Region-specific and age-related differences in astrocytes in the human brain.

Astrocyte heterogeneity and its relation to aging in the normal human brain remain poorly understood. We here analyzed astrocytes in gray and white matter brain tissues obtained from donors ranging in age between the neonatal period to over 100 years. We show that astrocytes are differently distributed with higher density in the white matter.

Surrogate endpoints for overall survival in randomized clinical trials testing immune checkpoint inhibitors: a systematic review and meta-analysis.

Introduction: There is debate on which are the best surrogate endpoint and metric to capture treatment effect on overall survival (OS) in RCTs testing immune-checkpoint inhibitors (ICIs).

Methods: We systematically searched for RCTs testing ICIs in patients with advanced solid tumors. Inclusion criteria were: RCTs i) assessing PD-(L)1 and CTLA-4 inhibitors either as monotherapy or in combination with another ICI, and/or targeted therapy, and/or chemotherapy, in patients with advanced solid tumors; ii) randomizing at least 100 patients.

Dissecting the Clinical Heterogeneity and Genotype-Phenotype Correlations of Mutations: A Systematic Review.

Background: Microtubule-associated protein tau () mutations are one of the main causes of genetic Frontotemporal dementia (FTD) and are characterised by high clinical heterogeneity. A behavioural variant of FTD is the principal phenotype, but other rarer phenotypes are described, mostly reported as single cases. In this review, we provide an overview of the clinical phenotypes associated with mutations in order to define their characteristics and explore genotype-phenotype correlations.

Linking acetylated α-Tubulin redistribution to α-Synuclein pathology in brain of Parkinson's disease patients.

Highly specialized microtubules in neurons are crucial to both health and disease of the nervous system, and their properties are strictly regulated by different post-translational modifications, including α-Tubulin acetylation. An imbalance in the levels of acetylated α-Tubulin has been reported in experimental models of Parkinson's disease (PD) whereas pharmacological or genetic modulation that leads to increased acetylated α-Tubulin successfully rescues axonal transport defects and inhibits α-Synuclein aggregation. However, the role of acetylation of α-Tubulin in the human nervous system is largely unknown as most studies are based on in vitro evidence.

Secondary Protein Aggregates in Neurodegenerative Diseases: Almost the Rule Rather than the Exception.

The presence of protein aggregates is a hallmark of many neurodegenerative diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD). Traditionally, each disease has been associated with the aggregation of specific proteins, which serve as disease-specific biomarkers. For example, aggregates of α-synuclein (α-syn) are found in α-synucleinopathies such as PD, dementia with Lewy bodies (DLB), and multiple system atrophy (MSA).

The International Association for the Study of Lung Cancer Thymic Epithelial Tumors Staging Project: Proposals for the N and the M Components for the Forthcoming (Ninth) Edition of the TNM Classification of Malignant Tumors.

Introduction: Stage classification is an important underpinning of management in patients with cancer and rests on a combination of three components-T for tumor extent, N for nodal involvement, and M for distant metastases. This article details the revision of the N and the M components of thymic epithelial tumors for the ninth edition of the TNM classification of malignant tumors proposed by the Thymic Domain of the International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee.

Methods: The N and M components of the eighth edition staging system were verified by a large international collaborative data source through a data-driven analysis.

Randomized open-label controlled study of cancer vaccine OSE2101 versus chemotherapy in HLA-A2-positive patients with advanced non-small-cell lung cancer with resistance to immunotherapy: ATALANTE-1.

Background: Patients with advanced non-small-cell lung cancer (NSCLC) treated with immune checkpoint blockers (ICBs) ultimately progress either rapidly (primary resistance) or after durable benefit (secondary resistance). The cancer vaccine OSE2101 may invigorate antitumor-specific immune responses after ICB failure. The objective of ATALANTE-1 was to evaluate its efficacy and safety in these patients.

The International Association for the Study of Lung Cancer Thymic Epithelial Tumors Staging Project: An Overview of the Central Database Informing Revision of the Forthcoming (Ninth) Edition of the TNM Classification of Malignant Tumors.

Introduction: In 2014, a TNM-based system for thymic epithelial tumors was proposed. The TNM stage classification system was published as a result of a joint project from the International Association for the Study of Lung Cancer and the International Thymic Malignancy Interest Group for the eighth edition of the American Joint Commission on Cancer and the Union for International Cancer Control stage classification system. The Thymic Domain of the Staging and Prognostic Factors Committee of the International Association for the Study of Lung Cancer received the mandate to make proposals for the ninth edition of the TNM stage classification.

The International Association for the Study of Lung Cancer Thymic Epithelial Tumors Staging Project: Proposal for a Stage Classification for the Forthcoming (Ninth) Edition of the TNM Classification of Malignant Tumors.

Introduction: A TNM-based system for all types of thymic epithelial tumors was introduced in the eighth edition of the TNM classification of thoracic malignancies. The Thymic Domain of the Staging and Prognostic Factors Committee of the International Association for the Study of Lung Cancer, composed of multispecialty international experts, was charged to develop proposals for the ninth edition. This article outlines the proposed definitions for the T, the N, and the M components and their combination into stage groups.

The International Association for the Study of Lung Cancer Thymic Epithelial Tumor Staging Project: A Re-Assessment of the International Thymic Malignancy Interest Group/International Association for the Study of Lung Cancer Lymph Node Map for Thymic Epithelial Tumors for the Forthcoming Ninth Edition of the TNM Classification of Malignant Tumors.

Introduction: A lymph node map is the pillar on which accurate assignment and documentation of nodal classification stands. The International Thymic Malignancy Interest Group created the first map for thymic epithelial malignancies in conjunction with the eighth edition of the TNM classification, representing the first official TNM classification of thymic epithelial malignancies. The map was based on clinical experience and published studies, but it was largely empirical because of limited available data.

The International Association for the Study of Lung Cancer Thymic Epithelial Tumor Staging Project: Proposal for the T Component for the Forthcoming (Ninth) Edition of the TNM Classification of Malignant Tumors.

Introduction: A TNM-based stage classification system of thymic epithelial tumors was adopted for the eighth edition of the stage classification of malignant tumors. The Thymic Domain of the Staging and Prognostics Factor Committee of the International Association for the Study of Lung Cancer developed a new database with the purpose to make proposals for the ninth edition stage classification system. This article outlines the proposed definitions for the T categories for the ninth edition TNM stage classification of thymic malignancies.

Current knowledge of small cell lung cancer transformation from non-small cell lung cancer.

Lung cancer is the leading cause of cancer related death, and is divided into two major histological subtypes, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Histological transformation from NSCLC to SCLC has been reported as a mechanism of treatment resistance in patients who received tyrosine kinase inhibitors (TKIs) targeting EGFR, ALK and ROS1 or immunotherapies. The transformed histology could be due to therapy-induced lineage plasticity or clonal selection of pre-existing SCLC cells.

Advancements in small cell lung cancer.

Small cell lung cancer (SCLC) is a recalcitrant cancer with an urgent need for novel therapeutics, preclinical models, and elucidation of the molecular pathways responsible for its rapid resistance. Recently, there have been many significant advancements in our knowledge of SCLC that led to the development of novel treatments. This review will go over the recent attempts to provide new molecular subcategorization of SCLC, recent breakthroughs in various systemic treatments including immunotherapy, targeted therapy, cellular therapy, as well as advancements in radiation therapy.

Creating the Pick's disease International Consortium: Association study of H2 haplotype with risk of Pick's disease.

Background: Pick's disease (PiD) is a rare and predominantly sporadic form of frontotemporal dementia that is classified as a primary tauopathy. PiD is pathologically defined by argyrophilic inclusion Pick bodies and ballooned neurons in the frontal and temporal brain lobes. PiD is characterised by the presence of Pick bodies which are formed from aggregated, hyperphosphorylated, 3-repeat tau proteins, encoded by the gene.

24-Hydroxycholesterol Induces Tau Proteasome-Dependent Degradation via the SIRT1/PGC1α/Nrf2 Pathway: A Potential Mechanism to Counteract Alzheimer's Disease.

Considerable evidence indicates that cholesterol oxidation products, named oxysterols, play a key role in several events involved in Alzheimer's disease (AD) pathogenesis. Although the majority of oxysterols causes neuron dysfunction and degeneration, 24-hydroxycholesterol (24-OHC) has recently been thought to be neuroprotective also. The present study aimed at supporting this concept by exploring, in SK-N-BE neuroblastoma cells, whether 24-OHC affected the neuroprotective SIRT1/PGC1α/Nrf2 axis.

Corrigendum: PMCA-based detection of prions in the olfactory mucosa of patients with sporadic Creutzfeldt-Jakob disease.

[This corrects the article DOI: 10.3389/fnagi.2022.

Spontaneous intracerebral haemorrhage associated with early-onset cerebral amyloid angiopathy and Alzheimer's disease neuropathological changes five decades after cadaveric dura mater graft.

Cerebral amyloid angiopathy (CAA) is a small vessel disease, causing spontaneous intracerebral hemorrhage (ICH) in the elderly. It is strongly associated with Alzheimer disease (AD), as most CAA patients show deposition of Aβ-i.e.