Frequency of ubiquitin and FUS-positive, TDP-43-negative frontotemporal lobar degeneration

Frontotemporal lobar degeneration (FTLD) is a clinically, genetically and pathologically heterogeneous disorder. Within FTLD with ubiquitin-positive inclusions (FTLD-U), a new pathological subtype named FTLD-FUS was recently found with fused in sarcoma (FUS) positive, TDP-43-negative inclusions, and striking atrophy of the caudate nucleus. The aim of this study was to determine the frequency of FTLD-FUS in our pathological FTLD series, and to describe the clinical, neuroimaging and neuropathological features of FTLD-FUS, especially caudate atrophy. Demographic and clinical data collected prospectively from 387 patients with frontotemporal dementia (FTD) yielded 74 brain specimens. Immunostaining was carried out using a panel of antibodies, including AT-8, ubiquitin, p62, FUS, and TDP-43. Cortical and caudate atrophy on MRI (n = 136) was rated as normal, mild-moderate or severe. Of the 37 FTLD-U cases, 33 were reclassified as FTLD-TDP and four (0.11, 95%: 0.00–0.21) as FTLD-FUS, with ubiquitin and FUS-positive, p62 and TDP-43-negative neuronal intranuclear inclusions (NII). All four FTLD-FUS cases had a negative family history, behavioural variant FTD (bvFTD), and three had an age at onset ≤40 years. MRI revealed mild-moderate or severe caudate atrophy in all, with a mean duration from onset till MRI of 63 months (range 16–119 months). In our total clinical FTD cohort, we found 11 patients (0.03; 95% CI: 0.01–0.05) with bvFTD, negative family history, and age at onset ≤40 years. Caudate atrophy was present in 10 out of 136 MRIs, and included all four FUS-cases. The newly identified FTLD-FUS has a frequency of 11% in FTLD-U, and an estimated frequency of three percent in our clinical FTD cohort. The existence of this pathological subtype can be predicted with reasonable certainty by age at onset ≤40 years, negative family history, bvFTD and caudate atrophy on MRI

The Role of Teachers' Expectations in the Association between Children's SES and Performance in Kindergarten: A Moderated Mediation Analysis

This study examines the role of teachers' expectations in the association between children's socio-economic background and achievement outcomes. Furthermore, the role of children's ethnicity in moderating this mediated relation is investigated. In the present study, 3,948 children from kindergarten are examined. Data are analysed by means of structural equation modeling. First, results show that teachers' expectations mediate the relation between children's SES and their later language and math achievement, after controlling for children's ethnicity, prior achievement and gender. This result indicates that teachers may exacerbate individual differences between children. Second, children's ethnicity moderates the mediation effect of teachers' expectations with respect to math outcomes. The role of teachers' expectations in mediating the relation between SES and math outcomes is stronger for majority children than for minority children

The electronic nose:emerging biomarkers in lung cancer diagnostics

Lung cancer is very common and the most common cause of cancer death worldwide. Despite recent progress in the systemic treatment of lung cancer (checkpoint inhibitors and tyrosine kinase inhibitors), each year, >1.5 million people die due to this disease. Most lung cancer patients already have advanced disease at the time of diagnosis. Computed tomography screening of high-risk individuals can detect lung cancer at an earlier stage but at a cost of false-positive findings. Biomarkers could lead towards a reduction of these false-positive findings and earlier lung cancer diagnosis, and have the potential to improve outcomes and treatment monitoring. To date, there is a lack of such biomarkers for lung cancer and other thoracic malignancies, although electronic nose (e-nose)-derived biomarkers are of interest. E-nose techniques using exhaled breath component measurements can detect lung cancer with a sensitivity ranging from 71% to 96% and specificity from 33 to 100%. In some case series, such results have been validated but this is mostly using internal validation and hence, more work is needed. Furthermore, standardised sampling and analysis methods are lacking, impeding interstudy comparison and clinical implementation. In this narrative review, we provide an overview of the currently available data on E-nose technology for lung cancer detection