rudyvdbrink/CitationDatabase huggingface dataset:
Divergent trajectories of cellular bioenergetics, intermediary metabolism and systemic redox status in survivors and non-survivors of critical illness.
Redox biology, 2021

Numerous pathologies result in multiple-organ failure, which is thought to be a direct consequence of compromised cellular bioenergetic status. Neither the nature of this phenotype nor its relevance to survival are well understood, limiting the efficacy of modern life-support.
Visual memory dysfunction as a neurocognitive endophenotype in bipolar disorder patients and their unaffected relatives. Evidence from a 5-year follow-up Valencia study.
Journal of affective disorders, 2019

Scarce research has focused on Visual Memory (VM) deficits as a possible neurocognitive endophenotype of bipolar disorder (BD). The main aim of this longitudinal, family study with healthy controls was to explore whether VM dysfunction represents a neurocognitive endophenotype of BD.
Single vesicle assaying of SNARE-synaptotagmin-driven fusion reveals fast and slow modes of both docking and fusion and intrasample heterogeneity.
Biophysical journal, 2011

Lipid mixing between vesicles functionalized with SNAREs and the cytosolic C2AB domain of synaptotagmin-1 recapitulates the basic Ca(2+) dependence of neuronal exocytosis. However, in the conventional ensemble lipid mixing assays it is not possible to discriminate whether Ca(2+) accelerates the docking or the fusion of vesicles. Here we report a fluorescence microscopy-based assay to monitor SNARE-mediated docking and fusion of individual vesicle pairs. In situ measurement of the concentration of diffusing particles allowed us to quantify docking rates by a maximum-likelihood approach. This analysis showed that C2AB and Ca(2+) accelerate vesicle-vesicle docking with more than two orders of magnitude. Comparison of the measured docking rates with ensemble lipid mixing kinetics, however, suggests that in most cases bilayer fusion remains the rate-limiting step. Our single vesicle results show that only ∼60% of the vesicles dock and only ∼6% of docked vesicles fuse. Lipid mixing on single vesicles was fast (t(mix) < 1 s) while an ensemble assay revealed two slow mixing processes with t(mix) ∼ 1 min and t(mix) ∼ 20 min. The presence of several distinct docking and fusion pathways cannot be rationalized at this stage but may be related to intrasample heterogeneities, presumably in the form of lipid and/or protein composition.
Bedroom light exposure at night and obesity in individuals with bipolar disorder: A cross-sectional analysis of the APPLE cohort.
Physiology & behavior, 2021

Obesity and overweight are highly prevalent in individuals with bipolar disorder and are associated with a risk of developing not only physical but also mental problems. The current study aimed to determine the association between bedroom light exposure at night and obesity in individuals with bipolar disorder. This cross-sectional study enrolled 200 outpatients with bipolar disorder. The light intensity in the bedroom between bedtime and rising time was measured for seven consecutive nights using a portable photometer. Body mass index (BMI) was determined using self-reported height and weight, and obesity was defined as a BMI ≥ 25 kg/m
Effectiveness of a Community-Based Intervention to Increase Supermarket Vendors' Compliance with Age Restrictions for Alcohol Sales in Spain: A Pilot Study.
International journal of environmental research and public health, 2020

In Spain the legal age to buy alcohol is 18 years. However, official surveys show that minors perceive alcohol availability to be easy. This paper describes the impacts of a community-based intervention to increase vendors' compliance with age limits regarding alcohol sales in supermarkets. The aim of this study was to explore the association between implementation of a multicomponent intervention to reduce adolescents' alcohol use and sale of alcohol to minors in the city of Palma (Spain). Twenty trained adolescents (14-17 years old) conducted 138 alcohol test purchases in nine supermarket chains in August 2018 (baseline;
Massive accumulation of luminal protease-deficient axonal lysosomes at Alzheimer's disease amyloid plaques.
Proceedings of the National Academy of Sciences of the United States of America, 2015

Through a comprehensive analysis of organellar markers in mouse models of Alzheimer's disease, we document a massive accumulation of lysosome-like organelles at amyloid plaques and establish that the majority of these organelles reside within swollen axons that contact the amyloid deposits. This close spatial relationship between axonal lysosome accumulation and extracellular amyloid aggregates was observed from the earliest stages of β-amyloid deposition. Notably, we discovered that lysosomes that accumulate in such axons are lacking in multiple soluble luminal proteases and thus are predicted to be unable to efficiently degrade proteinaceous cargos. Of relevance to Alzheimer's disease, β-secretase (BACE1), the protein that initiates amyloidogenic processing of the amyloid precursor protein and which is a substrate for these proteases, builds up at these sites. Furthermore, through a comparison between the axonal lysosome accumulations at amyloid plaques and neuronal lysosomes of the wild-type brain, we identified a similar, naturally occurring population of lysosome-like organelles in neuronal processes that is also defined by its low luminal protease content. In conjunction with emerging evidence that the lysosomal maturation of endosomes and autophagosomes is coupled to their retrograde transport, our results suggest that extracellular β-amyloid deposits cause a local impairment in the retrograde axonal transport of lysosome precursors, leading to their accumulation and a blockade in their further maturation. This study both advances understanding of Alzheimer's disease brain pathology and provides new insights into the subcellular organization of neuronal lysosomes that may have broader relevance to other neurodegenerative diseases with a lysosomal component to their pathology.
Similarities between borderline personality disorder and post traumatic stress disorder: Evidence from resting-state meta-analysis.
Neuroscience and biobehavioral reviews, 2019

Borderline personality disorder (BPD) and post-traumatic stress disorder (PTSD) are common psychiatric disorders. The nature of the relationship between BPD and PTSD remains controversial, but it has been suggested that these disorders should brought closer because of their many similarities. We thus performed a quantitative meta-analysis of resting-state functional imaging to assess similarities in the brain activation across BPD and PTSD diagnostic groups. Overlap analyses revealed decreased activation in the left and right precuneus of both BPD and PTSD groups when compared to control subjects. BPD showed significant increased, but PTSD showed decreased activation, relative to control subjects, in the anterior cingulate/paracingulate gyri and in the left superior frontal gyrus. Complementary overlap analyses on a subgroup of studies with similar sex and age distribution partially confirmed the main results as the same pattern of functional activation in the anterior cingulate and in the left superior frontal gyrus were found. Our findings are in agreement with the hypothesis that BPD and PTSD share common neuropathological pathways.
Subject-specific multi-poroelastic model for exploring the risk factors associated with the early stages of Alzheimer's disease.
Interface focus, 2018

There is emerging evidence suggesting that Alzheimer's disease is a vascular disorder, caused by impaired cerebral perfusion, which may be promoted by cardiovascular risk factors that are strongly influenced by lifestyle. In order to develop an understanding of the exact nature of such a hypothesis, a biomechanical understanding of the influence of lifestyle factors is pursued. An extended poroelastic model of perfused parenchymal tissue coupled with separate workflows concerning subject-specific meshes, permeability tensor maps and cerebral blood flow variability is used. The subject-specific datasets used in the modelling of this paper were collected as part of prospective data collection. Two cases were simulated involving male, non-smokers (control and mild cognitive impairment (MCI) case) during two states of activity (high and low). Results showed a marginally reduced clearance of cerebrospinal fluid (CSF)/interstitial fluid (ISF), elevated parenchymal tissue displacement and CSF/ISF accumulation and drainage in the MCI case. The peak perfusion remained at 8 mm s
The role of post-translational modifications in hearing and deafness.
Cellular and molecular life sciences : CMLS, 2016

Post-translational modifications (PTMs) are key molecular events that modify proteins after their synthesis and modulate their ultimate functional properties by affecting their stability, localisation, interaction potential or activity. These chemical changes expand the size of the proteome adding diversity to the molecular pathways governing the biological outcome of cells. PTMs are, thus, crucial in regulating a variety of cellular processes such as apoptosis, proliferation and differentiation and have been shown to be instrumental during embryonic development. In addition, alterations in protein PTMs have been implicated in the pathogenesis of many human diseases, including deafness. In this review, we summarize the recent progress made in understanding the roles of PTMs during cochlear development, with particular emphasis on the enzymes driving protein phosphorylation, acetylation, methylation, glycosylation, ubiquitination and SUMOylation. We also discuss how these enzymes may contribute to hearing impairment and deafness.
Effects of negative emotion on neural correlates of item and source memory during encoding and retrieval.
Brain research, 2019

The enhancing effect of emotion on item memory is well-established, but emotion's influence on source memory has proven more elusive. Previous studies recording event-related potentials (ERPs) associated with memory encoding (Dms) and retrieval (old/new effects) showed an emotional enhancement of ERPs related to item memory, whereas ERPs related to source memory yielded contradictory results in the presence of emotion. The present study examined the influence of item emotionality on the neural correlates of memory encoding and retrieval for items and temporal source details. Participants studied negative and neutral pictures in two temporally distinct blocks and, 24 h later, were asked to recognize the studied pictures and the blocks in which they appeared. Our results showed that negative items were more often remembered, with or without source information, than neutral images. This finding of an overall memory advantage for negative images was confirmed by the Dm effects, which demonstrated significant and indistinguishable Dms for negative images remembered with or without source. Overall, Dm effects were greater for negative as compared to neutral images. In contrast to the behavioral and Dm results, an emotional enhancement of the source-related old/new effect was seen over the left hemisphere, suggesting that only negative (and not neutral) images retrieved with correct source were accompanied by memory for additional details. These results suggest that retrieval of temporal source information is not enhanced for negative images but that item emotionality could lead to an enhancement for the retrieval of additional details, contingent on retrieval of temporal source information.
Contrasting temporal difference and opportunity cost reinforcement learning in an empirical money-emergence paradigm.
Proceedings of the National Academy of Sciences of the United States of America, 2018

Money is a fundamental and ubiquitous institution in modern economies. However, the question of its emergence remains a central one for economists. The monetary search-theoretic approach studies the conditions under which commodity money emerges as a solution to override frictions inherent to interindividual exchanges in a decentralized economy. Although among these conditions, agents' rationality is classically essential and a prerequisite to any theoretical monetary equilibrium, human subjects often fail to adopt optimal strategies in tasks implementing a search-theoretic paradigm when these strategies are speculative, i.e., involve the use of a costly medium of exchange to increase the probability of subsequent and successful trades. In the present work, we hypothesize that implementing such speculative behaviors relies on reinforcement learning instead of lifetime utility calculations, as supposed by classical economic theory. To test this hypothesis, we operationalized the Kiyotaki and Wright paradigm of money emergence in a multistep exchange task and fitted behavioral data regarding human subjects performing this task with two reinforcement learning models. Each of them implements a distinct cognitive hypothesis regarding the weight of future or counterfactual rewards in current decisions. We found that both models outperformed theoretical predictions about subjects' behaviors regarding the implementation of speculative strategies and that the latter relies on the degree of the opportunity costs consideration in the learning process. Speculating about the marketability advantage of money thus seems to depend on mental simulations of counterfactual events that agents are performing in exchange situations.
Harnessing the wisdom of crowds can improve guideline compliance of antibiotic prescribers and support antimicrobial stewardship.
Scientific reports, 2020

Antibiotic overprescribing is a global challenge contributing to rising levels of antibiotic resistance and mortality. We test a novel approach to antibiotic stewardship. Capitalising on the concept of "wisdom of crowds", which states that a group's collective judgement often outperforms the average individual, we test whether pooling treatment durations recommended by different prescribers can improve antibiotic prescribing. Using international survey data from 787 expert antibiotic prescribers, we run computer simulations to test the performance of the wisdom of crowds by comparing three data aggregation rules across different clinical cases and group sizes. We also identify patterns of prescribing bias in recommendations about antibiotic treatment durations to quantify current levels of overprescribing. Our results suggest that pooling the treatment recommendations (using the median) could improve guideline compliance in groups of three or more prescribers. Implications for antibiotic stewardship and the general improvement of medical decision making are discussed. Clinical applicability is likely to be greatest in the context of hospital ward rounds and larger, multidisciplinary team meetings, where complex patient cases are discussed and existing guidelines provide limited guidance.
Icariin exerts an antidepressant effect in an unpredictable chronic mild stress model of depression in rats and is associated with the regulation of hippocampal neuroinflammation.
Neuroscience, 2015

Icariin (ICA), a flavonoid extracted from the traditional Chinese herb Herba Epimedii that can freely cross the blood-brain barrier, inhibits neuroinflammation and attenuates oxidative stress damage. Our previous studies demonstrated that icariin exerts an antidepressant-like activity in a social defeat mouse model. However, it is unknown whether icariin is beneficial for the treatment of depression via its modulation of oxidative stress and neuroinflammation. The objective of this study was to investigate the effects of icariin on the depression-like behaviors in an unpredictable chronic mild stress (CMS) model of depression in rats. Rats exposed to CMS showed behavioral deficits in physical state, the sucrose preference test (SPT) and the forced swimming test (FST) and exhibited a significant increase in oxidative-nitrosative stress markers, inflammatory mediators, including tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β), activation of the nuclear factor kappa B (NF-κB) signaling pathway and increased inducible nitric oxide synthase (iNOS) mRNA expression in the hippocampus, which was reversed by chronic treatment with icariin (20 or 40 mg/kg). Interestingly, icariin negatively regulated the activation of the nod-like receptor protein 3 (NLRP3) inflammasome/caspase-1/IL-1β axis in the hippocampus of CMS rats. These results confirm that icariin exerts antidepressant-like effects, which may be mediated, at least in part, by enhanced antioxidant status and anti-inflammatory effects on the brain tissue via the inhibition of NF-κB signaling activation and the NLRP3-inflammasome/caspase-1/IL-1β axis. Our findings provide new information to understand the antidepressant action of icariin, which is targeted to the NLRP3-inflammasom in brain.
Hindbrain estrogen receptor-beta antagonism normalizes reproductive and counter-regulatory hormone secretion in hypoglycemic steroid-primed ovariectomized female rats.
Neuroscience, 2016

Hindbrain dorsal vagal complex A2 noradrenergic signaling represses the pre-ovulatory luteinizing hormone (LH) surge in response to energy deficiency. Insulin-induced hypoglycemia augments A2 neuron adenosine 5'-monophosphate-activated protein kinase (AMPK) activity and estrogen receptor-beta (ERβ) expression, coincident with LH surge suppression. We hypothesized that ERβ is critical for hypoglycemia-associated patterns of LH secretion and norepinephrine (NE) activity in key reproduction-relevant forebrain structures. The neural mechanisms responsible for tight coupling of systemic energy balance and procreation remain unclear; here, we investigated whether ERβ-dependent hindbrain signals also control glucose counter-regulatory responses to hypoglycemia. Gonadal steroid-primed ovariectomized female rats were pretreated by caudal fourth ventricular administration of the ERβ antagonist 4-[2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl]phenol (PHTPP) or vehicle before insulin injection at LH surge onset. Western blot analysis of laser-microdissected A2 neurons revealed hypoglycemic intensification of AMPK activity and dopamine-β-hydroxylase protein expression; the latter response was attenuated by PHTPP pretreatment. PHTPP regularized LH release, but not preoptic GnRH-I precursor protein expression in insulin-injected rats, and reversed hypoglycemic stimulation of glucagon and corticosterone secretion. Hypoglycemia caused PHTPP-reversible changes in NE and prepro-kisspeptin protein content in the hypothalamic arcuate (ARH), but not anteroventral periventricular nucleus. Results provide novel evidence for ERβ-dependent caudal hindbrain regulation of LH and counter-regulatory hormone secretion during hypoglycemia. Observed inhibition of LH likely involves mechanisms at the axon terminal that impede GnRH neurotransmission. Data also show that caudal hindbrain ERβ exerts site-specific control of NE activity in forebrain projection sites during hypoglycemia, including the ARH where prepro-kisspeptin may be a target of that signaling.
A new genetic locus for antipsychotic-induced weight gain: A genome-wide study of first-episode psychosis patients using amisulpride (from the OPTiMiSE cohort).
Journal of psychopharmacology (Oxford, England), 2020

Antipsychotic-induced weight gain is a common and debilitating side effect of antipsychotics. Although genome-wide association studies of antipsychotic-induced weight gain have been performed, few genome-wide loci have been discovered. Moreover, these genome-wide association studies have included a wide variety of antipsychotic compounds.
Computer work duration and its dependence on the used pause definition.
Applied ergonomics, 2008

Several ergonomic studies have estimated computer work duration using registration software. In these studies, an arbitrary pause definition (Pd; the minimal time between two computer events to constitute a pause) is chosen and the resulting duration of computer work is estimated. In order to uncover the relationship between the used pause definition and the computer work duration (PWT), we used registration software to record usage patterns of 571 computer users across almost 60,000 working days. For a large range of Pds (1-120 s), we found a shallow, log-linear relationship between PWT and Pds. For keyboard and mouse use, a second-order function fitted the data best. We found that these relationships were dependent on the amount of computer work and subject characteristics. Comparison of exposure duration from studies using different pause definitions should take this into account, since it could lead to misclassification. Software manufacturers and ergonomists assessing computer work duration could use the found relationships for software design and study comparison.
Association of HLA locus variant in Parkinson's disease.
Clinical genetics, 2013

A variant (rs3129882) in the genome-wide association study (GWAS)-linked variant [in the human leukocyte antigen (HLA) gene region] has been reported to associate with an increased risk of Parkinson's disease (PD) in Caucasian population. Studies among Chinese are limited. To address this, we analysed rs3129882 in a total of 1312 subjects of Chinese ethnicity from independent Asian centers comprising of 675 controls and 637 PD cases. The rs3129882 variant was associated with a decreased risk in our ethnic Chinese PD patients. Logistic regression analysis taking into consideration variables of age, gender and race showed that allele A reduced the risk of PD via a dominant model [odds ratio (OR) = 0.77, 95% confidence interval (CI) = 0.62, 0.96, p = 0.018]. As HLA is a highly polymorphic region, it is possible that ethnic-specific effect or environmental agents may modulate the effect of this GWAS-linked locus in influencing the risk of PD.
Clinical predictors of functional outcome of bipolar patients in remission.
Bipolar disorders, 2009

A number of studies have now shown that subjects with bipolar disorder (BD) have significant psychosocial impairment during interepisode intervals. This study was carried out to assess the level of functioning as well as to identify potential predictors of functioning in a well-defined, euthymic bipolar sample.
Four basic residues critical for the ion selectivity and pore blocker sensitivity of TMEM16A calcium-activated chloride channels.
Proceedings of the National Academy of Sciences of the United States of America, 2015

TMEM16A (transmembrane protein 16) (Anoctamin-1) forms a calcium-activated chloride channel (CaCC) that regulates a broad array of physiological properties in response to changes in intracellular calcium concentration. Although known to conduct anions according to the Eisenman type I selectivity sequence, the structural determinants of TMEM16A anion selectivity are not well-understood. Reasoning that the positive charges on basic residues are likely contributors to anion selectivity, we performed whole-cell recordings of mutants with alanine substitution for basic residues within the putative pore region and identified four residues on four different putative transmembrane segments that significantly increased the permeability of the larger halides and thiocyanate relative to that of chloride. Because TMEM16A permeation properties are known to shift with changes in intracellular calcium concentration, we further examined the calcium dependence of anion selectivity. We found that WT TMEM16A but not mutants with alanine substitution at those four basic residues exhibited a clear decline in the preference for larger anions as intracellular calcium was increased. Having implicated these residues as contributing to the TMEM16A pore, we scrutinized candidate small molecules from a high-throughput CaCC inhibitor screen to identify two compounds that act as pore blockers. Mutations of those four putative pore-lining basic residues significantly altered the IC50 of these compounds at positive voltages. These findings contribute to our understanding regarding anion permeation of TMEM16A CaCC and provide valuable pharmacological tools to probe the channel pore.