Brain-derived tau oligomer polymorphs: distinct aggregations, stability profiles, and biological activities.

Aggregation of microtubule-associated tau protein is a distinct hallmark of several neurodegenerative disorders such as Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and progressive supranuclear palsy (PSP). Tau oligomers are suggested to be the primary neurotoxic species that initiate aggregation and propagate prion-like structures. Furthermore, different diseases are shown to have distinct structural characteristics of aggregated tau, denoted as polymorphs.

Clinical outcomes of selective removal to soft dentin versus firm dentin for deep caries lesions: a randomized controlled trial up to 5 years.

Objectives: This study aimed to compare the success of selective removal to soft dentine (SRSD) with or without calcium silicate (CS) and selective removal to firm dentine (SRFD) in permanent dentition.

Materials And Methods: Between November 2018 and March 2020, 165 posterior deep caries lesions in 134 patients were included in the study and randomly assigned into test (n = 101) and control (n = 64) groups. The control group (n = 46) received the treatment of SRFD with CS, while the test group was further randomized into two groups to receive SRSD with CS (n = 45) and SRSD without CS (n = 45).

Exploring neural oscillations during speech perception via surrogate gradient spiking neural networks.

Understanding cognitive processes in the brain demands sophisticated models capable of replicating neural dynamics at large scales. We present a physiologically inspired speech recognition architecture, compatible and scalable with deep learning frameworks, and demonstrate that end-to-end gradient descent training leads to the emergence of neural oscillations in the central spiking neural network. Significant cross-frequency couplings, indicative of these oscillations, are measured within and across network layers during speech processing, whereas no such interactions are observed when handling background noise inputs.

Translation, cross-cultural adaptation, reliability and validity of the Brazilian Portuguese version of the 'Fit to Dance?' survey.

Background: The 'Fit to Dance?' survey has been used in a number of studies to understand the health and wellbeing of dancers. These data have not been collected in Brazil as there is no validated questionnaire available in Brazilian Portuguese, culturally validated in Brazil with a scope as broad and comprehensive as that of 'Fit to Dance?'.

Objective: Translate into Brazilian Portuguese and culturally validate the questionnaire 'Fit to Dance?' in Brazil.

Automatic detection of expressed emotion from Five-Minute Speech Samples: Challenges and opportunities.

Research into clinical applications of speech-based emotion recognition (SER) technologies has been steadily increasing over the past few years. One such potential application is the automatic recognition of expressed emotion (EE) components within family environments. The identification of EE is highly important as they have been linked with a range of adverse life events.

Traumatic brain injury derived pathological tau polymorphs induce the distinct propagation pattern and neuroinflammatory response in wild type mice.

The misfolding and aggregation of the tau protein into neurofibrillary tangles constitutes a central feature of tauopathies. Traumatic brain injury (TBI) has emerged as a potential risk factor, triggering the onset and progression of tauopathies. Our previous research revealed distinct polymorphisms in soluble tau oligomers originating from single versus repetitive mild TBIs.

Comparison of outcomes for fixed and weight-based four-factor prothrombin complex concentrate dosing regimens.

Objectives: Although fixed dose regimens using four-factor prothrombin complex concentrate (4F-PCC) are more widely accepted, using a 'one size fits all' approach remains an area of uncertainty. The primary objective of this study was to compare percentages of haemostasis between fixed dose and weight-based dose 4F-PCC regimens for multiple bleed types and anticoagulants. Secondary objectives compared differences in the time to administration and in-hospital mortality.

Tailoring Magnetite-Nanoparticle-Based Nanocarriers for Gene Delivery: Exploiting CRISPRa Potential in Reducing Conditions.

Gene delivery has emerged as a promising alternative to conventional treatment approaches, allowing for the manipulation of gene expression through gene insertion, deletion, or alteration. However, the susceptibility of gene delivery components to degradation and challenges associated with cell penetration necessitate the use of delivery vehicles for effective functional gene delivery. Nanostructured vehicles, such as iron oxide nanoparticles (IONs) including magnetite nanoparticles (MNPs), have demonstrated significant potential for gene delivery applications due to their chemical versatility, biocompatibility, and strong magnetization.

Investigating online activity in UK adolescent mental health patients: a feasibility study using a natural language processing approach for electronic health records.

Objectives: To assess the feasibility of using a natural language processing (NLP) application for extraction of free-text online activity mentions in adolescent mental health patient electronic health records (EHRs).

Setting: The Clinical Records Interactive Search system allows detailed research based on deidentified EHRs from the South London and Maudsley NHS Foundation Trust, a large south London Mental Health Trust providing secondary and tertiary mental healthcare.

Participants And Methods: We developed a gazetteer of online activity terms and annotation guidelines, from 5480 clinical notes (200 adolescents, aged 11-17 years) receiving specialist mental healthcare.

Passive Immunotherapy Targeting Tau Oligomeric Strains Reverses Tauopathy Phenotypes in Aged Human-Tau Mice in a Mouse Model-Specific Manner.

Background: Tau oligomers are one of the most toxic species, displaying prion-like strains which have different conformations resulting in different tauopathies. Passive immunotherapy targeting different tau species is a promising therapeutic approach. Age is one of the greatest risk factors; however, most immunotherapy studies are done in young to middle-aged mice tauopathy models, which is not representative of the many clinical trials done with older humans with established tauopathies.

A surrogate gradient spiking baseline for speech command recognition.

Artificial neural networks (ANNs) are the basis of recent advances in artificial intelligence (AI); they typically use real valued neuron responses. By contrast, biological neurons are known to operate using spike trains. In principle, spiking neural networks (SNNs) may have a greater representational capability than ANNs, especially for time series such as speech; however their adoption has been held back by both a lack of stable training algorithms and a lack of compatible baselines.

Divergence in brain size and brain region volumes across wild guppy populations.

Complex evolutionary dynamics have produced extensive variation in brain anatomy in the animal world. In guppies, , brain size and anatomy have been extensively studied in the laboratory contributing to our understanding of brain evolution and the cognitive advantages that arise with brain anatomical variation. However, it is unclear whether these laboratory results can be translated to natural populations.

Understanding the Potential of Genome Editing in Parkinson's Disease.

CRISPR is a simple and cost-efficient gene-editing technique that has become increasingly popular over the last decades. Various CRISPR/Cas-based applications have been developed to introduce changes in the genome and alter gene expression in diverse systems and tissues. These novel gene-editing techniques are particularly promising for investigating and treating neurodegenerative diseases, including Parkinson's disease, for which we currently lack efficient disease-modifying treatment options.

Developing a Natural Language Processing tool to identify perinatal self-harm in electronic healthcare records.

Background: Self-harm occurring within pregnancy and the postnatal year ("perinatal self-harm") is a clinically important yet under-researched topic. Current research likely under-estimates prevalence due to methodological limitations. Electronic healthcare records (EHRs) provide a source of clinically rich data on perinatal self-harm.

Tau oligomer induced HMGB1 release contributes to cellular senescence and neuropathology linked to Alzheimer's disease and frontotemporal dementia.

Aging, pathological tau oligomers (TauO), and chronic inflammation in the brain play a central role in tauopathies, including Alzheimer's disease (AD) and frontotemporal dementia (FTD). However, the underlying mechanism of TauO-induced aging-related neuroinflammation remains unclear. Here, we show that TauO-associated astrocytes display a senescence-like phenotype in the brains of patients with AD and FTD.

Temporal information extraction from mental health records to identify duration of untreated psychosis.

Background: Duration of untreated psychosis (DUP) is an important clinical construct in the field of mental health, as longer DUP can be associated with worse intervention outcomes. DUP estimation requires knowledge about when psychosis symptoms first started (symptom onset), and when psychosis treatment was initiated. Electronic health records (EHRs) represent a useful resource for retrospective clinical studies on DUP, but the core information underlying this construct is most likely to lie in free text, meaning it is not readily available for clinical research.

Advances and considerations in AD tau-targeted immunotherapy.

The multifactorial and complex nature of Alzheimer's disease (AD) has made it difficult to identify therapeutic targets that are causally involved in the disease process. However, accumulating evidence from experimental and clinical studies that investigate the early disease process point towards the required role of tau in AD etiology. Importantly, a large number of studies investigate and characterize the plethora of pathological forms of tau protein involved in disease onset and propagation.

Neurotoxic tau oligomers after single versus repetitive mild traumatic brain injury.

Mild traumatic brain injury accounts for the majority of head injuries and has been correlated with neurodegeneration and dementia. While repetitive mild traumatic brain injury is highly correlated to neurodegeneration, the correlation of a single mild traumatic brain injury with neurodegeneration is still unclear. Because tau aggregates are the main form of mild traumatic brain injury induced pathology, toxic forms of tau protein most likely play a role in the development of post-mild traumatic brain injury neurodegeneration.