Allele ages provide limited information about the strength of negative selection.

For many problems in population genetics, it is useful to characterize the distribution of fitness effects (DFE) of de novo mutations among a certain class of sites. A DFE is typically estimated by fitting an observed site frequency spectrum (SFS) to an expected SFS given a hypothesized distribution of selection coefficients and demographic history. The development of tools to infer gene trees from haplotype alignments, along with ancient DNA resources, provides us with additional information about the frequency trajectories of segregating mutations.

Lubert Stryer (1938-2024).

Trailblazing biochemist and author.

Addition of Contrast-enhanced Mammography to Tomosynthesis for Breast Cancer Detection in Women with a Personal History of Breast Cancer: Prospective TOCEM Trial Interim Analysis.

Background Digital breast tomosynthesis (DBT) is often inadequate for screening women with a personal history of breast cancer (PHBC). The ongoing prospective Tomosynthesis or Contrast-Enhanced Mammography, or TOCEM, trial includes three annual screenings with both DBT and contrast-enhanced mammography (CEM). Purpose To perform interim assessment of cancer yield, stage, and recall rate when CEM is added to DBT in women with PHBC.

Testing for differences in polygenic scores in the presence of confounding.

Polygenic scores have become an important tool in human genetics, enabling the prediction of individuals' phenotypes from their genotypes. Understanding how the pattern of differences in polygenic score predictions across individuals intersects with variation in ancestry can provide insights into the evolutionary forces acting on the trait in question, and is important for understanding health disparities. However, because most polygenic scores are computed using effect estimates from population samples, they are susceptible to confounding by both genetic and environmental effects that are correlated with ancestry.

Prospective Multicenter Diagnostic Performance of Technologist-Performed Screening Breast Ultrasound After Tomosynthesis in Women With Dense Breasts (the DBTUST).

Purpose: To assess diagnostic performance of digital breast tomosynthesis (DBT) alone or combined with technologist-performed handheld screening ultrasound (US) in women with dense breasts.

Methods: In an institutional review board-approved, Health Insurance Portability and Accountability Act-compliant multicenter protocol in western Pennsylvania, 6,179 women consented to three rounds of annual screening, interpreted by two radiologist observers, and had appropriate follow-up. Primary analysis was based on first observer results.

Exploring the use of cobalt(II) dipolar shifts in refining the structure of a zinc finger peptide.

The uses of dipolar shifts due to cobalt(II) substituted for zinc(II) in a consensus zinc finger peptide for refining the NMR-determined structure were examined. Substantial differences between the calculated and observed chemical shift differences between the cobalt(II) and zinc(II) complexes were observed when these dipolar shifts were not used as constraints in the structure refinement. However, inclusion of these constraints resulted in excellent agreement with minor adjustments in the structure and a slight improvement in the precision of the structure determination.

Polygenic score accuracy in ancient samples: Quantifying the effects of allelic turnover.

Polygenic scores link the genotypes of ancient individuals to their phenotypes, which are often unobservable, offering a tantalizing opportunity to reconstruct complex trait evolution. In practice, however, interpretation of ancient polygenic scores is subject to numerous assumptions. For one, the genome-wide association (GWA) studies from which polygenic scores are derived, can only estimate effect sizes for loci segregating in contemporary populations.

Cancer Yield Exceeds 2% for BI-RADS 3 Probably Benign Findings in Women Older Than 60 Years in the National Mammography Database.

Background Breast Imaging Reporting and Data System (BI-RADS) category 3 (BR3) (probably benign) mammographic assessments are reserved for imaging findings known to have likelihood of malignancy of 2% or less. Purpose To determine the effect of age, finding type, and prior mammography on cancer yield for BR3 findings in the National Mammography Database (NMD). Materials and Methods This HIPAA-compliant retrospective cohort institutional review board-exempt study evaluated women recalled from screening mammography followed by BR3 assessment at diagnostic evaluation from January 2009 to March 2018 and from 471 NMD facilities.

How well can we separate genetics from the environment?

A simulation study demonstrates a better method for separating genetic effects from environmental effects in genome-wide association studies, but there is still some way to go before this becomes a "solved" problem.

Cancer Yield and Patterns of Follow-up for BI-RADS Category 3 after Screening Mammography Recall in the National Mammography Database.

Background The literature supports the use of short-interval follow-up as an alternative to biopsy for lesions assessed as probably benign, Breast Imaging Reporting and Data System (BI-RADS) category 3, with an expected malignancy rate of less than 2%. Purpose To assess outcomes from 6-, 12-, and 24-month follow-up of probably benign findings first identified at recall from screening mammography in the National Mammography Database (NMD). Materials and Methods This retrospective study included women recalled from screening mammography with BI-RADS category 3 assessment at additional evaluation from January 2009 through March 2018 from 471 NMD facilities.

Measuring intolerance to mutation in human genetics.

In numerous applications, from working with animal models to mapping the genetic basis of human disease susceptibility, knowing whether a single disrupting mutation in a gene is likely to be deleterious is useful. With this goal in mind, a number of measures have been developed to identify genes in which protein-truncating variants (PTVs), or other types of mutations, are absent or kept at very low frequency in large population samples-genes that appear 'intolerant' to mutation. One measure in particular, the probability of being loss-of-function intolerant (pLI), has been widely adopted.

Reduced signal for polygenic adaptation of height in UK Biobank.

Unlabelled: Several recent papers have reported strong signals of selection on European polygenic height scores. These analyses used height effect estimates from the GIANT consortium and replication studies. Here, we describe a new analysis based on the the UK Biobank (UKB), a large, independent dataset.