rudyvdbrink/CitationDatabase huggingface dataset:
Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer's Disease.
Cell, 2020

To elucidate the role of Tau isoforms and post-translational modification (PTM) stoichiometry in Alzheimer's disease (AD), we generated a high-resolution quantitative proteomics map of 95 PTMs on multiple isoforms of Tau isolated from postmortem human tissue from 49 AD and 42 control subjects. Although Tau PTM maps reveal heterogeneity across subjects, a subset of PTMs display high occupancy and frequency for AD, suggesting importance in disease. Unsupervised analyses indicate that PTMs occur in an ordered manner, leading to Tau aggregation. The processive addition and minimal set of PTMs associated with seeding activity was further defined by analysis of size-fractionated Tau. To summarize, features in the Tau protein critical for disease intervention at different stages of disease are identified, including enrichment of 0N and 4R isoforms, underrepresentation of the C terminus, an increase in negative charge in the proline-rich region (PRR), and a decrease in positive charge in the microtubule binding domain (MBD).
Painful stimulation increases spontaneous blink rate in healthy subjects.
Scientific reports, 2020

Spontaneous blink rate is considered a biomarker of central dopaminergic activity. Recent evidence suggests that the central dopaminergic system plays a role in nociception. In the present study, we aimed to investigate whether pain modulates spontaneous blink rate in healthy subjects. We enrolled 15 participants. Spontaneous blink rate was quantified with an optoelectronic system before and after: (1) a painful laser stimulation, and (2) an acoustic startling stimulation. In control experiments, we investigated whether laser stimulation effects depended on stimulation intensity and whether laser stimulation induced any changes in the blink reflex recovery cycle. Finally, we investigated any relationship between spontaneous blink rate modification and pain modulation effect during the cold pressor test. Laser, but not acoustic, stimulation increased spontaneous blink rate. This effect was independent of stimulation intensity and negatively correlated with pain perception. No changes in trigeminal-facial reflex circuit excitability were elicited by laser stimulation. The cold pressor test also induced an increased spontaneous blink rate. Our study provides evidence on the role of dopamine in nociception and suggests that dopaminergic activity may be involved in pain modulation. These findings lay the groundwork for further investigations in patients with pathological conditions characterized by dopaminergic deficit and pain.
Clinical reasoning: a 39-year-old man with abdominal cramps.
Neurology, 2013

A 39-year-old lawyer presented with intermittent spasms and pain in his abdominal muscles, particularly the right upper quadrant. These had occurred since his mid-20s and there had been long asymptomatic periods, including 8 years prior to the most recent 4-month exacerbation. Trivial movement triggered a spasm of the abdominal muscles, leading to severe pain, which made breathing uncomfortable and interfered with sleep. The symptoms subsided spontaneously after 4 to 5 days, leaving him with a sore abdomen for several weeks. Past attacks had also been precipitated by specific forms of repetitive exercise such as jogging. He described ill-defined numbness in the left leg, but denied any muscle twitching, weakness, back pain, or sphincter disturbance. There was no significant past medical or family history.
Publisher Correction: IRE1α governs cytoskeleton remodelling and cell migration through a direct interaction with filamin A.
Nature cell biology, 2018

In the version of this Article originally published, the competing interests statement was missing. The authors declare no competing interests; this statement has now been added in all online versions of the Article.
[IMAGEN and beyond: novel population neuroscientific strategies for clinical and global cohorts in the STRATIFY and GIGA consortia].
Der Nervenarzt, 2021

Cohort studies provide the possibility to more precisely define treatment and preventive approaches to mental diseases, when genetic and personal influences as well as sociocultural and environmental factors and their interactions are taken into account. This article presents cohort research approaches, which are dedicated to this aim and reports the lessons learnt and achievements made in the IMAGEN cohort study and the resulting further developments. Specifically, we focus on novel assessment instruments, the implementation of larger clinical and geographic ranges and innovative forms of data analysis.
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EJNMMI research, 2020

The standard reference region (RR) for amyloid-beta (Aβ) PET studies is the cerebellar grey matter (GMCB), while alternative RRs have mostly been utilized without prior validation against the gold standard. This study compared five commonly used RRs to gold standard plasma input-based quantification using the GMCB.
My oh my(osin): Insights into how auditory hair cells count, measure, and shape.
The Journal of cell biology, 2016

The mechanisms underlying mechanosensory hair bundle formation in auditory sensory cells are largely mysterious. In this issue, Lelli et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201509017) reveal that a pair of molecular motors, myosin IIIa and myosin IIIb, is involved in the hair bundle's morphology and hearing.
JOINT for large-scale single-cell RNA-sequencing analysis via soft-clustering and parallel computing.
BMC genomics, 2021

Single-cell RNA-Sequencing (scRNA-Seq) has provided single-cell level insights into complex biological processes. However, the high frequency of gene expression detection failures in scRNA-Seq data make it challenging to achieve reliable identification of cell-types and Differentially Expressed Genes (DEG). Moreover, with the explosive growth of single-cell data using 10x genomics protocol, existing methods will soon reach the computation limit due to scalability issues. The single-cell transcriptomics field desperately need new tools and framework to facilitate large-scale single-cell analysis.
The Effects of Midline Cerebellar rTMS on Human Pharyngeal Cortical Activity in the Intact Swallowing Motor System.
Cerebellum (London, England), 2021

We sought to compare the effects of 10 Hz cerebellar vermis (vs. unilateral hemispheric and sham) repetitive transcranial magnetic stimulation (rTMS) on cortical neuroelectrical activity and thereafter 10 Hz cerebellar vermis (vs. sham) rTMS on swallowing behaviour. Healthy participants (n = 25) were randomly allocated to receive vermis, unilateral hemisphere or sham 10 Hz cerebellar rTMS. Recordings were made using pharyngeal electromyography and manometry catheters, obtaining motor-evoked potentials (MEPs) and pressure recordings. The amplitudes of MEPs elicited using single-pulse TMS delivered to the pharyngeal areas of the motor cortex bilaterally were measured pre- and post-cerebellar stimulation. As in previous studies, abductor policis brevis (APB) MEPs were measured to assess post-rTMS modulation specificity. Swallowing was assessed using a swallowing accuracy task. Measurements were made at baseline and 15-min intervals for an hour post-intervention. Measurements involved TMS being used to elicit 10 MEPs bilaterally over the pharyngeal areas of the motor cortex, over the APB cortical representation adjacent to the pharyngeal area with the lowest resting motor threshold and 5 MEPs bilaterally over pharyngeal areas of the cerebellar hemispheres. Swallowing accuracy was assessed by giving participants 10 attempts to swallow and hit a digital target. Cerebellar vermis rTMS caused significant suppression of cortical pharyngeal MEP amplitudes compared with unilateral rTMS and sham (P = 0.0005, 0.002). APB and cerebellar MEP amplitudes were unaffected as were pharyngeal and APB MEP latencies. Following cerebellar vermis rTMS there was a significant reduction in swallowing accuracy compared with sham (P = 0.001). Our findings demonstrate cerebellar vermis rTMS exerts a suppressive effect on pharyngeal motor cortical activity and swallowing behaviour.
Reproducing macaque lateral grasping and oculomotor networks using resting state functional connectivity and diffusion tractography.
Brain structure & function, 2020

Cortico-cortical networks involved in motor control have been well defined in the macaque using a range of invasive techniques. The advent of neuroimaging has enabled non-invasive study of these large-scale functionally specialized networks in the human brain; however, assessing its accuracy in reproducing genuine anatomy is more challenging. We set out to assess the similarities and differences between connections of macaque motor control networks defined using axonal tracing and those reproduced using structural and functional connectivity techniques. We processed a cohort of macaques scanned in vivo that were made available by the open access PRIME-DE resource, to evaluate connectivity using diffusion imaging tractography and resting state functional connectivity (rs-FC). Sectors of the lateral grasping and exploratory oculomotor networks were defined anatomically on structural images, and connections were reproduced using different structural and functional approaches (probabilistic and deterministic whole-brain and seed-based tractography; group template and native space functional connectivity analysis). The results showed that parieto-frontal connections were best reproduced using both structural and functional connectivity techniques. Tractography showed lower sensitivity but better specificity in reproducing connections identified by tracer data. Functional connectivity analysis performed in native space had higher sensitivity but lower specificity and was better at identifying connections between intrasulcal ROIs than group-level analysis. Connections of AIP were most consistently reproduced, although those connected with prefrontal sectors were not identified. We finally compared diffusion MR modelling with histology based on an injection in AIP and speculate on anatomical bases for the observed false negatives. Our results highlight the utility of precise ex vivo techniques to support the accuracy of neuroimaging in reproducing connections, which is relevant also for human studies.
How much time do we have? Longitudinal perception of prognosis in newly-diagnosed high grade glioma patients and caregivers compared to clinicians.
Journal of neuro-oncology, 2021

Discordant prognostic awareness (PA) can cause distress, impact goals of care and future planning, especially in patients with high grade glioma (pwHGG) who have limited survival. We aimed to evaluate the feasibility of assessing PA of pwHGG, caregivers and clinicians using a single question and to evaluate these responses for discord, alignment and fluctuation over time.
Impact of endometrial sampling technique and biopsy volume on the diagnostic accuracy of endometrial cancer.
Translational cancer research, 2020

Histotype and tumor grading of endometrial cancer are the most important factors that have to be assessed by preoperative endometrial sampling, and their concordance with the final surgical and definitive histological findings is of paramount importance. We aim to compare histotype and tumor grading concordance of various endometrial sampling techniques (ESTs) and to investigate the role of endometrial volume biopsy.
Neuropathology of viral infections of the central nervous system.
Neuroimaging clinics of North America, 2008

Many viral infections of the nervous system cause stereotyped pathologic features and overlapping clinical and imaging features. Neuroimaging usually offers neuroanatomical localization of the pathology, degree of involvement of the nervous system, and response to therapy during follow up in a few instances. Neuroimaging is a useful adjunct for diagnosis.
Neuroscience: Boosting the brain.
Current biology : CB, 2021

A therapeutic effect of vagus nerve stimulation has been reported for a wide range of neurological, medical and psychiatric conditions. New research provides evidence that this effect results from extensive increase of physiological arousal and brain activation.
Publisher Correction: Sensory experience remodels genome architecture in neural circuit to drive motor learning.
Nature, 2019

In this Letter, '≥' should be '≤' in the sentence: "Intra-chromosomal reads were further split into short-range reads (≥1 kb) and long-range reads (>1 kb)". This error has been corrected online.An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Incidence and risk factors of hepatocellular carcinoma in patients with hepatitis C in China and the United States.
Scientific reports, 2020

Hepatitis C virus (HCV) infection is the main cause of hepatocellular carcinoma (HCC) in the United States (US) and an increasingly common cause of HCC in China. We aimed to evaluate the incidence and risk factors of HCC in HCV patients in the US and China. 795 HCV RNA + patients without HCC from University of Michigan Health System (UMHS) in the US and 854 from Peking University Health Sciences Center (PUHSC) in China were prospectively followed for a median of 3.2 and 4.0 years, respectively. 45.4% UMHS and 16.2% PUHSC patients had cirrhosis. 57.6% UMHS and 52.0% PUHSC patients achieved SVR. 45 UMHS and 13 PUHSC patients developed HCC. Cumulative incidence of HCC at 5 years was 7.6% in UMHS and 1.8% in PUHSC cohort (P < 0.001). Ten patients not diagnosed with cirrhosis at enrollment but median APRI ≥ 2.0 developed HCC. Multivariate analysis showed age, gender, cirrhosis and APRI were predictors of HCC while study site and SVR were not. In this study of HCV patients, HCC incidence in the PUHSC cohort was lower than in the UMHS cohort, due to lower proportion of PUHSC patients with cirrhosis. APRI can identify risk of HCC among patients not diagnosed to have cirrhosis.
Subthalamic beta-targeted neurofeedback speeds up movement initiation but increases tremor in Parkinsonian patients.
eLife, 2020

Previous studies have explored neurofeedback training for Parkinsonian patients to suppress beta oscillations in the subthalamic nucleus (STN). However, its impacts on movements and Parkinsonian tremor are unclear. We developed a neurofeedback paradigm targeting STN beta bursts and investigated whether neurofeedback training could improve motor initiation in Parkinson's disease compared to passive observation. Our task additionally allowed us to test which endogenous changes in oscillatory STN activities are associated with trial-to-trial motor performance. Neurofeedback training reduced beta synchrony and increased gamma activity within the STN, and reduced beta band coupling between the STN and motor cortex. These changes were accompanied by reduced reaction times in subsequently cued movements. However, in Parkinsonian patients with pre-existing symptoms of tremor, successful volitional beta suppression was associated with an amplification of tremor which correlated with theta band activity in STN local field potentials, suggesting an additional cross-frequency interaction between STN beta and theta activities.
Internet-Delivered Acceptance and Commitment Therapy for Adolescents with Chronic Pain and Their Parents: A Nonrandomized Pilot Trial.
Journal of pediatric psychology, 2020

Acceptance and Commitment Therapy (ACT) is an empirically supported treatment for chronic pain in adults. There is also a small but growing evidence base of ACT for pediatric chronic pain. However, because of limited access to psychological treatment for pain, and geographical distances from pain facilities, many patients will not receive such treatment.
Metabolic engineering of non-pathogenic Escherichia coli strains for the controlled production of low molecular weight heparosan and size-specific heparosan oligosaccharides.
Biochimica et biophysica acta. General subjects, 2021

Heparin, a lifesaving blood thinner used in over 100 million surgical procedures worldwide annually, is currently isolated from over 700 million pigs and ~200 million cattle in slaughterhouses worldwide. Though animal-derived heparin has been in use over eight decades, it is a complex mixture that poses a risk for chemical adulteration, and its availability is highly vulnerable. Therefore, there is an urgent need in devising bioengineering approaches for the production of heparin polymers, especially low molecular weight heparin (LMWH), and thus, relying less on animal sources. One of the main challenges, however, is the rapid, cost-effective production of low molecular weight heparosan, a precursor of LMWH and size-defined heparosan oligosaccharides. Another challenge is N-sulfation of N-acetyl heparosan oligosaccharides efficiently, an essential modification required for subsequent enzymatic modifications, though chemical and enzymatic N-sulfation is effectively performed at the polymer level.
Supraorbital Approach to Basal Frontal Lobe for Resection of Brain Metastasis.
World neurosurgery, 2019

This video illustrates the use of the supraorbital craniotomy via an eyebrow incision for access to the basal frontal lobe. This approach is particularly useful for removal of lesions in the dominant hemisphere, where a transcortical approach could place speech centers at risk. The case is that of a 57-year-old woman who presented after a mental status change and was noted to have a large left frontal mass. The patient had a history of melanoma, and pathologic analysis of the intracranial lesion was consistent with metastatic melanoma. The patient underwent an uneventful gross-total lesion resection. The step-by-step techniques for performing this operation are illustrated (Video 1). Although not used in this case because we had an excellent view of the lesion, removal of the orbital rim allows the surgeon to obtain a better inferior-to-superior trajectory without using retraction. Of utmost importance to satisfactory cosmetic outcome are meticulous layer-by-layer closure of the eyebrow incision and maintaining pressure on the wound at the time of extubation. This pressure prevents accumulation of hematoma or cerebrospinal fluid, which places the wound under tension, impedes healing, and detrimentally affects cosmetic outcome. Additional adjuncts in this procedure may include hyperextending the head to bring the tumor into more direct view and drilling the skull base flush to expand the operative corridor. Minimally invasive approaches are excellent for the removal of metastasis because they are smaller incisions that remain well vascularized and heal quickly, allowing the patient to initiate adjuvant therapy sooner. The patient's family provided consent for publication.
The nonsense mutation stop+4 model correlates with motor changes in Duchenne muscular dystrophy.
Neuromuscular disorders : NMD, 2021

The aim was to assess 3-year longitudinal data using 6MWT in 26 ambulant boys affected by DMD carrying nonsense mutations and to compare their results to other small mutations. We also wished to establish, within the nonsense mutations group, patterns of change according to several variables. Patients with nonsense mutations were categorized according to the stop codon type newly created by the mutation and also including the adjacent 5' (upstream) and 3' (downstream) nucleotides. No significant difference was found between nonsense mutations and other small mutations (p > 0.05) on the 6MWT. Within the nonsense mutations group, there was no difference in 6MWT when the patients were subdivided according to: Type of stop codon, frame status of exons involved, protein domain affected. In contrast, there was a difference when the stop codon together with the 3' adjacent nucleotide ("stop+4 model") was considered (p < 0.05) with patients with stop codon TGA and 3' adjacent nucleotide G (TGAG) having a more rapid decline. Our finding suggest that the stop+4 model may help in predicting functional changes. This data will be useful at the time of interpreting the long term follow up of patients treated with Ataluren that are becoming increasingly available.
Rapid image deconvolution and multiview fusion for optical microscopy.
Nature biotechnology, 2020

The contrast and resolution of images obtained with optical microscopes can be improved by deconvolution and computational fusion of multiple views of the same sample, but these methods are computationally expensive for large datasets. Here we describe theoretical and practical advances in algorithm and software design that result in image processing times that are tenfold to several thousand fold faster than with previous methods. First, we show that an 'unmatched back projector' accelerates deconvolution relative to the classic Richardson-Lucy algorithm by at least tenfold. Second, three-dimensional image-based registration with a graphics processing unit enhances processing speed 10- to 100-fold over CPU processing. Third, deep learning can provide further acceleration, particularly for deconvolution with spatially varying point spread functions. We illustrate our methods from the subcellular to millimeter spatial scale on diverse samples, including single cells, embryos and cleared tissue. Finally, we show performance enhancement on recently developed microscopes that have improved spatial resolution, including dual-view cleared-tissue light-sheet microscopes and reflective lattice light-sheet microscopes.
Microglial depletion aggravates the severity of acute and chronic seizures in mice.
Brain, behavior, and immunity, 2020

Microglia are the resident immune cells of the center nervous system and participate in various neurological diseases. Here we determined the function of microglia in epileptogenesis using microglial ablation approaches. Three different microglia-specific genetic tools were used, CX3CR1
Agonistic behaviors and neuronal activation in sexually naïve female Mongolian gerbils.
Behavioural brain research, 2020

Agonistic interaction is important for establishing social hierarchy and determining access to limited resources. Although there are substantial studies investigating the neural mechanisms of aggressive or defensive behavior in male rodents, little attention has been paid to the mechanisms underlying agonistic behaviors in females. In the present study, we depicted patterns of agonistic behaviors in sexually naïve female Mongolian gerbils (Meriones unguiculatus) and examined the neuronal activation in the brain by Fos-immunoreactive (Fos-ir) staining. We found that the winner-loser relationship was established rapidly. Winners displayed higher levels of aggression, environmental exploration, scent marking, and self-grooming, but less defensive behavior, in comparison to losers. Several patterns of Fos-ir expression emerged following agonistic interactions. Winners had the number of Fos-ir cells in the ventrolateral subnucleus of the ventromedial hypothalamus (VMHvl) and dorsal periaqueductal grey (PAGd) more than the controls but less than the losers. Losers also had more Fos-ir cells in the paraventricular nucleus of the hypothalamus (PVN), anterior medial (BSTam) and anteriolateral (BSTal) subnuclei of the bed nucleus of the stria terminalis (BST), and the ventral subnucleus of the lateral septum (LSv), as well as less Fos-ir cells in the dentate gyrus of the hippocampus (DG), compared to the controls. In addition, the number of Fos-ir cells showed similar increases in the principal nucleus (BSTpr) and interfascicular nucleus (BSTif) of the BST and amygdala (AMYG) in both the winners and losers, compared to the controls. Together, these data illustrate the patterns of altered neuronal activation in a behavior-, social status-, and brain region-specific manner, implicating potential roles of the brain neural circuit in mediating agonistic interactions in female Mongolian gerbils.