Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Risk of second primary malignancies among cancer survivors in the United States, 1992 through 2008

BackgroundIn the current study, the authors attempted to describe the incidence, most common sites, and mortality of second primary malignancies among survivors of common cancers.MethodsThe authors identified patients aged ≥18 years who were diagnosed with a primary malignancy from the 10 most common cancer sites (prostate, breast, lung, colon, rectum, bladder, uterus, kidney, melanoma, and non-Hodgkin lymphoma) between 1992 and 2008 from Surveillance, Epidemiology, and End Results data. Factors associated with the incidence of second primary malignancies were explored using bivariable and multivariable models, and mortality attributable to first and second primary malignancies was examined.ResultsA cohort of 2,116,163 patients was identified, 170,865 of whom (8.1%) developed a second primary malignancy. Survivors of bladder cancer had the highest risk of developing a second cancer. In a multivariable model controlling for age, race, tumor grade, stage of disease, marital status, educational level, and income, a history of non-Hodgkin lymphoma (hazard ratios of 2.70 and 2.88, respectively, for men and women) and bladder cancer (hazard ratios of 1.88 and 1.66, respectively, for men and women) predicted the highest risk of developing a second cancer. For patients with 2 incident cancers, 13% died of their initial cancer, but greater than one-half (55%) died of their second primary malignancy. Lung cancer was the cause of death in 12% of patients with 2 incident cancers.ConclusionsNearly 1 in 12 patients diagnosed with a common cancer developed a second malignancy, the most common of which was lung cancer. Greater than one-half of patients with 2 incident cancers died of their secondary malignancy. The findings from the current study may inform care strategies among cancer survivors. Cancer 2016;122:3075-3086. © 2016 American Cancer Society

Effects of C-terminal deletions on cystic fibrosis transmembrane conductance regulator function in cystic fibrosis airway epithelia

To better understand the function of the conserved C terminus of the cystic fibrosis (CF) transmembrane conductance regulator, we studied constructs containing deletions in the C-terminal tail. When expressed in well differentiated CF airway epithelia, each construct localized predominantly to the apical membrane and generated transepithelial Cl(−) current. The results suggested that neither the C-terminal PSD-95/Discs-large/ZO-1 (PDZ)-interacting motif nor other C-terminal sequences were absolutely required for apical expression in airway epithelia. Surprisingly, deleting an acidic cluster near the C terminus reduced both channel opening rate and transepithelial Cl(−) transport, indicating that it influences channel gating. These results may help explain the relative paucity of CF-associated mutations in the C terminus