BCL-2 Expression in AML Patients over 65 Years: Impact on Outcomes across Different Therapeutic Strategies.
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ABSTRACT:
SUBMITTER: Tiribelli M
PROVIDER: S-EPMC8585096 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The observed gain in IQ scores over time has been examined and supported. Nonetheless, this phenomenon (also called Flynn effect) may depend on age groups and country types. This article provides raw data from three standardized intelligence tests, namely, Coloured Progressive Matrices (CPM), Standard Progressive Matrices (SPM), and Advanced Progressive Matrices (APM). The datasets contain mean IQ scores from APM, CPM, and SPM, and standard deviations, sample sizes, years of publication, participants' groups, types of countries, country-based samples, and gender of participants. This data was obtained from 199, 369, and 176 individual study samples for CPM, SPM, and APM, respectively, and covered a period of 65 years (1950-2014). There were 202,468 participants in total. An analysis and interpretation of results based on a cross-temporal meta-analysis for mean IQ scores from CPM, SPM, and APM over time can be found in the article "A Cross-Temporal Meta-Analysis of Raven's Progressive Matrices: Age groups and developing versus developed countries" (Wongupparaj, Kumari, Morris, 2015) [1]. These datasets can provide an extensive overview of the literature on Flynn effect across age groups, countries, and gender. In addition, they can serve as a useful starting point for further meta-analyses of IQ scores derived from CPM, SPM, and APM.
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Project description:PurposeHypereosinophilia represents a heterogenous group of severe medical conditions characterized by elevated numbers of eosinophil granulocytes in peripheral blood, bone marrow or tissue. Treatment options for hypereosinophilia remain limited despite recent approaches including IL-5-targeted monoclonal antibodies and tyrosine kinase inhibitors.MethodsTo understand aberrant survival patterns and options for pharmacologic intervention, we characterized BCL-2-regulated apoptosis signaling by testing for BCL-2 family expression levels as well as pharmacologic inhibition using primary patient samples from diverse subtypes of hypereosinophilia (hypereosinophilic syndrome n = 18, chronic eosinophilic leukemia not otherwise specified n = 9, lymphocyte-variant hypereosinophilia n = 2, myeloproliferative neoplasm with eosinophilia n = 2, eosinophilic granulomatosis with polyangiitis n = 11, reactive eosinophilia n = 3).ResultsContrary to published literature, we found no difference in the levels of the lncRNA Morrbid and its target BIM. Yet, we identified a near complete loss of expression of pro-apoptotic PUMA as well as a reduction in anti-apoptotic BCL-2. Accordingly, BCL-2 inhibition using venetoclax failed to achieve cell death induction in eosinophil granulocytes and bone marrow mononuclear cells from patients with hypereosinophilia. In contrast, MCL1 inhibition using S63845 specifically decreased the viability of bone marrow progenitor cells in patients with hypereosinophilia. In patients diagnosed with Chronic Eosinophilic Leukemia (CEL-NOS) or Myeloid and Lymphatic Neoplasia with hypereosinophilia (MLN-Eo) repression of survival was specifically powerful.ConclusionOur study shows that MCL1 inhibition might be a promising therapeutic option for hypereosinophilia patients specifically for CEL-NOS and MLN-Eo.
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Project description:In Australia, pneumococcal vaccine is provided free to all adults aged ≥65 years and Indigenous people aged 15-65 years, and is subsidized for non-Indigenous adults <65 years of age with risk factors. This study aimed to explore pneumococcal vaccination uptake in older patients attending 550 Australian general practices from 2010-2017 by patient sociodemographics, presence of comorbidities and practice characteristics. Study 1: a cross-sectional analysis of 'active' patients aged ≥65 years in each year was performed to calculate annual pneumococcal vaccination uptake. Study 2: a cohort of 58,589 'every year' patients aged 60-65 years in 2010 was analyzed to identify the number of patients immunized during the study period. Logistic regression models assessed associations between vaccination, patient and practice characteristics. Annual pneumococcal vaccine uptake varied by patient's age (65-74 or ≥75 years), presence of comorbidities and regularity of practice visits (range 36% to 76%), and it declined slowly from 2011-2016 amongst all groups. Cohort analyses showed that 69% of those aged 60-65 years in 2010 had a recorded pneumococcal vaccination by 2017 (peak age of vaccination = 66 years), and vaccination was more likely among those with comorbidities, ex-smokers and frequent attenders to practices. Findings demonstrate that the NPS MedicineInsight database provides estimates of vaccination uptake consistent with past surveys, reproducible every year and at low cost. It has the advantage of additional clinical information compared to the Australian Immunization Register. Whilst vaccination uptake was adequate among 'every year' patients, interventions are needed to improve pneumococcal vaccination for all older Australians.
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