Editors’ Picks

        Second skin

        Yu and colleagues reported the development of a novel, two-step polysiloxane-based elastic “second skin.” Following topical application, treatment with a crosslinking agent renders this crosslinked polymer layer (XPL) as an invisible wearable thin film on human skin, mimicking the appearance and properties of youthful skin. Multiple in vivo proof-of-concept human studies revealed that the XPL contraction reliably reshapes the skin surface and mechanically flattens fat pads that induce under-eye bagging. Furthermore, in a double-blind, placebo-controlled trial, under-eye bag severity and wrinkling was decreased dramatically in patients treated with XPL. The XPL also decreased moisture loss, contributing to an elastic skin memory, of sorts, that persisted in subjects following XPL removal. As the materials are considered safe for leave-on skin application and no adverse reactions or irritation were reported, this XPL “second skin” formulation offers exciting possibilities for future development of next-generation delivery of pharmaceuticals, ultraviolet protection, or other medical benefits in addition to improving the youthful appearance of skin. (Nat Mater, 2016) Selected by A. Christiano

        Misused, misunderstood, or miscommunicated?

        The use and usefulness of P-values has long been a subject of debate. The reliance on P-values alone to describe statistical significance is problematic as these values do not provide a direct estimate of the likelihood that a result is true, do not indicate whether the result is clinically or biologically significant, and are dependent on the statistical method and assumptions. Analysis of P-values reported in MEDLINE abstracts and in a large number of PMC articles from 1990–2015 by Chavalarias and colleagues revealed an increasing trend of reporting P-values over time. As expected, almost all abstracts and articles that included P-values reported statistically significant results. Furthermore, abstracts have a selection bias that favors results with small reported P-values. While not problematic on their own, these findings were concurrent with observations that few articles included confidence intervals, Bayes factors, or effect sizes. The investigators support the inclusion of P-values in biomedical studies but also recommend consideration of alternative statistics and increased reporting of both effect sizes and measures of uncertainty. (JAMA, 2016) Selected by E. Blalock

        Fountain of youth

        Perceived age predicts survival and is associated with molecular markers of aging; therefore, understanding the underlying molecular biology of perceived age is critical for combating aging. Liu and colleagues recently performed a genome-wide association study of 8,000,000 variants in 2,693 Dutch European subjects and found that the strongest genetic association with perceived facial age occurred with variants in the melanocortin 1 receptor (MC1R) gene. The homozygote MC1R risk haplotype (carrier of four single nucleotide polymorphisms) resulted in an increased perceived age of up to 2 years compared to non-carriers, and this effect was independent of age, sex, skin color, wrinkling, pigmented spots, and sun exposure. These novel findings support the use of genome-wide association studies to analyze perceived facial age and will ultimately provide insight into the biological pathways that underlie development of facial aging. (Curr Biol, 2016) Selected by B. A. Gilchrest

        Objective response in Merkel cell carcinoma

        Monoclonal antibodies that block the programmed death 1 (PD-1) immune checkpoint pathway are active against multiple types of tumors. In fact, the PD-1-blocking antibodies pembrolizumab and nivolumab are promising therapies for advanced metastatic melanoma and non-small-cell lung cancer patients. Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer linked to Merkel-cell polyomavirus or ultraviolet light exposure. Approximately half of MCCs express PD-1 on tumor-infiltrating lymphocytes and the ligand PD-L1 on tumor cells. Thus, Nghiem and colleagues assessed the efficacy of pembrolizumab in patients with MCC, as this immunogenic cancer has very poor response rates to cytotoxic chemotherapies. A 56% objective response rate was observed, and durable tumor regressions occurred in multiple organ sites. Both Merkel-cell polyomavirus-positive and -negative MCCs exhibited responses to pembrolizumab therapy. Serious adverse events were observed in 15% of recipients, but these effects were reversed by therapy discontinuation. Thus, MCCs appear to be susceptible to immune therapy via inhibition of the PD-1 pathway. (N Engl J Med, 2016) Selected by B. A. Gilchrest

        Navigating tight spaces

        Tumor cell invasion depends on cell migration and deformation to pass through tight interstitial spaces in three-dimensional tissue. Denais and colleagues reported rupture of the nuclear envelope (NE) and loss of DNA integrity during migration of fibrosarcoma and skin fibroblast cells through confining spaces in a microfluidic device, during migration in fibrillary collagen matrices, and during invasion of collagen-rich mouse dermis in live tumors. Depletion of nuclear lamins, which are often deregulated in cancers, as well as decreased pore size increased the likelihood of NE rupture. Protrusion of chromatin through the nuclear lamina was commonly observed in concert with NE rupture, often resulting in fragmented nuclei; however, cells rapidly restored NE integrity during interphase to ensure cell survival. Thus, cell migration through confining spaces, a typical situation during cancer cell invasion, threatens integrity of the NE, potentially leading to DNA damage, aneuploidy, and genomic instability in the absence of efficient repair. (Science, 2016) Selected by S. Yuspa