A5078662250- Hemoglobinopathies and Related Disorders
- Erythrocyte Function and Pathophysiology
- Iron Metabolism and Disorders
- RNA modifications and cancer
- Blood groups and transfusion
- Genomics and Rare Diseases
- Blood disorders and treatments
- Genetic factors in colorectal cancer
- Immunodeficiency and Autoimmune Disorders
- Cancer-related gene regulation
- Blood transfusion and management
- Neonatal Health and Biochemistry
- Acute Myeloid Leukemia Research
- Genomic variations and chromosomal abnormalities
- Single-cell and spatial transcriptomics
- Blood properties and coagulation
- Cystic Fibrosis Research Advances
- Trace Elements in Health
- RNA and protein synthesis mechanisms
- Pancreatic function and diabetes
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Infectious Diseases and Tuberculosis
- Spondyloarthritis Studies and Treatments
- Hematopoietic Stem Cell Transplantation
- CRISPR and Genetic Engineering
Oxford University Hospitals NHS Trust
2018-2025
University of Oxford
2016-2025
MRC Weatherall Institute of Molecular Medicine
2016-2025
John Radcliffe Hospital
2016-2025
National Health Service
2019-2024
Oxford BioMedica (United Kingdom)
2018-2023
Churchill Hospital
2017-2023
NHS Blood and Transplant
2016-2022
National Institute for Health Research
2020-2021
Centre Hospitalier de l’Université de Montréal
2020-2021
Abstract Background Whole genome sequencing is increasingly being used for the diagnosis of patients with rare diseases. However, diagnostic yields many studies, particularly those conducted in a healthcare setting, are often disappointingly low, at 25–30%. This part because although entire genomes sequenced, analysis confined to silico gene panels or coding regions genome. Methods We undertook WGS on cohort 122 unrelated disease and their relatives (300 genomes) who had been pre-screened by...
Regulation of macrophage capacity to remove apoptotic cells may control the balance and necrotic leukocytes at inflamed foci extent leukocyte-mediated tissue damage. Although molecules involved in phagocytic process are beginning be defined, little is known about underlying regulatory signaling mechanisms controlling this process. In paper, we have investigated effects treatment human monocyte-derived macrophages with PGs other agents that elevate intracellular cAMP on phagocytosis. PGE2...
Accurate diagnosis of rare inherited anaemias is challenging, requiring a series complex and expensive laboratory tests. Targeted next-generation-sequencing (NGS) has been used to investigate these disorders, but the selection genes on individual panels narrow validation strategies have fallen short standards required for clinical use. Clinical-grade negative results requires test distinguish between lack adequate sequencing reads at locations known mutations real absence mutations. To...
The authors applied whole-genome sequencing (WGS) in 9,802 patients with a rare disease national health system to streamline diagnosis and discover unknown aetiological variants the coding non-coding regions of genome. WGS identified genetic 1138/7065 extensively phenotyped participants. They 95 genes which mutations were very likely be cause Mendelian disease.
Summary Antenatal screening/testing of pregnant women should be carried out according to the guidelines National Health Service (NHS) Sickle Cell and Thalassaemia Screening Programme. Newborn screening and, when necessary, follow‐up testing referral, NHS All babies under 1 year age arriving in United Kingdom offered for sickle cell disease (SCD). Preoperative SCD patients from ethnic groups which there is a significant prevalence condition. Emergency with solubility test must always followed...
Haemoglobin E (HbE) β-thalassaemia causes approximately 50% of all severe thalassaemia worldwide; equating to around 30,000 births per year. HbE is due a point mutation in codon 26 the human HBB gene on one allele (GAG; glutamatic acid → AAG; lysine, E26K), and any causing other. When inherited together compound heterozygosity these mutations can cause thalassaemic phenotype. However, if only mutated individuals are carriers for respective have an asymptomatic phenotype (β-thalassaemia...
Transfusion-dependent myelodysplastic (MDS) patients are prone to iron overload. We evaluated 43 transfused MDS with T2* magnetic resonance imaging scans. 81% had liver and 16·8% cardiac Liver R2* (1000/T2*), but not R2*, was correlated number of units (r=0·72, P<0·0001) ferritin (r=0·53, P<0·0001). The area under the curve a time-ferritin plot found be much greater in loading (median 53·7x10(5) Megaunits vs. 12·2x10(5) Megaunits, P=0·002). HFE, HFE2, HAMP or SLC40A1 genotypes were...
Significance Blood is routinely tested for gas-carrying capacity (total hemoglobin), but this cannot determine the speed at which red blood cells (RBCs) exchange gases. Such information critical evaluating physiological fitness of RBCs, have very limited capillary transit times (<1 s) turning over substantial volumes gas. We developed a method to quantify gas in individual RBCs and used it show that restricted diffusion, imposed by hemoglobin crowding, major barrier flows. Consequently,...
Prostate cancer (PC) is the most frequently diagnosed in North American men. Pathologists are critical need of accurate biomarkers to characterize PC, particularly confirm presence intraductal carcinoma prostate (IDC-P), an aggressive histopathological variant for which therapeutic options now available. Our aim was identify IDC-P with Raman micro-spectroscopy (RμS) and machine learning technology following a protocol suitable routine clinical histopathology laboratories.
During tubo-ovarian high-grade serous carcinoma (HGSC) progression, tumoral cells undergo phenotypic changes in their epithelial marker profiles, which are essential for dissemination processes. Here, we set out to determine whether standard markers can predict HGSC patient prognosis. Levels of E-CADH, KRT7, KRT18, KRT19 were quantified 18 cell lines by Western blot and a Discovery cohort tissue microarray (TMA) (n = 101 patients) using immunofluorescence. E-CADH KRT7 levels subsequently...
METHODOLOGY The British Society for Haematology (BSH) produces Good Practice Papers to recommend good practice in areas where there is a limited evidence base but which degree of consensus or uniformity likely be beneficial patient care. Grading Recommendations Assessment, Development and Evaluation (GRADE) nomenclature was used evaluate levels assess the strength recommendations. GRADE criteria can found at http://www.gradeworkinggroup.org. This Paper produced as collaboration with European...
Many children leave the PICU with anemia. The mechanisms of post-PICU anemia are poorly investigated, and treatment anemia, other than blood, is rarely started during PICU. We aimed to characterize contributions iron depletion (ID) and/or inflammation in development explore utility hepcidin (a novel marker) at detecting ID inflammation.
Red blood cell development from erythroid progenitors requires profound reshaping of metabolism and gene expression. How these transcriptional metabolic alterations are coupled is unclear. Nprl3 (an inhibitor mTORC1) has remained in synteny with the α-globin genes for >500 million years, harbours most a-globin enhancers. However, whether serves an role unknown. We found that while haematopoietic require basal expression, expression further boosted by This lineage-specific upregulation...