Genetic alterations in lymphoblastic leukaemia / lymphoma – a practical guide to WHO HAEM5

\ua9 2024 the author(s), published by De Gruyter.We present a practical guide for analyzing the genetic aspects of lymphoblastic leukaemia/lymphoma according to the 5th edition of the World Health Organization (WHO) classification of haematolymphoid neoplasms (WHO-HAEM5) issued in 2024. The WHO-HAEM5 acknowledges the increasing importance of genetics in the diagnosis of lymphoid neoplasia. Classification is based on the established genetic subtypes according to cell lineage, with precursor cell neoplasms followed by mature malignancies. This guide describes those genetic abnormalities in acute precursor B- and T-cell neoplasms required for risk stratification, and for treatment, providing diagnostic algorithms under the headings of ‘essential’ and ‘desirable’ diagnostic criteria

Analyzing First-Person Stories Based on Socializing, Eating and Sedentary Patterns

First-person stories can be analyzed by means of egocentric pictures acquired throughout the whole active day with wearable cameras. This manuscript presents an egocentric dataset with more than 45,000 pictures from four people in different environments such as working or studying. All the images were manually labeled to identify three patterns of interest regarding people's lifestyle: socializing, eating and sedentary. Additionally, two different approaches are proposed to classify egocentric images into one of the 12 target categories defined to characterize these three patterns. The approaches are based on machine learning and deep learning techniques, including traditional classifiers and state-of-art convolutional neural networks. The experimental results obtained when applying these methods to the egocentric dataset demonstrated their adequacy for the problem at hand.Comment: Accepted at First International Workshop on Social Signal Processing and Beyond, 19th International Conference on Image Analysis and Processing (ICIAP), September 201

Manipulation of Polyhydroxybutyrate Properties through Blending with Ethyl-Cellulose for a Composite Biomaterial

Polyhydroxybutyrate (PHB) is widely used as a biomaterial in medical and tissue-engineering applications, a relatively high crystallinity limits its application. Blending PHB with ethyl-cellulose (EtC) was readily achieved to reduce PHB crystallinity and promote its degradation under physiological conditions without undue influence on biocompatibility. Material strength of composite films remained unchanged at 6.5 ± 0.6 MPa with 40% (w/w) EtC loadings. Phase separation between the two biopolymers was determined with PHB crystallinity decreasing from 63% to 47% for films with the same loading. This reduction in crystallinity supported an increase in the degradation rates of composite films from 0.39 to 0.81% wk−1 for PHB and its composite, respectively. No significant change in morphology and proliferation of olfactory ensheathing cells were observed with the composites despite significant increases in average surface roughness (Ra) of the films from 2.90 to 3.65 μm for PHB and blends with 80% (w/w) EtC, respectively. Copyright © 2011 Rodman T. H. Chan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Global network analysis in Schizosaccharomyces pombe reveals three distinct consequences of the common 1-kb deletion causing juvenile CLN3 disease

Juvenile CLN3 disease is a recessively inherited paediatric neurodegenerative disorder, with most patients homozygous for a 1-kb intragenic deletion in CLN3. The btn1 gene is the Schizosaccharomyces pombe orthologue of CLN3. Here, we have extended the use of synthetic genetic array (SGA) analyses to delineate functional signatures for two different disease-causing mutations in addition to complete deletion of btn1. We show that genetic-interaction signatures can differ for mutations in the same gene, which helps to dissect their distinct functional effects. The mutation equivalent to the minor transcript arising from the 1-kb deletion (btn1102–208del) shows a distinct interaction pattern. Taken together, our results imply that the minor 1-kb deletion transcript has three consequences for CLN3: to both lose and retain some inherent functions and to acquire abnormal characteristics. This has particular implications for the therapeutic development of juvenile CLN3 disease. In addition, this proof of concept could be applied to conserved genes for other mendelian disorders or any gene of interest, aiding in the dissection of their functional domains, unpacking the global consequences of disease pathogenesis, and clarifying genotype–phenotype correlations. In doing so, this detail will enhance the goals of personalised medicine to improve treatment outcomes and reduce adverse events

AGN feedback in the Phoenix cluster

Active galactic nuclei (AGN) release a huge amount of energy into the intracluster medium (ICM) with the consequence of offsetting cooling and star formation (AGN feedback) in the centers of cool core clusters. The Phoenix cluster is among the most massive clusters of galaxies known in the Universe. It hosts a powerful starburst of several hundreds of Solar masses per year and a large amount of molecular gas in the center. In this work we use the high-resolution Reflection Grating Spectrometer (RGS) on board XMM-Newton to study the X-ray emitting cool gas in the Phoenix cluster and heating-cooling balance. We detect for the first time evidence of O VIII and Fe XXI-XXII emission lines, the latter demonstrating the presence of gas below 2 keV. We find a cooling rate of 350 (-200,+250) Msun/year below 2 keV (at the 90% confidence level), which is consistent with the star formation rate in this object. This cooling rate is high enough to produce the molecular gas found in the filaments via instabilities during the buoyant rising time. The line broadening indicates that the turbulence (~ 300 km/s or less) is below the level required to produce and propagate the heat throughout the cool core. This provides a natural explanation to the coexistence of large amounts of cool gas, star formation and a powerful AGN in the core. The AGN activity may be either at a young stage or in a different feedback mode, due to a high accretion rate

Monorail/Foxa2 regulates floorplate differentiation and specification of oligodendrocytes, serotonergic raphe neurones and cranial motoneurones

In this study, we elucidate the roles of the winged-helix transcription factor Foxa2 in ventral CNS development in zebrafish. Through cloning of monorail (mol), which we find encodes the transcription factor Foxa2, and phenotypic analysis of mol(-/-) embryos, we show that floorplate is induced in the absence of Foxa2 function but fails to further differentiate. In mol(-/-) mutants, expression of Foxa and Hh family genes is not maintained in floorplate cells and lateral expansion of the floorplate fails to occur. Our results suggest that this is due to defects both in the regulation of Hh activity in medial floorplate cells as well as cell-autonomous requirements for Foxa2 in the prospective laterally positioned floorplate cells themselves. Foxa2 is also required for induction and/or patterning of several distinct cell types in the ventral CNS. Serotonergic neurones of the raphe nucleus and the trochlear motor nucleus are absent in mol(-/-) embryos, and oculomotor and facial motoneurones ectopically occupy ventral CNS midline positions in the midbrain and hindbrain. There is also a severe reduction of prospective oligodendrocytes in the midbrain and hindbrain. Finally, in the absence of Foxa2, at least two likely Hh pathway target genes are ectopically expressed in more dorsal regions of the midbrain and hindbrain ventricular neuroepithelium, raising the possibility that Foxa2 activity may normally be required to limit the range of action of secreted Hh proteins

Mycobacterium tuberculosis cords within lymphatic endothelial cells to evade host immunity

The ability of Mycobacterium tuberculosis to form serpentine cords is intrinsically related to its virulence, but specifically how M. tuberculosis cording contributes to pathogenesis remains obscure. Here, we show that several M. tuberculosis clinical isolates form intracellular cords in primary human lymphatic endothelial cells (hLECs) in vitro and in the lymph nodes of patients with tuberculosis. We identified via RNA-Seq a transcriptional program that activated, in infected-hLECs, cell survival and cytosolic surveillance of pathogens pathways. Consistent with this, cytosolic access was required for intracellular M. tuberculosis cording. Mycobacteria lacking ESX-1 type VII secretion system or phthiocerol dimycocerosates expression, which failed to access the cytosol, were indeed unable to form cords within hLECs. Finally, we show that M. tuberculosis cording is a size-dependent mechanism used by the pathogen to avoid its recognition by cytosolic sensors and evade either resting or IFN-γ–induced hLEC immunity. These results explain the long-standing association between M. tuberculosis cording and virulence and how virulent mycobacteria use intracellular cording as strategy to successfully adapt and persist in the lymphatic tracts

Spectrum, risk factors and outcomes of neurological and psychiatric complications of COVID-19: a UK-wide cross-sectional surveillance study

SARS-CoV-2 is associated with new-onset neurological and psychiatric conditions. Detailed clinical data, including factors associated with recovery, are lacking, hampering prediction modelling and targeted therapeutic interventions. In a UK-wide cross-sectional surveillance study of adult hospitalized patients during the first COVID-19 wave, with multi-professional input from general and sub-specialty neurologists, psychiatrists, stroke physicians, and intensivists, we captured detailed data on demographics, risk factors, pre-COVID-19 Rockwood frailty score, comorbidities, neurological presentation and outcome. A priori clinical case definitions were used, with cross-specialty independent adjudication for discrepant cases. Multivariable logistic regression was performed using demographic and clinical variables, to determine the factors associated with outcome. A total of 267 cases were included. Cerebrovascular events were most frequently reported (131, 49%), followed by other central disorders (95, 36%) including delirium (28, 11%), central inflammatory (25, 9%), psychiatric (25, 9%), and other encephalopathies (17, 7%), including a severe encephalopathy (n = 13) not meeting delirium criteria; and peripheral nerve disorders (41, 15%). Those with the severe encephalopathy, in comparison to delirium, were younger, had higher rates of admission to intensive care and a longer duration of ventilation. Compared to normative data during the equivalent time period prior to the pandemic, cases of stroke in association with COVID-19 were younger and had a greater number of conventional, modifiable cerebrovascular risk factors. Twenty-seven per cent of strokes occurred in patients 60 years old, the younger stroke patients presented with delayed onset from respiratory symptoms, higher rates of multi-vessel occlusion (31%) and systemic thrombotic events. Clinical outcomes varied between disease groups, with cerebrovascular disease conferring the worst prognosis, but this effect was less marked than the pre-morbid factors of older age and a higher pre-COVID-19 frailty score, and a high admission white cell count, which were independently associated with a poor outcome. In summary, this study describes the spectrum of neurological and psychiatric conditions associated with COVID-19. In addition, we identify a severe COVID-19 encephalopathy atypical for delirium, and a phenotype of COVID-19 associated stroke in younger adults with a tendency for multiple infarcts and systemic thromboses. These clinical data will be useful to inform mechanistic studies and stratification of patients in clinical trials