rudyvdbrink/CitationDatabase huggingface dataset:
Efficient generation of neural-like cells from porcine ovarian putative stem cells - morphological characterization and evaluation of their electrophysiological properties.
Theriogenology, 2020

Until recently, the mammalian ovary was considered to consist of fully differentiated tissues, but evidence for the presence of adult stem cells in this organ appeared. The differentiation potential of these cells, referred to as putative stem cells, is not well defined. Porcine ovarian putative stem cells (poPSCs) were immunomagnetically isolated from postnatal pig ovaries based on the presence of the SSEA-4 surface marker protein. First, they were cultured in the undifferentiated state. After the third passage, a novel 7-day culture method inducing their differentiation into neural-like cells by the addition of forskolin (FSK), retinoic acid (RA) and basic fibroblast growth factor (bFGF) to the culture medium was applied. After 7 days, poPSCs successfully differentiated into neural-like cells, as evidenced by neural morphology and the presence of the neuronal markers nestin, NeuN, and GFAP, as confirmed by immunofluorescence, western blot, and real-time PCR. Electrophysiological analysis of potassium and sodium channel activity (patch clamp) confirmed that they indeed differentiated into neurons. The plasticity of poPSCs offers an excellent opportunity, especially in the field of neuroscience, since they can differentiate into neurons or glial cells. Although poPSCs might not be pluripotent cells, they also escape the rigid classification framework of adult stem cells.
Simplified Postoperative Care After Spring-assisted Strip Craniotomy for Sagittal Synostosis: A Prospective Before-and-After Study.
The Journal of craniofacial surgery, 2021

Since the development of spring-assisted techniques for corrective craniofacial surgery, routine postoperative admission to intensive care units (ICUs) has been questioned. However, close monitoring is necessary if the continuous infusion of morphine is used as recommended for better pain relief. In this study, the authors evaluated a simplified postoperative protocol without continuous morphine infusion and no indwelling urinary catheter following spring-assisted surgery (SAS) for sagittal synostosis. Ten children were cared for according to a standard protocol with postoperative intravenous (i.v.) infusion of morphine and an indwelling urinary catheter, and 11 consecutive children were treated according to a simplified protocol with pain relief based on intermittent injections of morphine and clonidine [according to Face, Legs, Activity, Cry, Consolability (FLACC) scores >4] without the indwelling catheter. A Mann-Whitney U test was used for comparison of distributions between the two groups. The results revealed no differences between groups regarding the proportion of FLACC scores >4, total amount of administered i.v. morphine and clonidine, total volume of buffered glucose infused, time to first feeding on breast milk or substitute, or the length of stay. Despite the inherent limitations of our small observational study, the authors concluded that at our institution, it was possible to exclude a standard continuous i.v. infusion of morphine and an indwelling urinary catheter from our postoperative care protocol without decreasing the quality of pain relief in children submitted to SAS for sagittal synostosis. This finding supports downgrading the level of care from the ICU to a regular ward after limited immediate postoperative observation.
Embryology of Spinal Dysraphism and its Relationship to Surgical Treatment.
The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques, 2020

Spinal dysraphism is an umbrella term that encompasses a number of congenital malformations that affect the central nervous system. The etiology of these conditions can be traced back to a specific defect in embryological development, with the more disabling malformations occurring at an earlier gestational age. A thorough understanding of the relevant neuroembryology is imperative for clinicians to select the correct treatment and prevent complications associated with spinal dysraphism. This paper will review the neuroembryology associated with the various forms of spinal dysraphism and provide a clinical-pathological correlation for these congenital malformations.
Transcriptomic analysis of the signature of neurogenesis in human hippocampus suggests restricted progenitor cell progression post-childhood.
IBRO reports, 2020

Immunohistological investigations have given rise to divergent perspectives about adult hippocampal neurogenesis in humans. Therefore, this study aimed to examine whether a comprehensive transcriptomic analysis of signature markers of neurogenesis, supplemented with markers of gliogenesis, vasculogenesis, cell proliferation, and apoptosis, may help discern essential aspects of adult hippocampal neurogenesis in humans.
Understanding human individuation of unfamiliar faces with oddball fast periodic visual stimulation and electroencephalography.
The European journal of neuroscience, 2020

To investigate face individuation (FI), a critical brain function in the human species, an oddball fast periodic visual stimulation (FPVS) approach was recently introduced (Liu-Shuang et al., Neuropsychologia, 2014, 52, 57). In this paradigm, an image of an unfamiliar "base" facial identity is repeated at a rapid rate F (e.g., 6 Hz) and different unfamiliar "oddball" facial identities are inserted every nth item, at a F/n rate (e.g., every 5th item, 1.2 Hz). This stimulation elicits FI responses at F/n and its harmonics (2F/n, 3F/n, etc.), reflecting neural discrimination between oddball versus base facial identities, which is quantified in the frequency domain of the electroencephalogram (EEG). This paradigm, used in 20 published studies, demonstrates substantial advantages for measuring FI in terms of validity, objectivity, reliability, and sensitivity. Human intracerebral recordings suggest that this FI response originates from neural populations in the lateral inferior occipital and fusiform gyri, with a right hemispheric dominance consistent with the localization of brain lesions specifically affecting facial identity recognition (prosopagnosia). Here, we summarize the contributions of the oddball FPVS framework toward understanding FI, including its (a)typical development, with early studies supporting the application of this technique to clinical testing (e.g., autism spectrum disorder). This review also includes an in-depth analysis of the paradigm's methodology, with guidelines for designing future studies. A large-scale group analysis compiling data across 130 observers provides insights into the oddball FPVS FI response properties. Overall, we recommend the oddball FPVS paradigm as an alternative approach to behavioral or traditional event-related potential EEG measures of face individuation.
A comparison of AAV-vector production methods for gene therapy and preclinical assessment.
Scientific reports, 2020

Adeno Associated Virus (AAV)-mediated gene expression in the brain is widely applied in the preclinical setting to investigate the therapeutic potential of specific molecular targets, characterize various cellular functions, and model central nervous system (CNS) diseases. In therapeutic applications in the clinical setting, gene therapy offers several advantages over traditional pharmacological based therapies, including the ability to directly manipulate disease mechanisms, selectively target disease-afflicted regions, and achieve long-term therapeutic protein expression in the absence of repeated administration of pharmacological agents. Next to the gold-standard iodixanol-based AAV vector production, we recently published a protocol for AAV production based on chloroform-precipitation, which allows for fast in-house production of small quantities of AAV vector without the need for specialized equipment. To validate our recent protocol, we present here a direct side-by-side comparison between vectors produced with either method in a series of in vitro and in vivo assays with a focus on transgene expression, cell loss, and neuroinflammatory responses in the brain. We do not find differences in transduction efficiency nor in any other parameter in our in vivo and in vitro panel of assessment. These results suggest that our novel protocol enables most standardly equipped laboratories to produce small batches of high quality and high titer AAV vectors for their experimental needs.
Analyzing Neural Activity and Connectivity Using Intracranial EEG Data with SPM Software.
Journal of visualized experiments : JoVE, 2018

Measuring neural activity and connectivity associated with cognitive functions at high spatial and temporal resolutions is an important goal in cognitive neuroscience. Intracranial electroencephalography (EEG) can directly record electrical neural activity and has the unique potential to accomplish this goal. Traditionally, averaging analysis has been applied to analyze intracranial EEG data; however, several new techniques are available for depicting neural activity and intra- and inter-regional connectivity. Here, we introduce two analytical protocols we recently applied to analyze intracranial EEG data using the Statistical Parametric Mapping (SPM) software: time-frequency SPM analysis for neural activity and dynamic causal modeling of induced responses for intra- and inter-regional connectivity. We report our analysis of intracranial EEG data during the observation of faces as representative results. The results revealed that the inferior occipital gyrus (IOG) showed gamma-band activity at very early stages (110 ms) in response to faces, and both the IOG and amygdala showed rapid intra- and inter-regional connectivity using various types of oscillations. These analytical protocols have the potential to identify the neural mechanisms underlying cognitive functions with high spatial and temporal profiles.
Interoception and alcohol addiction: Vagotomy induces long-lasting suppression of relapse-type behavior.
Addiction biology, 2021

Drug addictions are chronic mental disorders characterized by compulsive drug seeking and drug use, despite their negative consequences. It is a priority to find therapeutic alternatives to prevent relapse, as there are still no treatments that can ensure abstinence. One of the neural systems implicated in the appearance of the states of discomfort that motivate relapse is the interoceptive system, which oversees our internal body states. However, less attention has been given to the peripheral components of the interoceptive system and their role in addictions. Within these pathways, the vagus nerve represents one of the main visceral afferents of the interoceptive system. We hypothesized that the interruption of visceral afferent pathways would decrease the motivational effects of the drug, thereby either decreasing or preventing drug cravings. To test this idea, we used rats of a high-alcohol-drinking line and measured the effect that vagus nerve resection had on the relapse-like alcohol drinking, expressed as the alcohol deprivation effect, a phenomenon that has been linked to addiction-related events such as alcohol cravings. We found that even though vagotomy completely eliminates the effect of alcohol deprivation, it has no impact on water consumption or animal weight. These results give us valuable information about the relationship between the autonomic nervous system and alcohol use disorders and allow us to propose new clinical research that might have translational options.
How Repair-or-Dispose Decisions Under Stress Can Initiate Disease Progression.
iScience, 2020

Glia, the helper cells of the brain, are essential in maintaining neural resilience across time and varying challenges: By reacting to changes in neuronal health glia carefully balance repair or disposal of injured neurons. Malfunction of these interactions is implicated in many neurodegenerative diseases. We present a reductionist model that mimics repair-or-dispose decisions to generate a hypothesis for the cause of disease onset. The model assumes four tissue states: healthy and challenged tissue, primed tissue at risk of acute damage propagation, and chronic neurodegeneration. We discuss analogies to progression stages observed in the most common neurodegenerative conditions and to experimental observations of cellular signaling pathways of glia-neuron crosstalk. The model suggests that the onset of neurodegeneration can result as a compromise between two conflicting goals: short-term resilience to stressors versus long-term prevention of tissue damage.
Acute Kidney Injury in a Patient With Cryoglobulinemia Secondary to Hepatic Mucosa-Associated Lymphoid Tissue Lymphoma: Case Report and Literature Review.
Cureus, 2020

We report a patient with IgM-predominant type I cryoglobulinemia (CG), who presented to our nephrology department with acute kidney injury. He was previously diagnosed with sensorimotor neuropathy, which was in remission with maintenance dose of corticosteroids. Upon admission, there were ulcerated, necrotic cutaneous lesions localized to the inner aspect of the thighs bilaterally. Further workup revealed a mucosa-associated lymphoid tissue lymphoma, causing type I CG. Screening tests for hepatitis viruses were negative at this time. Under treatment with diuretics and high-potency glucocorticoids, the patient had an acceptable recovery of renal function and was referred to oncology for treatment. Unfortunately, three months later the patient succumbed to fulminant hepatitis, presumably secondary to reactivation of an occult hepatitis B/D co-infection. We further conducted a literature review to better describe patient characteristics and renal involvement in type I CG.
Dopamine-Dependent QR2 Pathway Activation in CA1 Interneurons Enhances Novel Memory Formation.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2020

The formation of memory for a novel experience is a critical cognitive capacity. The ability to form novel memories is sensitive to age-related pathologies and disease, to which prolonged metabolic stress is a major contributing factor. Presently, we describe a dopamine-dependent redox modulation pathway within the hippocampus of male mice that promotes memory consolidation. Namely, following novel information acquisition, quinone reductase 2 (QR2) is suppressed by miRNA-182 (miR-182) in the CA1 region of the hippocampus via dopamine D1 receptor (D1R) activation, a process largely facilitated by locus coeruleus activity. This pathway activation reduces ROS generated by QR2 enzymatic activity, a process that alters the intrinsic properties of CA1 interneurons 3 h following learning, in a form of oxidative eustress. Interestingly, novel experience decreases QR2 expression predominately in inhibitory interneurons. Additionally, we find that in aged animals this newly described QR2 pathway is chronically under activated, resulting in miR-182 underexpression and QR2 overexpression. This leads to accumulative oxidative stress, which can be seen in CA1 via increased levels of oxidized, inactivated potassium channel Kv2.1, which undergoes disulfide bridge oligomerization. This newly described interneuron-specific molecular pathway lies alongside the known mRNA translation-dependent processes necessary for long-term memory formation, entrained by dopamine in CA1. It is a process crucial for the distinguishing features of novel memory, and points to a promising new target for memory enhancement in aging and age-dependent diseases.
Understanding Creutzfeldt-Jackob disease from a viewpoint of amyloidogenic evolvability.
Prion, 2020

Creutzfeldt-Jackob disease (CJD), the most common human prion disorder, is frequently accompanied by ageing-associated neurodegenerative conditions, such as Alzheimer's disease and Parkinson's disease. Although cross-seeding of amyloidogenic proteins (APs), including amyloid β and α-synuclein, may be critical in the co-morbidity of neurodegenerative disorders, the direct interaction of APs with prion protein (PrP), the central molecule involved in the pathogenesis of CJD, is unlikely. Currently, the nature of this biological interaction and its significance remain obscure. In this context, the objective of the present study is to discuss such interactions from the perspective of amyloidogenic evolvability, a putative function of APs. Hypothetically, both hereditary- and sporadic CJD might be attributed to the role of PrP in evolvability against multiple stressors, such as physical stresses relevant to concussions, which might be manifest through the antagonistic pleiotropy mechanism in ageing. Furthermore, accumulating evidence suggests that PrP- and other APs evolvability may negatively regulate each other. Provided that increased APs evolvability might be beneficial for acquired CJD in young adults, a dose-reduction of α-synuclein, a natural inhibitor of αS aggregation, might be therapeutically effective in upregulating APs evolvability. Collectively, a better understanding of amyloidogenic evolvability may lead to the development of novel therapies for CJD.
Hearing what you see: Distinct excitatory and disinhibitory mechanisms contribute to visually-evoked auditory sensations.
Cortex; a journal devoted to the study of the nervous system and behavior, 2020

Visual motion or flashing lights can evoke auditory sensations in some people. This large-scale internet study aimed to validate a combined subjective/objective test of the genuineness of this putative form of synaesthesia (visually-evoked auditory response, vEAR). Correlations were measured between each individual's ratings of the vividness of auditory sensations evoked by a series of looping videos, and measurement of the videos' physical low-level motion energy, calculated using Adelson and Bergen's (1985) computational model of low-level visual motion processing. The strength of this association for each individual provided a test of how strongly subjective vEAR was driven by objective motion energy ('ME-sensitivity'). A second aim was to infer whether vEAR depends on cortical excitation and/or disinhibition of early visual and/or auditory brain areas. To achieve this, correlations were measured between the above vEAR measures and visual contrast surround-suppression, which is thought to index lateral inhibition in the early visual system. As predicted by a disinhibition account of vEAR, video ratings were overall higher in individuals showing weaker surround-suppression. Interestingly, surround-suppression and ME-sensitivity did not correlate. Additionally, both surround-suppression and ME-sensitivity each independently predicted different clusters of trait measures selected for their possible association with cortical excitability and/or disinhibition: Surround-suppression was associated with vEAR self-ratings and auditory-evoked visual phosphenes, while ME-sensitivity was independently associated with ratings of other traits including susceptibility to migraine and pattern glare. Altogether, these results suggest there are two independent mechanisms underlying vEAR and its associated traits, based putatively on cortical disinhibition versus excitability.
Autism classified by magnetic resonance imaging: A pilot study of a potential diagnostic tool.
International journal of methods in psychiatric research, 2020

Individual anatomical biomarkers have limited power for the classification of autism. The present study introduces a multivariate classification approach using structural magnetic resonance imaging data from individuals with and without autism.
Trauma-focused psychotherapy response in youth with posttraumatic stress disorder is associated with changes in insula volume.
Journal of psychiatric research, 2021

Randomized controlled trials have shown efficacy of trauma-focused psychotherapies in youth with posttraumatic stress disorder (PTSD), but little is known about the relationship between treatment response and alternations in brain structures associated with PTSD. In this study, we longitudinally examined the association between treatment response and pre-to posttreatment changes in structural magnetic resonance imaging (MRI) scans using a voxel-based morphometry approach. We analyzed MRI scans of 35 patients (ages 8-18 years, 21 female) with PTSD (80%) or partial PTSD (20%) before and after eight weekly sessions of trauma-focused psychotherapy. PTSD severity was assessed longitudinally using the Clinician-Administered PTSD scale for Children and Adolescents to divide participants into responders and non-responders. Group by time interaction analysis showed significant differences in grey-matter volume in the bilateral insula due to volume reductions over time in non-responders compared to responders. Despite the significant group by time interaction, there were no significant group differences at baseline or follow-up. As typical development is associated with insula volume increase, these longitudinal MRI findings suggest that treatment non-response is associated with atypical neurodevelopment of the insula, which may underlie persistence of PTSD in youth. The absence of structural MRI changes in treatment responders, while in need of replication, suggest that successful trauma-focused psychotherapy may not directly normalize brain abnormalities associated with PTSD.
Autoantibodies against the C-terminus of Lipopolysaccharide binding protein are elevated in young adults with psychiatric disease.
Psychoneuroendocrinology, 2021

Growing evidence implies interactions between infections, the immune system and vulnerability for psychiatric disease. This study applies an affinity proteomic-based method to investigate potential disease associated autoantibody signatures in serum from patients from the "Young Adults" section of the Department of General Psychiatry at Uppsala University Hospital (n = 395) and population-based controls (n = 102). We found serum levels of antibodies against Lipopolysaccharide Binding Protein (LBP), a protein that is important for mediating innate immune responses involving the toll-like receptor-4 (TLR-4), to be higher in patients compared to controls (Mann Whitney U-test p = 5.248 × 10
Small molecule therapeutics for tauopathy in Alzheimer's disease: Walking on the path of most resistance.
European journal of medicinal chemistry, 2021

Alzheimer's disease (AD) is the most common form of dementia characterized by presence of extracellular amyloid plaques and intracellular neurofibrillary tangles composed of tau protein. Currently there are close to 50 million people living with dementia and this figure is expected to increase to 75 million by 2030 putting a huge burden on the economy due to the health care cost. Considering the effects on quality of life of patients and the increasing burden on the economy, there is an enormous need of new disease modifying therapies to tackle this disease. The current therapies are dominated by only symptomatic treatments including cholinesterase inhibitors and N-methyl-D-aspartate receptor blockers but no disease modifying treatments exist so far. After several failed attempts to develop drugs against amyloidopathy, tau targeting approaches have been in the main focus of drug development against AD. After an overview of the tauopathy in AD, this review summarizes recent findings on the development of small molecules as therapeutics targeting tau modification, aggregation, and degradation, and tau-oriented multi-target directed ligands. Overall, this work aims to provide a comprehensive and critical overview of small molecules which are being explored as a lead candidate for discovering drugs against tauopathy in AD.
Comparison of oral glucose tolerance test and HbA1c in detection of disorders of glucose metabolism in patients with acute stroke.
Cardiovascular diabetology, 2020

Diabetes is an increasingly important risk factor for ischemic stroke and worsens stroke prognosis. Yet a large proportion of stroke patients who are eventually diabetic are undiagnosed. Therefore, it is important to have sensitive assessment of unrecognized hyperglycaemia in stroke patients.