Touch Craft Ltd completed a feasibility study to understand the market position, technologies and user requirement for a smart sock sensing system designed to help monitor foot problems for people ...living with diabetes. The proposed system would involve a non-invasive, low-cost approach to gathering and measuring skin and foot data considering parameters such as pressure, temperature, and activity levels. The smart sock sensing system would enable both clinicians and patients to have a broader view of foot health and assist in improving the quality of life for patients and their carers.
T-cell acute lymphoblastic leukemia (T-ALL) is a genetically heterogeneous disease that can be classified into different molecular genetic subtypes according to their mRNA gene expression profile. In ...this study, we applied RNA sequencing to investigate the full spectrum of miRNA expression in primary T-ALL patient samples, T-ALL leukemia cell lines and healthy donor thymocytes. Notably, this analysis revealed that genetic subtypes of human T-ALL also display unique miRNA expression signatures, which are largely conserved in human T-ALL cell lines with corresponding genetic background. Furthermore, small RNA-sequencing also unraveled the variety of isoforms that are expressed for each miRNA in T-ALL and showed that a significant number of miRNAs are actually represented by an alternative isomiR. Finally, comparison of CD34
and CD4
CD8
healthy donor thymocytes and T-ALL miRNA profiles allowed identifying several novel miRNAs with putative oncogenic or tumor suppressor functions in T-ALL. Altogether, this study provides a comprehensive overview of miRNA expression in normal and malignant T-cells and sets the stage for functional evaluation of novel miRNAs in T-ALL disease biology.
Secondary myeloid neoplasms (sMNs) remain the most serious long-term complications in patients with aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH). However, sMNs lack specific ...predictors, dedicated surveillance measures, and early therapeutic interventions.
We studied a multicenter, retrospective cohort of 1,008 patients (median follow-up 8.6 years) with AA and PNH to assess clinical and molecular determinants of clonal evolution.
Although none of the patients transplanted upfront (n = 117) developed clonal complications (either sMN or secondary PNH), the 10-year cumulative incidence of sMN in nontransplanted cases was 11.6%. In severe AA, older age at presentation and lack of response to immunosuppressive therapy were independently associated with increased risk of sMN, whereas untreated patients had the highest risk among nonsevere cases. The elapsed time from AA to sMN was 4.5 years. sMN developed in 94 patients. The 5-year overall survival reached 40% and was independently associated with bone marrow blasts at sMN onset. Myelodysplastic syndrome with high-risk phenotypes, del7/7q, and
,
,
, and
pathway gene mutations were the most frequent characteristics. Cross-sectional studies of clonal dynamics from baseline to evolution revealed that
human leukocyte antigen lesions decreased over time, being replaced by clones with myeloid hits.
and
mutation carriers had a lower risk of sMN progression, whereas myeloid driver lesions marked the group with a higher risk.
The risk of sMN in AA is associated with disease severity, lack of response to treatment, and patients' age. sMNs display high-risk morphological, karyotypic, and molecular features. The landscape of acquired somatic mutations is complex and incompletely understood and should be considered with caution in medical management.
Oncogenic alterations underlying B-cell acute lymphoblastic leukemia (B-ALL) in adults remain incompletely elucidated. To uncover novel oncogenic drivers, we performed RNA sequencing and whole-genome ...analyses in a large cohort of unresolved B-ALL. We identified a novel subtype characterized by a distinct gene expression signature and the unique association of 2 genomic microdeletions. The 17q21.31 microdeletion resulted in a UBTF::ATXN7L3 fusion transcript encoding a chimeric protein. The 13q12.2 deletion resulted in monoallelic ectopic expression of the homeobox transcription factor CDX2, located 138 kb in cis from the deletion. Using 4C-sequencing and CRISPR interference experiments, we elucidated the mechanism of CDX2 cis-deregulation, involving PAN3 enhancer hijacking. CDX2/UBTF ALL (n = 26) harbored a distinct pattern of additional alterations including 1q gain and CXCR4 activating mutations. Within adult patients with Ph− B-ALL enrolled in GRAALL trials, patients with CDX2/UBTF ALL (n = 17/723, 2.4%) were young (median age, 31 years) and dramatically enriched in females (male/female ratio, 0.2, P = .002). They commonly presented with a pro-B phenotype ALL and moderate blast cell infiltration. They had poor response to treatment including a higher risk of failure to first induction course (19% vs 3%, P = .017) and higher post-induction minimal residual disease (MRD) levels (MRD ≥ 10−4, 93% vs 46%, P < .001). This early resistance to treatment translated into a significantly higher cumulative incidence of relapse (75.0% vs 32.4%, P = .004) in univariate and multivariate analyses. In conclusion, we discovered a novel B-ALL entity defined by the unique combination of CDX2 cis-deregulation and UBTF::ATXN7L3 fusion, representing a high-risk disease in young adults.
•CDX2 cis-deregulation and UBTF::ATXN7L3 fusion driven by focal deletions define a novel subtype of B-ALL.•CDX2/UBTF::ATXN7L3 is a high-risk B-ALL subtype in young adults, which warrants improved therapeutic strategies.
Display omitted
Background
Neurofibromatosis type 1 (NF1) is a tumor predisposition syndrome with a worldwide birth incidence of one in 2500. Genetic factors unrelated to the NF1 locus are thought to influence the ...number of plexiform neurofibromas (PNFs) in patients with NF1, but no factors have been identified to date.
Methods
We used high-resolution array comparative genomic hybridization of tissue from 22 PNFs obtained from 18 NF1 patients to identify modifier genes involved in PNF development. We used a family-based association test for five previously identified cancer-susceptibility tag single-nucleotide polymorphisms (rs1063192, rs2151280, rs2218220, rs10757257, and rs7023329) located in chromosomal region 9p21.3 in 1105 subjects (740 NF1 patients and 365 non-affected relatives) from 306 families. To confirm the functional role of rs2151280, we used real-time quantitative reverse transcription-polymerase chain reaction to analyze the expression of cyclin-dependent kinase inhibitor 2A (CDKN2A), CDKN2B, alternate reading frame (ARF), and antisense noncoding RNA in the INK4 locus (ANRIL) in the peripheral blood of 124 NF1 patients. Relationships between CDKN2A, CDKN2B, ARF, and ANRIL expression and the rs2151280 genotype were tested by the Kruskal-Wallis test. All statistical tests were two-sided.
Results
In NF1-associated PNFs, 9p21.3 deletions (including the CDKN2A/B-ANRIL locus) were found as the only recurrent somatic alterations. Single-nucleotide polymorphism rs2151280 (located in ANRIL) was statistically significantly associated with the number of PNFs (P < .001) in NF1 patients. In addition, allele T of rs2151280 was statistically significantly associated with reduced ANRIL transcript levels (P < .001), suggesting that modulation of ANRIL expression mediates PNF susceptibility.
Conclusion
Identification of ANRIL as a modifier gene in NF1 may offer clues to the molecular pathogenesis of PNFs, particularly neurofibroma formation, and emphasizes the unanticipated role of large noncoding RNA in activation of critical regulators of tumor development.
This paper introduces a framework and recommendations for crafting e-textiles, advocating craft as an embodied, knowledge-generating practice employing innovative materials and processes. It offers a ...material investigation into technology to create e-textiles that embed digital capabilities to support more meaningful and connected forms of expression. The framework and recommendations interweave concerns around collaborative, sensorial and aesthetic interaction to conceptualise the relationship between experiences and materials that are lively and animated. The framework conceives lively experiences as a central component of crafted e-textiles that aspire to be meaningful and worthwhile. A material practice activates our sensory awareness and facilitates embodied actions leading to experiences that have much to reveal about people and their interactions through participation and engagement. Applications of the framework and recommendations can structure a material approach to e-textiles and support open exploration and emergent participant behaviour. The framework and recommendations are intended to support more enriching, personally conceived design contexts engaging technology to craft e-textiles that contribute social value and stimulate emotional response in people.
Le processus de décrochage scolaire est un processus complexe, multidimensionnel, qui s’inscrit dans une temporalité de l’expérience scolaire et qui peut finir par déboucher sur la déscolarisation. ...Si de nombreuses études se sont orientées sur la diversité des manifestations du décrochage scolaire et des types de décrocheurs, l’objectif de notre étude est d’analyser, en amont, comment la socialisation entre pairs peut contribuer à susciter et/ou à accélérer ce processus de décrochage scolaire chez des adolescents de quatorze à seize ans. En effet, il nous paraît important d’inclure le rôle des pairs à propos de la vie scolaire dans la mesure où ils exercent une influence déterminante sur la socialisation et la construction identitaire de l’adolescent. L’étude a été réalisée par questionnaires auprès de 676 adolescents de quatorze à seize ans. L’outil appréhende d’une part la (dé)mobilisation scolaire et d’autre part, la position sociale via la qualité des relations aux pairs. Les résultats montrent que les élèves qui parviennent à ajuster leur mode de relations aux pairs (les « populaires ») sont les plus mobilisés scolairement. Leurs relations aux autres sont fondées sur la cohésion, le soutien, la solidarité et l’intimité. De même, les adolescents « en retrait », indépendants, autonomes et solitaires, sont également plutôt mobilisés dans leur scolarité. Enfin, les élèves ayant une représentation de l’amitié fondée sur la dépendance affective, les rapports de force, le conflit ou la conformité (les « négligés » et les « soumis ») sont démobilisés. Ils privilégient les apprentissages relationnels aux apprentissages intellectuels.
The process of dropping out of school is a complex and multidimensional process, which is part of a temporality of academic experience and can eventually lead to dropping out. While many studies have focused on the diversity of manifestations of dropout and types of dropouts, the objective of our study is to analyze how socialization among peers can generate and / or accelerate dropout among adolescents. Indeed, it seems important to include the role of peers about school life because that they have a decisive influence on adolescent’s socialization and on his identity construction. Questionnaires were administered to 676 adolescents, aged 14 to 16 years. Academic engagement and social position (quality of peer’s relationships) were evaluated. Results reveal that students who are able to adjust their mode of relation to peers (“popular”) are more engaged academically. Similarly, adolescents “withdrawn”, independent, autonomous and solitary are also engaged in their schooling. Finally, students too dependent of group and with a representation of friendship based on power relations, conflict or conformity (“neglected” and “scapegoat”) are disengaged. They prefer relational learning to intellectual learning.
Les problématiques actuelles liées à l’insertion professionnelle des jeunes ont amené chercheur.e.s et praticien.ne.s à s’intéresser à des compétences complémentaires aux compétences ...professionnelles : les compétences sociales. Dans cette perspective, des programmes destinés aux étudiant.e.s et favorisant le développement de ces compétences ont été créés. Cet article présente huit de ces programmes pour lesquels sont décrits, analysés et comparés objectifs, contenus (pédagogies, compétences ciblées, durée), évaluations et résultats. En soulignant les caractéristiques des programmes reconnues comme efficaces, mais également leurs limites au niveau théorique et méthodologique, l’objectif est de dégager des constats et propositions d’action utiles pour l’établissement de futurs programmes.
Bone marrow (BM) failure (BMF) in children and young adults is often suspected to be inherited, but in many cases diagnosis remains uncertain. We studied a cohort of 179 patients (from 173 families) ...with BMF of suspected inherited origin but unresolved diagnosis after medical evaluation and Fanconi anemia exclusion. All patients had cytopenias, and 12.0% presented ≥5% BM blast cells. Median age at genetic evaluation was 11 years; 20.7% of patients were aged ≤2 years and 36.9% were ≥18 years. We analyzed genomic DNA from skin fibroblasts using whole-exome sequencing, and were able to assign a causal or likely causal germ line mutation in 86 patients (48.0%), involving a total of 28 genes. These included genes in familial hematopoietic disorders (GATA2, RUNX1), telomeropathies (TERC, TERT, RTEL1), ribosome disorders (SBDS, DNAJC21, RPL5), and DNA repair deficiency (LIG4). Many patients had an atypical presentation, and the mutated gene was often not clinically suspected. We also found mutations in genes seldom reported in inherited BMF (IBMF), such as SAMD9 and SAMD9L (N = 16 of the 86 patients, 18.6%), MECOM/EVI1 (N = 6, 7.0%), and ERCC6L2 (N = 7, 8.1%), each of which was associated with a distinct natural history; SAMD9 and SAMD9L patients often experienced transient aplasia and monosomy 7, whereas MECOM patients presented early-onset severe aplastic anemia, and ERCC6L2 patients, mild pancytopenia with myelodysplasia. This study broadens the molecular and clinical portrait of IBMF syndromes and sheds light on newly recognized disease entities. Using a high-throughput sequencing screen to implement precision medicine at diagnosis can improve patient management and family counseling.
•Next-generation sequencing broadens the spectrum of germ line mutations in a cohort of patients with likely-inherited BMF.•Salient clinical features and distinct natural histories are consistently found in SAMD9L and SAMD9, MECOM/EVI1, and ERCC6L2 disorders.
Display omitted
PDF
