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... Consent for minors (age < 18) has been obtained from parents. Number of patients for the study has been stratified by power calculation with 90% power estimated for RA/control cohorts with over 28 patients each [19]. For disease scoring and sampling included in longitudinal study, the visit dates were within 10-day range from given time point. ...

... Data distribution normality has been confirmed by Shapiro-Wilk normality test in R [19]. Differences were analyzed for statistical significance with OLS and ANOVA in R. A P value of less than 0.05 was considered statistically significant. ...

... S1 Table. Triplicate results for ELISA: RA (samples 1-10) and HC (samples [11][12][13][14][15][16][17][18][19][20]. (PDF) S2 Appendix. ...

Rheumatoid arthritis (RA), caused by the abnormal recognition of human joint cells by autoimmune antibodies, remains the world's most prevalent autoimmune disease, with over five million people affected and as much as 4% of the population at risk of RA. To prevent rapid disease development, hormonal and anti-inflammatory therapies require fast and reliable RA diagnosis. However, difficulty in detecting early specific biomarkers for RA means that it is unclear when treatment needs to begin. Here, we combined synthesis of citrullinated peptide epitopes with molecular diagnostics to verify a new specific biomarker for early RA diagnosis and flare prediction. A fibrinogen-derived 21-amino-acid-long citrullinated peptide showed high reactivity toward autoantibodies in RA samples. Additionally, the level of antibodies to this epitope was elevated prior to flares. In contrast, other citrullinated protein variants had lower reactivity and poorer sensitivity to disease activity. In conclusion, fibrinogen-derived epitope E2 subjected to citrullination facilitated a reliable RA diagnosis with a strong correlation to disease activity. This is of a high value for the diagnosis and management of RA patients who respond poorly to treatment.

... For this pilot study, the sample size was calculated for a study comparing two independent groups with a dichotomous endpoint (incidence of SSI), with an estimated incidence of 40% in the control group. For a power of 80%, this calculated that we needed to include at least 14 patients in each group [19]. ...

Many medical schools practice commemorative ceremonies to honor body donors. Attitudes of medical education stakeholders toward these ceremonies have not yet been fully investigated. The aim of this study was to explore anatomy students' attitudes toward commemorations at a multicultural institution which has not introduced these ceremonies yet. A survey was carried out on different groups of anatomy students that were exposed and not yet exposed to human remains. The survey was used to record basic demographic data from the respondents, ask if they would support the establishment of an anatomy commemoration and in which format. A total of 756 anatomy students participated in the survey (response rate 69.8%). The majority (76.3%) were in favor of introducing a commemoration for donors. The associations of students' gender, attitude toward body donation, and level of exposure to human remains with attitudes toward commemoration for donors were identified (P < 0.05), whereas ethnicity and religion seemed to have no influence on attitudes (P > 0.05). Most students believed that anatomy staff and students should organize the commemoration. There was a preference for the commemoration to be secular, identities of donors to not be revealed, and not recorded for social media. The support for the establishment of commemorations transcended cultural and religious differences and confirmed students' respectful attitude toward donors. Anatomy commemorations seem to have potential not only to engage students with one another, and donor families, but to pave the way for students to become life‐long ethical and empathetic learners and practitioners.

  • Sung Won Han
  • Ji Young Ahn
  • Soobin Lee
  • Ji-Yun Lee

Colon cancer has been well studied using a variety of molecular techniques, including whole genome sequencing. However, genetic markers that could be used to predict lymph node (LN) involvement, which is the most important prognostic factor for colon cancer, have not been identified. In the present study, we compared LN(+) and LN(−) colon cancer patients using differential gene expression and network analysis. Colon cancer gene expression data were obtained from the Cancer Genome Atlas and divided into two groups, LN(+) and LN(−). Gene expression networks were constructed using LASSO (Least Absolute Shrinkage and Selection Operator) regression. We identified hub genes, such as APBB1, AHSA2, ZNF767, and JAK2, that were highly differentially expressed. Survival analysis using selected hub genes, such as AHSA2, CDK10, and CWC22, showed that their expression levels were significantly associated with the survival rate of colon cancer patients, which indicates their possible use as prognostic markers. In addition, protein-protein interaction network, GO enrichment, and KEGG pathway analysis were performed with selected hub genes from each group to investigate the regulatory relationships between hub genes and LN involvement in colon cancer; these analyses revealed differences between the LN(−) and LN(+) groups. Our network analysis may help narrow down the search for novel candidate genes for the treatment of colon cancer, in addition to improving our understanding of the biological processes underlying LN involvement. All R implementation codes are available at journal website as Supplementary Materials.

The retinoid cycle is a metabolic process in the vertebrate retina that continuously regenerates 11-cis-retinal (11-cisRAL) from the all-trans-retinal (atRAL) isomer. AtRAL accumulation can cause photoreceptor degeneration and irreversible visual dysfunction associated with incurable blinding retinal diseases such as stargardt disease, retinitis pigmentosa (RP), and atrophic age-related macular degeneration (AMD). The underlying cellular mechanisms leading to retinal degeneration remain uncertain, although previous studies have shown that atRAL promotes calcium influx associated with cell apoptosis. To identify compounds that mitigate the effects of atRAL toxicity, here we developed an unbiased and robust image-based assay that can detect changes in intracellular calcium levels in U2OS cells. Using our assay in a high-throughput screen of 2400 compounds, we noted that selective estrogen receptor modulators (SERMs) potentpotently stabilize intracellular calcium and thereby counteract atRAL-induced toxicity. In a light-induced retinal degeneration mouse model (Abca4−/−Rdh8−/−), raloxifene (a benzothiophene-type scaffold SERM) prevented the onset of photoreceptor apoptosis and thus protected the retina from degeneration. The minor structural differences between raloxifene and one of its derivatives (Y 134) had a major impact on calcium homeostasis after atRAL exposure in vitro, and we verified this differential impact in vivo. In summary, the SERM raloxifene has structural and functional neuroprotective effects in the retina. We propose that the highly sensitive image-based assay developed here could be applied for the discovery of additional drug candidates preventing photoreceptor degeneration.

  • Daniel L. Gillen
  • S.S. Emerson

Transitivity is an important property of any statistic applied in the setting of multi-arm clinical trials and non-inferiority trials where active-controls are used. The G[rho],[gamma] class of weighted logrank statistics for right-censored survival data as proposed by Fleming and Harrington [1991. Counting Processes and Survival Analysis. Wiley, New York] is often used to improve efficiency in the setting of nonproportional hazards. These statistics utilize a weighting scheme based upon the combined Kaplan-Meier estimate of survival for all comparison groups. Members of this class include the usual logrank statistic as well as the generalized Wilcoxon statistic. It is demonstrated that all useful members of this class exhibit nontransitivity. We propose a general modification of the G[rho],[gamma] statistic which asymptotically achieves transitivity.

The origins of statistical computing. www.amstat.org/about/statisticians inhistory/index.cfm?fuseaction= paperinfo&PaperID=4

  • D A Grier

Grier, D. A. (n.d.) The origins of statistical computing. www.amstat.org/about/statisticians inhistory/index.cfm?fuseaction= paperinfo&PaperID=4 (last accessed July 2011).