26 research outputs found
Prevalence of and trends in metabolic syndrome and associated cardiovascular risk factors among US adolescents between 1999 and 2008
Effect of severe obesity in childhood and adolescence on risk of type 2 diabetes in youth and early adulthood in an American Indian population
A qualitative study of cognitive, behavioral, and environmental influences on Hispanic mothers’ early childhood feeding practices
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Neoadjuvant durvalumab plus radiation versus durvalumab alone in stages I-III non-small cell lung cancer: survival outcomes and molecular correlates of a randomized phase II trial.
We previously reported the results of a randomized phase II trial (NCT02904954) in patients with early-stage non-small cell lung cancer (NSCLC) who were treated with either two preoperative cycles of the anti-PD-L1 antibody durvalumab alone or combined with immunomodulatory doses of stereotactic radiation (DRT). The trial met its primary endpoint of major pathological response, which was significantly higher following DRT with no new safety signals. Here, we report on the prespecified secondary endpoint of disease-free survival (DFS) regardless of treatment assignment and the prespecified exploratory analysis of DFS in each arm of the trial. DFS at 2 and 3 years across patients in both arms of the trial were 73% (95% CI: 62.1-84.5) and 65% (95% CI: 52.5-76.9) respectively. For the exploratory endpoint of DFS in each arm of the trial, three-year DFS was 63% (95% CI: 46.0-80.4) in the durvalumab monotherapy arm compared to 67% (95% CI: 49.6-83.4) in the dual therapy arm. In addition, we report post hoc exploratory analysis of progression-free survival as well as molecular correlates of response and recurrence through high-plex immunophenotyping of sequentially collected peripheral blood and gene expression profiles from resected tumors in both treatment arms. Together, our results contribute to the evolving landscape of neoadjuvant treatment regimens for NSCLC and identify easily measurable potential biomarkers of response and recurrence
The role of parents in pre-adolescent and adolescent overweight and obesity treatment: a systematic review of clinical recommendations
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Multimodal single-cell and whole-genome sequencing of small, frozen clinical specimens
Single-cell genomics enables dissection of tumor heterogeneity and molecular underpinnings of drug response at an unprecedented resolution1-11. However, broad clinical application of these methods remains challenging, due to several practical and preanalytical challenges that are incompatible with typical clinical care workflows, namely the need for relatively large, fresh tissue inputs. In the present study, we show that multimodal, single-nucleus (sn)RNA/T cell receptor (TCR) sequencing, spatial transcriptomics and whole-genome sequencing (WGS) are feasible from small, frozen tissues that approximate routinely collected clinical specimens (for example, core needle biopsies). Compared with data from sample-matched fresh tissue, we find a similar quality in the biological outputs of snRNA/TCR-seq data, while reducing artifactual signals and compositional biases introduced by fresh tissue processing. Profiling sequentially collected melanoma samples from a patient treated in the KEYNOTE-001 trial12, we resolved cellular, genomic, spatial and clonotype dynamics that represent molecular patterns of heterogeneous intralesional evolution during anti-programmed cell death protein 1 therapy. To demonstrate applicability to banked biospecimens of rare diseases13, we generated a single-cell atlas of uveal melanoma liver metastasis with matched WGS data. These results show that single-cell genomics from archival, clinical specimens is feasible and provides a framework for translating these methods more broadly to the clinical arena
UV irradiation induces a postreplication DNA damage checkpoint
Eukaryotic cells irradiated with high doses of UV exhibit cell-cycle responses referred to as G(1)/S, intraS, and G(2)/M checkpoints. After a moderate UV dose that approximates sunlight exposure and is lethal to fission yeast checkpoint mutants, we found unexpectedly that these cell-cycle responses do not occur. Instead, cells at all stages of the cell cycle carry lesions into S phase and delay cell-cycle progression for hours after the completion of bulk DNA synthesis. Both DNA replication and the checkpoint kinase, Chk1, are required to generate this cell-cycle response. UV-irradiation of Δchk1 cells causes chromosome damage and loss of viability only after cells have replicated irradiated DNA and entered mitosis. These data suggest that an important physiological role of the cell-cycle response to UV is to provide time for postreplication repair