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Background: Older adults comprise the majority of patients with gastrointestinal (GI) cancer. Geriatric assessments (GAs) are recommended for older adults with cancer in part to detect aging‐related impairments (e.g., frailty) associated with early mortality. Social factors like social vulnerability may also influence aging‐related impairments. However, the association between social vulnerability and aging outcomes among older adults with cancer is understudied. Methods: The authors included 908 older adults aged 60 years and older who were recently diagnosed with GI cancer undergoing GA at their first prechemotherapy visit to the University of Alabama at Birmingham oncology clinic. The primary exposure of interest was the social vulnerability index (SVI). Outcomes were frailty (frail vs. robust/prefrail) and total number of GA impairments (range, 0–13). The authors examined the association between SVI and outcomes using Poisson regression with robust variance estimation and generalized estimating equations. Results: The median age at GA was 69 years (interquartile range, 64–75 years), 58.2% of patients were male, 22.6% were non‐Hispanic Black, 29.1% had colorectal cancer, 28.2% had pancreatic cancer, and 70.3% had stage III/IV disease. Adjusting for age, sex, cancer type, and disease stage, each decile increase in the SVI was associated with an 8% higher prevalence of frailty (prevalence ratio, 1.08; 95% confidence interval, 1.05–1.11) and a 4% higher average count of total GA impairments (risk ratio, 1.04; 95% confidence interval, 1.02–1.06). The results were attenuated after further adjustment for race and education. Conclusions: Greater social vulnerability was associated with a higher prevalence of frailty and an increasing average number of GA impairments among older adults with GI cancers before systemic treatment. Intervening on social vulnerability may be a target for improving the risk of frailty and GA impairments, but associations of race and education should be further evaluated. Higher social vulnerability at the census tract level is associated with higher prevalence of frailty and risk of additional geriatric assessment impairments among older adults with gastrointestinal malignancies before systemic treatment. These associations are attenuated with adjustment for individual‐level measures of social determinants of health, but multilevel interventions may be a target to prevent these important aging‐related outcomes in cancer. [ABSTRACT FROM AUTHOR]

Multiple mammalian lineages independently evolved a definitive mammalian middle ear (DMME) through breakdown of Meckel's cartilage (MC). However, the cellular and molecular drivers of this evolutionary transition remain unknown for most mammal groups. Here, we identify such drivers in the living marsupial opossum Monodelphis domestica, whose MC transformation during development anatomically mirrors the evolutionary transformation observed in fossils. Specifically, we link increases in cellular apoptosis and TGF-BR2 signalling to MC breakdown in opossums. We demonstrate that a simple change in TGF-β signalling is sufficient to inhibit MC breakdown during opossum development, indicating that changes in TGF-β signalling might be key during mammalian evolution. Furthermore, the apoptosis that we observe during opossum MC breakdown does not seemingly occur in mouse, consistent with homoplastic DMME evolution in the marsupial and placental lineages.

A central issue in biology concerns the presence, timing and nature of phylotypic periods of development, but whether, when and why species exhibit conserved morphologies remains unresolved. Here, we construct a developmental morphospace to show that amniote faces share a period of reduced shape variance and convergent growth trajectories from prominence formation through fusion, after which phenotypic diversity sharply increases. We predict in silico the phenotypic outcomes of unoccupied morphospaces and experimentally validate in vivo that observed convergence is not due to developmental limits on variation but instead from selection against novel trajectories that result in maladaptive facial clefts. These results illustrate how epigenetic factors such as organismal geometry and shape impact facial morphogenesis and alter the locus of adaptive selection to variation in later developmental events.

The vestibular lamina (VL) forms the oral vestibule, creating a gap between the teeth, lips and cheeks. In a number of ciliopathies, formation of the vestibule is defective, leading to the creation of multiple frenula. In contrast to the neighbouring dental lamina, which forms the teeth, little is known about the genes that pattern the VL. Here, we establish a molecular signature for the usually nonodontogenic VL in mice and highlight several genes and signalling pathways that may play a role in its development. For one of these, the Sonic hedgehog (Shh) pathway, we show that co-receptors Gas1, Cdon and Boc are highly expressed in the VL and act to enhance the Shh signal from the forming incisor region. In Gas1 mutant mice, expression of Gli1 was disrupted and the VL epithelium failed to extend due to a loss of proliferation. This defect was exacerbated in Boc/Gas1 double mutants and could be phenocopied using cyclopamine in culture. Signals from the forming teeth, therefore, control development of the VL, coordinating the development of the dentition and the oral cavity. [ABSTRACT FROM AUTHOR]