Precision annotation of digital samples in NCBI's gene expression omnibus.

The Gene Expression Omnibus (GEO) contains more than two million digital samples from functional genomics experiments amassed over almost two decades. However, individual sample meta-data remains poorly described by unstructured free text attributes preventing its largescale reanalysis. We introduce the Search Tag Analyze Resource for GEO as a web application (http://STARGEO.org) to curate better annotations of sample phenotypes uniformly across different studies, and to use these sample annotations to define robust genomic signatures of disease pathology by meta-analysis. In this paper, we target a small group of biomedical graduate students to show rapid crowd-curation of precise sample annotations across all phenotypes, and we demonstrate the biological validity of these crowd-curated annotations for breast cancer. STARGEO.org makes GEO data findable, accessible, interoperable and reusable (i.e., FAIR) to ultimately facilitate knowledge discovery. Our work demonstrates the utility of crowd-curation and interpretation of open 'big data' under FAIR principles as a first step towards realizing an ideal paradigm of precision medicine.

Low-dose cyclophosphamide improves survival in a murine treatment model of sepsis.

Sepsis is a complex medical condition characterized by a systemic inflammatory response in the setting of infection. We hypothesized that combining antibiotics plus an immunosuppressant would protect against the morbidity and mortality of polymicrobial sepsis in mice better than would antibiotics alone. We used a murine cecal-ligation-and-puncture model in which mice were treated either with imipenem plus cyclophosphamide or imipenem alone. Titration to a low cyclophosphamide dose revealed that combination therapy increased survival by 20% compared with imipenem alone (56% vs. 36%, P < 0.001). To investigate the mechanism by which combination therapy did this, we reviewed quantitative and qualitative markers of the systemic immune response, end-organ damage, and the local immune response at the site of injury. Cyclophosphamide treatment was not associated with depletion of peripheral leukocytes or differences in pulmonary damage. However, mice that received combination therapy had higher plasma granulocyte colony-stimulating factor levels than did those treated with antibiotics alone. In addition, mice treated with cyclophosphamide had higher levels of bacterial colonization in intestinal Peyer's patch lymph nodes at 72 h after the septic insult. Intraperitoneal macrophage phenotypes and phagocytosis activity did not differ between groups. We conclude that the inflammatory response plays a significant role in the mortality of polymicrobial sepsis and that the regulation of this element is both feasible and beneficial in this disease model.

Nasal tip projection and facial attractiveness.

OBJECTIVES/HYPOTHESIS: Six nasal tip projection (NTP) ratios from Goode, Simons, Baum, Powell, and Crumley guide clinical and academic practice on quantifying NTP, but none have been empirically correlated with facial attractiveness. This study's objectives were to determine: 1) if there is a correlation between these ratios and facial attractiveness; and 2) which of the six ratios has the greatest linkage to overall facial attractiveness. STUDY DESIGN: Basic research study. METHODS: There were 300 digital portraits of women (ages 18-25 years) randomly paired and morphed to create 300 synthetic lateral facial images rated by 78 raters in the community. NTP ratios were measured in each portrait. RESULTS: None of the ratios correlated with facial attractiveness. For the Baum, Powell, and Simons ratio, facial attractiveness increased as NTP deviated 1 and 2 standard deviations from the ideal, whereas facial attractiveness decreased as NTP deviated from the Goode and Crumley ideal ratios. The most attractive faces had NTP ratios consistent with previous expert opinion findings. CONCLUSIONS: To our knowledge, this is the first study to empirically correlate these six landmark NTP ratios with facial attractiveness. Although there was no correlation with any of the six ratios, the ideal ratios proposed by Goode and Crumley impacted facial aesthetics the most. Although the ideal ratios are useful in establishing rhinoplasty guidelines, they should only be used as a part of the management in achieving an aesthetic face on the whole, as they may not be robust enough to correlate with overall facial attractiveness.