Towards the design of ligands of the internal pocket TEADs C-terminal domain.

The Hippo pathway controls in organ size and tissue homeostasis through regulating cell growth, proliferation and apoptosis. Phosphorylation of the transcription co-activator YAP (Yes associated protein) and TAZ (Transcriptional coactivator with PDZ-binding motif) regulates their nuclear import and therefore their interaction with TEAD (Transcriptional Enhanced Associated Domain). YAP, TAZ and TEADs are dysregulated in several solid cancers making YAP/TAZ-TEAD interaction a new anti-cancer target.

Pseudohypoaldosteronism type II and sensory neuropathy associated with a heterozygous pathogenic variant in KLHL3 gene, a case report.

Pseudohypoaldosteronism type II is a rare Mendelian disorder characterized by hypertension, hyperkalemia, hyperchloremia and metabolic acidosis, despite a normal glomerular filtration rate. Four genes (, , and ) are associated with this disease. Mutations in the gene cause pseudohypoaldosteronism type II in either an autosomal dominant or a recessive inheritance pattern.

Magnetic resonance imaging characterization of an α-synuclein model of Parkinson's disease.

Parkinson's disease (PD) is primarily characterized by three histological hallmarks: dopaminergic neuronal degeneration, α-synuclein accumulation and iron deposition. Over the last years, neuroimaging, particularly magnetic resonance imaging (MRI) has provided invaluable insights into the mechanisms underlying the disease. However, no imaging method has yet been able to translate α-synuclein protein accumulation and spreading.

IGUANe: A 3D generalizable CycleGAN for multicenter harmonization of brain MR images.

In MRI studies, the aggregation of imaging data from multiple acquisition sites enhances sample size but may introduce site-related variabilities that hinder consistency in subsequent analyses. Deep learning methods for image translation have emerged as a solution for harmonizing MR images across sites. In this study, we introduce IGUANe (Image Generation with Unified Adversarial Networks), an original 3D model that leverages the strengths of domain translation and straightforward application of style transfer methods for multicenter brain MR image harmonization.

An international core outcome set for primary progressive aphasia (COS-PPA): Consensus-based recommendations for communication interventions across research and clinical settings.

Introduction: Interventions to treat speech-language difficulties in primary progressive aphasia (PPA) often use word accuracy as a highly comparable outcome. However, there are more constructs of importance to people with PPA that have received less attention.

Methods: Following Core Outcome Set Standards for Development Recommendations (COSSTAD), this study comprised: Stage 1 - systematic review to identify measures; Stage 2 - consensus groups to identify important outcome constructs for people with PPA (n = 82) and care partners (n = 91); Stage 3 - e-Delphi consensus with 57 researchers.

Association of Changes in Cerebral and Hypothalamic Structure With Sleep Dysfunction in Patients With Genetic Frontotemporal Dementia.

Background And Objectives: Sleep dysfunction is common in patients with neurodegenerative disorders; however, its neural underpinnings remain poorly characterized in genetic frontotemporal dementia (FTD). Hypothalamic nuclei important for sleep regulation may be related to this dysfunction. Thus, we examined changes in hypothalamic structure across the lifespan in patients with genetic FTD and whether these changes related to sleep dysfunction.

Association of Initial Side of Brain Atrophy With Clinical Features and Disease Progression in Patients With Frontotemporal Dementia.

Background And Objectives: Pathogenic variants in the gene cause frontotemporal dementia (FTD-) with marked brain asymmetry. This study aims to assess whether the disease progression of FTD- depends on the initial side of the atrophy. We also investigated the potential use of brain asymmetry as a biomarker of the disease.

Early movement restriction impairs the development of sensorimotor integration, motor skills and memory in rats: Towards a preclinical model of developmental coordination disorder?

Children with neurodevelopmental disorders, such as developmental coordination disorder (DCD), exhibit gross to fine sensorimotor impairments, reduced physical activity and interactions with the environment and people. This disorder co-exists with cognitive deficits, executive dysfunctions and learning impairments. Previously, we demonstrated in rats that limited amounts and atypical patterns of movements and somatosensory feedback during early movement restriction manifested in adulthood as degraded postural and locomotor abilities, and musculoskeletal histopathology, including muscle atrophy, hyperexcitability within sensorimotor circuitry and maladaptive cortical plasticity, leading to functional disorganization of the primary somatosensory and motor cortices in the absence of cortical histopathology.

Sonic Hedgehog Is an Early Oligodendrocyte Marker During Remyelination.

Failure of myelin regeneration by oligodendrocytes contributes to progressive decline in many neurological diseases. Here, using in vitro and in vivo rodent models, functional blockade, and mouse brain demyelination, we demonstrate that Sonic hedgehog (Shh) expression in a subset of oligodendrocyte progenitor cells precedes the expression of myelin basic protein (MBP), a major myelin sheath protein. Primary cultures of rodent cortical oligodendrocytes show that Shh mRNA and protein are upregulated during oligodendrocyte maturation before the upregulation of MBP expression.

Phenotypic and epigenetic heterogeneity in FGFR2-fused glial and glioneuronal tumours.

Aims: FGFR-fused central nervous system (CNS) tumours are rare and are usually within the glioneuronal and neuronal tumours or the paediatric-type diffuse low-grade glioma spectrum. Among this spectrum, FGFR2 fusion has been documented in tumours classified by DNA-methylation profiling as polymorphous low-grade neuroepithelial tumours of the young (PLNTY), a recently described tumour type. However, FGFR2 fusions have also been reported in glioneuronal tumours, highlighting the overlapping diagnostic criteria and challenges.

Distinct neuroinflammatory patterns between cerebral microbleeds and microinfarcts in cerebral amyloid angiopathy.

In this neuropathological study, we investigated neuroinflammation surrounding recent and old cerebral microbleeds (CMBs) and cerebral microinfarcts (CMIs) in 18 cases of cerebral amyloid angiopathy (CAA). We used several serial stainings and immunolabellings to identify microvascular lesions, define their recent or old stage, and characterize neuroinflammatory response (scavenging activity and astrogliosis). We found that both CMBs and CMIs induce a neuroinflammatory response, which was more pronounced in old lesion than recent.

Deferiprone in Alzheimer Disease: A Randomized Clinical Trial.

Importance: Interventions that substantially slow neurodegeneration are needed to address the growing burden of Alzheimer disease (AD) to societies worldwide. Elevated brain iron observed in AD has been associated with accelerated cognitive decline and may be a tractable drug target.

Objective: To investigate whether the brain-permeable iron chelator deferiprone slows cognitive decline in people with AD.

Long-term cognitive outcomes after decompressive hemicraniectomy for right-hemisphere large middle cerebral artery ischemic stroke.

Background And Purpose: Decompressive hemicraniectomy (DH) improves survival and functional outcome in large middle cerebral artery (MCA) infarcts. However, long-term cognitive outcomes after DH remain underexplored. In a cohort of patients with large right-hemisphere MCA infarction undergoing DH, we assessed the rates of long-term cognitive impairment over 3-year follow-up.

Postural balance and visual dependence in patients with demyelinating neuropathies differ between acquired and hereditary etiologies.

Background: Demyelinating polyneuropathies affect posture and can be either hereditary, as in Charcot-Marie-Tooth type 1A (CMT1A), or autoimmune, as in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Clinical differentiation between these two neuropathies can be challenging and biomarkers are lacking. No comparative analysis of their balance profiles has been conducted.

A French multicenter analytical evaluation of the automated Lumipulse G sNfL blood assay (Fujirebio®) and its comparison to four other immunoassays for serum neurofilament light chain assessment in clinical settings.

Objectives: Measurement of serum neurofilament light chain (sNfL) protein is becoming a key biomarker for many neurological diseases. Several immunoassays have been developed to meet these clinical needs, revealing significant differences in terms of variability and results. Here, we propose a French multicenter comparison of 5 sNfL assays.

Doses of Botulinum Toxin in Cervical Dystonia: Does Ultrasound Guidance Change Injection Practices?

Background: Cervical dystonia is widely understood to benefit from botulinum toxin injections. The injection practices may be influenced by specific factors, including the method of injection. Three main guidance methods can be used: palpation of anatomical landmarks, ultrasound, and electromyography.