Refining breast cancer genetic risk and biology through multi-ancestry fine-mapping analyses of 192 risk regions.

Genome-wide association studies have identified approximately 200 genetic risk loci for breast cancer, but the causal variants and target genes are mostly unknown. We sought to fine-map all known breast cancer risk loci using genome-wide association study data from 172,737 female breast cancer cases and 242,009 controls of African, Asian and European ancestry. We identified 332 independent association signals for breast cancer risk, including 131 signals not reported previously, and for 50 of them, we narrowed the credible causal variants down to a single variant.

12″ Wafer-Scale Mass-Manufactured Metal-Insulator-Metal Reflective Metaholograms by Nanotransfer Printing.

The unique characteristics of metasurfaces to precisely control the amplitude, phase, and polarization of light within a thin, flat footprint make them a promising replacement for bulky optical components. However, fabrication methods of conventional metasurfaces have suffered from low throughput and high costs, limiting scalability and practical application. To address these challenges, an advanced fabrication technique is developed by combining deep-ultraviolet argon fluoride photolithography with wafer-scale nanotransfer printing to facilitate the scalable fabrication of metal-insulator-metal structures.

Basic Science and Pathogenesis.

Background: Traumatic brain injury (TBI) is recognized as one major, potentially modifiable risk factor for neurodegenerative disease (NDD). Autopsy studies describe a range of neuropathologies in a proportion of individuals surviving late after TBI, most frequently the tau associated pathology, chronic traumatic encephalopathy neuropathologic change (CTE-NC). In addition to tau, other NDD pathologies are described.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD), an age-associated neurodegenerative disorder, is characterized by progressive neuronal loss and the accumulation of misfolded proteins such as amyloid-β and tau. While neuroinflammation, mediated by microglia and brain-resident macrophages, plays a pivotal role in AD pathogenesis, the intricate interactions among age, genes, and other risk factors remain elusive. Somatic mutations, known to accumulate with age, instigate clonal expansion across diverse cell types, impacting both cancer and non-cancerous conditions.

Basic Science and Pathogenesis.

Background: In AD, neurofibrillary tangles (NFTs) develop earliest in the limbic system before spreading to neocortical areas. When accounting for covariates of AD pathology, such as age and APOE, there remains interindividual variation in NFT spread in the brain. We therefore used a machine-learning approach to investigate whether age-independent DNA methylation (DNAm) changes in brain associate with histopathological differences in AD.