Tumor-infiltrating B cells play a significant role in tumor development, progression, and prognosis, yet a comprehensive classification system is lacking. To address this gap, we present a pan-cancer single-cell RNA sequencing (scRNA-seq) atlas of tumor-infiltrating B and plasma cells across a large sample cohort. We identify key B cell subset signatures, revealing distinct subpopulations and highlighting the heterogeneity and functional diversity of these cells in the tumor microenvironment.
View Article and Find Full Text PDFDecades of research shows that sexual minority youth (SMY) display heightened risk for mental health problems, although the onset of such disparities remains unclear. The Millennium Cohort Study is the largest nationally representative longitudinal study of adolescents in the United Kingdom. In this study, participants ( = 10,047, 50% female) self-reported their sexual identity at age 17 and had parent-reported mental health data, from the Strengths and Difficulties Questionnaire, reported across five waves at ages 5, 7, 11, 14, and 17.
View Article and Find Full Text PDFIt is often important to minimise the time participants in social science studies spend on completing questionnaire-based measures, reducing response burden, and increasing data quality. Here, we investigated the performance of the short versions of some widely used depression, anxiety, and psychological distress scales and compared them to the performance of longer versions of these scales (PHQ-2 vs PHQ-9, GAD-2 vs GAD-7, Malaise-3 vs Malaise-9, K6 vs K10). Across a sample of UK adults (N = 987, ages 18-86), we tested the existing factor structure and accuracy of the scales through confirmatory factor analyses and exploration of the total information functions, observing adequate model fit indices across the measures.
View Article and Find Full Text PDFChild Adolesc Psychiatry Ment Health
May 2023
Background: This paper examined whether distinct life-course trajectories of psychological distress from adolescence to midlife were associated with poorer mental health outcomes during the pandemic.
Methods: We present a secondary analysis of two nationally representative British birth cohorts, the 1958 National Child Development Study (NCDS) and 1970 British Cohort Study (BCS70). We used latent variable mixture models to identify pre-pandemic longitudinal trajectories of psychological distress and a modified Poisson model with robust standard errors to estimate associations with psychological distress, life satisfaction and loneliness at different points during the pandemic.
Background: Employment disruptions can impact smoking and alcohol consumption. During the COVID-19 pandemic, many countries implemented furlough schemes to prevent job loss. We examine how furlough was associated with smoking, vaping and alcohol consumption in the UK.
View Article and Find Full Text PDFThis study uses longitudinal data from the UK Millennium Cohort Study (N = 13,277) to examine the childhood and early adolescence factors that predict weapon involvement in middle adolescence, which in this study is exemplified by having carried or used a weapon. It finds that childhood experiences of low family income and domestic abuse between parents predict weapon involvement at age 17 years. Other predictors include childhood externalizing problems and self-harm in early adolescence.
View Article and Find Full Text PDFA DNA bank has been created from the Millennium Cohort Study (MCS) saliva samples. A total of 23,336 samples are available, from 9,259 cohort members (4,630 males and 4,629 females), 8,898 mothers and 5,179 fathers. There are 4,533 mother, child, father 'triads'.
View Article and Find Full Text PDFThe acquisition of a multidrug refractory state is a major cause of mortality in myeloma. Myeloma drugs that target the cereblon (CRBN) protein include widely used immunomodulatory drugs (IMiDs), and newer CRBN E3 ligase modulator drugs (CELMoDs), in clinical trials. CRBN genetic disruption causes resistance and poor outcomes with IMiDs.
View Article and Find Full Text PDFPurpose: We designed a comprehensive multiple myeloma targeted sequencing panel to identify common genomic abnormalities in a single assay and validated it against known standards.
Experimental Design: The panel comprised 228 genes/exons for mutations, 6 regions for translocations, and 56 regions for copy number abnormalities (CNA). Toward panel validation, targeted sequencing was conducted on 233 patient samples and further validated using clinical FISH (translocations), multiplex ligation probe analysis (MLPA; CNAs), whole-genome sequencing (WGS; CNAs, mutations, translocations), or droplet digital PCR (ddPCR) of known standards (mutations).
Background: The COVID-19 pandemic has disrupted lives and livelihoods, and people already experiencing mental ill health may have been especially vulnerable.
Aims: Quantify mental health inequalities in disruptions to healthcare, economic activity and housing.
Method: We examined data from 59 482 participants in 12 UK longitudinal studies with data collected before and during the COVID-19 pandemic.
The benefit of autologous stem cell transplantation (ASCT) in newly diagnosed myeloma patients, apart from supporting high dose chemotherapy, may include effects on T cell function in the bone marrow (BM). We report our exploratory findings on marrow infiltrating T cells early post-ASCT (day+100), examining phenotype and T cell receptor (TCR) repertoire, seeking correlations with timing of relapse. Compared to healthy donors (HD), we observed an increase in regulatory T cells (CD4+FoxP3+, Tregs) with reduction in CD4 T cells, leading to lower CD4:8 ratios.
View Article and Find Full Text PDFBackground: Childhood socioeconomic position (SEP) is robustly associated with cognitive function later in life. However, it is unclear whether this reflects a direct relationship, or an indirect association via modifiable factors such as educational attainment and occupation. We sought to clarify these associations using retrospectively harmonised data from three ongoing British birth cohorts.
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