Drug Development.

Background: Alzheimer's disease (AD) is the most common cause of dementia worldwide. It is characterized by dysfunction in the U1 small nuclear ribonucleoproteins (snRNPs) complex, which may precede TAU aggregation, enhancing premature polyadenylation, spliceosome dysfunction, and causing cell cycle reentry and death. Thus, we evaluated the effects of a synthetic single-stranded cDNA, called APT20TTMG, in induced pluripotent stem cells (iPSC) derived neurons from healthy and AD donors and in the Senescence Accelerated Mouse-Prone 8 (SAMP8) model.

Drug Development.

Background: Immunotherapy of Alzheimer's disease (AD) is a promising approach to reducing the accumulation of beta-amyloid, a critical event in the onset of the disease. Targeting the group II metabotropic glutamate receptors, mGluR2 and mGluR3, could be important in controlling Aβ production, although their respective contribution remains unclear due to the lack of selective tools.

Method: 5xFAD mice were chronically treated by a brain penetrant camelid single domain antibody (VHH or nanobody) that is an activator of mGluR2.

Drug Development.

Background: Tau proteins aggregate in a number of neurodegenerative disorders known as tauopathies. Various studies have highlighted the role of microtubule-binding domains in the intracellular aggregation of Tau protein.

Method: Using a library of synthetic VHHs humanized in collaboration with Hybrigenics, we have developed a number of anti-tau VHHs.

Drug Development.

Background: Oral ALZ-801 (valiltramiprosate), a brain-penetrant agent that inhibits amyloid-oligomer formation is being evaluated in a fully enrolled APOLLOE4 Phase 3 trial in APOE4/4 homozygotes with Early Alzheimer's disease (AD). ALZ-801 effects on plasma AD biomarkers were evaluated in a 104-week Phase 2 study in APOE4-carriers with CSF+ AD biomarkers. APOE4 is a major risk factor for amyloid-related imaging abnormalities (ARIA) in AD patients.

Drug Development.

Background: Progranulin (PGRN), a glycoprotein secreted by microglia and neurons, regulates lysosomal function, neuroinflammation, and has neurotrophic effects. Variants in the granulin gene (GRN) that cause a reduction of PGRN in plasma and cerebrospinal fluid (CSF) are associated with an increased risk of Alzheimer's disease (AD). The sortilin receptor (SORT1) on neurons and microglia regulates PGRN degradation.

Drug Development.

Background: Chronic innate neuroinflammation mediated by microglia and astrocytes in response to Aβ and pathological Tau species is a cardinal feature of AD that contributes to disease pathogenesis. Accumulating evidence now also highlight an instrumental role of T cells and peripheral-central immune crosstalk in the pathophysiology of AD. Both preclinical and clinical reports suggest the potential therapeutic interest of peripheral immunomodulatory approaches aimed at amplifying regulatory T cells (Tregs), e.

Dementia Care Research and Psychosocial Factors.

Background: Using artificial intelligence approaches enable automated assessment and analysis of speech biomarkers for Alzheimer's disease, for example using chatbot technology. However, current chatbots often are unsuitable for people with cognitive impairment. Here, we implemented a user-centred-design approach to evaluate and improve usability of a chatbot system for automated speech assessments for people with preclinical, prodromal and early dementia.

Dementia Care Research and Psychosocial Factors.

Background: The progressive nature of dementia and the complex needs means that people living with dementia require tailored approaches to address their changing care needs over time. These include physical multimorbidity, psychological, behavioural, and cognitive symptoms and possible risks arising from these and helping family caregivers. However, provision of these interventions is highly variable between and within countries, partly due to uncertainty about their efficacy and scarce resources.

Dementia Care Research and Psychosocial Factors.

Background: Data from high-income countries (HICs) suggest a decline in age-specific incidence rates of dementia. However, this has happened primarily in HICs, with low- and middle- income countries (LMICs) facing two main challenges: a higher burden of risk factors and, in general, a faster ageing population. Most people with dementia live in LMICs, and this is set to increase, thus requiring urgent and robust action to prevent, treat and support people with dementia and their families.

Dementia Care Research and Psychosocial Factors.

Background: Our authors from around the world met to summarise the available knowledge, decide which potentially modifiable risk factors for dementia have compelling evidence and create the most comprehensive analysis to date for potentially modifiable risk factors to inform policy, give individuals the opportunity to control their risks and generate research.

Method: We incorporated all risk factors for which we judged there was strong enough evidence. We used the largest recent worldwide meta-analyses for risk factor prevalence and relative risk and if not available the best data.

Dementia Care Research and Psychosocial Factors.

Background: Facial emotion recognition testing in Alzheimer's disease (AD) patients has been identified as key for early detection and as a marker for disease progression. Emotion recognition remains one of the most difficult domains to assess in culturally diverse populations due to a lack of culturally adapted tools. This study assessed the feasibility of a cross-cultural test for emotion recognition, the TIE-93, in French and North African populations living in France.

Dementia Care Research and Psychosocial Factors.

Background: In sub-Saharan Africa (SSA), the number of people living with dementia is expected to double every 20 years, from 2.7 to 7.6 million.

Dementia Care Practice.

Alzheimer's disease significantly impacts decision-making abilities, potentially increasing risk-taking behaviors and complicating the process of aging-in-place, particularly in cases of anosognosia (self-awareness impairment). To understand how this affects patient and caregiver perspectives, we conducted a qualitative study to identify arguments used by older patients with Alzheimer's disease and their family caregivers about aging-in-place. We included 18 dyads, each comprising an older adult living at home with mild dementia and their family caregiver.

Dementia Care Practice.

Aims: The Alzheimer Association (AA) has proposed new diagnostic criteria for Alzheimer's disease (AD) based on biomarkers coinciding with β-amyloidosis onset. However, there are concerns regarding the implications of these criteria.

Methods: We reviewed several perspectives, including disease definition, public health, philosophy, therapeutic, and diagnostic.

An IS element-driven antisense RNA attenuates the expression of serotype 2 fimbriae and the cytotoxicity of .

Insertion sequences (IS) represent mobile genetic elements that have been shown to be associated with bacterial evolution and adaptation due to their effects on genome plasticity. In , the causative agent of whooping cough, the numerous IS elements induce genomic rearrangements and contribute to the diversity of the global population. Previously, we have shown that the majority of IS-specific endogenous promoters induce the synthesis of alternative transcripts and thereby affect the transcriptional landscape of .

Taylor's swimming sheet near a soft boundary.

In 1951, G. I. Taylor modeled swimming microorganisms by hypothesizing an infinite sheet in 2D moving in a viscous medium due to a wave passing through it.

Small-angle neutron scattering differentiates molecular-level structural models of nanoparticle interfaces.

The highly anisotropic and nonadditive nature of nanoparticle surfaces restricts their characterization by limited types of techniques that can reach atomic or molecular resolution. While small-angle neutron scattering (SANS) is a unique tool for analyzing complex systems, it has been traditionally considered a low-resolution method due to its limited scattering vector range and wide wavelength spread. In this article, we present a novel perspective on SANS by showcasing its exceptional capability to provide molecular-level insights into nanoparticle interfaces.

Draft genomes and assemblies of the ectomycorrhizal basidiomycetes hr and jo associated with chestnut trees.

The earthball , an ectomycorrhizal basidiomycete belonging to the Sclerodermataceae family, serves as a significant mutualistic tree symbiont globally. Originally, two genetically sequenced strains of this genus were obtained from fruiting bodies collected under chestnut trees (). These strains were utilized to establish ectomycorrhizal roots of chestnut seedlings.

The effect of sevelamer on serum calcification propensity in patients with chronic kidney disease: the results of a multicentre, double-blind, placebo-controlled, randomized clinical trial.

Background: The serum calcification propensity test (or T50 test) might become a standard tool for the assessment of vascular calcification risk and T50 might be a valuable biomarker in clinical trials of treatments intended to slow the progression of vascular calcification. Literature data suggest that non-calcium-containing phosphate binders can influence T50 in chronic dialysed patients. However, it is not clear whether similar interventions are effective in patients at earlier stages of chronic kidney disease (CKD).

Quantifying the potential contribution of drugs to the occurrence of acute kidney injury in patients with chronic kidney disease.

Background: We sought to comprehensively describe drug-related components associated with acute kidney injury (AKI) in patients with chronic kidney disease (CKD), describing the incidence of drug-related AKI, the proportion of preventable AKI, identified the various drugs potentially associated with it, explored the risk factors, and assessed the 1-year incidences of the recurrence of drug-related AKI, kidney failure, and death.

Methods: CKD-REIN is a French national prospective cohort of 3033 nephrology outpatients with a confirmed diagnosis of CKD (eGFR <60 ml/min/1.73 m²).

Clinical and magnetic resonance imaging findings of presumed limber tail syndrome in a cat.

A 4-year-old neutered female domestic shorthair indoor cat was presented with sudden onset of abnormal and painful tail-carriage. The tail was held horizontally for the first centimeters from the base and a flaccid paralysis was evident more distally. Magnetic resonance imaging of the lumbosacral spine and tail revealed a lesion located in the right and muscles along the 1st coccygeal vertebrae.

Bibliometric Analysis of the Composition of Landmark Cerebral Venous Sinus Thrombosis Research.

Background: Cerebral Venous Sinus Thrombosis (CVST) is a relatively rare type of stroke, accounting for less than 3% of all stroke cases, and is associated with significant morbidity and mortality in young females. However, when promptly diagnosed and treated, it can have favorable outcomes. Several knowledge gaps remain regarding pathophysiology, diagnosis, and management of CVST, so critical assessment of past and present research could help close these gaps or establish targeted future research goals.

How Can Overlooking Social Interactions, Space Familiarity or Other "Invisible Landscapes" Shaping Animal Movement Bias Habitat Selection Estimations and Species Distribution Predictions?

Species' future distributions are commonly predicted using models that link the likelihood of occurrence of individuals to the environment. Although animals' movements are influenced by physical and non-physical landscapes, for example related to individual experiences such as space familiarity or previous encounters with conspecifics, species distribution models developed from observations of unknown individuals cannot integrate these latter variables, turning them into 'invisible landscapes'. In this theoretical study, we address how overlooking 'invisible landscapes' impacts the estimation of habitat selection and thereby the projection of future distributions.

A Riemannian multimodal representation to classify parkinsonism-related patterns from noninvasive observations of gait and eye movements.

Parkinson's disease is a neurodegenerative disorder principally manifested as motor disabilities. In clinical practice, diagnostic rating scales are available for broadly measuring, classifying, and characterizing the disease progression. Nonetheless, these scales depend on the specialist's expertise, introducing a high degree of subjectivity.