bronchiectasis. High tumor mRNA levels of the EGFR ligands amphiregulin (AREG) and epiregulin (EREG) are associated with anti-EGFR agent response in metastatic colorectal cancer (mCRC). However, ligand RNA assays have not been adopted into routine practice due to issues with analytic precision and practicality. We investigated whether AREG/EREG IHC could predict benefit from the anti-EGFR agent panitumumab. Artificial intelligence algorithms were developed to assess AREG/EREG IHC in 274 patients from the PICCOLO trial of irinotecan with or without panitumumab (Ir vs. IrPan) in wild-type mCRC. The primary endpoint was progression-free survival (PFS). Secondary endpoints were RECIST response rate (RR) and overall survival (OS). Models were repeated adjusting separately for mutation status and primary tumor location (PTL). High ligand expression was associated with significant PFS benefit from IrPan compared with Ir [8.0 vs. 3.2 months; HR, 0.54; 95% confidence interval (CI), 0.37-0.79; = 0.001]; whereas low ligand expression was not (3.4 vs. MK-8776 4.4 months; HR, 1.05; 95% CI, 0.74-1.49; = 0.78). The ligand-treatment interaction was significant ( = 0.02) and remained significant after adjustment for -mutation status and PTL. Likewise, RECIST RR was significantly improved in patients with high ligand expression (IrPan vs. Ir 48% vs. 6%; < 0.0001) but not those with low ligand expression (25% vs. 14%; = 0.10; = 0.01). The effect on OS was similar but not statistically significant. AREG/EREG IHC identified patients who benefitted from the addition of panitumumab to irinotecan chemotherapy. IHC is a practicable assay that may be of use in routine practice.AREG/EREG IHC identified patients who benefitted from the addition of panitumumab to irinotecan chemotherapy. IHC is a practicable assay that may be of use in routine practice. We aimed to explore the associations between type 2 diabetes onset age and cardiovascular disease (CVD) and all-cause mortality in the Chinese population. This study included 101,080 participants free of prevalent diabetes and CVD at baseline from the Kailuan Study. All participants were monitored biennially until 31 December 2017. During follow-up, 11,384 participants were diagnosed as having type 2 diabetes. For each case subject, one control subject was randomly selected, matched for age (± 1 years) and sex. The final analysis comprised 10,777 case-control pairs. Weighted Cox regression models were used to evaluate the average hazard ratios (AHRs) and 95% CIs of incident CVD and all-cause mortality among patients with new-onset type 2 diabetes versus control subjects across age-groups. During a median follow-up of 5.57 years, 1,794 incident events (907 CVD events, of which there were 725 strokes and 887 deaths) occurred. After adjustment for potential confounders, participants with type 2 diabetes diagnosed at age <45 years had the highest relative risks of CVD and all-cause mortality relative to the matched control subjects, with AHRs of 3.21 (95% CI 1.18-8.72) for CVD, 2.99 (95% CI 1.01-9.17) for stroke, and 4.79 (95% CI 1.95-11.76) for all-cause mortality. The risks gradually attenuated with each decade increase in type 2 diabetes onset age. The relative risks of CVD and all-cause mortality differed across type 2 diabetes onset age-groups, and the associations were more evident in younger-onset type 2 diabetes.The relative risks of CVD and all-cause mortality differed across type 2 diabetes onset age-groups, and the associations were more evident in younger-onset type 2 diabetes. Haemorrhoidal disease (HEM) affects a large and silently suffering fraction of the population but its aetiology, including suspected genetic predisposition, is poorly understood. We report the first genome-wide association study (GWAS) meta-analysis to identify genetic risk factors for HEM to date. We conducted a GWAS meta-analysis of 218 920 patients with HEM and 725 213 controls of European ancestry. Using GWAS summary statistics, we performed multiple genetic correlation analyses between HEM and other traits as well as calculated HEM polygenic risk scores (PRS) and evaluated their translational potential in independent datasets. Using functional annotation of GWAS results, we identified HEM candidate genes, which differential expression and coexpression in HEM tissues were evaluated employing RNA-seq analyses. The localisation of expressed proteins at selected loci was investigated by immunohistochemistry. We demonstrate modest heritability and genetic correlation of HEM with several other diseases from the GI, neuroaffective and cardiovascular domains. HEM PRS validated in 180 435 individuals from independent datasets allowed the identification of those at risk and correlated with younger age of onset and recurrent surgery. We identified 102 independent HEM risk loci harbouring genes whose expression is enriched in blood vessels and GI tissues, and in pathways associated with smooth muscles, epithelial and endothelial development and morphogenesis. Network transcriptomic analyses highlighted HEM gene coexpression modules that are relevant to the development and integrity of the musculoskeletal and epidermal systems, and the organisation of the extracellular matrix. HEM has a genetic component that predisposes to smooth muscle, epithelial and connective tissue dysfunction.HEM has a genetic component that predisposes to smooth muscle, epithelial and connective tissue dysfunction.Recommended colorectal cancer screening modalities vary with respect to safety, efficacy, and cost. Better understanding of the factors that influence patient preference is, therefore, critical for improving population adherence to colorectal cancer screening. To address this knowledge gap, we conducted a panel survey focused on three commonly utilized colorectal cancer screening options [fecal immunochemical test or guaiac-based fecal occult blood test (FIT/gFOBT), multi-target stool DNA (mt-sDNA) test, and colonoscopy] with a national sample of U.S. adults, ages 40-75 years and at average risk of colorectal cancer, in November 2019. Of 5,097 panelists invited to participate, 1,595 completed the survey (completion rate, 31.3%). Our results showed that when presented a choice between two colorectal cancer screening modalities, more respondents preferred mt-sDNA (65.4%) over colonoscopy, FIT/gFOBT (61%) over colonoscopy, and mt-sDNA (66.9%) over FIT/gFOBT. Certain demographic characteristics and awareness of and/or experience with various screening modalities influenced preferences.