Longitudinal Clinical Performance of the RNA-Based Aptima Human Papillomavirus (AHPV) Assay in Comparison to the DNA-Based Hybrid Capture 2 HPV Test in Two Consecutive Screening Rounds with a 6-Year Interval in Germany.

Longitudinal data on the E6/E7 mRNA-based Aptima human papillomavirus (AHPV) assay exceeding three years in comparison to the gold standard Digene Hybrid Capture 2 (HC2) test are not available. We previously reported the cross-sectional data of the German AHPV Screening Trial (GAST) in which 10,040 women were recruited and tested by liquid-based cytology, the HC2 assay, and the AHPV assay. Four hundred eleven test-positive women were followed for up to six years. In addition, 3,295 triple-negative women were screened after a median time of six years. Overall, 28 high-grade cervical intraepithelial neoplasia (CIN3) cases were detected. The absolute risk of developing high-risk HPV-positive CIN3+ over six years among those women that tested negative at baseline was 2.2 (95% confidence interval [95% CI], 1.0 to 4.9) and 3.1 (95% CI, 1.7 to 5.7) per 1,000 women screened by the HC2 and the AHPV tests; the additional risk for those with AHPV-negative compared with HC2-negative results was 0.9 (95% CI, -0.2 to 2.1) per 1,000. In comparison, the absolute risk following a negative LBC test was 9.3 (95% CI, 2.9 to 30.2). The relative sensitivity of AHPV compared to HC2 was 91.5% for CIN3+, and the negative predictive values were 99.8% (95% CI, 99.5 to 99.9%) for HC2 and 99.7% (95% CI, 99.4 to 99.8%) for AHPV. Our data show that the longitudinal performance of the AHPV test over six years is comparable to the performance of the HC2 test and that the absolute risk of CIN3+ over six years following a negative AHPV result in a screening population is low. (This study is registered at ClinicalTrials.gov under registration number NCT02634190.).

Rigid, Branched Porphyrin Antennas: Control over Cascades of Unidirectional Energy Funneling and Charge Transfer.

Porphyrin arrays consisting of three peripheral Zinc porphyrins (ZnPs) and a central free base porphyrin (H2P)-all rigidly linked to each other-serve as light-harvesting antennas as well as electron donors and are flexibly coupled to an electron-accepting C60 to realize the unidirectional flow of (i) excited-state energy from the ZnPs at the periphery to the H2P, (ii) electrons to C60, and (iii) holes to H2P and, subsequently, to ZnP. Dynamics following photoexcitation are elucidated by time-resolved transient absorption measurements on the femto-, pico-, nano-, and microsecond time scales and are examined by multiwavelength as well as target analyses. Hereby, full control over the charge shift between H2P and ZnP to convert the (ZnP)3-H2P•+-C60•- charge-separated state into (ZnP)3•+-H2P-C60•- charge-separated state is enabled by the solvent polarity: It is deactivated/switched-off in apolar toluene, while in polar benzonitrile it is activated/switched-on. Activating/switching impacts the recovery of the ground state via charge recombination rates, which differ by up to 2 orders of magnitude. All charge-separated states lead to the repopulation of the ground state with dynamics that are placed in the inverted region of the Marcus parabola.

New artesunic acid homodimers: potent reversal agents of multidrug resistance in leukemia cells.

To evade the problem of multidrug resistance, hybridization of natural products in dimers is considered as an effective method. After the successful synthesis of three artesunic acid homodimers connected by different types of chemical linkers, we analyzed their activity against human CCRF-CEM and multidrug-resistant P-glycoprotein-overexpressing CEM/ADR 5000 leukemia cells and observed, that multidrug resistant cells were not cross-resistant to the new compounds. Collateral sensitivity was observed for artesunic acid homodimer 2. The obtained results deliver valuable information about the linker's structure which is required for homodimers to be highly cytotoxic.