Consumption of Diet and Nutrition Information in Digital Magazines Marketing to Latinx Women

Objective: To examine the types of nutrition and health-related articles published in digital magazines directed toward Latinx women; and to examine the extent to which advertisements about food, nutrition, and weight-loss are prevalent in these media. Design: A descriptive content analysis was completed for five digital magazines marketing to Latinx women. A total of 1,234 articles and 3,001 advertisements were examined for nutrition and health-related content. Results: Early editions of digital magazines directed towards Latinx women included more advertisements than articles on the topics of food and health. Among the articles, very few (0-30%) included health and nutrition information that came from a reliable, evidenced-based source. Conclusions and Implications: Public health researchers should continue to examine mass media exposures of health and nutrition messages, especially media directed towards populations disproportionately affected by diet-related diseases. Overall, this study provides recommendations for health and nutrition professionals to contribute expert content to digital media targeting the Latinx community

Assessment of Cultural Sensitivity in Dietetics Education

Cultural sensitivity and competency are skills needed for agricultural professionals including nutrition and dietetics practitioners. The objective of the current study was to examine the learning transference of cultural sensitivity topics taught in a cultural foods course into case study assessments of a capstone-level course. This study is a cross-sectional, content analysis of cultural sensitivity assessment rubric (CSAR) scores for two case study assessments. The study was conducted in a landgrant, research-intensive university and 55 students (60%) from a capstone-level dietetics course participated. T-tests were used to compare CSAR scores between students who had completed a cultural foods course and those who had not. Students who completed the cultural foods course, n= 39 (71%), on average scored significantly higher (p\u3c 0.037) on the CSAR, 2.11/10, versus an average score of 1.03/10 among the students who had not completed the course, n=16 (29%). Students who completed the cultural foods course were more likely to apply cultural sensitivity knowledge and awareness without explicit elicitation than those who had not completed the course. Findings reinforce the use of intentional assessments of cultural sensitivity and competency topics and provide support for laying a cultural sensitivity foundation in undergraduate education

Communication of Professional Readiness in Dietetics and Human Nutrition Undergraduates: A Pilot Study

Learning experiences within the dietetics and human nutrition undergraduate curricula develop knowledge and skills pertinent to student career goals. Core competency requirements are extensively assessed in these programs, yet the communication of transferable skills gained and student professional readiness are rarely examined. The purpose of this study was to evaluate undergraduate students\u27 perceived professional readiness following six professional development workshops on transferable skills and career preparedness communicated through resumes and personal statements. In this pilot study, twelve upper-level dietetics and human nutrition students self-assessed their resumes and personal statements with rubrics and completed surveys before and after the intervention. Following the workshops, four professionals in the students\u27 respective career field of interest assessed the resumes and personal statements using the same rubrics. Trends toward improvements were seen in three of 15 transferable skills and in six out of 10 skills assessing confidence in career preparedness. Four out of seven resume components saw trends toward improvements, and all items on the personal statements improved after the intervention. No differences were observed between the student and professional assessments. Providing structured time for student reflection to effectively articulate professional readiness may better prepare students for success in future professional endeavors

Intermediate Molecular Phenotypes to Identify Genetic Markers of Anthracycline-Induced Cardiotoxicity Risk.

Cardiotoxicity due to anthracyclines (CDA) affects cancer patients, but we cannot predict who may suffer from this complication. CDA is a complex trait with a polygenic component that is mainly unidentified. We propose that levels of intermediate molecular phenotypes (IMPs) in the myocardium associated with histopathological damage could explain CDA susceptibility, so variants of genes encoding these IMPs could identify patients susceptible to this complication. Thus, a genetically heterogeneous cohort of mice (n = 165) generated by backcrossing were treated with doxorubicin and docetaxel. We quantified heart fibrosis using an Ariol slide scanner and intramyocardial levels of IMPs using multiplex bead arrays and QPCR. We identified quantitative trait loci linked to IMPs (ipQTLs) and cdaQTLs via linkage analysis. In three cancer patient cohorts, CDA was quantified using echocardiography or Cardiac Magnetic Resonance. CDA behaves as a complex trait in the mouse cohort. IMP levels in the myocardium were associated with CDA. ipQTLs integrated into genetic models with cdaQTLs account for more CDA phenotypic variation than that explained by cda-QTLs alone. Allelic forms of genes encoding IMPs associated with CDA in mice, including AKT1, MAPK14, MAPK8, STAT3, CAS3, and TP53, are genetic determinants of CDA in patients. Two genetic risk scores for pediatric patients (n = 71) and women with breast cancer (n = 420) were generated using machine-learning Least Absolute Shrinkage and Selection Operator (LASSO) regression. Thus, IMPs associated with heart damage identify genetic markers of CDA risk, thereby allowing more personalized patient management.J.P.L.’s lab is sponsored by Grant PID2020-118527RB-I00 funded by MCIN/AEI/10.13039/ 501100011039; Grant PDC2021-121735-I00 funded by MCIN/AEI/10.13039/501100011039 and by the “European Union Next Generation EU/PRTR”, the Regional Government of Castile and León (CSI144P20). J.P.L. and P.L.S. are supported by the Carlos III Health Institute (PIE14/00066). AGN laboratory and human patients’ studies are supported by an ISCIII project grant (PI18/01242). The Human Genotyping unit is a member of CeGen, PRB3, and is supported by grant PT17/0019 of the PE I + D + i 2013–2016, funded by ISCIII and ERDF. SCLl is supported by MINECO/FEDER research grants (RTI2018-094130-B-100). CH was supported by the Department of Defense (DoD) BCRP, No. BC190820; and the National Cancer Institute (NCI) at the National Institutes of Health (NIH), No. R01CA184476. Lawrence Berkeley National Laboratory (LBNL) is a multi-program national laboratory operated by the University of California for the DOE under contract DE AC02-05CH11231. The Proteomics Unit belongs to ProteoRed, PRB3-ISCIII, supported by grant PT17/0019/0023 of the PE I + D +i, 2017–2020, funded by ISCIII and FEDER. RCC is funded by fellowships from the Spanish Regional Government of Castile and León. NGS is a recipient of an FPU fellowship (MINECO/FEDER). hiPSC-CM studies were funded in part by the “la Caixa” Banking Foundation under the project code HR18-00304 and a Severo Ochoa CNIC Intramural Project (Exp. 12-2016 IGP) to J.J.S

Interaction between sodium dodecyl sulfate and membrane reconstituted aquaporins: A comparative study of spinach SoPIP2;1 and E. coli AqpZ

AbstractThis study describes the interaction between sodium dodecyl sulfate (SDS) and membrane proteins reconstituted into large unilamellar lipid vesicles and detergent micelles studied by circular dichroism (CD) and polarity sensitive probe labeling. Specifically, we carried out a comparative study of two aquaporins with high structural homology SoPIP2;1 and AqpZ using identical reconstitution conditions. Our CD results indicate that SDS, when added to membrane-reconstituted aquaporins in concentrations below the SDS critical micelle concentration (CMC, ~8mM), causes helical rearrangements of both aquaporins. However, we do not find compelling evidence for unfolding. In contrast when SDS is added to detergent stabilized aquaporins, SoPIP2;1 partly unfolds, while AqpZ secondary structure is unaffected. Using a fluorescent polarity sensitive probe (Badan) we show that SDS action on membrane reconstituted SoPIP2;1 as well as AqpZ is associated with initial increased hydrophobic interactions in protein transmembrane (TM) spanning regions up to a concentration of 0.1× CMC. At higher SDS concentrations TM hydrophobic interactions, as reported by Badan, decrease and reach a plateau from SDS CMC up to 12.5× CMC. Combined, our results show that SDS does not unfold neither SoPIP2;1 nor AqpZ during transition from a membrane reconstituted form to a detergent stabilized state albeit the native folds are changed

Datasets related to a study aimed to identify genetic markers of CDA by subphenotypes associated with cardiotoxicity

Who produced the data? The data has been created by the authors listed above. Is the title specific enough? "Datasets related to a study aimed to identify genetic markers of CDA by subphenotypes associated with cardiotoxicity." Why has the data been created? These datasets are supplementary material with which the principal and supplementary figures and tables of our indicated work were generated. What limitations do the data have (for example, sensitive data has been deleted)? All confidential patient information is not present. We have not had access to that information, following current legal regulations. How should the data be interpreted? These data sets should not be separated from the main article in which they were utilized. Thus, to better understand their context, researchers should see them in the global scenario of our work. Are there gaps in the data, or do they give a complete picture of the topic studied? As indicated above, data should be considered and interpreted in the global context of our study. What processes have generated the data? The processes that generated the data are indicated in the summary of the data above and individually for each of them. Thus, each dataset is accompanied by a legend within the document. What does the data measure in the columns of the files? As indicated, each dataset individually shows the information contained in the legend of each dataset. What software is required to be able to read the data? The datasets are in Excel format. How should the data be quoted? Researchers should cite the data in the context of the work they belong to once it is published and free of the embargo. Can the data be reused? What use licenses are assigned to you? In principle, yes. If additional clinical information is required, these data were previously published by some of us, and the references are included in our manuscript. These data are available from the principal investigators of the references listed in our work upon reasonable request. Are there more versions of the data? Where? I do not think so beyond our files and copies. Have the technical terms and acronyms referenced by the data been defined? A legend with the appropriate descriptions accompanies each dataset. Have the geographic and chronological parameters of the data been qualified? The authors of the work have generated the data. Elsewhere, we indicate the authors of the work, their contributions, and affiliations. Are keywords sufficiently data-specific? Are they based on any thesaurus? Keywords are based on our study. We include cardiotoxicity due to anthracyclines, missing heritability, subphenotype, pathophenotype, complex trait. What is the name of the research project in which the data are framed? The main research project in which the data is prepared is: Títle: "Chemotherapy cardiotoxicity in the elderly: a translational and personnel approach." Ref.: PIE14/00066 Who has financed data production and management? Each of the authors of the study has its funding. The grants are included in the acknowledgments section of our manuscript.Here we present a series of supplemental datasets that complement our study entitled "A Systems Genetics approach to identify genetic markers of cardiotoxicity due to anthracyclines in cancer patients." The datasets presented here were used to generate the main and supplementary figures and tables of the indicated study. The study consists of the identification of genetic markers of cardiotoxicity due to anthracyclines (CDA). CDA is a complex genesis disease or complex trait, and because of this, there is a component of missing heritability. Therefore, it is not possible to identify genetic markers associated with CDA risk. Here, we propose that molecular subphenotypes associated with the CDA may be a strategy for identifying some of this missing heritability and risk markers associated with it. A similar strategy could be applied to identify markers of other diseases of complex genesis. This study is done using a genetically heterogeneous cohort of mice that developed breast cancer and was treated with doxorubicin or a combined treatment of doxorubicin and docetaxel. The mouse cohort was generated by backcrossing, so each mouse is genetically unique. Post-chemotherapy heart damage was assessed by quantifying fibrosis's cardiac area and the thickness of myocardial fibers. The genetic regions associated with CDA were assessed by massive genotyping and genetic linkage analysis. Several molecular subphenotypes were quantified in the myocardium, and their association with the CDA was evaluated. Subsequently, we identified which of them were most statistically associated with CDA in multivariate models. Moreover, which complex trait loci (QTLs) associated with molecular subphenotypes best explained CDA. This strategy served to identify in the cohort of mice genes whose allelic forms could be candidates for the risk of CDA. Allelic variants of these genes were evaluated in four cohorts of cancer patients treated with anthracyclines and whose CDA was evaluated by echocardiography or cardiac magnetic resonance imaging (CMR).JPL laboratory was partially supported by the European Regional Development Fund (ERDF) and the Ministry of Science, Innovation, and Universities (SAF2014-56989-R, SAF2017-88854R), the Carlos III Health Institute (PIE14/00066), "Proyectos Integrados IBSAL 2015" (IBY15/00003), the Regional Government of Castile and Leon (CSI234P18), and "We can be heroes" Foundation. AGN laboratory and human patients' study are supported by funds from the ISCIII project grant (PI18/01242). The Human Genotyping unit is a member of CeGen, PRB3, and is supported by grant PT17/0019, of the PE I+D+i 2013-2016, funded by ISCIII and ERDF. SCLL was the recipient of a Ramón y Cajal research contract from the Spanish Ministry of Economy and Competitiveness, and the work was supported by MINECO/FEDER research grants (RTI2018-094130-B-100). The Proteomics Unit belongs to ProteoRed, PRB3-ISCIII, supported by grant PT17/0019/0023, of the PE I + D + I 2017-2020, funded by ISCIII and FEDER. RCC is funded by fellowships from the Spanish Regional Government of Castile and León. NGS is a recipient of an FPU fellowship (MINECO/FEDER). hiPSC-CM studies were funded in part by the "la Caixa" Banking Foundation under the project code HR18-00304" and Severo Ochoa CNIC Intramural Project (Expediente 12-2016 IGP) to JJ.Supplemental Dataset 1: CDA pathophenotypes after doxorubicin treatment. We treated 71 mice carrying breast cancer with doxorubicin. Each mouse was generated by backcrossing; thus, each one is genetically unique. Cardiotoxicity due to anthracyclines (CDA) was evaluated by automatically quantifying the heart fibrosis area and the average area of myocardial fibers as pathophenotypes of cardiotoxicity using the Ariol slide scanner. The histopathological damage was evaluated in the subendocardium and subepicardium from five randomly chosen regions of each sample (averages in μm2 are shown).-- Supplemental Dataset 2: CDA pathophenotypes after the combined therapy. We treated 61 mice carrying breast cancer with the combined therapy with doxorubicin and docetaxel. Each mouse was generated by backcrossing; thus, each one is genetically unique. Cardiotoxicity due to anthracyclines (CDA) was evaluated by automatically quantifying the heart fibrosis area and the average area of myocardial fibers as pathophenotypes of cardiotoxicity using the Ariol slide scanner. The histopathological damage was evaluated in the subendocardium and subepicardium from five randomly chosen regions of each sample (averages in μm2 are shown).-- Supplemental Dataset 3: CDA subphenotypes after doxorubicin therapy. Myocardium molecular subphenotypes after doxorubicin therapy. Proteins were quantified by a multiplex bead array (Luminex). TGFβ units are shown in pg/mL. The rest of the protein levels are shown in molecular fluorescence intensity (MFI) Units. The telomeric length was quantified by QPCR (RQ units). miRNAs were quantified by QPCR (RQ units). QPCR analyses were assessed by the ΔΔCT method; we show the averages of triplicates.-- Supplemental Dataset 4: CDA subphenotypes after the combined therapy. Myocardium molecular subphenotypes after the combined therapy with doxorubicin and docetaxel. Proteins were quantified by a multiplex bead array (Luminex). TGFβ units are shown in pg/mL. The rest of the protein levels are shown in molecular fluorescence intensity (MFI) Units. The telomeric length was quantified by QPCR (RQ units). miRNAs were quantified by QPCR (RQ units). QPCR analyses were assessed by the ΔΔCT method; we show the averages of triplicates.-- Supplemental Dataset 5: Correlations identified between molecular subphenotype levels in the myocardium and pathophenotypes of cardiotoxicity due to anthracyclines (CDA) after doxorubicin therapy in all mice.-- Supplemental Dataset 6: Correlations identified between molecular subphenotype levels in the myocardium and pathophenotypes of cardiotoxicity due to anthracyclines (CDA) after doxorubicin therapy in young mice. Correlation of Spearman.-- Supplemental Dataset 7: Correlations identified between molecular subphenotype levels in the myocardium and pathophenotypes of cardiotoxicity due to anthracyclines (CDA) after doxorubicin therapy in old mice. Correlation of Spearman.-- Supplemental Dataset 8: Correlations identified between molecular subphenotype levels in the myocardium and pathophenotypes of cardiotoxicity due to anthracyclines (CDA) after the combined therapy in all mice. Correlation of Spearman.-- Supplemental Dataset 9: Correlations identified between molecular subphenotype levels in the myocardium and pathophenotypes of cardiotoxicity due to anthracyclines (CDA) after the combined therapy in young mice. Correlation of Spearman.-- Supplemental Dataset 10: Correlations identified between molecular subphenotype levels in the myocardium and pathophenotypes of cardiotoxicity due to anthracyclines (CDA) after the combined therapy in old mice. Correlation of Spearman.-- Supplemental Dataset 11: Linkage analysis of molecular subphenotype levels quantified in the myocardium. Lod scores after doxorubicin therapy in all mice. The Illumina Mouse Medium Density Linkage Panel Assay was used to genotype 130 F1BX mice at 1449 single nucleotide polymorphisms (SNPs). Genotypes were classified as FVB/FVB (F/F) or FVB/C57BL/6 (F/B). Ultimately, 806 SNPs are informative from the FVB and C57BL/6 mice; the average genomic distance between these SNPs was 9.9 Mb. The genotype proportion among the F1BX mice showed a normal distribution. Linkage analysis was carried out using interval mapping with the expectation-maximization (EM) algorithm and R/QTL software. The criteria for significant and suggestive linkages for single markers were chosen based on Lander and Kruglyak (see methods section of our manuscript).-- Supplemental Dataset 12: Linkage analysis of molecular subphenotype levels quantified in the myocardium. Lod scores after doxorubicin therapy in young mice. The Illumina Mouse Medium Density Linkage Panel Assay was used to genotype 130 F1BX mice at 1449 single nucleotide polymorphisms (SNPs). Genotypes were classified as FVB/FVB (F/F) or FVB/C57BL/6 (F/B). Ultimately, 806 SNPs are informative from the FVB and C57BL/6 mice; the average genomic distance between these SNPs was 9.9 Mb. The genotype proportion among the F1BX mice showed a normal distribution. Linkage analysis was carried out using interval mapping with the expectation-maximization (EM) algorithm and R/QTL software. The criteria for significant and suggestive linkages for single markers were chosen based on Lander and Kruglyak (see methods section of our manuscript).-- Supplemental Dataset 13: Linkage analysis of molecular subphenotype levels quantified in the myocardium. Lod scores after doxorubicin therapy in old mice. The Illumina Mouse Medium Density Linkage Panel Assay was used to genotype 130 F1BX mice at 1449 single nucleotide polymorphisms (SNPs). Genotypes were classified as FVB/FVB (F/F) or FVB/C57BL/6 (F/B). Ultimately, 806 SNPs are informative from the FVB and C57BL/6 mice; the average genomic distance between these SNPs was 9.9 Mb. The genotype proportion among the F1BX mice showed a normal distribution. Linkage analysis was carried out using interval mapping with the expectation-maximization (EM) algorithm and R/QTL software. The criteria for significant and suggestive linkages for single markers were chosen based on Lander and Kruglyak (see methods section of our manuscript).-- Supplemental Dataset 14: Linkage analysis of molecular subphenotype levels quantified in the myocardium. Lod scores after the combined therapy in all mice. The Illumina Mouse Medium Density Linkage Panel Assay was used to genotype 130 F1BX mice at 1449 single nucleotide polymorphisms (SNPs). Genotypes were classified as FVB/FVB (F/F) or FVB/C57BL/6 (F/B). Ultimately, 806 SNPs are informative from the FVB and C57BL/6 mice; the average genomic distance between these SNPs was 9.9 Mb. The genotype proportion among the F1BX mice showed a normal distribution. Linkage analysis was carried out using interval mapping with the expectation-maximization (EM) algorithm and R/QTL software. The criteria for significant and suggestive linkages for single markers were chosen based on Lander and Kruglyak (see methods section of our manuscript).-- Supplemental Dataset 15: Linkage analysis of molecular subphenotype levels quantified in the myocardium. Lod scores after the combined therapy in young mice. The Illumina Mouse Medium Density Linkage Panel Assay was used to genotype 130 F1BX mice at 1449 single nucleotide polymorphisms (SNPs). Genotypes were classified as FVB/FVB (F/F) or FVB/C57BL/6 (F/B). Ultimately, 806 SNPs are informative from the FVB and C57BL/6 mice; the average genomic distance between these SNPs was 9.9 Mb. The genotype proportion among the F1BX mice showed a normal distribution. Linkage analysis was carried out using interval mapping with the expectation-maximization (EM) algorithm and R/QTL software. The criteria for significant and suggestive linkages for single markers were chosen based on Lander and Kruglyak (see methods section of our manuscript).-- Supplemental Dataset 16: Linkage analysis of molecular subphenotype levels quantified in the myocardium. Lod scores after the combined therapy in old mice. The Illumina Mouse Medium Density Linkage Panel Assay was used to genotype 130 F1BX mice at 1449 single nucleotide polymorphisms (SNPs). Genotypes were classified as FVB/FVB (F/F) or FVB/C57BL/6 (F/B). Ultimately, 806 SNPs are informative from the FVB and C57BL/6 mice; the average genomic distance between these SNPs was 9.9 Mb. The genotype proportion among the F1BX mice showed a normal distribution. Linkage analysis was carried out using interval mapping with the expectation-maximization (EM) algorithm and R/QTL software. The criteria for significant and suggestive linkages for single markers were chosen based on Lander and Kruglyak (see methods section of our manuscript).-- Supplemental Dataset 17: Massive genotyping of mouse cohort treated with doxorubicin. The genome-wide scan was carried out at the Spanish National Centre of Genotyping (CeGEN) at the Spanish National Cancer Research Centre (CNIO, Madrid, Spain). The Illumina Mouse Medium Density Linkage Panel Assay was used to genotype 130 F1BX mice at 1449 single nucleotide polymorphisms (SNPs). Genotypes were classified as FVB/FVB (F/F) or FVB/C57BL/6 (F/B). Ultimately, 806 SNPs are informative from the FVB and C57BL/6 mice; the average genomic distance between these SNPs was 9.9 Mb. The genotype proportion among the F1BX mice showed a normal distribution.-- Supplemental Dataset 18: Massive genotyping of mouse cohort treated with the combined therapy. The genome-wide scan was carried out at the Spanish National Centre of Genotyping (CeGEN) at the Spanish National Cancer Research Centre (CNIO, Madrid, Spain). The Illumina Mouse Medium Density Linkage Panel Assay was used to genotype 130 F1BX mice at 1449 single nucleotide polymorphisms (SNPs). Genotypes were classified as FVB/FVB (F/F) or FVB/C57BL/6 (F/B). Ultimately, 806 SNPs are informative from the FVB and C57BL/6 mice; the average genomic distance between these SNPs was 9.9 Mb. The genotype proportion among the F1BX mice showed a normal distribution.-- Supplemental Dataset 19: Linkage analysis of CDA pathophenotypes quantified in the myocardium. Lod scores after doxorubicin therapy in all mice. The Illumina Mouse Medium Density Linkage Panel Assay was used to genotype 130 F1BX mice at 1449 single nucleotide polymorphisms (SNPs). Genotypes were classified as FVB/FVB (F/F) or FVB/C57BL/6 (F/B). Ultimately, 806 SNPs are informative from the FVB and C57BL/6 mice; the average genomic distance between these SNPs was 9.9 Mb. The genotype proportion among the F1BX mice showed a normal distribution. Linkage analysis was carried out using interval mapping with the expectation-maximization (EM) algorithm and R/QTL software. The criteria for significant and suggestive linkages for single markers were chosen based on Lander and Kruglyak (see methods section of our manuscript).-- Supplemental Dataset 20: Linkage analysis of CDA pathophenotypes quantified in the myocardium. Lod scores after doxorubicin therapy in young mice. The Illumina Mouse Medium Density Linkage Panel Assay was used to genotype 130 F1BX mice at 1449 single nucleotide polymorphisms (SNPs). Genotypes were classified as FVB/FVB (F/F) or FVB/C57BL/6 (F/B). Ultimately, 806 SNPs are informative from the FVB and C57BL/6 mice; the average genomic distance between these SNPs was 9.9 Mb. The genotype proportion among the F1BX mice showed a normal distribution. Linkage analysis was carried out using interval mapping with the expectation-maximization (EM) algorithm and R/QTL software. The criteria for significant and suggestive linkages for single markers were chosen based on Lander and Kruglyak (see methods section of our manuscript).-- Supplemental Dataset 21: Linkage analysis of CDA pathophenotypes quantified in the myocardium. Lod scores after doxorubicin therapy in old mice. The Illumina Mouse Medium Density Linkage Panel Assay was used to genotype 130 F1BX mice at 1449 single nucleotide polymorphisms (SNPs). Genotypes were classified as FVB/FVB (F/F) or FVB/C57BL/6 (F/B). Ultimately, 806 SNPs are informative from the FVB and C57BL/6 mice; the average genomic distance between these SNPs was 9.9 Mb. The genotype proportion among the F1BX mice showed a normal distribution. Linkage analysis was carried out using interval mapping with the expectation-maximization (EM) algorithm and R/QTL software. The criteria for significant and suggestive linkages for single markers were chosen based on Lander and Kruglyak (see methods section of our manuscript).-- Supplemental Dataset 22: Linkage analysis of CDA pathophenotypes quantified in the myocardium. Lod scores after the combined therapy in all mice. The Illumina Mouse Medium Density Linkage Panel Assay was used to genotype 130 F1BX mice at 1449 single nucleotide polymorphisms (SNPs). Genotypes were classified as FVB/FVB (F/F) or FVB/C57BL/6 (F/B). Ultimately, 806 SNPs are informative from the FVB and C57BL/6 mice; the average genomic distance between these SNPs was 9.9 Mb. The genotype proportion among the F1BX mice showed a normal distribution. Linkage analysis was carried out using interval mapping with the expectation-maximization (EM) algorithm and R/QTL software. The criteria for significant and suggestive linkages for single markers were chosen based on Lander and Kruglyak (see methods section of our manuscript).-- Supplemental Dataset 23: Linkage analysis of CDA pathophenotypes quantified in the myocardium. Lod scores after the combined therapy in young mice. The Illumina Mouse Medium Density Linkage Panel Assay was used to genotype 130 F1BX mice at 1449 single nucleotide polymorphisms (SNPs). Genotypes were classified as FVB/FVB (F/F) or FVB/C57BL/6 (F/B). Ultimately, 806 SNPs are informative from the FVB and C57BL/6 mice; the average genomic distance between these SNPs was 9.9 Mb. The genotype proportion among the F1BX mice showed a normal distribution. Linkage analysis was carried out using interval mapping with the expectation-maximization (EM) algorithm and R/QTL software. The criteria for significant and suggestive linkages for single markers were chosen based on Lander and Kruglyak (see methods section of our manuscript).-- Supplemental Dataset 24: Linkage analysis of CDA pathophenotypes quantified in the myocardium. Lod scores after the combined therapy in old mice. The Illumina Mouse Medium Density Linkage Panel Assay was used to genotype 130 F1BX mice at 1449 single nucleotide polymorphisms (SNPs). Genotypes were classified as FVB/FVB (F/F) or FVB/C57BL/6 (F/B). Ultimately, 806 SNPs are informative from the FVB and C57BL/6 mice; the average genomic distance between these SNPs was 9.9 Mb. The genotype proportion among the F1BX mice showed a normal distribution. Linkage analysis was carried out using interval mapping with the expectation-maximization (EM) algorithm and R/QTL software. The criteria for significant and suggestive linkages for single markers were chosen based on Lander and Kruglyak (see methods section of our manuscript).-- Supplemental Dataset 25: Human breast cancer cohort-1 genotyping. The association of genetic variants with CDA was evaluated in four patient cohorts p

Intermediate Molecular Phenotypes to Identify Genetic Markers of Anthracycline-Induced Cardiotoxicity Risk.

Cardiotoxicity due to anthracyclines (CDA) affects cancer patients, but we cannot predict who may suffer from this complication. CDA is a complex trait with a polygenic component that is mainly unidentified. We propose that levels of intermediate molecular phenotypes (IMPs) in the myocardium associated with histopathological damage could explain CDA susceptibility, so variants of genes encoding these IMPs could identify patients susceptible to this complication. Thus, a genetically heterogeneous cohort of mice (n = 165) generated by backcrossing were treated with doxorubicin and docetaxel. We quantified heart fibrosis using an Ariol slide scanner and intramyocardial levels of IMPs using multiplex bead arrays and QPCR. We identified quantitative trait loci linked to IMPs (ipQTLs) and cdaQTLs via linkage analysis. In three cancer patient cohorts, CDA was quantified using echocardiography or Cardiac Magnetic Resonance. CDA behaves as a complex trait in the mouse cohort. IMP levels in the myocardium were associated with CDA. ipQTLs integrated into genetic models with cdaQTLs account for more CDA phenotypic variation than that explained by cda-QTLs alone. Allelic forms of genes encoding IMPs associated with CDA in mice, including AKT1, MAPK14, MAPK8, STAT3, CAS3, and TP53, are genetic determinants of CDA in patients. Two genetic risk scores for pediatric patients (n = 71) and women with breast cancer (n = 420) were generated using machine-learning Least Absolute Shrinkage and Selection Operator (LASSO) regression. Thus, IMPs associated with heart damage identify genetic markers of CDA risk, thereby allowing more personalized patient management

Intermediate Molecular Phenotypes to Identify Genetic Markers of Anthracycline-Induced Cardiotoxicity Risk

Cardiotoxicity due to anthracyclines (CDA) affects cancer patients, but we cannot predict who may suffer from this complication. CDA is a complex trait with a polygenic component that is mainly unidentified. We propose that levels of intermediate molecular phenotypes (IMPs) in the myocardium associated with histopathological damage could explain CDA susceptibility, so variants of genes encoding these IMPs could identify patients susceptible to this complication. Thus, a genetically heterogeneous cohort of mice (n = 165) generated by backcrossing were treated with doxorubicin and docetaxel. We quantified heart fibrosis using an Ariol slide scanner and intramyocardial levels of IMPs using multiplex bead arrays and QPCR. We identified quantitative trait loci linked to IMPs (ipQTLs) and cdaQTLs via linkage analysis. In three cancer patient cohorts, CDA was quantified using echocardiography or Cardiac Magnetic Resonance. CDA behaves as a complex trait in the mouse cohort. IMP levels in the myocardium were associated with CDA. ipQTLs integrated into genetic models with cdaQTLs account for more CDA phenotypic variation than that explained by cda-QTLs alone. Allelic forms of genes encoding IMPs associated with CDA in mice, including AKT1, MAPK14, MAPK8, STAT3, CAS3, and TP53, are genetic determinants of CDA in patients. Two genetic risk scores for pediatric patients (n = 71) and women with breast cancer (n = 420) were generated using machine-learning Least Absolute Shrinkage and Selection Operator (LASSO) regression. Thus, IMPs associated with heart damage identify genetic markers of CDA risk, thereby allowing more personalized patient management.Ministerio de Ciencia, Innovación y Universidades (España)European ComissionJunta de Castilla y LeónInstituto de Salud Carlos IIIMinisterio de Economía, Comercio y Empresa (España)Federación Española de Enfermedades RarasDepartamento de Defensa (Estados Unidos)National Institutes of Health (Estados Unidos)Universidad de California (Estados Unidos)Instituto Nacional del Cáncer (Estados Unidos)Fundación "la Caixa"Agencia Estatal de InvestigaciónDepto. de Estadística e Investigación OperativaFac. de FarmaciaTRUEpu