rudyvdbrink/CitationDatabase huggingface dataset:
Considerations underlying the use of mixed group validation.
Psychological assessment, 2013

Mixed Group Validation (MGV) is an approach for estimating the diagnostic accuracy of tests. MGV is a promising alternative to the more commonly used Known Groups Validation (KGV) approach for estimating diagnostic accuracy. The advantage of MGV lies in the fact that the approach does not require a perfect external validity criterion or gold standard. However, the research designs where MGV is most appropriate have not been thoroughly explored. We give a brief description of the ideal research design to minimize error for MGV studies, test whether the MGV assumptions hold with clinical data, evaluate whether there is evidence of assumption violation among published MGV studies, give a practical description of the MGV assumptions, and describe an example of an optimal use of MGV. Ultimately, we conclude that MGV is not generally superior to KGV but may be used in some cases where the assumptions and standard error have been considered appropriately.
Gut Microbiota and Epilepsy: A Systematic Review on Their Relationship and Possible Therapeutics.
ACS chemical neuroscience, 2020

Dysbiosis of gut microbiota may lead to a range of diseases including neurological disorders. Thus, it is hypothesized that regulation of the intestinal microbiota may prevent or treat epilepsy. The purpose of this systematic review is to evaluate the evidence investigating the relationship between gut microbiota and epilepsy and possible interventions. A systematic review of the literature was done on four databases (PubMed, Scopus, EMBASE, and Web of Science). Study selection was restricted to original research articles while following the PRISMA guidelines. Six studies were selected. These studies cohesively support the interaction between gut microbiota and epileptic seizures. Gut microbiota analysis identified increases in Firmicutes, Proteobacteria, Verrucomicrobia, and Fusobacteria with decreases in Bacteroidetes and Actinobacteria in epileptic patients. Ketogenic diet, probiotics, and fecal microbiota transplantation (FMT) improved the dysbiosis of the gut microbiota and seizure activity. However, the studies either had a small sample size, lack of subject variability, or short study or follow-up period, which may question their reliability. Nevertheless, these limited studies conclusively suggest that gut microbiota diversity and dysbiosis may be involved in the pathology of epilepsy. Future studies providing more reliable and in depth insight into the gut microbial community will spark promising alternative therapies to current epilepsy treatment.
A Non-covalent Ligand Reveals Biased Agonism of the TRPA1 Ion Channel.
Neuron, 2021

The TRPA1 ion channel is activated by electrophilic compounds through the covalent modification of intracellular cysteine residues. How non-covalent agonists activate the channel and whether covalent and non-covalent agonists elicit the same physiological responses are not understood. Here, we report the discovery of a non-covalent agonist, GNE551, and determine a cryo-EM structure of the TRPA1-GNE551 complex, revealing a distinct binding pocket and ligand-interaction mechanism. Unlike the covalent agonist allyl isothiocyanate, which elicits channel desensitization, tachyphylaxis, and transient pain, GNE551 activates TRPA1 into a distinct conducting state without desensitization and induces persistent pain. Furthermore, GNE551-evoked pain is relatively insensitive to antagonist treatment. Thus, we demonstrate the biased agonism of TRPA1, a finding that has important implications for the discovery of effective drugs tailored to different disease etiologies.
FGF13 Is a Novel Regulator of NF-κB and Potentiates Pathological Cardiac Hypertrophy.
iScience, 2020

FGF13 is an intracellular FGF factor. Its role in cardiomyopathies has been rarely investigated. We revealed that endogenous FGF13 is up-regulated in cardiac hypertrophy accompanied by increased nuclear localization. The upregulation of FGF13 plays a deteriorating role both in hypertrophic cardiomyocytes and mouse hearts. Mechanistically, FGF13 directly interacts with p65 by its nuclear localization sequence and co-localizes with p65 in the nucleus in cardiac hypertrophy. FGF13 deficiency inhibits NF-κB activation in ISO-treated NRCMs and TAC-surgery mouse hearts, whereas FGF13 overexpression shows the opposite trend. Moreover, FGF13 overexpression alone is sufficient to activate NF-κB in cardiomyocytes. The interaction between FGF13 and p65 or the effects of FGF13 on NF-κB have nothing to do with IκB. Together, an IκB-independent mechanism for NF-κB regulation has been revealed in cardiomyocytes both under basal and stressful conditions, suggesting the promising application of FGF13 as a therapeutic target for pathological cardiac hypertrophy and heart failure.
Blueberry Consumption Challenges Hepatic Mitochondrial Bioenergetics and Elicits Transcriptomics Reprogramming in Healthy Wistar Rats.
Pharmaceutics, 2020

An emergent trend of blueberries' (BB) "prophylactic" consumption, due to their phytochemicals' richness and well-known health-promoting claims, is widely scaled-up. However, the benefits arising from BB indiscriminate intake remains puzzling based on incongruent preclinical and human data. To provide a more in-depth elucidation and support towards a healthier and safer consumption, we conducted a translation-minded experimental study in healthy Wistar rats that consumed BB in a juice form (25 g/kg body weight (BW)/day; 14 weeks' protocol). Particular attention was paid to the physiological adaptations succeeding in the gut and liver tissues regarding the acknowledged BB-induced metabolic benefits. Systemically, BB boosted serum antioxidant activity and repressed the circulating levels of 3-hydroxybutyrate (3-HB) ketone bodies and 3-HB/acetoacetate ratio. Moreover, BB elicited increased fecal succinic acid levels without major changes on gut microbiota (GM) composition and gut ultra-structural organization. Remarkably, an accentuated hepatic mitochondrial bioenergetic challenge, ensuing metabolic transcriptomic reprogramming along with a concerted anti-inflammatory pre-conditioning, was clearly detected upon long-term consumption of BB phytochemicals. Altogether, the results disclosed herein portray a quiescent mitochondrial-related metabolomics and hint for a unified adaptive response to this nutritional challenge. The beneficial or noxious consequences arising from this dietary trend should be carefully interpreted and necessarily claims future research.
Preparation of PLA/chitosan nanoscaffolds containing cod liver oil and experimental diabetic wound healing in male rats study.
Journal of nanobiotechnology, 2020

Diabetes mellitus is one of the most common metabolic disorders. One of the important metabolic complications in diabetes is diabetic foot ulcer syndrome, which causes delayed and abnormal healing of the wound. The formulation of nanoscaffolds containing cod liver oil by altering the hemodynamic balance toward the vasodilators state, increasing wound blood supply, and altering plasma membrane properties, namely altering the membrane phospholipids composition, can be effective in wound healing. In this study, electrospinning method was used to produce poly lactic acid/chitosan nanoscaffolds as a suitable bio-substitute. After preparing the nanoscaffolds, the products were characterized with dynamic light scattering (DLS), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Also optical properties of polymer and comparison between adsorption between single polymer and polymer-drug calculated with UV-Vis spectra. The structure and functional groups of the final products were characterized by Fourier-transform infrared spectroscopy (FT-IR) and energy dispersive spectroscopy (EDAX) as elemental analysis. The results showed that the optimum formulation of cod liver oil was 30%, which formed a very thin fiber that rapidly absorbed to the wound and produced significant healing effects. According to the results, poly lactic acid/chitosan nanoscaffolds containing cod liver oil can be a suitable bio-product to be used in treating the diabetic foot ulcer syndrome.
Divergent age-dependent peripheral immune transcriptomic profile following traumatic brain injury.
Scientific reports, 2019

The peripheral immune system is a major regulator of the pathophysiology associated with traumatic brain injury (TBI). While age-at-injury influences recovery from TBI, the differential effects on the peripheral immune response remain unknown. Here, we investigated the effects of TBI on gene expression changes in murine whole blood using RNAseq analysis, gene ontology and network topology-based key driver analysis. Genome-wide comparison of CCI-injured peripheral whole blood showed a significant increase in genes involved in proteolysis and oxidative-reduction processes in juvenile compared to adult. Conversely, a greater number of genes, involved in migration, cytokine-mediated signaling and adhesion, were found reduced in CCI-injured juvenile compared to CCI-injured adult immune cells. Key driver analysis also identified G-protein coupled and novel pattern recognition receptor (PRR), P2RY10, as a central regulator of these genes. Lastly, we found Dectin-1, a c-type lectin PRR to be reduced at the protein level in both naïve neutrophils and on infiltrating immune cells in the CCI-injured juvenile cortex. These findings demonstrate a distinct peripheral inflammatory profile in juvenile mice, which may impact the injury and repair response to brain trauma.
An examination of adults on antipsychotic medication at risk for metabolic syndrome: a comparison with obese and eating disorder populations.
European eating disorders review : the journal of the Eating Disorders Association, 2013

Little research has explored how eating disorders (ED) may be involved in the increased risk for metabolic syndrome in adults on antipsychotic medication. This pilot study compared participants on antipsychotic medication with obese and ED samples with respect to demographic and psychosocial factors. Participants (antipsychotic medication n = 12; obese n = 12; ED n = 12), were adults presenting to an outpatient psychiatry department (83.3% women; M age = 45.75 ± 11.5). Analysis of variance, analysis of covariance and chi-square tests were used to compare the samples. Participants on antipsychotic medications had a significantly lower mean body mass index than the obese (p < .001) and ED (p < .05) samples, as well as significantly lower Restraint Total scores (p < .05) and subjective binge episode frequency (p < .05) than the ED sample. The lack of significant differences that occurred between the antipsychotic medication sample and two eating disorder samples significantly different from one another indicates that this population may have unique symptomology and treatment needs.
Circuit Mechanisms Underlying the Segregation and Integration of Parallel Processing Streams in the Inferior Colliculus.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2020

The lateral cortex of the inferior colliculus (LCIC) forms a nexus between diverse multisensory, motor, and neuromodulatory streams. Like other integration hubs, it contains repeated neurochemical motifs with distinct inputs: GABA-rich modules are innervated by somatosensory structures, while auditory inputs to the LCIC target the surrounding extramodular matrix. To investigate potential mechanisms of convergence between these input streams, we used laser photostimulation circuit mapping to interrogate local LCIC circuits in adult mice of both sexes and found that input patterns are highly dependent on cell type (GABAergic/non-GABAergic) and location (module/matrix). At the circuit level, these inputs yield a directional flow of local information, primarily from the matrix to the modules. Further, the two compartments were found to project to distinct targets in the midbrain and thalamus. These data show that, while connectional modularity in the LCIC gives rise to segregated input-output channels, local circuits provide the architecture for integration between these two streams.
Neural mechanism of priming in visual search.
Attention, perception & psychophysics, 2021

Selective attention affords scrutinizing items in our environment. However, attentional selection changes over time and across space. Empirically, repetition of visual search conditions changes attentional processing. Priming of pop-out is a vivid example. Repeatedly searching for the same pop-out search feature is accomplished with faster response times and fewer errors. We review the psychophysical background of priming of pop-out, focusing on the hypothesis that it arises through changes in visual selective attention. We also describe research done with macaque monkeys to understand the neural mechanisms supporting visual selective attention and priming of pop-out, and survey research on priming of pop-out using noninvasive brain measures with humans. We conclude by hypothesizing three alternative neural mechanisms and highlighting open questions.
Towards formal models of psychopathological traits that explain symptom trajectories.
BMC medicine, 2020

A dominant methodology in contemporary clinical neuroscience is the use of dimensional self-report questionnaires to measure features such as psychological traits (e.g., trait anxiety) and states (e.g., depressed mood). These dimensions are then mapped to biological measures and computational parameters. Researchers pursuing this approach tend to equate a symptom inventory score (plus noise) with some latent psychological trait.
Calcium cytotoxicity sensitizes prostate cancer cells to standard-of-care treatments for locally advanced tumors.
Cell death & disease, 2020

Therapy resistance is a major roadblock in oncology. Exacerbation of molecular dysfunctions typical of cancer cells have proven effective in twisting oncogenic mechanisms to lethal conditions, thus offering new therapeutic avenues for cancer treatment. Here, we demonstrate that selective agonists of Transient Receptor Potential cation channel subfamily M member 8 (TRPM8), a cation channel characteristic of the prostate epithelium frequently overexpressed in advanced stage III/IV prostate cancers (PCa), sensitize therapy refractory models of PCa to radio, chemo or hormonal treatment. Overall, our study demonstrates that pharmacological-induced Ca
Cerebral venous sinus thrombosis-A primer for emergency physician.
Journal of family medicine and primary care, 2020

Cerebral venous sinus thrombosis (CVT) is notoriously known for its varied presentations and extremely high risk of mortality, if remains undetected and untreated. On the other hand, life can be saved with full functional recovery if CVT can be identified with high index of clinical suspicion with supportive imaging and treatment with appropriate anticoagulation. It is important for clinicians to be meticulous to screen for both the potential reversible and heritable causes of CVT so that appropriate measures can be taken to prevent such catastrophe. Here we report a case of CVT involving right sigmoid and transverse sinuses presenting with acute onset left sided hemiplegic without antecedent headache or seizures. Patient was successfully treated with anticoagulants with nearly full functional recovery. Multiple predisposing factors were identified. As per our knowledge, this is the first case of CVT with underlying conglomeration of multiple acquired (lactation, folate deficiency, hyperhomocysteinemia, depot medroxyprogesterone acetate injection) and hereditary risk factors (deficiency of protein C, protein S and antithrombin-III) in a single patient.
Early life stress causes sex-specific changes in adult fronto-limbic connectivity that differentially drive learning.
eLife, 2020

It is currently unclear whether early life stress (ELS) affects males and females differently. However, a growing body of work has shown that sex moderates responses to stress and injury, with important insights into sex-specific mechanisms provided by work in rodents. Unfortunately, most of the ELS studies in rodents were conducted only in males, a bias that is particularly notable in translational work that has used human imaging. Here we examine the effects of unpredictable postnatal stress (UPS), a mouse model of complex ELS, using high resolution diffusion magnetic resonance imaging. We show that UPS induces several neuroanatomical alterations that were seen in both sexes and resemble those reported in humans. In contrast, exposure to UPS induced fronto-limbic hyper-connectivity in males, but either no change or hypoconnectivity in females. Moderated-mediation analysis found that these sex-specific changes are likely to alter contextual freezing behavior in males but not in females.
Relationship of prosthesis ownership and phantom limb pain: results of a survey in 2383 limb amputees.
Pain, 2021

Phantom limb pain (PLP) accounts for a significant reduction in quality of life and is difficult to treat. Prosthesis use has been shown to negatively covary with PLP. Recent research on body perception in amputees suggest that prosthesis ownership, defined as the extent to which a prosthesis is experienced as being part of the body rather than an artificial device foreign to the body, might interact with PLP. We used survey data from 2383 unilateral prosthesis-using upper-limb or lower-limb amputees and performed regression analyses to determine the relationship between prosthesis ownership and PLP. To test for specificity, we examined the role of prosthesis ownership also for residual limb pain (RLP) and nonpainful phantom limb sensations (npPLS). Prosthesis ownership was reduced in older participants and higher in lower-limb compared to upper-limb amputees. A longer residual limb and more frequent prosthesis use as well as a longer time since amputation also yielded higher values. Prostheses based on natural principles were associated with higher prosthesis ownership. Phantom limb pain and RLP were lower with higher prosthesis ownership, and RLP but not PLP was lower when prosthesis use was frequent. There were no significant associations for npPLS. The regression results differ in some aspects from those revealed by univariate analyses, emphasizing the importance of multivariate statistical approaches. Our findings provide insights into the interplay of body- and pain-related sensations after amputation, and could help to develop new treatment approaches for both PLP and RLP.
Acute reversible SERCA blockade facilitates or blocks exocytosis, respectively in mouse or bovine chromaffin cells.
Pflugers Archiv : European journal of physiology, 2021

Pre-blockade of the sarco-endoplasmic reticulum (ER) calcium ATPase (SERCA) with irreversible thapsigargin depresses exocytosis in adrenal bovine chromaffin cells (BCCs). Distinct expression of voltage-dependent Ca
Sporadic Meningioangiomatosis Presenting as a Middle Cranial Fossa Arachnoid Cyst.
World neurosurgery, 2020

Meningioangiomatosis is an extremely rare meningovascular disease of the central nervous system that is characterized by the proliferation of leptomeninges, cortical vessels, and perivascular spindled cells. Although it is a benign, neoplastic disorder that carries a good prognosis after surgical excision, initial diagnosis may be challenging as radiologic findings are often variable and nonspecific.
Prediction of Alzheimer's disease using multi-variants from a Chinese genome-wide association study.
Brain : a journal of neurology, 2021

Previous genome-wide association studies have identified dozens of susceptibility loci for sporadic Alzheimer's disease, but few of these loci have been validated in longitudinal cohorts. Establishing predictive models of Alzheimer's disease based on these novel variants is clinically important for verifying whether they have pathological functions and provide a useful tool for screening of disease risk. In the current study, we performed a two-stage genome-wide association study of 3913 patients with Alzheimer's disease and 7593 controls and identified four novel variants (rs3777215, rs6859823, rs234434, and rs2255835; Pcombined = 3.07 × 10-19, 2.49 × 10-23, 1.35 × 10-67, and 4.81 × 10-9, respectively) as well as nine variants in the apolipoprotein E region with genome-wide significance (P < 5.0 × 10-8). Literature mining suggested that these novel single nucleotide polymorphisms are related to amyloid precursor protein transport and metabolism, antioxidation, and neurogenesis. Based on their possible roles in the development of Alzheimer's disease, we used different combinations of these variants and the apolipoprotein E status and successively built 11 predictive models. The predictive models include relatively few single nucleotide polymorphisms useful for clinical practice, in which the maximum number was 13 and the minimum was only four. These predictive models were all significant and their peak of area under the curve reached 0.73 both in the first and second stages. Finally, these models were validated using a separate longitudinal cohort of 5474 individuals. The results showed that individuals carrying risk variants included in the models had a shorter latency and higher incidence of Alzheimer's disease, suggesting that our models can predict Alzheimer's disease onset in a population with genetic susceptibility. The effectiveness of the models for predicting Alzheimer's disease onset confirmed the contributions of these identified variants to disease pathogenesis. In conclusion, this is the first study to validate genome-wide association study-based predictive models for evaluating the risk of Alzheimer's disease onset in a large Chinese population. The clinical application of these models will be beneficial for individuals harbouring these risk variants, and particularly for young individuals seeking genetic consultation.
An ethics framework for consolidating and prioritizing COVID-19 clinical trials.
Clinical trials (London, England), 2021

Given the dearth of established safe and effective interventions to respond to COVID-19, there is an urgent ethical imperative to conduct meaningful clinical research. The good news is that interventions to be tested are not in short supply. Unfortunately, the human and material resources needed to conduct these trials are finite. It is essential that trials be robust and meet enrollment targets and that lower-quality studies not be permitted to displace higher-quality studies, delaying answers to critical questions. Yet, with few exceptions, existing research review bodies and processes are not designed to ensure these conditions are satisfied. To meet this challenge, we offer guidance for research institutions about how to ethically consolidate and prioritize COVID-19 clinical trials, while recognizing that consolidation and prioritization should also take place upstream (among manufacturers and funders) and at a higher level (e.g. nationally). In our proposed three-stage process, trials must first meet threshold criteria. Those that do are evaluated in a second stage to determine whether the institution has sufficient capacity to support all proposed trials. If it does not, the third stage entails evaluating studies against two additional sets of comparative prioritization criteria: those specific to the study and those that aim to advance diversification of an institution's research portfolio. To implement these criteria fairly, we propose that research institutions form COVID-19 research prioritization committees. We briefly discuss some important attributes of these committees, drawing on the authors' experiences at our respective institutions. Although we focus on clinical trials of COVID-19 therapeutics, our guidance should prove useful for other kinds of COVID-19 research, as well as non-pandemic research, which can raise similar challenges due to the scarcity of research resources.