Publications by authors named "P C Prorok"

Background: Determining whether screening with multicancer detection (MCD) tests saves lives requires randomized controlled trials (RCTs). To inform RCT design, we estimated cancer-mortality outcomes from hypothetical MCD RCTs.

Methods: We used the Hu-Zelen model, previously used to plan the NLST, to estimate mortality reductions, sample-size, and power for 9 cancers for different RCT design parameters and MCD test parameters.

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Background: Cancer screening trials have required large sample sizes and long time-horizons to demonstrate cancer mortality reductions, the primary goal of cancer screening. We examine assumptions and potential power gains from exploiting information from testing control-arm specimens, which we call the "intended effect" (IE) analysis that we explain in detail herein. The IE analysis is particularly suited to tests that can be conducted on stored specimens in the control arm, such as stored blood for multicancer detection (MCD) tests.

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MacroH2A has been linked to transcriptional silencing, cell identity, and is a hallmark of the inactive X chromosome (Xi). However, it remains unclear whether macroH2A plays a role in DNA replication. Using knockdown/knockout cells for each macroH2A isoform, we show that macroH2A-containing nucleosomes slow down replication progression rate in the Xi reflecting the higher nucleosome stability.

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Background: Cancer screening trials have required large sample sizes and long time-horizons to demonstrate cancer mortality reductions, the primary goal of cancer screening. We examine assumptions and potential power gains from exploiting information from testing control-arm specimens, which we call the "intended effect" (IE) analysis that we explain in detail herein. The IE analysis is particularly suited to tests that can be conducted on stored specimens in the control arm, such as stored blood for multicancer detection (MCD) tests.

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Article Synopsis
  • DNA replication is crucial for maintaining the genome during cell division, especially in early development when rapid cell division is necessary for organ formation.
  • The study compares the replication processes of human embryonic stem cells, induced pluripotent stem cells, and differentiated cells, revealing different timing and characteristics of genome replication in these cell types.
  • Results indicate that while many genomic repeats maintain consistent replication timing across cell types, significant differences are observed in the replication of rDNA repeats, along with variations in fork speed in pluripotent cells compared to differentiated somatic cells.
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