85 research outputs found
KITD816V+ systemic mastocytosis associated with KITD816V+ acute erythroid leukaemia: first case report with molecular evidence for same progenitor cell derivation
Toll-like receptor (TLR)-9 recognizes CpG motifs in microbial DNA. TLR9 signalling stimulates innate antimicrobial immunity and modulates adaptive immune responses including autoimmunity against chromatin, e.g., in systemic lupus erythematosus (SLE). This review summarizes the available data for a role of TLR9 signalling in lupus and discusses the following questions that arise from these observations: 1) Is CpG-DNA/TLR9 interaction involved in infection-induced disease activity of lupus? 2) What are the risks of CpG motifs in vaccine adjuvants for lupus patients? 3) Is TLR9 signalling involved in the pathogenesis of lupus by recognizing self DNA
Aligning Synthetic Medical Images with Clinical Knowledge using Human Feedback
Generative models capable of capturing nuanced clinical features in medical
images hold great promise for facilitating clinical data sharing, enhancing
rare disease datasets, and efficiently synthesizing annotated medical images at
scale. Despite their potential, assessing the quality of synthetic medical
images remains a challenge. While modern generative models can synthesize
visually-realistic medical images, the clinical validity of these images may be
called into question. Domain-agnostic scores, such as FID score, precision, and
recall, cannot incorporate clinical knowledge and are, therefore, not suitable
for assessing clinical sensibility. Additionally, there are numerous
unpredictable ways in which generative models may fail to synthesize clinically
plausible images, making it challenging to anticipate potential failures and
manually design scores for their detection. To address these challenges, this
paper introduces a pathologist-in-the-loop framework for generating
clinically-plausible synthetic medical images. Starting with a diffusion model
pretrained using real images, our framework comprises three steps: (1)
evaluating the generated images by expert pathologists to assess whether they
satisfy clinical desiderata, (2) training a reward model that predicts the
pathologist feedback on new samples, and (3) incorporating expert knowledge
into the diffusion model by using the reward model to inform a finetuning
objective. We show that human feedback significantly improves the quality of
synthetic images in terms of fidelity, diversity, utility in downstream
applications, and plausibility as evaluated by experts
Vitamin C in Haemopoiesis
Twenty one cases of severe vitamin C deficiency, including thirteen cases of scurvy, are studied. The blood and bone marrow pictures and the effects of treatment are considered. Theories as to whether or not vitamin C is an erythropoietic factor are discussed. Reasons are given for concluding that the vitamin does not play a specific part in erythropoiesis
Erythrocyte Morphology and Its Disorders
Blood cell morphology is a key tool in laboratory haematology. Erythrocyte morphology points to possible aetiopathogenetic events in several primary and secondary haemopathies. Despite advances in medical technology and laboratory automation, red cell morphology remains a basic aspect of haematological evaluation. The human erythrocytes are discoid (bi-concave), about 7–8 μm (size of the nucleus of a small lymphocyte) in diameter, with a central area of pallor (which occupies a third of the red cell diameter) and is well haemoglobinised in the outer two thirds of the red cell diameters, without any inclusions. Deviations from the normal in terms of size, shape, colour, distribution or presence of inclusion bodies suggests possible disease processes. This chapter is therefore dedicated to morphologic description of the human erythrocytes, a study of possible abnormalities, its underlying pathophysiology and the associated differential diagnosis in humans
Speciation in the baboon and its relation to gamma-chain heterogeneity and to the response to induction of HbF by 5-azacytidine
In the baboon (Papio species), the two nonallelic gamma-genes produce gamma-chains that differ at a minimum at residue 75, where isoleucine (I gamma-chain) or valine (V gamma) may be present. This situation obtains in baboons that are sometimes designated as Papio anubis, Papio hamadryas, and Papio papio. However, in Papio cynocephalus, although the I gamma-chains are identical with those in the above mentioned types, the V gamma-chains have the substitutions ala----gly at residue 9 and ala----val at residue 23. The V gamma-chains of P. cynocephalus are called V gamma C to distinguish them from the V gamma A-chains of P. anubis, etc. A single cynocephalus animal has been found to have only normal I gamma-chains and I gamma C-chains (that is, glycine in residue 9, valine in 23, and isoleucine in 75). When HbF is produced in response to stress with 5-azacytidine, P. anubis baboons respond with greater production than do P. cynocephalus, and hybrids fall between. Minimal data on P. hamadryas and P. papio suggest an even lower response than P. cynocephalus. As HbF increases under stress, the ratio of I gamma to V gamma-chains changes from the value in the adult or juvenile baboon toward the ratio in the newborn baboon. However, it does not attain the newborn value. The V gamma A and V gamma C-genes respond differently to stress. In hybrids, the production of V gamma A- chains exceeds that of V gamma C-chains. A controlling factor in cis apparently is present and may be responsible for the species-related extent of total HbF production. It may be concluded that the more primitive the cell in the erythroid maturation series that has been subjected to 5-azacytidine, the more active is the I gamma-gene
- …