rudyvdbrink/CitationDatabase huggingface dataset:
Phantom limbs: pain, embodiment, and scientific advances in integrative therapies.
Wiley interdisciplinary reviews. Cognitive science, 2014

Research over the past two decades has begun to identify some of the key mechanisms underlying phantom limb pain and sensations; however, this continues to be a clinically challenging condition to manage. Treatment of phantom pain, like all chronic pain conditions, demands a holistic approach that takes into consideration peripheral, spinal, and central neuroplastic mechanisms. In this review, we focus on nonpharmacological treatments tailored to reverse the maladaptive neuroplasticity associated with phantom pain. Recent scientific advances emerging from interdisciplinary research between neuroscience, virtual reality, robotics, and prosthetics show the greatest promise for alternative embodiment and maintaining the integrity of the multifaceted representation of the body in the brain. Importantly, these advances have been found to prevent and reduce phantom limb pain. In particular, therapies that involve sensory and/or motor retraining, most naturally through the use of integrative prosthetic devices, as well as peripheral (e.g., transcutaneous electrical nerve stimulation) or central (e.g., transcranial magnetic stimulation or deep brain stimulation) stimulation techniques, have been found to both restore the neural representation of the missing limb and to reduce the intensity of phantom pain. While the evidence for the efficacy of these therapies is mounting, but well-controlled and large-scale studies are still needed. WIREs Cogn Sci 2014, 5:221-231. doi: 10.1002/wcs.1277 CONFLICT OF INTEREST: The authors have no financial or other relationship that might lead to a conflict of interest. For further resources related to this article, please visit the WIREs website.
Temporary Versus Permanent Synaptic Loss from Repeated Noise Exposure in Guinea Pigs and C57 Mice.
Neuroscience, 2020

A single brief noise exposure can cause a significant loss of cochlear afferent synapses without causing permanent threshold shift. Previously we reported that the initial synaptic loss is partially reversible in Guinea pigs, indicating that synaptic loss can be categorized as either temporary or permanent. Since synaptic loss is biased to innervating auditory nerve fibers (ANFs) with low spontaneous spike rates (SSR), which are critical to the coding of in-background noise, coding-in-noise deficits (CIND) have been predicted to result from noise-induced synaptic damage. However, recent study of the noise masking of amplitude-modulation (AM) evoked compound action potentials (CAP) tailed to find evidence for such deficits in either mice or Guinea pigs. The present study sought to determine the effects of repeated noise exposure on temporary and permanent synaptic loss in Guinea pigs and C57 mice, whether such effects were additive, and whether repeated noise exposure induced CIND in Guinea pigs. The results show that the second noise exposure caused much less temporary synaptic loss and no additional permanent loss in Guinea pigs; however, an additional permanent loss was seen after the second noise was in the mice, although it was not significant. In Guinea pigs, the observed increased masking of the AM CAP provides evidence for CIND after repeated noise exposure.
Application of an Adaptive, Digital, Game-Based Approach for Cognitive Assessment in Multiple Sclerosis: Observational Study.
Journal of medical Internet research, 2021

Cognitive impairment is one of the most debilitating manifestations of multiple sclerosis. Currently, the assessment of cognition relies on a time-consuming and extensive neuropsychological examination, which is only available in some centers.
Information and communication technology for increasing healthy ageing in people with non-communicable diseases: identifying challenges and further areas for development.
Aging clinical and experimental research, 2019

Information and communication technology (ICT) within healthcare covers a range of technologies that aim to improve disease management or help modify health behaviors. We discuss clinical practice and system-related ICT challenges in Europe in relation to healthy ageing in people with non-communicable diseases (NCD). Although ICT use within healthcare is increasing, several challenges remain, including: (i) variations in ICT use within Europe; (ii) under-use of electronic health records; (iii) frequent use of single domain outcomes; (iv) shortage of clinical trials on current technologies; (v) lack of involvement of patients in ICT development; (vii) need to develop and adapt ICTs for people with cognitive or sensory impairment; and (viii) need to use longitudinal big data better. Close collaboration between key stakeholders (academia, biopharmaceutical and technology industries, healthcare, policy makers, patients, and caregivers) should foster both technological innovation and innovative models to facilitate more cost-effective approaches, ultimately leading to increased healthy ageing.
Resilience, lifestyle and symptoms of anxiety and depression in adolescence: the Young-HUNT study.
Social psychiatry and psychiatric epidemiology, 2013

This study investigated the symptoms of anxiety and depression in adolescence, their associations with lifestyle and resilience and the possibility that resilience factors can attenuate the associations between unhealthy lifestyle and symptoms of anxiety and depression.
Emerging promise of sulforaphane-mediated Nrf2 signaling cascade against neurological disorders.
The Science of the total environment, 2020

Neurological disorders represent a great challenge and are the leading cause of death and disability globally. Although numerous complicated mechanisms are involved in the progressions of chronic and acute neurodegenerative disorders, most of the diseases share mutual pathogenic features such as oxidative stress, mitochondrial dysfunction, neuroinflammation, protein misfolding, excitotoxicity, and neuronal damage, all of these are the common targets of nuclear factor erythroid 2 related factor 2 (Nrf2) signaling cascade. No cure has yet been discovered to tackle these disorders, so, intervention approaches targeting phytochemicals have been recommended as an alternative form of treatment. Sulforaphane is a sulfur-rich dietary phytochemical which has several activities such as antioxidant, anti-inflammatory, and anti-tumor via multiple targets and various mechanisms. Given its numerous actions, sulforaphane has drawn considerable attention for neurological disorders in recent years. Nrf2 is one of the most crucial targets of sulforaphane which has potential in regulating the series of cytoprotective enzyme expressions that have neuroprotective, antioxidative, and detoxification actions. Neurological disorders are auspicious candidates for Nrf2-targeted treatment strategy. Sulforaphane protects various neurological disorders by regulating the Nrf2 pathway. In this article, we recapitulate current studies of sulforaphane-mediated Nrf2 activation in the treatment of various neurological disorders.
Lack of parvalbumin in mice leads to behavioral deficits relevant to all human autism core symptoms and related neural morphofunctional abnormalities.
Translational psychiatry, 2015

Gene mutations and gene copy number variants are associated with autism spectrum disorders (ASDs). Affected gene products are often part of signaling networks implicated in synapse formation and/or function leading to alterations in the excitation/inhibition (E/I) balance. Although the network of parvalbumin (PV)-expressing interneurons has gained particular attention in ASD, little is known on PV's putative role with respect to ASD. Genetic mouse models represent powerful translational tools for studying the role of genetic and neurobiological factors underlying ASD. Here, we report that PV knockout mice (PV(-/-)) display behavioral phenotypes with relevance to all three core symptoms present in human ASD patients: abnormal reciprocal social interactions, impairments in communication and repetitive and stereotyped patterns of behavior. PV-depleted mice also showed several signs of ASD-associated comorbidities, such as reduced pain sensitivity and startle responses yet increased seizure susceptibility, whereas no evidence for behavioral phenotypes with relevance to anxiety, depression and schizophrenia was obtained. Reduced social interactions and communication were also observed in heterozygous (PV(+/-)) mice characterized by lower PV expression levels, indicating that merely a decrease in PV levels might be sufficient to elicit core ASD-like deficits. Structural magnetic resonance imaging measurements in PV(-/-) and PV(+/-) mice further revealed ASD-associated developmental neuroanatomical changes, including transient cortical hypertrophy and cerebellar hypoplasia. Electrophysiological experiments finally demonstrated that the E/I balance in these mice is altered by modification of both inhibitory and excitatory synaptic transmission. On the basis of the reported changes in PV expression patterns in several, mostly genetic rodent models of ASD, we propose that in these models downregulation of PV might represent one of the points of convergence, thus providing a common link between apparently unrelated ASD-associated synapse structure/function phenotypes.
Regular cannabis use is associated with altered activation of central executive and default mode networks even after prolonged abstinence in adolescent users: Results from a complementary meta-analysis.
Neuroscience and biobehavioral reviews, 2019

Whether the effects of cannabis use on brain function persist or recover following abstinence remains unclear. Therefore, using meta-analytic techniques, we examined whether functional alterations measured using fMRI persist in cannabis users abstinent for over 25 days (or 600 h) as evidence suggests that the effects on cognitive performance no longer persist beyond this period. Systematic literature search identified 20 studies, of which, 12 examined current cannabis users (CCU) (361 CCU versus 394 non-cannabis using controls (NU)) and 3 examined abstinent cannabis users (ACU) in 5 separate comparisons (98 ACU versus 106 NU). Studies in ACU were carried out in adolescents and suggest significantly greater activation in components of the central executive and default mode networks in adolescent ACU compared to NU. While this evidence is to be interpreted with caution because studies were carried out in overlapping samples, they indicate a pressing need for independent confirmation whether certain neurofunctional alterations in adolescent cannabis users may persist even after cannabis and its metabolites are likely to have left their bodies.
Systematic Review on Intensive Interdisciplinary Pain Treatment of Children With Chronic Pain.
Pediatrics, 2015

Pediatric debilitating chronic pain is a severe health problem, often requiring complex interventions such as intensive interdisciplinary pain treatment (IIPT). Research is lacking regarding the effectiveness of IIPT for children. The objective was to systematically review studies evaluating the effects of IIPT.
Leveraging real-world data to investigate multiple sclerosis disease behavior, prognosis, and treatment.
Multiple sclerosis (Houndmills, Basingstoke, England), 2020

Randomized controlled clinical trials and real-world observational studies provide complementary information but with different validity. Some clinical questions (disease behavior, prognosis, validation of outcome measures, comparative effectiveness, and long-term safety of therapies) are often better addressed using real-world data reflecting larger, more representative populations. Integration of disease history, clinician-reported outcomes, performance tests, and patient-reported outcome measures during patient encounters; imaging and biospecimen analyses; and data from wearable devices increase dataset utility. However, observational studies utilizing these data are susceptible to many potential sources of bias, creating barriers to acceptance by regulatory agencies and the medical community. Therefore, data standardization and validation within datasets, harmonization across datasets, and application of appropriate analysis methods are important considerations. We review approaches to improve the scope, quality, and analyses of real-world data to advance understanding of multiple sclerosis and its treatment, as an example of opportunities to better support patient care and research.
Client and program factors associated with dropout from court mandated drug treatment.
Evaluation and program planning, 2009

To examine why court mandated offenders dropout of drug treatment and to compare their characteristics, treatment experiences, perceptions, and outcomes with treatment completers, we analyzed self-reported and administrative data on 542 dropouts (59%) and 384 completers (41%) assessed for Proposition 36 treatment by thirty sites in five California counties during 2004. At intake, dropouts had lengthier criminal histories, lower treatment motivation, more severe employment and psychiatric problems, and more were using drugs, especially heroin. Relatively fewer dropouts received residential treatment and their retention was much shorter. A similar proportion of dropouts received services as completers and the mean number of services received per day by dropouts was generally more, especially to address psychiatric problems, during the first three months of treatment. The most commonly offender-reported reasons for dropout included low treatment motivation (46.2%) and the difficulty of the Proposition 36 program (20.0%). Consequences for dropout included incarceration (25.3%) and permission to try treatment again (24.0%). Several factors predicting drug treatment dropout were identified. Both groups demonstrated improved functioning at one-year follow-up, but fewer dropouts had a successful outcome (34.5% vs. 59.1%) and their recidivism rate was significantly higher (62.9% vs. 28.9%) even after controlling for baseline differences. Understanding factors associated with drug treatment dropout can aid efforts to improve completion rates, outcomes, and overall effectiveness of California's Proposition 36 program. Findings may also aid a broader audience of researchers and policy analysts who are charged with designing and evaluating criminal-justice diversion programs for treating drug-addicted offenders.
Bile acid disease: the emerging epidemic.
Current opinion in gastroenterology, 2017

Our objective was to review advances in bile acids in health and disease published in the last 2 years. Bile acid diarrhea (BAD) is recognized as a common cause of chronic diarrhea, and its recognition has been facilitated by development of new screening tests.
The Cortical Neuroimmune Regulator TANK Affects Emotional Processing and Enhances Alcohol Drinking: A Translational Study.
Cerebral cortex (New York, N.Y. : 1991), 2019

Alcohol abuse is a major public health problem worldwide. Understanding the molecular mechanisms that control regular drinking may help to reduce hazards of alcohol consumption. While immunological mechanisms have been related to alcohol drinking, most studies reported changes in immune function that are secondary to alcohol use. In this report, we analyse how the gene "TRAF family member-associated NF-κB activator" (TANK) affects alcohol drinking behavior. Based on our recent discovery in a large GWAS dataset that suggested an association of TANK, SNP rs197273, with alcohol drinking, we report that SNP rs197273 in TANK is associated both with gene expression (P = 1.16 × 10-19) and regional methylation (P = 5.90 × 10-25). A tank knock out mouse model suggests a role of TANK in alcohol drinking, anxiety-related behavior, as well as alcohol exposure induced activation of insular cortex NF-κB. Functional and structural neuroimaging studies among up to 1896 adolescents reveal that TANK is involved in the control of brain activity in areas of aversive interoceptive processing, including the insular cortex, but not in areas related to reinforcement, reward processing or impulsiveness. Our findings suggest that the cortical neuroimmune regulator TANK is associated with enhanced aversive emotional processing that better protects from the establishment of alcohol drinking behavior.
Retina-Targeted Delivery of 17β-Estradiol by the Topically Applied DHED Prodrug.
Pharmaceutics, 2020

The purpose of this study was to explore retina-targeted delivery of 17β-estradiol (E2), a powerful neuroprotectant, by its bioprecursor prodrug 10β,17β-dihydroxyestra-1,4-dien-3-one (DHED) administered as eye drops in animal models. Compared to the parent hormone, DHED displayed increased transcorneal flux ex vivo both with and without the presence of 2-hydroxypropyl-β-cyclodextrin used as a penetration-enhancing excipient in rat, rabbit, and pig. In vitro, the prodrug also showed facile bioactivation to E2 in the retina but not in the cornea. After topical administration to rats and rabbits, peak DHED-derived E2 concentrations reached 13 ± 5 ng/g and 18 ± 7 ng/g in the retina of female rats and rabbits, respectively. However, the prodrug remained inert in the rest of the body and, therefore, did not cause increase in circulating hormone concentration, as well as wet uterine and anterior pituitary weights as typical markers of E2's endocrine impact. Altogether, our studies presented here have demonstrated the premise of topical retina-selective estrogen therapy by the DHED prodrug approach for the first time and provide compelling support for further investigation into the full potential of DHED for an efficacious and safe ocular neurotherapy.
Relative sensitivity of magnetic resonance spectroscopy and quantitative magnetic resonance imaging to cognitive function among nondemented individuals infected with HIV.
Journal of the International Neuropsychological Society : JINS, 2008

In the present study, we examined the relationships among cognitive function, magnetic resonance spectroscopy (MRS) brain metabolite indices measured in the basal ganglia, and quantitative magnetic resonance imaging (MRI) of the caudate nucleus and the putamen in the earliest stages of HIV-related cognitive involvement. Participants included 22 HIV-positive individuals and 20 HIV-negative individuals. HIV-positive individuals performed significantly more poorly than the HIV-negative individuals on several cognitive measures. In addition, the choline/creatine ratio was significantly higher and the N-acetyl aspartate/choline ratio was significantly lower among HIV patients. The caudate and putamen sizes were smaller among HIV-positive patients compared with controls; however, the differences did not reach statistical significance. Correlation analyses revealed associations between cognitive function and select MRS indices. In addition, caudate size was significantly correlated with performances on higher-order thinking tests whereas putamen size was significantly correlated with performances on motor tests. The results suggest that MRS differences are more pronounced than area size differences between seropositive and seronegative individuals in mild stages of HIV-related cognitive impairment. However, basal ganglia size remains an important contributor to cognitive status in this population. Longitudinal studies are needed to determine the evolution of these imaging correlates of HIV-cognitive impairment in HIV.
Genome-wide association study of Alzheimer's disease CSF biomarkers in the EMIF-AD Multimodal Biomarker Discovery dataset.
Translational psychiatry, 2020

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder and the most common form of dementia in the elderly. Susceptibility to AD is considerably determined by genetic factors which hitherto were primarily identified using case-control designs. Elucidating the genetic architecture of additional AD-related phenotypic traits, ideally those linked to the underlying disease process, holds great promise in gaining deeper insights into the genetic basis of AD and in developing better clinical prediction models. To this end, we generated genome-wide single-nucleotide polymorphism (SNP) genotyping data in 931 participants of the European Medical Information Framework Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD) sample to search for novel genetic determinants of AD biomarker variability. Specifically, we performed genome-wide association study (GWAS) analyses on 16 traits, including 14 measures derived from quantifications of five separate amyloid-beta (Aβ) and tau-protein species in the cerebrospinal fluid (CSF). In addition to confirming the well-established effects of apolipoprotein E (APOE) on diagnostic outcome and phenotypes related to Aβ42, we detected novel potential signals in the zinc finger homeobox 3 (ZFHX3) for CSF-Aβ38 and CSF-Aβ40 levels, and confirmed the previously described sex-specific association between SNPs in geminin coiled-coil domain containing (GMNC) and CSF-tau. Utilizing the results from independent case-control AD GWAS to construct polygenic risk scores (PRS) revealed that AD risk variants only explain a small fraction of CSF biomarker variability. In conclusion, our study represents a detailed first account of GWAS analyses on CSF-Aβ and -tau-related traits in the EMIF-AD MBD dataset. In subsequent work, we will utilize the genomics data generated here in GWAS of other AD-relevant clinical outcomes ascertained in this unique dataset.
Antioxidant micronutrient supplementation in critically ill adults: A systematic review with meta-analysis and trial sequential analysis.
Clinical nutrition (Edinburgh, Scotland), 2021

The role of antioxidant micronutrient (AxM) supplementation in the critically ill patients has been controversial, and recent trials have suggested a tendency to harm. Therefore, we performed a systematic review with meta-analysis and trial sequential analysis (TSA) of randomized controlled trials (RCT) to examine the effect of AxM supplementation on clinical outcomes among critically ill adults.
Cognitive Control of Working Memory: A Model-Based Approach.
Brain sciences, 2021

Working memory (WM)-based decision making depends on a number of cognitive control processes that control the flow of information into and out of WM and ensure that only relevant information is held active in WM's limited-capacity store. Although necessary for successful decision making, recent work has shown that these control processes impose performance costs on both the speed and accuracy of WM-based decisions. Using the reference-back task as a benchmark measure of WM control, we conducted evidence accumulation modeling to test several competing explanations for six benchmark empirical performance costs. Costs were driven by a combination of processes, running outside of the decision stage (longer non-decision time) and showing the inhibition of the prepotent response (lower drift rates) in trials requiring WM control. Individuals also set more cautious response thresholds when expecting to update WM with new information versus maintain existing information. We discuss the promise of this approach for understanding cognitive control in WM-based decision making.