A phase 1 dose-escalation study of the poly(ADP-ribose) polymerase inhibitor senaparib in Australian patients with advanced solid tumors

Background: Senaparib is a novel, selective poly(ADP-ribose) polymerase-1/2 inhibitor with strong antitumor activity in preclinical studies. This first-in-human, phase 1, dose-escalation study examined the safety and preliminary efficacy of senaparib in patients with advanced solid tumors. Methods: Patients with advanced solid tumors were enrolled from three centers in Australia, using a conventional 3 + 3 design. Dose-escalation cohorts continued until the maximum tolerated dose or a recommended phase 2 dose was determined. Patients received one dose of oral senaparib and, if no dose-limiting toxicity occurred within 7 days, they received senaparib once daily in 3-week cycles. The primary end points were safety and tolerability. Results: Thirty-nine patients were enrolled at 10 dose levels ranging from 2 to 150 mg. No dose-limiting toxicities were observed in any cohort. Most treatment-emergent adverse events were grade 1–2 (91%). Seven patients (17.9%) reported hematologic treatment-emergent adverse events. Treatment-related adverse events occurred in eight patients (20.5%), and the most frequent was nausea (7.7%). Two deaths were reported after the end of study treatment, one of which was considered a complication from senaparib-related bone marrow failure. Pharmacokinetic analysis indicated that senaparib the accumulation index was 1.06–1.67, and absorption saturation was 80–150 mg daily. In 22 patients with evaluable disease, the overall response rate was 13.6%, and the disease control rate was 81.8%. The overall response rate was 33.3% for the BRCA mutation-positive subgroup and 6.3% for the nonmutated subgroup. Conclusions: Senaparib was well tolerated in Australian patients with advanced solid tumors, with encouraging signals of antitumor activity. The recommended phase 2 dose for senaparib was determined to be 100 mg daily. ClinicalTrials.gov ID: NCT03507543

Interaction between smoking during pregnancy and gestational diabetes mellitus and the risk of cesarean delivery: evidence from the National Vital Statistics System 2019

To explore the interaction between smoking during pregnancy (SDP) and gestational diabetes mellitus (GDM) on the risk of cesarean delivery. This retrospective cohort study utilized data from the National Vital Statistics System (NVSS) 2019. The NVSS database provides data on births and deaths as well as maternal characteristics in the United States. The duration of follow-up was 38.74 ± 2.12 weeks. The outcome was the method of delivery, including vaginal and cesarean delivery. The multivariate logistic regression model was adopted to assess the associations of SDP and GDM with the method of delivery. The interaction between SDP and GDM was examined via calculating the relative excess risk of interaction (RERI), the attributable proportion of interaction (API) and the synergy index (S). Subgroup analyses were conducted based on age, race, prepregnancy body mass index (BMI), and primiparity. The study included 3352615 puerperae. Compared with women who did not smoke during pregnancy, those who smoked during pregnancy had a significantly higher risk of cesarean delivery [odds ratio (OR)=1.07, 95% confidence intervals (CI): 1.05–1.10, p p p S = 1.17, 95%CI: 1.001–1.36), in white women (RERI = 0.08, 95%CI: 0.004-0.16; API = 0.05, 95%CI: 0.01–0.10; S = 1.19, 95%CI: 1.02–1.39), in women who were overweight before pregnancy (RERI = 0.13, 95%CI: 0.05–0.21; API = 0.08, 95%CI: 0.04–0.13; S = 1.33, 95%CI: 1.14–1.55), and in primiparae (RERI = 0.20, 95%CI: 0.08–0.31; API = 0.12, 95%CI: 0.06–0.19; S = 1.50, 95%CI: 1.23–1.84). SDP and GDM were associated with an increased risk of cesarean delivery, and a synergistic effect existed between SDP and GDM on the risk of cesarean delivery, especially in women of non-advanced age, white women, women who were overweight before pregnancy, and primiparae.</p

Performance and Durability of Single HT-PEM Fuel Cell with Bare and CrN/Cr-coated 316LStainless Steel Bipolar Plates

Abstract attached as file

Corrosion and Electrical Properties of SS316L Materials in a Simulated HT-PEFC Environment

Increasing attention is being paid to the use of metallic materials as a replacement for non-porous graphite in the bipolar plates of polymer membrane fuel cells, including high-temperature polymer membrane fuel cells (HT-PEFCs). This work investigates the corrosion and electrical properties of SS316L stainless steel in the simulated anode and cathode environments of HT-PEFCs. The influence of gases on the free corrosion potential (Ecorr), free corrosion current (icorr) and dynamic formation of passive layers were analyzed in 85 wt% phosphoric acid at RT and 130°C by means of potentiodynamic and potentiostatic tests, together with open circuit potential (OCP) measurements. The working potential of the anode (0.05V) is located in the active corrosion region, while the working potential of the cathode (0.65V) is located in the passive corrosion region. The potentiostatic tests show that the corrosion rate of SS316L in the simulated anode environment of an HT-PEFC is 10 times higher than that in the simulated cathode environment of an HT-PEFC. The free corrosion potentials, immediately noted after potentiostatic tests, show that the existence of oxygen could improve the stability of the passive layer formed during the potentiostatic stage. Scanning electron microscopy (SEM) results showed different morphologies of the corroded surface. Inductively-coupled plasma optical emission spectrometry (ICP-OES) and interfacial contact resistance (ICR) was then used to determine the levels of metal ions in the solution after corrosion and the influence of the passive layer on the ICR of metallic bipolar-plates separately made from SS316L. X-ray photoelectron spectroscopy (XPS) was used to investigate the distribution of elements on the surface of samples before and after the corrosion tests. These ex-situ measurements showed that in the anode environment, SS316L undergoes active corrosion, which results in a higher level of leaching metal ions and lower value of ICR compared to that in a cathode environment, which has a passive corrosion environment. The specimen in the cathode environment showed lower values of ICR and the number of leaching metal ions when exposed to oxygen compared with the nitrogen atmosphere. The passive layer formed in a simulated cathode environment with an oxygen purge shows the best corrosion resistance within hot phosphoric acid. The XPS results indicate that this is a Cr-rich layer. The thickness of the surface films was estimated to range from 1.1–2.2 nm