DataSheet1_Associations of serum cystatin C concentrations with total mortality and mortality of 12 site-specific cancers.docx

Purpose:Cystatin C (CysC), beyond its biomarker role of renal function, has been implicated in various physical and pathological activities. However, the impact of serum CysC on cancer mortality in a general population remains unknown. We aimed to examine the associations of serum CysC concentrations with total mortality and mortality of 12 site-specific cancers.Methods:We included 241,008 participants of the UK Biobank cohort with CysC measurements who had normal creatinine-based estimated glomerular filtration rates and were free of cancer and renal diseases at baseline (2006–2010). Death information was obtained from the National Health Service death records through 28 February 2021. Multivariable Cox proportional hazards models were used to compute hazard ratios (HR) per one standard deviation increase in log-transformed CysC concentrations and 95% confidence intervals (95% CI) for mortality.Results:Over a median follow-up of 12.1 (interquartile range, 11.3–12.8) years, 5,744 cancer deaths occurred. We observed a positive association between serum CysC concentrations and total cancer mortality (HR = 1.16, 95% CI: 1.12–1.20). Specifically, participants with higher serum CysC concentrations had increased mortality due to lung cancer (HR = 1.12, 95% CI: 1.05–1.20), blood cancer (HR = 1.29, 95% CI: 1.16–1.44), brain cancer (HR = 1.19, 95% CI: 1.04–1.36), esophageal cancer (HR = 1.20, 95% CI: 1.05–1.37), breast cancer (HR = 1.18, 95% CI: 1.03–1.36), and liver cancer (HR = 1.49, 95% CI: 1.31–1.69).Conclusion:Our findings indicate that higher CysC concentrations are associated with increased mortality due to lung, blood, brain, esophageal, breast, and liver cancers. Future studies are necessary to clarify underlying mechanisms.</p

Table1_Genetically predicted circulating levels of cytokines and the risk of oral cavity and pharyngeal cancer: a bidirectional mendelian-randomization study.XLSX

Background: Epidemiological research has established associations between various inflammatory cytokines and the occurrence of oral cancer and oropharyngeal cancer (OCPC). We performed a Mendelian randomization (MR) analysis to systematically investigate the causal relationship between inflammatory cytokines and OCPC.Methods: We performed a bidirectional two-sample MR analysis using OCPC from 12 studies (6,034 cases and 6,585 controls) and genome-wide association study (GWAS) results for 41 serum cytokines from 8,293 Finns, respectively. Inverse variance weighting was used as the primary MR method and four additional MR methods (MR Egger, Weighted median, Simple mode, Weighted mode) were used to examine genetic associations between inflammatory traits and OCPC, and Cochran’s Q test, MR-Egger intercept, leave-one-out analysis, funnel plot, and multivariate MR (MVMR) analysis were used to assess the MR results.Results: The results suggested a potential association between high gene expression of Macrophage inflammatory protein-1α (MIP1α/CCL3) and an increased risk of OCPC (Odds Ratio (OR): 1.71, 95% Confidence Interval (CI): 1.09–2.68, p = 0.019). Increasing the expression levels of the interleukin-7 (IL-7) gene by 1 standard deviation reduced the risk of OCPC (OR: 0.64, 95%CI: 0.48–0.86, p = 0.003). In addition, multivariate Mendelian randomization analysis also showed the same results (MIP1α/CCL3, OR: 1.002, 95% CI: 0.919–1.092, p = 0.044; IL-7, OR: 0.997, 95% CI: 0.994–0.999, p = 0.011). Conversely, there was a positive correlation between genetic susceptibility to OCPC and an increase in Interleukin-4 (IL-4) (OR: 1.04, 95%CI: 1.00–1.08, p = 0.027).Conclusion: Our study systematically assessed the association between inflammatory cytokines and the risk of OCPC. We identified two upstream regulatory factors (IL-7 and CCL3) and one downstream effector factor (IL-4) that were associated with OCPC, offering potential avenues for the development of novel treatments.</p

Image1_Genetically predicted circulating levels of cytokines and the risk of oral cavity and pharyngeal cancer: a bidirectional mendelian-randomization study.pdf

Background: Epidemiological research has established associations between various inflammatory cytokines and the occurrence of oral cancer and oropharyngeal cancer (OCPC). We performed a Mendelian randomization (MR) analysis to systematically investigate the causal relationship between inflammatory cytokines and OCPC.Methods: We performed a bidirectional two-sample MR analysis using OCPC from 12 studies (6,034 cases and 6,585 controls) and genome-wide association study (GWAS) results for 41 serum cytokines from 8,293 Finns, respectively. Inverse variance weighting was used as the primary MR method and four additional MR methods (MR Egger, Weighted median, Simple mode, Weighted mode) were used to examine genetic associations between inflammatory traits and OCPC, and Cochran’s Q test, MR-Egger intercept, leave-one-out analysis, funnel plot, and multivariate MR (MVMR) analysis were used to assess the MR results.Results: The results suggested a potential association between high gene expression of Macrophage inflammatory protein-1α (MIP1α/CCL3) and an increased risk of OCPC (Odds Ratio (OR): 1.71, 95% Confidence Interval (CI): 1.09–2.68, p = 0.019). Increasing the expression levels of the interleukin-7 (IL-7) gene by 1 standard deviation reduced the risk of OCPC (OR: 0.64, 95%CI: 0.48–0.86, p = 0.003). In addition, multivariate Mendelian randomization analysis also showed the same results (MIP1α/CCL3, OR: 1.002, 95% CI: 0.919–1.092, p = 0.044; IL-7, OR: 0.997, 95% CI: 0.994–0.999, p = 0.011). Conversely, there was a positive correlation between genetic susceptibility to OCPC and an increase in Interleukin-4 (IL-4) (OR: 1.04, 95%CI: 1.00–1.08, p = 0.027).Conclusion: Our study systematically assessed the association between inflammatory cytokines and the risk of OCPC. We identified two upstream regulatory factors (IL-7 and CCL3) and one downstream effector factor (IL-4) that were associated with OCPC, offering potential avenues for the development of novel treatments.</p

Additional file 1 of Additive interaction between birth asphyxia and febrile seizures on autism spectrum disorder: a population-based study

Supplementary Material 1: Table S1. Logistic regression: associations between BA/FS and ASD, including age and sex stratification in all three statistical model

Can galls evolve toward a simpler morphology: a test of disruptive selection on gall morphology driven by parasitoid wasp

Gall evolution is not a one-way path. Our investigations revealed that a chestnut gall wasp employed contrasting defense strategies: simple galls use camouflage to evade detection, while complex galls sacrifice their outer layer to protect the core larvae. Both forms are equally effective against parasitoids, suggesting that gall morphology has undergone disruptive selection, rather than the commonly accepted directional selection favoring more complex galls.</p

Additional file 1 of Analytical performance of Envisia: a genomic classifier for usual interstitial pneumonia

RNA-seq raw counts of samples used in Envisia analytical verification studies. This file includes the raw expression counts of 190 classifier genes across all samples (n=292) used in the analytical verification studies described in this manuscript; each row represents a gene and each column represents a sample. (CSV 199 kb