Partisan divide and Racial/Ethnic disparities in COVID-19 vaccine hesitancy among Parents/Guardians and vaccine uptake among children in the U.S.

OBJECTIVES: We undertook an observational study to assess the impact of state-level partisanship and parents'/guardians' race/ethnicity on their degree of COVID-19 vaccine hesitancy. MATERIAL AND METHODS: We observed a pooled cross-section of 59,280 U.S. adults residing with children in the same household between June 29 and November 14, 2022. Using household-weighted logistic regression models, we evaluated the association between partisanship, race/ethnicity, and vaccine hesitancy, while controlling for other social determinants of COVID-19 vaccine hesitancy. RESULTS AND CONCLUSIONS: We found that children were less likely to receive a COVID-19 vaccine if they resided in Republican as compared to Democratic states, with the difference in probability greatest among those households where parents/guardians identified as White. We also found that children were less likely to receive a COVID-19 vaccine if their parents/guardians identified as White as compared to any other race/ethnicity, with the differences in probability greatest among households in Republican states.

A multidimensional platform of patient-derived tumors identifies drug susceptibilities for clinical lenvatinib resistance

Lenvatinib, a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer, facing limitations due to drug resistance. Here, we applied a multidimensional, high-throughput screening platform comprising patient-derived resistant liver tumor cells (PDCs), organoids (PDOs), and xenografts (PDXs) to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant settings. Expansion and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment, expediting drug repurposing screens. Pharmacological screening identified romidepsin, YM155, apitolisib, NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO models. Notably, romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway. A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX models. Collectively, our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer, providing a feasible multidimensional platform for personalized medicine.