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18,251 grants found

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Adaptation and Validation of Tablet-based Cognitive Assessments for Diverse Populations in Cameroon

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NIA - National Institute on Aging

Project Abstract Dementia prevalence in Sub-Saharan Africa is projected to increase by over 300% within the next 25 years as the population aged 60 years and older triples to more than 235 million. Beyond the demographic transition and population growth, a major driver of these increases is the growing burden of communicable and non- communicable diseases, which contributes to disability and adverse brain health outcomes. Currently, there are limited data on Alzheimer's Disease and related dementias to inform healthcare and research policies within resource-strained health systems in SSA. This gap is especially evident in French-speaking African countries (30-40% of SSA), which are critically underrepresented in ADRD research. Indeed, our recent review highlights the cultural, ethnic, linguistic, and socioeconomical challenges to dementia research in this setting. In Cameroon, ADRD mortality has increased by over 130% in 20 years and ADRD represents 12.4% of outpatient neurology consultations. Our prior work highlights the urgent need to develop and validate scalable and accessible assessment tools for ADRD to establish a robust infrastructure to support dementia diagnosis, care, and research nationwide. The growing field of digital cognitive tools offers an innovative opportunity for developing easily accessible and highly accurate neuropsychological tools for cost- and time-efficient case identification. Standardized administration, automated scoring/interpretation, and cross platform integration features can address several challenges and support the development of dementia registries – a valuable resource for dementia research and care. The main objectives of this proposal are to culturally adapt and validate a brief multi-domain digital cognitive assessment tool in Cameroon and to develop and pilot the infrastructure needed for improved dementia care and research. Specifically, we plan to culturally adapt TabCAT-BHA digital cognitive assessment in Cameroon, evaluate demographic effects on performance and generate regression-based norms in a community representative sample of healthy adults in rural and urban areas (Aim 1). Concurrently, we will examine TabCAT-BHA’s diagnostic accuracy to detect mild cognitive impairment (MCI) and dementia in the existing BRAIN Cohort and examine its neuroanatomical validity to domain specific regional patterns of brain atrophy on MRI (Aim 2). Finally, as an exploratory aim, we will determine implementation barriers to cognitive testing and dementia diagnosis in a clinical setting in Cameroon to develop the infrastructure needed for improved dementia care and research (Aim 3). These proposed studies will begin to fill the data gap on dementia research in French-Speaking Sub-Saharan Africa (FS-SSA) and provide the first ever neuroimaging data in people living with dementia in Cameroon and set the stage for more comprehensive dementia studies in FS-SSA. For future research following this proposal, we anticipate that valid digital neuropsychological tools coupled with blood biomarkers that still need validation in this setting, could be a scalable and sustainable path for ADRD research, diagnosis and care (R01 proposal)

Up to $216K
2028-01-31
health research
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Adding spatial resolution and technical improvements to a novel single-cell DNA methylation sequencing technology

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NHGRI - National Human Genome Research Institute

ABSTRACT DNA methylation (DNAme) is a core layer of epigenetic regulation with central roles in the establishment and maintenance of cellular identity. Methods to profile DNAme at single-cell resolution are needed to elucidate epigenetic networks governing cell state in healthy tissues and understand their dysregulation in disease and aging. However, existing methods for single-cell methylome profiling are highly inaccessible, and no methods to experimentally profile both DNAme and spatial location currently exist. I have developed a novel method for single-cell DNAme profiling that leverages the widely available 10x Single Cell Multiome and NEB EM-seq kits, which I have named droplet-implemented single-cell DNA methylation sequencing (discDNAme). Applied to nuclei isolated from mouse brain, discDNAme recovered ~3,000 high-quality methylomes that clustered into clearly separated neuronal and non-neuronal subtypes and displayed stereotyped patterns of CpG dinucleotide methylation around key genomic features. However, these measurements lack spatial information on the native tissue contexts of profiled cells, and the protocol’s per-cell library size is lower than current gold-standard methods for measuring single-cell DNAme. I propose (1) development of a spatially resolved single-cell DNA methylation technology by combining discDNAme with slide-tags, a platform for spatially resolved single-nucleus RNA- and/or ATAC-seq developed by our group. To integrate slide-tags with discDNAme, I will develop a protocol in which the “spatial barcode oligos” we use to position nuclei are physically separated from genomic DNA prior to unmethylated cytosine conversion, benchmark this technology in the mouse hippocampus, and apply it to study glioblastoma multiforme. I further propose (2) experiments to improve and benchmark my discDNAme technology. I will systematically test various independent approaches to increase library complexity at different steps of the discDNAme protocol, combine these optimizations into a second-generation protocol, and benchmark this against our original protocol and other leading methods for single-cell DNAme profiling. Completion of this proposal will result in (1) the first high-resolution method to measure spatially resolved single- cell methylomes—a major advancement in spatial omics technologies—and (2) an accessible yet capable tool for single-cell DNAme profiling that will open single-cell DNAme studies to the broader single-cell community.

Up to $44K
2028-01-31
Health
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Addressing disparities in pediatric intestinal failure

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NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases

The proposed K23 Career Development Award will enable Vikram Raghu, MD, MS, to establish an independent research career focused on improving outcomes in pediatric intestinal failure. Pediatric intestinal failure is a rare, chronic, life-altering condition that requires many children to depend on daily infusions of parenteral nutrition to survive. Complications include life-threatening sepsis events, progressive liver disease, and venous thrombosis, with mortality estimated at over 10% by six years. Despite advances in care, outcomes vary widely, and emerging evidence suggests that geographic and socioeconomic factors strongly influence survival, healthcare use, and quality of life in this population. To address this knowledge gap, Dr. Raghu has assembled a multidisciplinary team of mentors and designed a training program in health disparities research (with a focus on socioeconomic and geographic drivers), multicenter health utility measurement, patient preference elicitation, transplant policy, and leadership in research conduct. These skills will support his overarching goal of optimizing intestinal failure management through decision sciences. The central hypothesis of this project is that variation in outcomes is partly explained by differences in geographic and socioeconomic conditions, such as access to healthcare, school resources, and environmental context, independent of clinical severity. To evaluate this hypothesis, he will accomplish the following specific aims: (1) Identify the effect of the Child Opportunity Index on survival and healthcare utilization in pediatric intestinal failure; (2) Examine socioeconomic and geographic differences in quality of life among children with intestinal failure using the Child Health Utility 9D; and (3) Determine patient and caregiver priorities for addressing socioeconomic and geographic barriers to care through a modified Delphi process and discrete choice experiment. By successfully completing these training objectives and research aims, Dr. Raghu will be positioned to become an independent investigator with the expertise to integrate decision modeling, disparities research, and patient-centered methods to improve outcomes for children with intestinal failure.

Up to $177K
2031-01-31
Health