Browsing by Author "Cao Y"

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    Critical power is a key threshold determining the magnitude of post-exercise hypotension in non-hypertensive young males.
    (Wiley & Sons Ltd on behalf of The Physiological Society, 2023-09-15) Lei T-H; Wang I-L; Chen Y-M; Liu X-H; Fujii N; Koga S; Perry B; Mundel T; Wang F; Cao Y; Dobashi K; Kondo N; Li H-Y; Goulding RP; Poole D
    The effect of different exercise intensities on the magnitude of post-exercise hypotension has not been rigorously clarified with respect to the metabolic thresholds that partition discrete exercise intensity domains (i.e., critical power and the gas exchange threshold (GET)). We hypothesized that the magnitude of post-exercise hypotension would be greater following isocaloric exercise performed above versus below critical power. Twelve non-hypertensive men completed a ramp incremental exercise test to determine maximal oxygen uptake and the GET, followed by five exhaustive constant load trials to determine critical power and W' (work available above critical power). Subsequently, criterion trials were performed at four discrete intensities matched for total work performed (i.e., isocaloric) to determine the impact of exercise intensity on post-exercise hypotension: 10% above critical power (10% > CP), 10% below critical power (10% < CP), 10% above GET (10% > GET) and 10% below GET (10% < GET). The post-exercise decrease (i.e., the minimum post-exercise values) in mean arterial (10% > CP: -12.7 ± 8.3 vs. 10% < CP: v3.5 ± 2.9 mmHg), diastolic (10% > CP: -9.6 ± 9.8 vs. 10% < CP: -1.4 ± 5.0 mmHg) and systolic (10% > CP: -23.8 ± 7.0 vs. 10% < CP: -9.9 ± 4.3 mmHg) blood pressures were greater following exercise performed 10% > CP compared to all other trials (all P < 0.01). No effects of exercise intensity on the magnitude of post-exercise hypotension were observed during exercise performed below critical power (all P > 0.05). Critical power represents a threshold above which the magnitude of post-exercise hypotension is greatly augmented. NEW FINDINGS: What is the central questions of this study? What is the influence of exercise intensity on the magnitude of post-exercise hypotension with respect to metabolic thresholds? What is the main finding and its importance? The magnitude of post-exercise hypotension is greatly increased following exercise performed above critical power. However, below critical power, there was no clear effect of exercise intensity on the magnitude of post-exercise hypotension.
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    Identifying colorectal cancer caused by biallelic MUTYH pathogenic variants using tumor mutational signatures
    (Springer Nature Limited, 6/06/2022) Georgeson P; Harrison TA; Pope BJ; Zaidi SH; Qu C; Steinfelder RS; Lin Y; Joo JE; Mahmood K; Clendenning M; Walker R; Amitay EL; Berndt SI; Brenner H; Campbell PT; Cao Y; Chan AT; Chang-Claude J; Doheny KF; Drew DA; Figueiredo JC; French AJ; Gallinger S; Giannakis M; Giles GG; Gsur A; Gunter MJ; Hoffmeister M; Hsu L; Huang W-Y; Limburg P; Manson JE; Moreno V; Nassir R; Nowak JA; Obón-Santacana M; Ogino S; Phipps AI; Potter JD; Schoen RE; Sun W; Toland AE; Trinh QM; Ugai T; Macrae FA; Rosty C; Hudson TJ; Jenkins MA; Thibodeau SN; Winship IM; Peters U; Buchanan DD
    Carriers of germline biallelic pathogenic variants in the MUTYH gene have a high risk of colorectal cancer. We test 5649 colorectal cancers to evaluate the discriminatory potential of a tumor mutational signature specific to MUTYH for identifying biallelic carriers and classifying variants of uncertain clinical significance (VUS). Using a tumor and matched germline targeted multi-gene panel approach, our classifier identifies all biallelic MUTYH carriers and all known non-carriers in an independent test set of 3019 colorectal cancers (accuracy = 100% (95% confidence interval 99.87-100%)). All monoallelic MUTYH carriers are classified with the non-MUTYH carriers. The classifier provides evidence for a pathogenic classification for two VUS and a benign classification for five VUS. Somatic hotspot mutations KRAS p.G12C and PIK3CA p.Q546K are associated with colorectal cancers from biallelic MUTYH carriers compared with non-carriers (p = 2 × 10-23 and p = 6 × 10-11, respectively). Here, we demonstrate the potential application of mutational signatures to tumor sequencing workflows to improve the identification of biallelic MUTYH carriers.