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C. Abbosh, Nicolai J. Birkbak, G. Wilson, M. Jamal-Hanjani, T. Constantin, R. Salari, J. Le Quesne, D. Moore et al.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies.

G. Cao, E. Sofić, R. Prior

Previously, some fruits were shown to contain high antioxidant activities. In this paper, we report the antioxidant activities of 22 common vegetables, one green tea, and one black tea measured using the automated oxygen radical absorbance capacity assay with three different reactive species:  a peroxyl radical generator, a hydroxyl radical generator, and Cu2+, a transition metal. Based on the fresh weight of the vegetable, garlic had the highest antioxidant activity (μmol of Trolox equiv/g) against peroxyl radicals (19.4) followed by kale (17.7), spinach (12.6), Brussels sprouts, alfalfa sprouts, broccoli flowers, beets, red bell pepper, onion, corn, eggplant (9.8−3.9), cauliflower, potato, sweet potato, cabbage, leaf lettuce, string bean, carrot, yellow squash, iceberg lettuce, celery, and cucumber (3.8−0.5); kale had the highest antioxidant activity against hydroxyl radicals followed by Brussels sprouts, alfalfa sprouts, beets, spinach, broccoli flowers, and the others. The green and black teas had muc...

R. Prior, G. Cao, Anda Martin, E. Sofić, J. McEwen, C. O'brien, N. Lischner, M. Ehlenfeldt et al.

Different cultivars of four Vaccinium species [Vaccinium corymbosum L (Highbush), Vaccinium ashei Reade (Rabbiteye), Vaccinium angustifolium (Lowbush), and Vaccinium myrtillus L (Bilberry)] were analyzed for total phenolics, total anthocyanins, and antioxidant capacity (oxygen radical absorbance capacity, ORAC). The total antioxidant capacity of different berries studied ranged from a low of 13.9 to 45.9 μmol Trolox equivalents (TE)/g of fresh berry (63.2−282.3 μmol TE/g of dry matter) in different species and cultivars of Vaccinium. Brightwell and Tifblue cultivars of rabbiteye blueberries were harvested at 2 times, 49 days apart. Increased maturity at harvest increased the ORAC, the anthocyanin, and the total phenolic content. The growing location (Oregon vs Michigan vs New Jersey) did not affect ORAC, anthocyanin or total phenolic content of the cv. Jersey of highbush blueberries. A linear relationship existed between ORAC and anthocyanin (rxy = 0.77) or total phenolic (rxy = 0.92) content. In general,...

K. Ong, Lauryn K. Stafford, Susan A. Mclaughlin, E. Boyko, S. Vollset, Amanda E. Smith, Bronte E Dalton, J. Duprey et al.

K. Michailidou, S. Lindström, J. Dennis, J. Beesley, Shirley Hui, S. Kar, Audrey Lemaçon, P. Soucy et al.

Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10−8. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2–5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.

C. Abbosh, N. Birkbak, G. Wilson, M. Jamal-Hanjani, T. Constantin, R. Salari, J. Le Quesne, D. Moore et al.

Nina Haug, Lukas Geyrhofer, A. Londei, Elma Dervić, A. Desvars-Larrive, V. Loreto, B. Pinior, S. Thurner et al.

J. Bentham, M. Cesare, M. Cesare, Gretchen A. Stevens, Bin Zhou, Honor Bixby, Melanie J. Cowan, L. Fortunato et al.

Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3–19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8–144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries. DOI: http://dx.doi.org/10.7554/eLife.13410.001

K. Michailidou, P. Hall, A. González-Neira, M. Ghoussaini, J. Dennis, R. Milne, M. Schmidt, J. Chang-Claude et al.

A. Pelliccia, Sanjay Sharma, S. Gati, Maria Bäck, M. Börjesson, S. Caselli, J. Collet, D. Corrado et al.

A. Kurilshikov, C. Medina-Gomez, Rodrigo Bacigalupe, D. Radjabzadeh, J. Wang, A. Demirkan, C. L. Le Roy, J. R. Raygoza Garay et al.

Klaus Hermann Maier-Hein, P. Neher, Jean-Christophe Houde, Marc-Alexandre Côté, E. Garyfallidis, J. Zhong, Maxime Chamberland, F. Yeh et al.

Tractography based on non-invasive diffusion imaging is central to the study of human brain connectivity. To date, the approach has not been systematically validated in ground truth studies. Based on a simulated human brain data set with ground truth tracts, we organized an open international tractography challenge, which resulted in 96 distinct submissions from 20 research groups. Here, we report the encouraging finding that most state-of-the-art algorithms produce tractograms containing 90% of the ground truth bundles (to at least some extent). However, the same tractograms contain many more invalid than valid bundles, and half of these invalid bundles occur systematically across research groups. Taken together, our results demonstrate and confirm fundamental ambiguities inherent in tract reconstruction based on orientation information alone, which need to be considered when interpreting tractography and connectivity results. Our approach provides a novel framework for estimating reliability of tractography and encourages innovation to address its current limitations. Though tractography is widely used, it has not been systematically validated. Here, authors report results from 20 groups showing that many tractography algorithms produce both valid and invalid bundles.

E. Arbelo, Alexandros Protonotarios, J. Gimeno, E. Arbustini, R. Barriales-Villa, C. Basso, C. Bezzina, E. Biagini et al.

S. Sanna, Natalie R. van Zuydam, A. Mahajan, A. Kurilshikov, A. Vich Vila, U. Võsa, Z. Mujagic, A. Masclee et al.

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