Prevalence of mastocytosis and hymenoptera venom allergy in the United States

Background : Mastocytosis is a risk factor for hymenoptera venom anaphylaxis (HVA). Current guidelines recommend measuring tryptase in HVA patients and that those with mastocytosis pursue lifelong venom immunotherapy (VIT). Available data on HVA and mastocytosis largely derives from European single-center studies and the prevalence of HVA with and without mastocytosis in the United States (US) is unknown. Objective : We sought to determine the prevalence of HVA and mastocytosis in the US using an insurance claims database and evaluate the impact of mastocytosis on VIT in HVA patients in a US cohort. Methods :The IBM Watson Database, consisting of insurance claims from approximately 27 million US patients in 2018, was queried to identify patients with HVA and/or mastocytosis. Further, a retrospective study of 161 patients undergoing VIT between 2015 – 2018 at the University of Michigan (U-M) was conducted. Results :In the IBM Watson Database, the prevalence of HVA was 167 per 100,000 (0.167%) and the prevalence of mastocytosis 10 per 100,000 (0.010%) overall and 97 per 100,000 (0.097%) among those with HVA. Mastocytosis showed a 9.7-fold increase among HVA patients versus the general population. In the U-M cohort, 2.6% of VIT patients had mastocytosis. Tryptase level did not correlate with venom reaction severity but was higher in patients with systemic VIT reactions. Conclusions :We observed a lower US HVA prevalence than previously reported. Mastocytosis was more common in US HVA patients, though at lower rates than previously reported. In VIT patients there was no correlation between tryptase level and reaction severity. Key words :Tryptasevenom allergyvenom immunotherapyanaphylaxismastocytosismast cell activation syndromemast cell disease Abbreviations Hymenoptera venom allergyHVAUnited StatesUSVenom immunotherapyVITMast Cell DiseaseMCDAmerican Academy of Allergy, Asthma, and ImmunologyWOS:000717466600002Scopus - Affiliation ID: 60105072PMID: 33895259Science Citation Index ExpandedQ1ArticleUluslararası işbirliği ile yapılan - EVETKasım2021YÖK - 2021-2

What do adolescents value most and is this affected by HIV status? Aspirations and self-perceptions from a large cohort study in South Africa.

Hundreds of millions of adolescents across Africa face challenges in many areas of their lives, including elevated risk of HIV exposure and acquisition. Understanding the aspirations and self-perceptions of adolescents could play an important role in better targeting effective investments to break the cycle of adversity for adolescents and into their adulthood. Aiming to understand what adolescents value most for themselves and their future, we analysed and summarised cross-sectional data on the aspirations and self-perceptions of 1519 adolescents living in South Africa, overall and by HIV status. Outcomes were coded from participant responses to two open-ended questions: 'What job do you want to do when you grow up?' and 'What are you most proud of about yourself?'. Associations with HIV status were then evaluated using multivariable logistic regression adjusting for six sociodemographic factors measured from the same cohort. The sample had a mean age of 14 years, 55% were female, and 70% were living with HIV. The five most common job aspirations were: 'Health and Medical Science Professionals' (28%), 'Law Enforcement and Public Safety Professionals' (14%), 'Social Work Associate Professionals' (12%), 'Legal Professionals' (9%), and 'Education Institutions Teaching Professionals' (6%). The top five themes for what adolescents were most proud of about themselves were 'School performance' (22%), 'Outward appearance' (15%), 'Sports skills' (12%), 'Personality' (11%), and 'Behaviour at home/with elders' (7%). Adjusted analysis showed no evidence that HIV status was associated with important differences in aspirations or self-perceptions. In conclusion, adolescents facing high levels of adversity in South Africa hold high value for their education and aspirations for their futures. Policies and initiatives should focus on meeting these aspirations as vehicles for development, independent of their HIV status. Therefore, more needs to be done to not just help adolescents survive but thrive into adulthood

Data management instruments to protect the personal information of children and adolescents in sub-Saharan Africa

Recent data protection regulatory frameworks, such as the Protection of Personal Information Act (POPI Act) in South Africa and the General Data Protection Regulation (GDPR) in the European Union, impose governance requirements for research involving high-risk and vulnerable groups such as children and adolescents. Our paper's objective is to unpack what constitutes adequate safeguards to protect the personal information of vulnerable populations such as children and adolescents. We suggest strategies to adhere meaningfully to the principal aims of data protection regulations. Navigating this within established research projects raises questions about how to interpret regulatory frameworks to build on existing mechanisms already used by researchers. Therefore, we will explore a series of best practices in safeguarding the personal information of children, adolescents and young people (0-24 years old), who represent more than half of sub-Saharan Africa's population. We discuss the actions taken by the research group to ensure regulations such as GDPR and POPIA effectively build on existing data protection mechanisms for research projects at all stages, focusing on promoting regulatory alignment throughout the data lifecycle. Our goal is to stimulate a broader conversation on improving the protection of sensitive personal information of children, adolescents and young people in sub-Saharan Africa. We join this discussion as a research group generating evidence influencing social and health policy and programming for young people in sub-Saharan Africa. Our contribution draws on our work adhering to multiple transnational governance frameworks imposed by national legislation, such as data protection regulations, funders, and academic institutions

Targeted suppression of AR-V7 using PIP5K1α inhibitor overcomes enzalutamide resistance in prostate cancer cells

One mechanism of resistance of prostate cancer (PCa) to enzalutamide (MDV3100) treatment is the increased expression of AR variants lacking the ligand binding-domain, the best characterized of which is AR-V7. We have previously reported that Phosphatidylinositol-4-phosphate 5-kinase alpha (PIP5Kα), is a lipid kinase that links to CDK1 and AR pathways. The discovery of PIP5Kα inhibitor highlight the potential of PIP5K1α as a drug target in PCa. In this study, we show that AR-V7 expression positively correlates with PIP5K1α in tumor specimens from PCa patients. Overexpression of AR-V7 increases PIP5K1α, promotes rapid growth of PCa in xenograft mice, whereas inhibition of PIP5K1α by its inhibitor ISA-2011B suppresses the growth and invasiveness of xenograft tumors overexpressing AR-V7. PIP5K1α is a key co-factor for both AR-V7 and AR, which are present as protein-protein complexes predominantly in the nucleus of PCa cells. In addition, PIP5K1α and CDK1 influence AR-V7 expression also through AKT-associated mechanism dependent on PTEN-status. ISA-2011B disrupts protein stabilization of AR-V7 which is dependent on PIP5K1α, leading to suppression of invasive growth of AR-V7-high tumors in xenograft mice. Our study suggests that combination of enzalutamide and PIP5K1α may have a significant impact on refining therapeutic strategies to circumvent resistance to antiandrogen therapies

Perturb-Seq: Dissecting Molecular Circuits with Scalable Single-Cell RNA Profiling of Pooled Genetic Screens

Genetic screens help infer gene function in mammalian cells, but it has remained difficult to assay complex phenotypes—such as transcriptional profiles—at scale. Here, we develop Perturb-seq, combining single-cell RNA sequencing (RNA-seq) and clustered regularly interspaced short palindromic repeats (CRISPR)-based perturbations to perform many such assays in a pool. We demonstrate Perturb-seq by analyzing 200,000 cells in immune cells and cell lines, focusing on transcription factors regulating the response of dendritic cells to lipopolysaccharide (LPS). Perturb-seq accurately identifies individual gene targets, gene signatures, and cell states affected by individual perturbations and their genetic interactions. We posit new functions for regulators of differentiation, the anti-viral response, and mitochondrial function during immune activation. By decomposing many high content measurements into the effects of perturbations, their interactions, and diverse cell metadata, Perturb-seq dramatically increases the scope of pooled genomic assays. Keywords: single-cell RNA-seq; pooled screen; CRISPR; epistasis; genetic interaction

IRIM at TRECVID 2013: Semantic Indexing and Instance Search

International audienceThe IRIM group is a consortium of French teams working on Multimedia Indexing and Retrieval. This paper describes its participation to the TRECVID 2013 semantic indexing and instance search tasks. For the semantic indexing task, our approach uses a six-stages processing pipelines for computing scores for the likelihood of a video shot to contain a target concept. These scores are then used for producing a ranked list of images or shots that are the most likely to contain the target concept. The pipeline is composed of the following steps: descriptor extraction, descriptor optimization, classiffication, fusion of descriptor variants, higher-level fusion, and re-ranking. We evaluated a number of different descriptors and tried different fusion strategies. The best IRIM run has a Mean Inferred Average Precision of 0.2796, which ranked us 4th out of 26 participants

Exploring the cognitive development of children born to adolescent mothers in South Africa

This study explores the cognitive development of children born to adolescent mothers within South Africa compared to existing reference data, and explores development by child age bands to examine relative levels of development. Cross-sectional analyses present data from 954 adolescents (10–19 years) and their first-born children (0–68 months). All adolescents completed questionnaires relating to themselves and their children, and standardized child cognitive assessments (Mullen Scales of Early Learning) were undertaken. Cognitive development scores of the sample were lower than USA reference population scores and relative performance compared to the reference population was found to decline with increasing child age. When compared to children born to adult mothers in the sub-Saharan African region, children born to adolescent mothers (human immunodeficiency virus [HIV] unexposed; n = 724) were found to have lower cognitive development scores. Findings identify critical periods of development where intervention may be required to bolster outcomes for children born to adolescent mothers

Achieving the health and well-being Sustainable Development Goals among adolescent mothers and their children in South Africa: Cross-sectional analyses of a community-based mixed HIV-status cohort.

The Sustainable Development Goals (SDGs) are a visionary and multi-sectoral agenda for human development. With less than a decade left to reach these targets, it is important to identify those at greatest risk of not meeting these ambitious targets. Adolescent mothers and their children are a highly vulnerable group. We mapped 35 SGD-related targets among 1,046 adolescent mothers and their oldest child (n = 1046). Questionnaires using validated scales were completed by 10- to 24-year-old adolescent girls and young women who had their first child before age 20 in an HIV-endemic district in the Eastern Cape province of South Africa. Maternal outcomes included 26 SDG-aligned indicators, while child-related outcomes included 9 indicators. Data was collected by trained researchers, following informed voluntary consent by the adolescent mothers and their caregivers. Frequencies and chi-square tests were conducted to compare progress along SDG-aligned indicators among adolescent mothers by HIV status. Overall, adolescent mothers reported low attainment of SDG-aligned indicators. While four in five adolescent mothers lived in poor households, nearly 93% accessed at least one social cash transfer and 80% accessed a child support grant for their children. Food security rates among adolescent mothers (71%) were lower than among their children (91%). Only two-thirds of adolescent mothers returned to school after childbirth, and only one-fifth were either studying or employed. Over half of adolescent mothers had experienced at least one type of violence (domestic, sexual or community). HIV-positive status was associated with higher rates of hunger and substance use, poorer school attendance, and higher rates of exposure to violence. Understanding progress and gaps in meeting the SDGs among highly vulnerable groups is critical, particularly for adolescent mothers and their children. These complex vulnerabilities suggest that programming for adolescent mothers must address their unique needs

The NORAD lncRNA assembles a topoisomerase complex critical for genome stability

The human genome contains thousands of long non-coding RNAs, but specific biological functions and biochemical mechanisms have been discovered for only about a dozen. A specific long non-coding RNA—non-coding RNA activated by DNA damage (NORAD)—has recently been shown to be required for maintaining genomic stability, but its molecular mechanism is unknown. Here we combine RNA antisense purification and quantitative mass spectrometry to identify proteins that directly interact with NORAD in living cells. We show that NORAD interacts with proteins involved in DNA replication and repair in steady-state cells and localizes to the nucleus upon stimulation with replication stress or DNA damage. In particular, NORAD interacts with RBMX, a component of the DNA-damage response, and contains the strongest RBMX-binding site in the transcriptome. We demonstrate that NORAD controls the ability of RBMX to assemble a ribonucleoprotein complex—which we term NORAD-activated ribonucleoprotein complex 1 (NARC1)—that contains the known suppressors of genomic instability topoisomerase I (TOP1), ALYREF and the PRPF19–CDC5L complex. Cells depleted for NORAD or RBMX display an increased frequency of chromosome segregation defects, reduced replication-fork velocity and altered cell-cycle progression—which represent phenotypes that are mechanistically linked to TOP1 and PRPF19–CDC5L function. Expression of NORAD in trans can rescue defects caused by NORAD depletion, but rescue is significantly impaired when the RBMX-binding site in NORAD is deleted. Our results demonstrate that the interaction between NORAD and RBMX is important for NORAD function, and that NORAD is required for the assembly of the previously unknown topoisomerase complex NARC1, which contributes to maintaining genomic stability. In addition, we uncover a previously unknown function for long non-coding RNAs in modulating the ability of an RNA-binding protein to assemble a higher-order ribonucleoprotein complex