rudyvdbrink/CitationDatabase huggingface dataset:
Effectivity of Two Cell Proliferation Markers in Brain of a Songbird Zebra Finch.
Biology, 2020

There are two most heavily used markers of cell proliferation, thymidine analogues 5-bromo-2'-deoxyuridine (BrdU) and 5-ethynyl-2'-deoxyuridine (EdU) that are incorporated into the DNA during its synthesis. In neurosciences, they are often used consecutively in the same animal to detect neuronal populations arising at multiple time points, their migration and incorporation. The effectivity of these markers, however, is not well established. Here, we studied the effectivity of equimolar doses of BrdU and EdU to label new cells and looked for the dose that will label the highest number of proliferating cells in the neurogenic ventricular zone (VZ) of adult songbirds. We found that, in male zebra finches (
Clinical negligence: Understanding why things go wrong.
The Medico-legal journal, 2020

Clinical negligence claims are on the rise, with lawyers often playing a leading part in ascertaining what went wrong, why it went wrong and what lessons can be learned. I present a schema which may help lawyers better understand what goes wrong in clinical negligence cases.
Primary mitochondrial myopathy: Clinical features and outcome measures in 118 cases from Italy.
Neurology. Genetics, 2020

To determine whether a set of functional tests, clinical scales, patient-reported questionnaires, and specific biomarkers can be considered reliable outcome measures in patients with primary mitochondrial myopathy (PMM), we analyzed a cohort of Italian patients.
Comparing SNNs and RNNs on neuromorphic vision datasets: Similarities and differences.
Neural networks : the official journal of the International Neural Network Society, 2020

Neuromorphic data, recording frameless spike events, have attracted considerable attention for the spatiotemporal information components and the event-driven processing fashion. Spiking neural networks (SNNs) represent a family of event-driven models with spatiotemporal dynamics for neuromorphic computing, which are widely benchmarked on neuromorphic data. Interestingly, researchers in the machine learning community can argue that recurrent (artificial) neural networks (RNNs) also have the capability to extract spatiotemporal features although they are not event-driven. Thus, the question of "what will happen if we benchmark these two kinds of models together on neuromorphic data" comes out but remains unclear. In this work, we make a systematic study to compare SNNs and RNNs on neuromorphic data, taking the vision datasets as a case study. First, we identify the similarities and differences between SNNs and RNNs (including the vanilla RNNs and LSTM) from the modeling and learning perspectives. To improve comparability and fairness, we unify the supervised learning algorithm based on backpropagation through time (BPTT), the loss function exploiting the outputs at all timesteps, the network structure with stacked fully-connected or convolutional layers, and the hyper-parameters during training. Especially, given the mainstream loss function used in RNNs, we modify it inspired by the rate coding scheme to approach that of SNNs. Furthermore, we tune the temporal resolution of datasets to test model robustness and generalization. At last, a series of contrast experiments are conducted on two types of neuromorphic datasets: DVS-converted (N-MNIST) and DVS-captured (DVS Gesture). Extensive insights regarding recognition accuracy, feature extraction, temporal resolution and contrast, learning generalization, computational complexity and parameter volume are provided, which are beneficial for the model selection on different workloads and even for the invention of novel neural models in the future.
Thirst Increases Chorda Tympani Responses to Sodium Chloride.
Chemical senses, 2017

In nature, water is present as a low-salt solution, thus we hypothesized that thirst would increase taste responses to low-salt solutions. We investigated the effect of thirst on the 2 different salt detection mechanisms present in the rat chorda tympani (CT) nerve. The first mechanism is dependent upon the epithelial sodium channel (ENaC), is blocked by benzamil, and is specific to the cation sodium. The second mechanism, while undefined, is independent of ENaC, and detects multiple cations. We expected thirst to increase benzamil-sensitive sodium responses due to mechanistically increasing the benzamil-sensitive ENaC. We recorded CT whole-nerve electrophysiological responses to lingual application of NaCl, KCl (30, 75, 150, 300, 500, and 600 mM), and imitation rainwater in both control and 24-h water-restricted male rats. NaCl solutions were presented in artificial saliva before and after lingual application of 5µM benzamil. Water restriction significantly increased the integrated CT responses to NaCl but not to KCl or imitation rainwater. Consistent with our hypothesis, only the benzamil-sensitive, and not the benzamil-insensitive, CT sodium response significantly increased. Additionally, CT responses to salt were recorded following induction of either osmotic or volemic thirst. Both thirsts significantly enhanced the integrated CT responses to NaCl and KCl, but not imitation rainwater. Interestingly, osmotic and volemic thirsts increased CT responses by increasing both the benzamil-sensitive and benzamil-insensitive CT sodium responses. We propose that thirst increases the sensitivity of the CT nerve to sodium.
The role of CT body scans in the investigation of patients with newly diagnosed brain tumours.
British journal of neurosurgery, 2014

In the UK approximately 4000 patients are diagnosed with brain tumours each year. Many patients undergo CT scans of the chest, abdomen and pelvis as part of the investigation of such tumours. We aimed to determine the value of CT body scans in patients with newly diagnosed brain tumours.
Reduction of AMPA receptor activity on mature oligodendrocytes attenuates loss of myelinated axons in autoimmune neuroinflammation.
Science advances, 2020

Glutamate dysregulation occurs in multiple sclerosis (MS), but whether excitotoxic mechanisms in mature oligodendrocytes contribute to demyelination and axonal injury is unexplored. Although current treatments modulate the immune system, long-term disability ensues, highlighting the need for neuroprotection. Glutamate is elevated before T2-visible white matter lesions appear in MS. We previously reported that myelin-reactive T cells provoke microglia to release glutamate from the system x
Mitoxantrone in relapsing-remitting and rapidly progressive multiple sclerosis: Ten-year clinical outcomes post-treatment with mitoxantrone.
Multiple sclerosis and related disorders, 2020

Mitoxantrone (MTX) has been used as an effective disease modifying treatment (DMT) in multiple sclerosis (MS). Evidence from studies demonstrates benefits of reduced relapse rates, MRI disease activity and disability progression in patients treated with MTX. While effective, MTX use has been limited due to potential adverse effects (AE) ranging from mild to potentially life-threatening AEs such as cardiotoxicity, bone marrow suppression and hematological malignancies. In this study we aimed to review the long-term clinical efficacy, tolerability, and AE profile of treatment with MTX in patients both with relapsing-remitting and rapidly progressive MS over a 10-year follow-up period.
Frontotemporal dementia: a conference report from the 2nd FinFTD Symposium.
Neurodegenerative disease management, 2020

The 2nd FinFTD Symposium was held on 13 September 2019, in Kuopio, Finland, and attracted 80 attendees from six different countries. The program, spanning from molecular mechanisms to biomarkers, prevention, diagnosis and treatment of frontotemporal lobar degeneration and related diseases, provided a great opportunity for researchers, clinicians, healthcare professionals and other participants to discuss about the current status and future directions of frontotemporal lobar degeneration research.
Top ten discoveries of the year: Neurooncology.
Free neuropathology, 2020

This article briefly discusses 10 topics that were selected by the author as top 10 discoveries published in 2019 in the broader field of neuro-oncological pathology (so including neurosciences as well as clinical neuro-oncology but with implications for neuro-oncological pathology). Some topics concern new information on immunohistochemical and molecular markers that enable improved diagnosis of particular tumors of the central nervous system (CNS) and information on a refined classification of medulloblastomas. Subsequently, several papers are discussed that further elucidate some pathobiological aspects of especially medulloblastomas (histogenesis, molecular evolution) and diffuse gliomas (mechanisms involved in CNS infiltration, role of cancer stem(-like) cells, longitudinal molecular evolution). The remaining topics concern progress made in vaccination therapy for glioblastomas and in using cerebrospinal fluid for liquid biopsy diagnosis of gliomas. Clearly, substantial, and sometimes even amazing progress has been made in increasing our understanding in several areas of neuro-oncological pathology. At the same time, almost every finding raises new questions, and translation of new insights in improving the outcome for patients suffering from CNS tumors remains a huge challenge.
Preparation of DNA-crosslinked polyacrylamide hydrogels.
Journal of visualized experiments : JoVE, 2014

Mechanobiology is an emerging scientific area that addresses the critical role of physical cues in directing cell morphology and function. For example, the effect of tissue elasticity on cell function is a major area of mechanobiology research because tissue stiffness modulates with disease, development, and injury. Static tissue-mimicking materials, or materials that cannot alter stiffness once cells are plated, are predominately used to investigate the effects of tissue stiffness on cell functions. While information gathered from static studies is valuable, these studies are not indicative of the dynamic nature of the cellular microenvironment in vivo. To better address the effects of dynamic stiffness on cell function, we developed a DNA-crosslinked polyacrylamide hydrogel system (DNA gels). Unlike other dynamic substrates, DNA gels have the ability to decrease or increase in stiffness after fabrication without stimuli. DNA gels consist of DNA crosslinks that are polymerized into a polyacrylamide backbone. Adding and removing crosslinks via delivery of single-stranded DNA allows temporal, spatial, and reversible control of gel elasticity. We have shown in previous reports that dynamic modulation of DNA gel elasticity influences fibroblast and neuron behavior. In this report and video, we provide a schematic that describes the DNA gel crosslinking mechanisms and step-by-step instructions on the preparation DNA gels.
Lamellipodia-like protrusions and focal adhesions contribute to collective cell migration in zebrafish.
Developmental biology, 2021

Collective cell migration is a process where cohorts of cells exhibit coordinated migratory behavior. During individual and collective cellular migration, cells must extend protrusions to interact with the extracellular environment, sense chemotactic cues, and act as points of attachment. The mechanisms and regulators of protrusive behavior have been widely studied in individually migrating cells; however, how this behavior is regulated throughout collectives is not well understood. To address this, we used the zebrafish posterior lateral line primordium (pLLP) as a model. The pLLP is a cluster of ~150 ​cells that migrates along the zebrafish trunk, depositing groups of cells that will become sensory organs. To define protrusive behavior, we performed mosaic analysis to sparsely label pLLP cells with a transgene marking filamentous actin. This approach revealed an abundance of brush-like protrusions throughout the pLLP that orient in the direction of migration. Formation of these protrusions depends on the Arp2/3 complex, a regulator of dendritic actin. This argues that these brush-like protrusions are an in vivo example of lamellipodia. Mosaic analysis demonstrated that these lamellipodia-like protrusions are located in a close proximity to the overlying skin. Immunostaining revealed an abundance of focal adhesion complexes surrounding the pLLP. Disruption of these complexes specifically in pLLP cells led to impaired pLLP migration. Finally, we show that Erk signaling, a known regulator of focal adhesions, is required for proper formation of lamellipodia-like protrusions and pLLP migration. Altogether, our results suggest a model where the coordinated dynamics of lamellipodia-like protrusions, making contact with either the overlying skin or the extracellular matrix through focal adhesions, promotes migration of pLLP cells.
[The Peripheral Neuropathy and Myopathy Associated with Severe Acute Respiratory Syndrome-Correlated New Coronavirus (SARS-Cov-2)].
Brain and nerve = Shinkei kenkyu no shinpo, 2020

Severe acute respiratory syndrome-correlated new coronavirus (SARS-Cov-2) continues to spread rapidly around the world. Reports regarding the neuropathy and myopathy associated with SARS-Cov-2 increase everyday. SARS-Cov-2 infection may result in peripheral neuropathy and myopathy, although direct infection of the peripheral nerve and muscle by SARS-Cov-2 is exceedingly rare. When initiating clinical treatment for COVID-19, it is crutial to distinguish the peripheral neuropathy or myopathy caused directly or indirectly by SARS-Cov-2 from those caused by other conditions. In this review, we aimed to report the peripheral nerve and muscle disorders associated with SARS-Cov-2 and their possible underlying pathophysiological mechanisms.
Phase imaging with computational specificity (PICS) for measuring dry mass changes in sub-cellular compartments.
Nature communications, 2020

Due to its specificity, fluorescence microscopy has become a quintessential imaging tool in cell biology. However, photobleaching, phototoxicity, and related artifacts continue to limit fluorescence microscopy's utility. Recently, it has been shown that artificial intelligence (AI) can transform one form of contrast into another. We present phase imaging with computational specificity (PICS), a combination of quantitative phase imaging and AI, which provides information about unlabeled live cells with high specificity. Our imaging system allows for automatic training, while inference is built into the acquisition software and runs in real-time. Applying the computed fluorescence maps back to the quantitative phase imaging (QPI) data, we measured the growth of both nuclei and cytoplasm independently, over many days, without loss of viability. Using a QPI method that suppresses multiple scattering, we measured the dry mass content of individual cell nuclei within spheroids. In its current implementation, PICS offers a versatile quantitative technique for continuous simultaneous monitoring of individual cellular components in biological applications where long-term label-free imaging is desirable.
Endoscopic needle biopsy of thalamic tumors: technical note.
Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery, 2020

Neuroendoscopic biopsy represents the procedure of choice for pure intraventricular lesions. Instead, in case of deep-seated paraventricular tumors, with intact ependyma, the advantage of neuroendoscopy over stereotactic biopsy is not so evident, because the lesion is not under direct vision; the tissue sample may be limited to more superficial ependymal layer, and bleeding may obscurate vision. Also, stereotactic biopsy may reserve additional problems for these lesions: inaccuracy caused by leak of cerebrospinal fluid and increased risk of severe hemorrhage due to damage of the ependymal vessels.
Creutzfeldt-Jakob disease masked by head trauma and features of Wilson's disease.
The International journal of neuroscience, 2015

Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disorder typically characterized by progressive dementia associated with myoclonus, cerebellar and other focal neurological signs. Electroencephalogram, brain MRI and cerebrospinal fluid (CSF) analyses are helpful diagnostic tools, but diagnosis in patients with atypical presenting neurological signs is often difficult to make. A 55-year-old woman developed disorientation, drowsiness and focal motor signs after a traumatic brain injury due to an accidental fall. In two weeks, her symptoms worsened in spite of a brain MRI showed an improvement of traumatic lesions, but the presence of bilateral hyperintensity in the basal nuclei was suggestive of a metabolic or prion encephalopathy. The high 24-h urinary copper level and reduction of ceruloplasmin initially supported the diagnosis of Wilson's disease, but the absence of Kayser-Fleischer rings, and the positivity of 14-3-3 protein test and elevated tau concentrations in the CSF oriented toward a diagnosis of CJD. She died 5 months after the onset, and the postmortem examination of the brain revealed immunochemical features of CJD. This case exemplifies the difficulty of a timely diagnosis when rapid progressive dementia is masked by concomitant factors (i.e., head trauma) and neurological signs are associated with unclear laboratory findings.
Patients with fibromyalgia show increased beta connectivity across distant networks and microstates alterations in resting-state electroencephalogram.
NeuroImage, 2020

Fibromyalgia (FM) is a chronic condition characterized by widespread pain of unknown etiology associated with alterations in the central nervous system. Although previous studies demonstrated altered patterns of brain activity during pain processing in patients with FM, alterations in spontaneous brain oscillations, in terms of functional connectivity or microstates, have been barely explored so far. Here we recorded the EEG from 43 patients with FM and 51 healthy controls during open-eyes resting-state. We analyzed the functional connectivity between different brain networks computing the phase lag index after group Independent Component Analysis, and also performed an EEG microstates analysis. Patients with FM showed increased beta band connectivity between different brain networks and alterations in some microstates parameters (specifically lower occurrence and coverage of microstate class C). We speculate that the observed alterations in spontaneous EEG may suggest the dominance of endogenous top-down influences; this could be related to limited processing of novel external events and the deterioration of flexible behavior and cognitive control frequently reported for FM. These findings provide the first evidence of alterations in long-distance phase connectivity and microstate indices at rest, and represent progress towards the understanding of the pathophysiology of fibromyalgia and the identification of novel biomarkers for its diagnosis.
Visual and Semantic Representations Predict Subsequent Memory in Perceptual and Conceptual Memory Tests.
Cerebral cortex (New York, N.Y. : 1991), 2021

It is generally assumed that the encoding of a single event generates multiple memory representations, which contribute differently to subsequent episodic memory. We used functional magnetic resonance imaging (fMRI) and representational similarity analysis to examine how visual and semantic representations predicted subsequent memory for single item encoding (e.g., seeing an orange). Three levels of visual representations corresponding to early, middle, and late visual processing stages were based on a deep neural network. Three levels of semantic representations were based on normative observed ("is round"), taxonomic ("is a fruit"), and encyclopedic features ("is sweet"). We identified brain regions where each representation type predicted later perceptual memory, conceptual memory, or both (general memory). Participants encoded objects during fMRI, and then completed both a word-based conceptual and picture-based perceptual memory test. Visual representations predicted subsequent perceptual memory in visual cortices, but also facilitated conceptual and general memory in more anterior regions. Semantic representations, in turn, predicted perceptual memory in visual cortex, conceptual memory in the perirhinal and inferior prefrontal cortex, and general memory in the angular gyrus. These results suggest that the contribution of visual and semantic representations to subsequent memory effects depends on a complex interaction between representation, test type, and storage location.
Intensity- and timing-dependent modulation of motion perception with transcranial magnetic stimulation of visual cortex.
Neuropsychologia, 2020

Despite the widespread use of transcranial magnetic stimulation (TMS) in research and clinical care, the dose-response relations and neurophysiological correlates of modulatory effects remain relatively unexplored. To fill this gap, we studied modulation of visual processing as a function of TMS parameters. Our approach combined electroencephalography (EEG) with application of single pulse TMS to visual cortex as participants performed a motion perception task. During each participants' first visit, motion coherence thresholds, 64-channel visual evoked potentials (VEPs), and TMS resting motor thresholds (RMT) were measured. In second and third visits, single pulse TMS was delivered at one of two latencies, either 30 ms before the onset of motion or at the onset latency of the N2 VEP component derived from the first session. TMS was delivered at 0%, 80%, 100%, or 120% of RMT over the site of N2 peak activity, or at 120% over vertex. Behavioral results demonstrated a significant main effect of TMS timing on accuracy, with better performance when TMS was applied at the N2-Onset timing versus Pre-Onset, as well as a significant interaction, indicating that 80% intensity produced higher accuracy than other conditions at the N2-Onset. TMS effects on the P3 VEP showed reduced amplitudes in the 80% Pre-Onset condition, an increase for the 120% N2-Onset condition, and monotonic amplitude scaling with stimulation intensity. The N2 component was not affected by TMS. These findings reveal the influence of TMS intensity and timing on visual perception and electrophysiological responses, with optimal facilitation at stimulation intensities below RMT.
How achievable are COVID-19 clinical trial recruitment targets? A UK observational cohort study and trials registry analysis.
BMJ open, 2020

To analyse enrolment to interventional trials during the first wave of the COVID-19 pandemic in England and describe the barriers to successful recruitment in the circumstance of a further wave or future pandemics.
Drebrin expression patterns in patients with refractory temporal lobe epilepsy and hippocampal sclerosis.
Epilepsia, 2020

Drebrins are crucial for synaptic function and dendritic spine development, remodeling, and maintenance. In temporal lobe epilepsy (TLE) patients, a significant hippocampal synaptic reorganization occurs, and synaptic reorganization has been associated with hippocampal hyperexcitability. This study aimed to evaluate, in TLE patients, the hippocampal expression of drebrin using immunohistochemistry with DAS2 or M2F6 antibodies that recognize adult (drebrin A) or adult and embryonic (pan-drebrin) isoforms, respectively.