DNA methyltransferase and poly (ADP-ribose) polymerase inhibitors (DNMTis, PARPis) induce a stimulator of interferon genes (STING)-dependent pathogen mimicry response (PMR) in ovarian and other cancers. Here, we showed that combining DNMTis and PARPis upregulates expression of the nucleic-acid sensor NFX1-type zinc finger-containing 1 protein (ZNFX1). ZNFX1 mediated induction of PMR in mitochondria, serving as a gateway for STING-dependent interferon/inflammasome signaling.
View Article and Find Full Text PDFPurpose: Item response theory (IRT) models are an increasingly popular method choice for evaluating clinical outcome assessments (COAs) for use in clinical trials. Given common constraints in clinical trial design, such as limits on sample size and assessment lengths, the current study aimed to examine the appropriateness of commonly used polytomous IRT models, specifically the graded response model (GRM) and partial credit model (PCM), in the context of how they are frequently used for psychometric evaluation of COAs in clinical trials.
Methods: Data were simulated under varying sample sizes, measure lengths, response category numbers, and slope strengths, as well as under conditions that violated some model assumptions, namely, unidimensionality and equality of item slopes.
Eggshell breakage and broiler bone disorders are major problems for the breeder and broiler industries which are linked to mineral metabolism and animal genetics. The purpose of this work was to discover the link between individual animal phenotypic differences in mineral metabolism against concentrations of novel plasma biomarkers including tartrate resistant acid phosphatase (TRAP) and bone alkaline phosphatase (BAP). A subset of hens were selected from a flock of Cobb 500 breeders with the best or worst eggshell quality based upon dual energy x-ray absorptiometry (DEXA) and specific gravity (SG).
View Article and Find Full Text PDFDNA methyltransferase and poly(ADP-ribose) polymerase inhibitors (DNMTis, PARPis) induce a stimulator of interferon (IFN) genes (STING)-dependent pathogen mimicry response (PMR) in ovarian (OC) and other cancers. We now show that combining DNMTis and PARPis upregulates expression of a little-studied nucleic-acid sensor, NFX1-type zinc finger-containing 1 protein (ZNFX1). We demonstrate that ZNFX1 is a novel master regulator for PMR induction in mitochondria, serving as a gateway for STING-dependent PMR.
View Article and Find Full Text PDFPurpose: Determining if group-level differences in health outcomes are meaningful has recently been neglected in favour of determining if individuals have experienced a meaningful change. We explore interpretation of a meaningful between-group difference (MBGD) in clinical outcome assessment scores, primarily in the context of randomized clinical trials.
Methods: We constructed a series of possible 'viewpoints' on how to conceptualize MBGD thresholds.