rudyvdbrink/CitationDatabase huggingface dataset:
A Novel, Integrative Approach for Evaluating Progression in Multiple Sclerosis: Development of a Scoring Algorithm.
JMIR medical informatics, 2020

There is an unmet need for a tool that helps to evaluate patients who are at risk of progressing from relapsing-remitting multiple sclerosis to secondary progressive multiple sclerosis (SPMS). A new tool supporting the evaluation of early signs suggestive of progression in multiple sclerosis (MS) has been developed. In the initial stage, concepts relevant to progression were identified using a mixed method approach involving regression on data from a real-world observational study and qualitative research with patients and physicians. The tool was drafted in a questionnaire format to assess these variables.
Rare cadaveric finding of a grossly enlarged mucocele appendix.
Case reports in gastroenterology, 2013

Appendicular mucoceles are rare clinical findings characterized by dilation and distention of the appendicular lumen by the accumulation of mucus. Their discovery is often incidental from abdominal imaging or more commonly as a secondary surgical finding. In this case study we report the first known recorded case of a cadaveric mucocele appendix discovered during routine dissection of the gastrointestinal system. The recorded cause of death for the 86-year-old female patient was congestive heart failure. We compared the gross anatomy and histology of this enormous appendix with another cadaveric appendix. A pathology report identified the appendicular mucocele as a mucinous cystadenoma.
Progress and challenges in CRISPR-mediated therapeutic genome editing for monogenic diseases.
Journal of biomedical research, 2020

There are an estimated 10 000 monogenic diseases affecting tens of millions of individuals worldwide. The application of CRISPR/Cas genome editing tools to treat monogenic diseases is an emerging strategy with the potential to generate personalized treatment approaches for these patients. CRISPR/Cas-based systems are programmable and sequence-specific genome editing tools with the capacity to generate base pair resolution manipulations to DNA or RNA. The complexity of genomic insults resulting in heritable disease requires patient-specific genome editing strategies with consideration of DNA repair pathways, and CRISPR/Cas systems of different types, species, and those with additional enzymatic capacity and/or delivery methods. In this review we aim to discuss broad and multifaceted therapeutic applications of CRISPR/Cas gene editing systems including in harnessing of homology directed repair, non-homologous end joining, microhomology-mediated end joining, and base editing to permanently correct diverse monogenic diseases.
The physiological roles of tau and Aβ: implications for Alzheimer's disease pathology and therapeutics.
Acta neuropathologica, 2020

Tau and amyloid beta (Aβ) are the prime suspects for driving pathology in Alzheimer's disease (AD) and, as such, have become the focus of therapeutic development. Recent research, however, shows that these proteins have been highly conserved throughout evolution and may have crucial, physiological roles. Such functions may be lost during AD progression or be unintentionally disrupted by tau- or Aβ-targeting therapies. Tau has been revealed to be more than a simple stabiliser of microtubules, reported to play a role in a range of biological processes including myelination, glucose metabolism, axonal transport, microtubule dynamics, iron homeostasis, neurogenesis, motor function, learning and memory, neuronal excitability, and DNA protection. Aβ is similarly multifunctional, and is proposed to regulate learning and memory, angiogenesis, neurogenesis, repair leaks in the blood-brain barrier, promote recovery from injury, and act as an antimicrobial peptide and tumour suppressor. This review will discuss potential physiological roles of tau and Aβ, highlighting how changes to these functions may contribute to pathology, as well as the implications for therapeutic development. We propose that a balanced consideration of both the physiological and pathological roles of tau and Aβ will be essential for the design of safe and effective therapeutics.
Speech discrimination impairments as a marker of disease severity in multiple sclerosis.
Multiple sclerosis and related disorders, 2021

Multiple Sclerosis (MS) pathology is likely to disrupt central auditory pathways, thereby affecting an individual's ability to discriminate speech from noise. Despite the importance of speech discrimination in daily communication, it's characterization in the context of MS remains limited. This cross-sectional study evaluated speech discrimination in MS under "real world" conditions where sentences were presented in ecologically valid multi-talker speech or broadband noise at several signal-to-noise ratios (SNRs).
Corticostriatal Connectivity in Antisocial Personality Disorder by MAO-A Genotype and Its Relationship to Aggressive Behavior.
The international journal of neuropsychopharmacology, 2018

The influence of genetic variation on resting-state neural networks represents a burgeoning line of inquiry in psychiatric research. Monoamine oxidase A, an X-linked gene, is one example of a molecular target linked to brain activity in psychiatric illness. Monoamine oxidase A genetic variants, including the high and low variable nucleotide tandem repeat polymorphisms, have been shown to differentially affect brain functional connectivity in healthy humans. However, it is currently unknown whether these same polymorphisms influence resting-state brain activity in clinical conditions. Given its high burden on society and strong connection to violent behavior, antisocial personality disorder is a logical condition to study, since in vivo markers of monoamine oxidase A brain enzyme are reduced in key affect-modulating regions, and striatal levels of monoamine oxidase A show a relation with the functional connectivity of this same region.
Mapping Human Laryngeal Motor Cortex during Vocalization.
Cerebral cortex (New York, N.Y. : 1991), 2020

The representations of the articulators involved in human speech production are organized somatotopically in primary motor cortex. The neural representation of the larynx, however, remains debated. Both a dorsal and a ventral larynx representation have been previously described. It is unknown, however, whether both representations are located in primary motor cortex. Here, we mapped the motor representations of the human larynx using functional magnetic resonance imaging and characterized the cortical microstructure underlying the activated regions. We isolated brain activity related to laryngeal activity during vocalization while controlling for breathing. We also mapped the articulators (the lips and tongue) and the hand area. We found two separate activations during vocalization-a dorsal and a ventral larynx representation. Structural and quantitative neuroimaging revealed that myelin content and cortical thickness underlying the dorsal, but not the ventral larynx representation, are similar to those of other primary motor representations. This finding confirms that the dorsal larynx representation is located in primary motor cortex and that the ventral one is not. We further speculate that the location of the ventral larynx representation is in premotor cortex, as seen in other primates. It remains unclear, however, whether and how these two representations differentially contribute to laryngeal motor control.
Differentiating poor validity from probable impairment on the medical symptom validity test: a cross-validation study.
The International journal of neuroscience, 2019

In neuropsychological evaluations, it is often difficult to ascertain whether poor performance on measures of validity is due to poor effort or malingering, or whether there is genuine cognitive impairment. Dunham and Denney created an algorithm to assess this question using the Medical Symptom Validity Test (MSVT). We assessed the ability of their algorithm to detect poor validity versus probable impairment, and concordance of failure on the MSVT with other freestanding tests of performance validity.
[Roles of Microglia in Neurodegenerative Diseases].
Brain and nerve = Shinkei kenkyu no shinpo, 2017

Recent advances in glial research have elucidated the roles of microglia under various contexts in health and disease. Microglial activation used to be considered only as a consequence of neuronal damage. However, a series of studies using mouse models of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease selectively affecting motor neurons, indicated that microglia actively influence the disease course. In this review, we summarize the growing evidence that microglia play a critical role in the survival and demise of motor neurons in ALS. These observations suggest microglia as a promising therapeutic target of neurodegenerative diseases.
Acute and chronic bupropion treatment does not prevent morphine-induced conditioned place preference in mice.
European journal of pharmacology, 2020

A substantial barrier to the treatment of Opioid Use Disorder (OUD) is the elevated relapse rates in affected patients, and a significant contributor to these events of relapse is exposure to cues and contexts that are intensely associated with prior drug abuse. The neurotransmitter dopamine plays a key role in reward-related behaviors, and previous studies have illustrated that dopamine hypofunction in periods of abstinence serves to prompt drug craving and seeking. We hypothesized that restoration of dopaminergic signaling could attenuate drug-seeking behaviors. Therefore, we investigated whether use of an FDA-approved drug, bupropion, an inhibitor of the dopamine transporter (DAT), or a dopamine uptake inhibitor with high affinity for DAT, JHW 007, was able to decrease preference for a drug-paired context. In these experiments, mice underwent 5 days of non-contingent morphine (10 mg/kg) exposure in a conditioned place preference (CPP) paradigm. We found that systemic injection of bupropion (20 mg/kg, i. p.) or intracranial injection of JHW 007 into the nucleus accumbens shell did not prevent the expression of morphine CPP. We then investigated whether chronic bupropion treatment (via implanted osmotic pumps) would influence morphine CPP. We observed that chronic bupropion treatment for 21 days following morphine conditioning did not attenuate the prolonged preference for morphine-paired contexts. Overall, with our dose and paradigm, neither acute nor chronic bupropion diminishes morphine CPP. Continued studies should address FDA-approved medications and their potential for recovery in OUD patients.
Phosphatidic acid increases Notch signalling by affecting Sanpodo trafficking during Drosophila sensory organ development.
Scientific reports, 2020

Organ cell diversity depends on binary cell-fate decisions mediated by the Notch signalling pathway during development and tissue homeostasis. A clear example is the series of binary cell-fate decisions that take place during asymmetric cell divisions that give rise to the sensory organs of Drosophila melanogaster. The regulated trafficking of Sanpodo, a transmembrane protein that potentiates receptor activity, plays a pivotal role in this process. Membrane lipids can regulate many signalling pathways by affecting receptor and ligand trafficking. It remains unknown, however, whether phosphatidic acid regulates Notch-mediated binary cell-fate decisions during asymmetric cell divisions, and what are the cellular mechanisms involved. Here we show that increased phosphatidic acid derived from Phospholipase D leads to defects in binary cell-fate decisions that are compatible with ectopic Notch activation in precursor cells, where it is normally inactive. Null mutants of numb or the α-subunit of Adaptor Protein complex-2 enhance dominantly this phenotype while removing a copy of Notch or sanpodo suppresses it. In vivo analyses show that Sanpodo localization decreases at acidic compartments, associated with increased internalization of Notch. We propose that Phospholipase D-derived phosphatidic acid promotes ectopic Notch signalling by increasing receptor endocytosis and inhibiting Sanpodo trafficking towards acidic endosomes.
IL-25 prevents T cell-mediated neurotoxicity by decreasing LFA-1 expression.
Journal of neuroimmunology, 2013

Autoimmune diseases such as multiple sclerosis (MS) are thought to develop due to a dysregulation in the normal T(H)1-T(H)17/T(H)2 immune system balance, where pro-inflammatory responses with a T(H)1/T(H)17 prevalence develop. Some therapeutic treatments in MS promote a shift toward a TH2-prevalent environment and this has been shown to be protective. However, not all patients respond to current immunomodulatory treatments in MS so that new immunomodulatory drugs that can promote a shift of the immune system into an anti-inflammatory T(H)2 status are needed. IL-25 is a cytokine of the IL-17 family with powerful anti-inflammatory properties. This study demonstrates that IL-25 exerts neuroprotective functions by reducing T cell-mediated killing of human fetal neurons. The mechanism of action of this IL-25-mediated neuroprotective effect appears to be linked to reduction in the expression of the adhesion molecule LFA-1, which is relevant in stabilizing the immune synapse during cytotoxicity.
Patients' anticipated actions following transient ischaemic attack symptoms: a qualitative vignette-based study.
BMC family practice, 2017

Transient Ischaemic Attack (TIA) requires urgent investigation and management. Urgent management reduces the risk of subsequent stroke markedly, but non-presentation or delays in patient presentation to health services have been found to compromise timely management. We aimed to explore general practice patients' anticipated responses to TIA symptoms.
Nectin-like molecule 2, a necessary sexual maturation regulator, participates in congenital hypogonadotropic hypogonadism.
Gene, 2020

Congenital hypogonadotropic hypogonadism (CHH) is a rare genetically heterogeneous disorder. We aimed to determine the prevalence and pathogenesis of NECL2 (Nectin-like molecule 2) variants in a cohort of female patients with CHH.
Action representations activated by task-irrelevant information: is it really irrelevant?
Scandinavian journal of psychology, 2015

Accessing action knowledge is believed to rely on the activation of action representations through the retrieval of functional, manipulative, and spatial information associated with objects. However, it remains unclear whether action representations can be activated in this way when the object information is irrelevant to the current judgment. The present study investigated this question by independently manipulating the correctness of three types of action-related information: the functional relation between the two objects, the grip applied to the objects, and the orientation of the objects. In each of three tasks in Experiment 1, participants evaluated the correctness of only one of the three information types (function, grip or orientation). Similar results were achieved with all three tasks: "correct" judgments were facilitated when the other dimensions were correct; however, "incorrect" judgments were facilitated when the other two dimensions were both correct and also when they were both incorrect. In Experiment 2, when participants attended to an action-irrelevant feature (object color), there was no interaction between function, grip, and orientation. These results clearly indicate that action representations can be activated by retrieval of functional, manipulative, and spatial knowledge about objects, even though this is task-irrelevant information.
Development and validation of the therapeutic alliance in physiotherapy questionnaire for patients with chronic musculoskeletal pain.
Patient education and counseling, 2021

The purpose of this study is to present the development and analysis of the factorial structure and psychometric properties of a new self-administered questionnaire (Therapeutic Alliance in Physiotherapy Questionnaire-Patients [CAF-P]) designed to measure therapeutic alliance in physiotherapy.
Understanding the Binding Specificity of G-Protein Coupled Receptors toward G-Proteins and Arrestins: Application to the Dopamine Receptor Family.
Journal of chemical information and modeling, 2020

G-Protein coupled receptors (GPCRs) are involved in a myriad of pathways key for human physiology through the formation of complexes with intracellular partners such as G-proteins and arrestins (Arrs). However, the structural and dynamical determinants of these complexes are still largely unknown. Herein, we developed a computational big-data pipeline that enables the structural characterization of GPCR complexes with no available structure. This pipeline was used to study a well-known group of catecholamine receptors, the human dopamine receptor (DXR) family and its complexes, producing novel insights into the physiological properties of these important drug targets. A detailed description of the protein interfaces of all members of the DXR family (D1R, D2R, D3R, D4R, and D5R) and the corresponding protein interfaces of their binding partners (Arrs: Arr2 and Arr3; G-proteins: Gi1, Gi2, Gi3, Go, Gob, Gq, Gslo, Gssh, Gt2, and Gz) was generated. To produce reliable structures of the DXR family in complex with either G-proteins or Arrs, we performed homology modeling using as templates the structures of the β2-adrenergic receptor (β2AR) bound to Gs, the rhodopsin bound to Gi, and the recently acquired neurotensin receptor-1 (NTSR1) and muscarinic 2 receptor (M2R) bound to arrestin (Arr). Among others, the work demonstrated that the three partner groups, Arrs and Gs- and Gi-proteins, are all structurally and dynamically distinct. Additionally, it was revealed the involvement of different structural motifs in G-protein selective coupling between D1- and D2-like receptors. Having constructed and analyzed 50 models involving DXR, this work represents an unprecedented large-scale analysis of GPCR-intracellular partner interface determinants. All data is available at www.moreiralab.com/resources/dxr.
Decomposing complex links between the childhood environment and brain structure in school-aged youth.
Developmental cognitive neuroscience, 2021

Childhood experiences play a profound role in conferring risk and resilience for brain and behavioral development. However, how different facets of the environment shape neurodevelopment remains largely unknown. Here we sought to decompose heterogeneous relationships between environmental factors and brain structure in 989 school-aged children from the Adolescent Brain Cognitive Development Study. We applied a cross-modal integration and clustering approach called 'Similarity Network Fusion', which combined two brain morphometrics (i.e., cortical thickness and myelin-surrogate markers), and key environmental factors (i.e., trauma exposure, neighborhood safety, school environment, and family environment) to identify homogeneous subtypes. Depending on the subtyping resolution, results identified two or five subgroups, each characterized by distinct brain structure-environment profiles. Notably, more supportive caregiving and school environments were associated with greater myelination, whereas less supportive caregiving, higher family conflict and psychopathology, and higher perceived neighborhood safety were observed with greater cortical thickness. These subtypes were highly reproducible and predicted externalizing symptoms and overall mental health problems. Our findings support the theory that distinct environmental exposures are differentially associated with alterations in structural neurodevelopment. Delineating more precise associations between risk factors, protective factors, and brain development may inform approaches to enhance risk identification and optimize interventions targeting specific experiences.
Flexible contextual modulation of naturalistic texture perception in peripheral vision.
Journal of vision, 2021

Peripheral vision comprises most of our visual field, and is essential in guiding visual behavior. Its characteristic capabilities and limitations, which distinguish it from foveal vision, have been explained by the most influential theory of peripheral vision as the product of representing the visual input using summary statistics. Despite its success, this account may provide a limited understanding of peripheral vision, because it neglects processes of perceptual grouping and segmentation. To test this hypothesis, we studied how contextual modulation, namely the modulation of the perception of a stimulus by its surrounds, interacts with segmentation in human peripheral vision. We used naturalistic textures, which are directly related to summary-statistics representations. We show that segmentation cues affect contextual modulation, and that this is not captured by our implementation of the summary-statistics model. We then characterize the effects of different texture statistics on contextual modulation, providing guidance for extending the model, as well as for probing neural mechanisms of peripheral vision.
From motor planning to execution: a sensorimotor loop perspective.
Journal of neurophysiology, 2020

How is an evanescent wish to move translated into a concrete action? This simple question and puzzling miracle remains a focal point of motor systems neuroscience. Where does the difficulty lie? A great deal has been known about biomechanics for quite some time. More recently, there have been significant advances in our understanding of how the spinal system is organized into modules corresponding to spinal synergies, which are fixed patterns of multimuscle recruitment. But much less is known about how the supraspinal system recruits these synergies in the correct spatiotemporal pattern to effectively control movement. We argue that what makes the problem of supraspinal control so difficult is that it emerges as a result of multiple convergent and redundant sensorimotor loops. Because these loops are convergent, multiple modes of information are mixed before being sent to the spinal system; because they are redundant, information is overlapping such that a mechanism must exist to eliminate the redundancy before the signal is sent to the spinal system. Given these complex interactions, simple correlation analyses between movement variables and neural activity are likely to render a confusing and inconsistent picture. Here, we suggest that the perspective of sensorimotor loops might help in achieving a better systems-level understanding. Furthermore, state-of-the-art techniques in neurotechnology, such as optogenetics, appear to be well suited for investigating the problem of motor control at the level of loops.
Developmental clock and mechanism of de novo polarization of the mouse embryo.
Science (New York, N.Y.), 2020

Embryo polarization is critical for mouse development; however, neither the regulatory clock nor the molecular trigger that it activates is known. Here, we show that the embryo polarization clock reflects the onset of zygotic genome activation, and we identify three factors required to trigger polarization. Advancing the timing of transcription factor AP-2 gamma (Tfap2c) and TEA domain transcription factor 4 (Tead4) expression in the presence of activated Ras homolog family member A (RhoA) induces precocious polarization as well as subsequent cell fate specification and morphogenesis. Tfap2c and Tead4 induce expression of actin regulators that control the recruitment of apical proteins on the membrane, whereas RhoA regulates their lateral mobility, allowing the emergence of the apical domain. Thus, Tfap2c, Tead4, and RhoA are regulators for the onset of polarization and cell fate segregation in the mouse.