SummaryCentriole duplication is of crucial importance during both mitotic and male meiotic divisions, but it is currently not known whether this process is regulated differently during the two modes of division. In Caenorhabditis elegans, the kinase ZYG-1 plays an essential role in both mitotic and meiotic centriole duplication. We have found that the C-terminus of ZYG-1 is necessary and sufficient for targeting to centrosomes and is important for differentiating mitotic and meiotic centriole duplication. Small truncations of the Cterminus dramatically lower the level of ZYG-1 at mitotic centrosomes but have little effect on the level of ZYG-1 at meiotic centrosomes. Interestingly, truncation of ZYG-1 blocks centrosome duplication in the mitotic cycle but leads to centrosome amplification in the meiotic cycle. Meiotic centriole amplification appears to result from the overduplication of centrioles during meiosis I and leads to the formation of multipolar meiosis II spindles. The extra centrioles also disrupt spermatogenesis by inducing the formation of supernumerary fertilization-competent spermatids that contain abnormal numbers of chromosomes and centrioles. Our data reveal differences in the regulation of mitotic and meiotic centrosome duplication, particularly with regard to ZYG-1 activity, and reveal an important role for centrosomes in spermatid formation.

Background and objectives: Little is known about outcome improvements and disparities in cardiac arrest and active cancer. We performed the first known AI and propensity score (PS)-augmented clinical, cost-effectiveness, and computational ethical analysis of cardio-oncology cardiac arrests including left heart catheterization (LHC)-related mortality reduction and related disparities. Materials and methods: A nationally representative cohort analysis was performed for mortality and cost by active cancer using the largest United States all-payer inpatient dataset, the National Inpatient Sample, from 2016 to 2018, using deep learning and machine learning augmented propensity score-adjusted (ML-PS) multivariable regression which informed cost-effectiveness and ethical analyses. The Cardiac Arrest Cardio-Oncology Score (CACOS) was then created for the above population and validated. The results informed the computational ethical analysis to determine ethical and related policy recommendations. Results: Of the 101,521,656 hospitalizations, 6,656,883 (6.56%) suffered cardiac arrest of whom 61,300 (0.92%) had active cancer. Patients with versus without active cancer were significantly less likely to receive an inpatient LHC (7.42% versus 20.79%, p < 0.001). In ML-PS regression in active cancer, post-arrest LHC significantly reduced mortality (OR 0.18, 95%CI 0.14–0.24, p < 0.001) which PS matching confirmed by up to 42.87% (95%CI 35.56–50.18, p < 0.001). The CACOS model included the predictors of no inpatient LHC, PEA initial rhythm, metastatic malignancy, and high-risk malignancy (leukemia, pancreas, liver, biliary, and lung). Cost-benefit analysis indicated 292 racial minorities and $2.16 billion could be saved annually by reducing racial disparities in LHC. Ethical analysis indicated the convergent consensus across diverse belief systems that such disparities should be eliminated to optimize just and equitable outcomes. Conclusions: This AI-guided empirical and ethical analysis provides a novel demonstration of LHC mortality reductions in cardio-oncology cardiac arrest and related disparities, along with an innovative predictive model that can be integrated within the digital ecosystem of modern healthcare systems to improve equitable clinical and public health outcomes.

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