RESUMO
OBJECTIVE: Approximately 20% of ovarian cancers are due to an underlying germline pathogenic variant. While pathogenic variants in several genes have been well-established in the development of hereditary ovarian cancer (e.g. BRCA1/2, RAD51C, RAD51D, BRIP1, mismatch repair genes), the role of partner and localizer of BRCA2 (PALB2) remains uncertain. We sought to utilize meta-analysis to evaluate the association between PALB2 germline pathogenic variants and ovarian cancer. METHODS: We conducted a systematic review and meta-analysis. We searched key electronic databases to identify studies evaluating multigene panel testing in people with ovarian cancer. Eligible trials were subjected to meta-analysis. RESULTS: Fifty-five studies met inclusion criteria, including 48,194 people with ovarian cancer and information available on germline PALB2 pathogenic variant status. Among people with ovarian cancer and available PALB2 sequencing data, 0.4% [95% CI 0.3-0.4] harbored a germline pathogenic variant in the PALB2 gene. The pooled odds ratio (OR) for carrying a PALB2 pathogenic variant among the ovarian cancer population of 20,474 individuals who underwent germline testing was 2.48 [95% CI 1.57-3.90] relative to 123,883 controls. CONCLUSIONS: Our meta-analysis demonstrates that the pooled OR for harboring a PALB2 germline pathogenic variant among people with ovarian cancer compared to the general population is 2.48 [95% CI 1.57-3.90]. Prospective studies evaluating the role of germline PALB2 pathogenic variants in the development of ovarian cancer are warranted.
RESUMO
From flocking birds to swarming insects, interactions of organisms large and small lead to the emergence of collective dynamics. Here, we report striking collective swimming of bovine sperm in dynamic clusters, enabled by the viscoelasticity of the fluid. Sperm oriented in the same direction within each cluster, and cluster size and cell-cell alignment strength increased with viscoelasticity of the fluid. In contrast, sperm swam randomly and individually in Newtonian (nonelastic) fluids of low and high viscosity. Analysis of the fluid motion surrounding individual swimming sperm indicated that sperm-fluid interaction was facilitated by the elastic component of the fluid. In humans, as well as cattle, sperm are naturally deposited at the entrance to the cervix and must swim through viscoelastic cervical mucus and other mucoid secretions to reach the site of fertilization. Collective swimming induced by elasticity may thus facilitate sperm migration and contribute to successful fertilization. We note that almost all biological fluids (e.g. mucus and blood) are viscoelastic in nature, and this finding highlights the importance of fluid elasticity in biological function.