Improving catalyst activity in secondary amine catalysed transformations.

The effect on catalyst performance of altering substituents at the 2-position of the Macmillan imidazolidinone has been examined. Condensation of L-phenylalanine N-methyl amide with acetophenone derivatives results in a series of imidazolidinones whose salts can be used to accelerate the Diels-Alder cycloaddition. Electron withdrawing groups significantly increase the overall rate of cycloaddition without compromise in selectivity. The most effective catalyst was shown to be efficient for a variety of substrates and the applicability of this catalyst to alternative secondary amine catalysed transformations is also discussed.

Delaware Healthcare Workforce Update.

Working from data provided by the Delaware Division of Professional Regulation from May 2022 to September 2023, this 16-month update supports a general rebound in active licensing numbers across the Delaware Healthcare industry in professions licensed through the Division of Professional Regulation's DelPros system. This report articulates the types of data analysis currently available through the data and research initiative of Delaware Health Force, provides a high-level overview of the data, and offers preliminary recommendations based on the data. Overall, the healthcare workforce in Delaware shows a steady rebound, with many license types appearing to reach new highs. There are some areas in which continued loss of active licenses is of concern.

Racial/Ethnic and Sex Differences in Somatic Cancer Gene Mutations among Patients with Early-Onset Colorectal Cancer.

Molecular features underlying colorectal cancer disparities remain uncharacterized. Here, we investigated somatic mutation patterns by race/ethnicity and sex among 5,856 non-Hispanic white (NHW), 535 non-Hispanic Black (NHB), and 512 Asian/Pacific Islander (API) patients with colorectal cancer (2,016 early-onset colorectal cancer patients: sequencing age <50 years). NHB patients with early-onset nonhypermutated colorectal cancer, but not API patients, had higher adjusted tumor mutation rates than NHW patients. There were significant differences for LRP1B, FLT4, FBXW7, RNF43, ATRX, APC, and PIK3CA mutation frequencies in early-onset nonhypermutated colorectal cancers between racial/ethnic groups. Heterogeneities by race/ethnicity were observed for the effect of APC, FLT4, and FAT1 between early-onset and late-onset nonhypermutated colorectal cancer. By sex, heterogeneity was observed for the effect of EP300, BRAF, WRN, KRAS, AXIN2, and SMAD2. Males and females with nonhypermutated colorectal cancer had different trends in EP300 mutations by age group. These findings define genomic patterns of early-onset nonhypermutated colorectal cancer by race/ethnicity and sex, which yields novel biological clues into early-onset colorectal cancer disparities. SIGNIFICANCE: NHBs, but not APIs, with early-onset nonhypermutated colorectal cancer had higher adjusted tumor mutation rates versus NHWs. Differences for FLT4, FBXW7, RNF43, LRP1B, APC, PIK3CA, and ATRX mutation rates between racial/ethnic groups and EP300, KRAS, AXIN2, WRN, BRAF, and LRP1B mutation rates by sex were observed in tumors of young patients. See related commentary by Shen et al., p. 530 . This article is highlighted in the In This Issue feature, p. 517.

Histologic and Racial/Ethnic Patterns of Appendiceal Cancer among Young Patients.

BACKGROUND: Appendiceal cancer incidence among individuals age < 50 years (early-onset appendiceal cancer) is rising with unknown etiologies. Distinct clinicopathologic/demographic features of early-onset appendiceal cancer remain unexplored. We compared patterns of appendiceal cancer among individuals by age of disease-onset. METHODS: Using the NIH/NCI's Surveillance, Epidemiology, and End Results program data, we identified individuals age 20+ years diagnosed with appendiceal cancer from 2007 to 2016. Cochran-Armitage trend tests and multinomial logistic regression models were used to examine age-related differences in clinicopathologic/demographic features of appendiceal cancer. RESULTS: We identified 8,851 patients with appendiceal cancer during the 10-year study period. Histologic subtype, tumor grade, stage, sex and race/ethnicity all significantly differed by age of appendiceal cancer diagnosis. After adjustment for race/ethnicity, sex, stage, insurance status, and tumor grade, young patients were 82% more likely to be Hispanic [OR, 1.82; 95% confidence interval (CI), 1.48-2.25; P < 0.001] and 4-fold more likely to be American Indian or Alaska Native (OR, 4.02; 95% CI, 1.77-9.16; P = 0.0009) compared with late-onset cases. Patients with early-onset appendiceal cancer were also 2- to 3.5-fold more likely to be diagnosed with neuroendocrine tumors of the appendix (goblet cell carcinoid: OR, 1.96; 95% CI, 1.59-2.41; P < 0.0001; carcinoid: OR, 3.52; 95% CI, 2.80-4.42; P < 0.0001) compared with patients with late-onset appendiceal cancer. Among patients with neuroendocrine tumors, early-onset cases were also 45% to 61% less likely to present with high-grade (III-IV) tumors. CONCLUSIONS: Approximately one in every three patients with appendiceal cancer is diagnosed before age 50 years in the United States. Appendiceal cancer in young patients is classified by distinct histologic and demographic features. IMPACT: Early-onset appendiceal cancer determinants can inform discovery of risk factors and molecular biomarkers of appendiceal cancer in young patients, with implications for appendiceal cancer prevention, detection, and treatment.