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The diagnosis of neurodegenerative diseases is made complex by the heterogenous phenotype of the patients and the regular occurrence of concomitant pathology. Studying clinicopathological correlations in autopsy series is a central approach to improve pathological prediction in clinical practice. However, such method requires a wealth of information, and the use of standard spreadsheet software is hardly suitable. To overcome this constraint, we designed a customizable and freely available neuropathology form with 456 data entry fields driven by an open‐source DataBase Management Systems (DBMS) using Structured Query Language (SQL). This approach allowed us to optimize the compilation of clinical and pathological data from our brain collection (264 autopsied patients, 22,885 data points). Information was then easily retrieved using general and specific queries, facilitating the analysis of demographics, clinicopathological correlations, and incidental and concomitant proteinopathies. Tau, amyloid‐β and α‐synuclein incidental pathology was observed in respectively 78.1%, 42.8%, and 10.7% of all the patients. These proportions increased with age, reaching 100% for Tau pathology after 80. Concomitant proteinopathy was observed in 46.4% of the patients diagnosed with neurodegenerative diseases and prion disease. We observed a particularly high rate of co‐pathology in patients with Dementia with Lewy bodies (81.3% of associated Tau and amyloid‐β pathology) and Creutzfeldt–Jakob disease (68.4% of associated Tau pathology). Finally, we used specific queries to identify old cases that could meet newly defined neuropathological criteria and revised the diagnosis of a 90‐year‐old patient to LATE Stage 2. Increasing our understanding of clinicopathological correlations in neurodegenerative diseases is crucial given the implications in clinical diagnosis, biomarker identification and targeted therapies assessment. The precise characterization of clinical and pathological data of autopsy series remains a central approach but the large amount of generated data should encourage a more systematic use of DBMS. [ABSTRACT FROM AUTHOR]

Background: myotilinopathy is a very rare inherited muscle disease that belongs to the group of myofibrillar myopathies. These diseases share a common alteration of the sarcomere organization at the level of the Z disk resulting in pathological protein aggregation, autophagic abnormalities, and ultimately muscle degeneration. Most reported cases are due to dominant missense mutations in the MYOT gene, two of which are largely recurrent., Methods: We describe the clinical, radiological, pathological, and molecular analysis including long-read sequencing of a family affected by late-onset dominant proximodistal myopathy and muscle hypertrophy., Results: We identified a duplication of the entire MYOT gene as the molecular cause of late-onset-myotilinopapthy with typical clinical and pathological features., Conclusions: This study expands the molecular spectrum of myotilinopathy and highlights the use of long-read sequencing in the diagnosis of genetic neurological diseases caused by duplications and genomic structural variants. Myotilinopathy as well as other myofibrillar and distal myopathies should be considered in the differential diagnosis of patients affected by distal muscle weakness, even when presenting at an old age., (© 2025 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Between 1975 and 2014, the number of people suffering from obesity tripled, reaching 17% of the adult population in France and more than 35% in the United States. Obesity is defined by a Body Mass Index (BMI)>30kg/m 2 and characterized by a significant accumulation of adipose tissue responsible for the increase in weight. This accumulation leads to physiological changes capable of modifying the pharmacokinetics of drugs, which can lead to the administration of inappropriate doses. For this reason, some significant dosage adjustments are necessary for obese patients. However, data on these adaptations are not easily accessible and sometimes complex to implement in practice., Aim: To perform a new online tool allowing to calculate and propose an adjusted dose of a drug that should be administered to an obese patient., Method: (i) carrying out an extensive bibliographic research according to the PRISMA methodology; and (ii) the development of a new website site proposing an adjusted dose for obese patients., Results: Firstly, 49 reviews concerning the dose adaptation have been evaluated and, secondly, 319 articles have been selected. Among them, 204 articles have been included in the database to justify the adjusted dose of 84 drugs and administration methods including antibiotics, antifungals, anticoagulants or even cancer drugs. This database is available online through a calculator on the website named Adapt'Obese. Thus, with the sex, height and weight of an obese patient, Adapt'Obese proposes a personalized and adjusted dose of the drug to administer., Perspectives: Other drugs will be added soon, and functional improvements are planned, with the aim of adapting the dosages in obese patients, as for patients with renal insufficiency., (Copyright © 2023 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.)

Glioblastoma is an aggressive brain tumor with a poor prognosis. Glioblastoma Stem Cells (GSC) are involved in glioblastoma resistance and relapse. Effective glioblastoma treatment must include GSC targeting strategy. Robust and well defined in vitro GSC models are required for new therapies evaluation. In this study, we extensively characterized 4 GSC models obtained by dedifferentiation of commercially available glioblastoma cell lines and compared them to 2 established patient derived GSC lines (Brain Tumor Initiating Cells). Dedifferentiated cells formed gliospheres, typical for GSC, with self-renewal ability. Gene expression and protein analysis revealed an increased expression of several stemness associated markers such as A2B5, integrin α6, Nestin, SOX2 and NANOG . Cells were oriented toward a mesenchymal GSC phenotype as shown by elevated levels of mesenchymal and EMT related markers (CD44, FN1 , integrin α5). Dedifferentiated GSC were similar to BTIC in terms of size and heterogeneity. The characterization study also revealed that CXCR4 pathway was activated by dedifferentiation, emphasizing its role as a potential therapeutic target. The expression of resistance-associated markers and the phenotypic diversity of the 4 GSC models obtained by dedifferentiation make them relevant to challenge future GSC targeting therapies., Competing Interests: None., (AJCR Copyright © 2023.)