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  • 1
    Keywords: breast cancer ; Citizen science ; Crowd science ; Crowdsourcing
    Abstract: BACKGROUND: Citizen science, scientific research conducted by non-specialists, has the potential to facilitate biomedical research using available large-scale data, however validating the results is challenging. The Cell Slider is a citizen science project that intends to share images from tumors with the general public, enabling them to score tumor markers independently through an internet-based interface. METHODS: From October 2012 to June 2014, 98,293 Citizen Scientists accessed the Cell Slider web page and scored 180,172 sub-images derived from images of 12,326 tissue microarray cores labeled for estrogen receptor (ER). We evaluated the accuracy of Citizen Scientist's ER classification, and the association between ER status and prognosis by comparing their test performance against trained pathologists. FINDINGS: The area under ROC curve was 0.95 (95% CI 0.94 to 0.96) for cancer cell identification and 0.97 (95% CI 0.96 to 0.97) for ER status. ER positive tumors scored by Citizen Scientists were associated with survival in a similar way to that scored by trained pathologists. Survival probability at 15 years were 0.78 (95% CI 0.76 to 0.80) for ER-positive and 0.72 (95% CI 0.68 to 0.77) for ER-negative tumors based on Citizen Scientists classification. Based on pathologist classification, survival probability was 0.79 (95% CI 0.77 to 0.81) for ER-positive and 0.71 (95% CI 0.67 to 0.74) for ER-negative tumors. The hazard ratio for death was 0.26 (95% CI 0.18 to 0.37) at diagnosis and became greater than one after 6.5 years of follow-up for ER scored by Citizen Scientists, and 0.24 (95% CI 0.18 to 0.33) at diagnosis increasing thereafter to one after 6.7 (95% CI 4.1 to 10.9) years of follow-up for ER scored by pathologists. INTERPRETATION: Crowdsourcing of the general public to classify cancer pathology data for research is viable, engages the public and provides accurate ER data. Crowdsourced classification of research data may offer a valid solution to problems of throughput requiring human input.
    Type of Publication: Journal article published
    PubMed ID: 26288840
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  • 2
    Keywords: RISK ; chemotherapy ; MUTATION CARRIERS ; METAANALYSIS ; GENOME-WIDE ASSOCIATION ; CONFER SUSCEPTIBILITY ; CANCER SUSCEPTIBILITY LOCI ; COMMON VARIANTS ; 14Q24.1 RAD51L1 ; IDENTIFIES 3
    Abstract: Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95% CI) for ILC = 1.13 (1.09-1.18), P = 6.0x10(-10); P-het for ILC vs IDC ER+ tumors = 1.8x10(-4)). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P〈0.05. Two SNPs showed significantly stronger associations for ILC than LCIS (rs2981579/10q26/FGFR2, P-het = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03); and two showed stronger associations for LCIS than ILC (rs6678914/1q32/LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04). In addition, seven of the 75 known loci showed significant differences between ER+ tumors with IDC and ILC histology, three of these showing stronger associations for ILC (rs11249433/1p11, rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365) and four associated only with IDC (5p12/rs10941679; rs2588809/14q24/RAD51L1, rs6472903/8q21 and rs1550623/2q31/CDCA7). In conclusion, we have identified one novel lobular breast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there is some heterogeneity between ER+ lobular and ER+ IDC tumors. These data provide evidence for overlapping, but distinct etiological pathways within ER+ breast cancer between morphological subtypes.
    Type of Publication: Journal article published
    PubMed ID: 24743323
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  • 3
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Animal Behaviour 22 (1974), S. 836-849 
    ISSN: 0003-3472
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 182 (1958), S. 654-655 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] We have followed the rate of deuterium exchange by measuring the strength of the hydrogen-bonded peptide NH band at about 3,300 cm.-1. Since chloroform is more transparent in this region than ethylene dichloride, we have used a mixture of chloroform and O-deuterated dichloracetic acid as solvent. ...
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 178 (1956), S. 1170-1170 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The stability and sense of the a-helix can be examined by measuring the optical rotation of a series of polypeptides in which the proportion of D- to L-residues is varied. The addition of a proportion of D-residues, randomly arranged along a chain of L-residues in the a-helix form, will not affect ...
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 176 (1955), S. 396-397 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] It has recently been found5 that the two forms have different infra-red spectra. Whereas polyglycine I is a typical (3-polypeptide, with absorption bands at 1,630 cm.-1 (C=O) and 1,530 cm.-1, polyglycine II has bands at 1,648 cm.-1 (C=O) and 1,558 cm.-1. The C=O mode of the second form, therefore, ...
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 168 (1951), S. 824-825 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] As regards (a) we have no special comment, although we feel that Mercer's view is probably correct. On the other hand, Mercer's arguments against the presence of 7-10 per cent of p-keratin in wool are far from convincing. It is by no means certain that this amount of (partially disoriented) ...
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 168 (1951), S. 340-341 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The X-ray data on poly-Y-benzyl-L-glutamate are interpreted in terms of a helical structure containing 11 amino-acid residues in three turns and a pseudo-orthorhombic unit cell with a0 = 25 A., b0 = 17-3 A. (fibre axis), o0 = 14-42 A., and (3 = 90 26. The near meridional reflexions at 5-27 A., ...
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] We have shown that in many cases the two forms are readily interconvertible ; in particular, a complete transformation to the extended β-modification can be effected by treating the folded polymer (which we shall call the aII-polypeptide) with formic acid. Some aII-polypeptides with hydrocarbon ...
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 163 (1949), S. 483-484 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] A STUDY of polypeptides prepared by Leuchs's method1,2 is being carried out in this Laboratory. We have recently prepared the polypeptide I (below) by the polymerization of the N-carbonic anhydride of γ-methyl L-glutamate (II), and wish to describe here observations ...
    Type of Medium: Electronic Resource
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