Despite epidemiological data on anaemia being available on a global scale, its prevalence in the United Kingdom is not well described. To investigate anaemia prevalence and testing patterns for haemoglobin and other blood parameters. A population-based cohort study using data drawn from the Clinical Practice Research Datalink Aurum database in 2019.
View Article and Find Full Text PDFClin Epigenetics
November 2024
Objectives: In this multi-center study, we proposed a structured reporting (SR) framework for non-small cell lung cancer (NSCLC) and developed a software-assisted tool to automatically translate image-based findings and annotations into TNM classifications. The aim of this study was to validate the software-assisted SR tool for NSCLC, assess its potential clinical impact in a proof-of-concept study, and evaluate current reporting standards in participating institutions.
Methods: A framework for SR and staging of NSCLC was developed in a multi-center collaboration.
Engineered cellular therapy with CD19-targeting chimeric antigen receptor T cells (CAR-Ts) has revolutionized outcomes for patients with relapsed/refractory large B-cell lymphoma (LBCL), but the cellular and molecular features associated with response remain largely unresolved. We analyzed serial peripheral blood samples ranging from the day of apheresis (day -28/baseline) to 28 days after CAR-T infusion from 50 patients with LBCL treated with axicabtagene ciloleucel by integrating single-cell RNA and T-cell receptor sequencing, flow cytometry, and mass cytometry to characterize features associated with response to CAR-T. Pretreatment patient characteristics associated with response included the presence of B cells and increased absolute lymphocyte count to absolute monocyte count ratio (ALC/AMC).
View Article and Find Full Text PDFCharacterizing cell-cell communication and tracking its variability over time are crucial for understanding the coordination of biological processes mediating normal development, disease progression, and responses to perturbations such as therapies. Existing tools fail to capture time-dependent intercellular interactions and primarily rely on databases compiled from limited contexts. We introduce DIISCO, a Bayesian framework designed to characterize the temporal dynamics of cellular interactions using single-cell RNA-sequencing data from multiple time points.
View Article and Find Full Text PDFImportance: Endometriosis has been associated with an increased risk of ovarian cancer; however, the associations between endometriosis subtypes and ovarian cancer histotypes have not been well-described.
Objective: To evaluate the associations of endometriosis subtypes with incidence of ovarian cancer, both overall and by histotype.
Design, Setting, And Participants: Population-based cohort study using data from the Utah Population Database.
Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for many hematologic malignancies as well as non-malignant conditions. Part of the curative basis underlying HSCT for hematologic malignancies relies upon induction of the graft versus leukemia (GVL) effect in which donor immune cells recognize and eliminate residual malignant cells within the recipient, thereby maintaining remission. GVL is a clinically evident phenomenon; however, specific cell types responsible for inducing this effect and molecular mechanisms involved remain largely undefined.
View Article and Find Full Text PDFUnderstanding how intra-tumoral immune populations coordinate to generate anti-tumor responses following therapy can guide precise treatment prioritization. We performed systematic dissection of an established adoptive cellular therapy, donor lymphocyte infusion (DLI), by analyzing 348,905 single-cell transcriptomes from 74 longitudinal bone-marrow samples of 25 patients with relapsed myeloid leukemia; a subset was evaluated by protein-based spatial analysis. In acute myelogenous leukemia (AML) responders, diverse immune cell types within the bone-marrow microenvironment (BME) were predicted to interact with a clonally expanded population of CD8+ cytotoxic T lymphocytes (CTLs) which demonstrated specificity for autologous leukemia.
View Article and Find Full Text PDFCancer Treat Res Commun
February 2024
Background: Glioblastoma is the most common primary malignant and treatment-resistant human brain tumor. Rodent models have played an important role in understanding brain cancer biology and treatment. However, due to their small cranium and tumor volume mismatch, relative to human disease, they have been less useful for translational studies.
View Article and Find Full Text PDFSingle-cell transcriptomics has become the definitive method for classifying cell types and states, and can be augmented with genotype information to improve cell lineage identification. Due to constraints of short-read sequencing, current methods to detect natural genetic barcodes often require cumbersome primer panels and early commitment to targets. Here we devise a flexible long-read sequencing workflow and analysis pipeline, termed nanoranger, that starts from intermediate single-cell cDNA libraries to detect cell lineage-defining features, including single-nucleotide variants, fusion genes, isoforms, sequences of chimeric antigen and TCRs.
View Article and Find Full Text PDFBackground: The JoyPop™ smartphone app is a digital intervention designed to enhance day-to-day resilience in youth, particularly those exposed to traumatogenic events [adverse childhood experiences (ACEs)]. Processes of adaptation that foster resilience in response to high stress include affect, cognitive, and behavioral regulation, and social interaction. Digital interventions have application for youth and those who provide them support, including social work trainees navigating the stressors of university studies concurrent with practice internships.
View Article and Find Full Text PDFCharacterizing cell-cell communication and tracking its variability over time is essential for understanding the coordination of biological processes mediating normal development, progression of disease, or responses to perturbations such as therapies. Existing tools lack the ability to capture time-dependent intercellular interactions, such as those influenced by therapy, and primarily rely on existing databases compiled from limited contexts. We present DIISCO, a Bayesian framework for characterizing the temporal dynamics of cellular interactions using single-cell RNA-sequencing data from multiple time points.
View Article and Find Full Text PDFBackground: Rapid evolution of ultrasound technology has allowed widespread use of handheld ultrasound devices (HHUDs) for many possible applications. Along with the adult population, the use of HHUDs for Point of Care Ultrasound (POCUS) in pediatric medicine has been increasing over the last few years. However, pediatric-specific literature is still scarce on mobile vascular ultrasound.
View Article and Find Full Text PDFCell therapies have yielded durable clinical benefits for patients with cancer, but the risks associated with the development of therapies from manipulated human cells are understudied. For example, we lack a comprehensive understanding of the mechanisms of toxicities observed in patients receiving T cell therapies, including recent reports of encephalitis caused by reactivation of human herpesvirus 6 (HHV-6). Here, through petabase-scale viral genomics mining, we examine the landscape of human latent viral reactivation and demonstrate that HHV-6B can become reactivated in cultures of human CD4 T cells.
View Article and Find Full Text PDFIntroduction: The curative basis of allogeneic hematopoietic stem cell transplantation (HSCT) relies in part upon the graft versus leukemia (GvL) effect, whereby donor immune cells recognize and eliminate recipient malignant cells. However, alloreactivity of donor cells against recipient tissues may also be deleterious. Chronic graft versus host disease (cGvHD) is an immunologic phenomenon wherein alloreactive donor T cells aberrantly react against host tissues, leading to damaging inflammatory symptoms.
View Article and Find Full Text PDFImpairment of both the central and peripheral nervous system is a major cause of mortality and disability. It varies from an affection of the brain to various types of enteric dysganglionosis. Congenital enteric dysganglionosis is characterized by the local absence of intrinsic innervation due to deficits in either migration, proliferation or differentiation of neural stem cells.
View Article and Find Full Text PDFThe ability of posttransplant cyclophosphamide (PTCY) to facilitate haploidentical transplantation has spurred interest in whether PTCY can improve clinical outcomes in patients with HLA-matched unrelated donors undergoing peripheral blood stem cell transplantation (PBSCT). We investigated our institutional experience using PTCY-based graft-versus-host disease (GVHD) prophylaxis compared with conventional tacrolimus-based regimens. We compared overall survival, progression-free survival (PFS), relapse, nonrelapse mortality, and acute and chronic GVHD in 107 adult patients receiving a PTCY-based regimen vs 463 patients receiving tacrolimus-based regimens for GVHD prophylaxis.
View Article and Find Full Text PDFAlthough discovered in the 1940s (Mandel and Metais, C R Seances Soc Biol Fil 142:241-243, 1948), cell-free DNA has only recently become a tool practical for use in clinical settings. The challenges associated with detection of circulating tumor DNA (ctDNA) in patient plasma are many and exist in the pre-analytical, analytical, and post-analytical periods. Initiation of a ctDNA program in a small academic clinical laboratory setting can be challenging.
View Article and Find Full Text PDFBackground: The T w sequence is a standard component of a prostate MRI examination; however, it is time-consuming, requiring multiple signal averages to achieve acceptable image quality.
Purpose/hypothesis: To determine whether a denoised, single-average T sequence (T -R) is noninferior to the standard multiaverage T sequence (T -S) in terms of lesion detection and PI-RADS score assessment.
Study Type: Retrospective.