Due to insufficient disease-modifying treatments, there is an unmet and urgent need for elucidating disease mechanisms that occur early and represent common triggers in both familial and sporadic ALS. Emerging evidence suggests that impaired DNA damage response contributes to age-related somatic accumulation of genomic instability and can trigger or accelerate ALS pathological manifestations. In this review, we summarize and discuss recent studies indicating a direct link between DNA damage response and ALS. Further mechanistic understanding of the role genomic instability is playing in ALS disease pathophysiology will be critical for discovering new therapeutic avenues.
Analyzing diffusion tensor images with ghosting artifacts: the effects of direct and indirect normalization.
Magnetic resonance imaging, 2010

The current study aims to assess the applicability of direct or indirect normalization for the analysis of fractional anisotropy (FA) maps in the context of diffusion-weighted images (DWIs) contaminated by ghosting artifacts. We found that FA maps acquired by direct normalization showed generally higher anisotropy than indirect normalization, and the disparities were aggravated by the presence of ghosting artifacts in DWIs. The voxel-wise statistical comparisons demonstrated that indirect normalization reduced the influence of artifacts and enhanced the sensitivity of detecting anisotropy differences between groups. This suggested that images contaminated with ghosting artifacts can be sensibly analyzed using indirect normalization.
Performance and Self-reported Functioning of People With Chronic Idiopathic Axonal Polyneuropathy: A 4-Year Follow-up Study.
Archives of physical medicine and rehabilitation, 2020

To describe the course of performance of activities (observed and self-reported) of people with chronic idiopathic axonal polyneuropathy (CIAP) over 4 years and to assess the associations with muscle strength, sensory function, and psychological personal factors (intention, perceived behavior control [PBC], and feelings of depression or anxiety).