Lin28b is an RNA-binding protein that inhibits biogenesis of let-7 microRNAs. LIN28B is overexpressed in diverse cancers, yet a specific role in the molecular pathogenesis of colon cancer has yet to be elucidated. We have determined that human colon tumors exhibit decreased levels of mature let-7 isoforms and increased expression of LIN28B. In order to determine LIN28B's mechanistic role in colon cancer, we expressed LIN28B in immortalized colonic epithelial cells and human colon cancer cell lines. We found that LIN28B promotes cell migration, invasion, and transforms immortalized colonic epithelial cells. In addition, constitutive LIN28B expression increases expression of intestinal stem cell markers LGR5 and PROM1 in the presence of let-7 restoration. This may occur as a result of Lin28b protein binding LGR5 and PROM1 mRNA, suggesting that a subset of LIN28B functions are independent of its ability to repress let-7. Our findings establish a new role for LIN28B in human colon cancer pathogenesis, and suggest LIN28B post-transcriptionally regulates LGR5 and PROM1 through a let-7 independent mechanism.

In a population-based study in California, we found that following S-colo, rates of serious GI adverse events were low but clinically relevant, and that rates of myocardial infarction, stroke, and serious pulmonary events were no higher than after low-risk comparator procedures. Rates of myocardial infarction are similar to, but rates of stroke are higher than, those reported for the general population.

A method is described for the catheterization of the carotid of the rat which permits blood volume determinations to be made on unanesthetized animals. The cell volume (P32) and plasma volume (T-1824) were measured simultaneously on the day after catheterization. The average Fcells factor was 0.739 (S.D., 0.053) in 11 normal rats and 0.726 (S.D., 0.041) in 10 splenectomized rats. In 50 unanesthetized normal rats the plasma volume averaged 3.90 ml/100 gm body weight. The blood and cell volumes calculated by using the Fcells factor of 0.74 and the separately determined plasma trapping' factor of 0.95 averaged 5.93 ml/ 100 gm and 2.14 ml/100 gm, respectively. These values agree closely with those determined from the simultaneous measurement of cell and plasma volumes and also with the values obtained on 27 normal rats under ether.

The use of liquid biofuels has expanded over the past decade in response to policies such as the U.S. Renewable Fuel Standard (RFS) that promote their use for transportation. One rationale is the belief that biofuels are inherently carbon neutral, meaning that only productionrelated greenhouse gas (GHG) emissions need to be tallied when comparing them to fossil fuels. This assumption is embedded in the lifecycle analysis (LCA) modeling used to justify and administer such policies. LCA studies have often found that crop-based biofuels such as corn ethanol and biodiesel offer at least modest net GHG reductions relative to petroleum fuels. Data over the period of RFS expansion enable empirical assessment of net CO 2 emission effects. This analysis evaluates the direct carbon exchanges (both emissions and uptake) between the atmosphere and the U.S. vehicle-fuel system (motor vehicles and the physical supply chain for motor fuels) over 2005-2013. While U.S. biofuel use rose from 0.37 to 1.34 EJ/yr over this period, additional carbon uptake on cropland was enough to offset only 37 % of the biofuel-related biogenic CO 2 emissions. This result falsifies the assumption of a full offset made by LCA and other GHG accounting methods that assume biofuel carbon neutrality. Once estimates from the literature for process emissions and displacement effects including land-use change are considered, the conclusion is that U.S. biofuel use to date is associated with a net increase rather than a net decrease in CO 2 emissions.

ObjectiveOver 9.6 million ED visits occur annually for abdominal pain in the US, but little is known about the medical outcomes of these patients based on demographics. We aimed to identify disparities in outcomes among children presenting to the ED with abdominal pain linked to race and SES.MethodsData from 4.2 million pediatric encounters of abdominal pain were analyzed from 43 tertiary US children’s hospitals, including 2.0 million encounters in the emergency department during 2004-2011. Abdominal pain was categorized as functional or organic abdominal pain. Appendicitis (with and without perforation) was used as a surrogate for abdominal pain requiring emergent care. Multivariate analysis estimated likelihood of hospitalizations, radiologic imaging, ICU admissions, appendicitis, appendicitis with perforation, and time to surgery and hospital discharge.ResultsBlack and low income children had increased odds of perforated appendicitis (aOR, 1.42, 95% CI, 1.32- 1.53; aOR, 1.20, 95% CI 1.14 – 1.25). Blacks had increased odds of an ICU admission (aOR, 1.92, 95% CI 1.53 - 2.42) and longer lengths of stay (aHR, 0.91, 95% CI 0.86 – 0.96) than Whites. Minorities and low income also had lower rates of imaging for their appendicitis, including CT scans. The combined effect of race and income on perforated appendicitis, hospitalization, and time to surgery was greater than either separately.ConclusionsBased on race and SES, disparity of health outcomes exists in the acute ED setting among children presenting with abdominal pain, with differences in appendicitis with perforation, length of stay, and time until surgery.

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Genome-wide association studies have identified hundreds of single nucleotide variations (formerly single nucleotide polymorphisms) associated with several cancers, but the predictive ability of polygenic risk scores (PRSs) is unclear, especially among non-Whites. Methods: PRSs were derived from genome-wide significant single-nucleotide variations for 15 cancers in 20,079 individuals in an academic biobank. We evaluated the improvement in discriminatory accuracy by including cancer-specific PRS in patients of geneticallydetermined African and European ancestry. Results: Among the individuals of European genetic ancestry, PRSs for breast, colon, melanoma, and prostate were significantly associated with their respective cancers. Among the individuals of African genetic ancestry, PRSs for breast, colon, prostate, and thyroid were significantly associated with their respective cancers. The area under the curve of the model consisting of age, sex, and principal components was 0.621 to 0.710, and it increased by 1% to 4% with the inclusion of PRS in individuals of European genetic ancestry. In individuals of African genetic ancestry, area under the curve was overall higher in the model without the PRS (0.723-0.810) but increased by <1% with the inclusion of PRS for most cancers. Conclusion: PRS moderately increased the ability to discriminate the cancer status in individuals of European but not African ancestry. Further large-scale studies are needed to identify ancestryspecific genetic factors in non-White populations to incorporate PRS into cancer risk assessment.