Long-term use of low-dose aspirin has been demonstrated to reduce cancer risk, but the duration of necessary medication use remains uncertain. This study aimed to investigate the long-term chemoprotective effect of aspirin among the Chinese population. This population-based study included all aspirin users between 2000 and 2019. Aspirin users were age-sex matched with non-users at a 1:2 ratio. Cancer incidence and mortality were the main outcomes measured. Survival analyses with the Fine-Gray modelling were performed. The chemoprotective effects were measured by the sub-distribution hazard ratios (SHR) with control for the competing risks. A total of 538,147 aspirin users and 968,378 non-users were included, with a mean age of 64.8 years, 9,543,399 person-years of follow-up and 90% of users with 80 mg aspirin. The long-term use of aspirin was associated with a reduced risk of cancer (SHR 0.92, 95% CI 0.91-0.94) and a reduced risk of cancer mortality (SHR 0.80, 95% CI 0.79-0.82). Stronger chemopreventive effects were observed among those who used aspirin for more than 10 years, including risk reductions for lung (SHR 0.56, 95% CI 0.51-0.60), breast (SHR 0.34, 95% CI 0.29-0.38) and colorectal (SHR 0.37, 95% CI 0.33-0.40) cancers, but not for bladder cancer and leukaemia. Low-dose use of aspirin was associated with lower risk of cancer among Chinese. The association was even stronger for those using aspirin for more than 10 years. Prescription of aspirin may be started as early as at age of 40, as the chemoprotective effect also applied for early cancers.

Background & AimsCombined 18F-fluorodeoxyglucose (FDG) and 11C-acetate (dual-tracer) positron emission tomography-computed tomography (PET-CT) is being increasingly performed for the management of hepatocellular carcinoma (HCC), although its role is not well defined. Therefore, we evaluated its effectiveness in (i) staging, (ii) characterization of indeterminate lesions on conventional imaging, and (iii) detection of HCC in patients with unexplained elevations in serum alpha-fetoprotein (AFP) levels.MethodsWe retrospectively assessed 525 consecutive patients from three tertiary centers between 2014 and 2020. For staging, we recorded new lesion detection rates, changes in the Barcelona Clinic Liver Cancer (BCLC) classification, and treatment allocation due to dual-tracer PET-CT. To characterize indeterminate lesions and unexplained elevation of serum AFP levels, the sensitivity and specificity of dual-tracer PET-CT in diagnosing HCC were evaluated. A Multidisciplinary external review and a cost-benefit analysis of patients for metastatic screening were also performed.ResultsDual-tracer PET/CT identified new lesions in 14.3% of 273 staging patients, resulting in BCLC upstaging in 11.7% and treatment modifications in 7.7%. It upstaged 8.1% of 260 patients undergoing metastatic screening, with an estimated savings of US$495 per patient. It had a sensitivity and specificity of 80.7% (95% CI 71.2-88.6%) and 94.8% (95% CI 90.4-98.6%), respectively, for diagnosing HCC in 201 indeterminate lesions. It detected HCC in 45.1% of 51 patients with unexplained elevations in serum AFP concentrations. External review revealed substantial agreement between local and external image interpretation and patient assessment (n=273, κ=0.822; 95% CI 0.803-0.864).ConclusionsDual-tracer PET/CT provides additional value to conventional imaging in HCC patients by improving staging, confirming HCC diagnosis with high accuracy in patients with indeterminate lesions, and detecting HCC in patients with unexplained elevation of serum AFP.• Impact and implications• Dual-tracer PET-CT detected 12% more disease in HCC patients undergoing staging than CT or MRI, resulting in change in treatment in 8% of cases and a cost saving of US$495 per patient.• It is also able to accurately detect HCC in high-risk cases where CT or MRI are equivocal or normal.• Dual-tracer PET/CT provides additional value to conventional imaging in HCC patients by improving staging, confirming HCC diagnosis with high accuracy in patients with indeterminate lesions, and detecting HCC in patients with unexplained elevation of serum AFP.

When people think of creative careers, typical fields that first come to mind are those within the arts and humanities, including design, writing, illustration, photography, advertising, architecture, videography, music, and the performing arts. However, to truly expand the power and reach of fields within science and medicine, including radiology, creativity is profoundly necessary. In this special issue, we aim to showcase innovative projects and efforts in the field of radiology that have the potential to impact our work as clinicians, academic investigators, educators - and humans - across a spectrum of techniques.

PDF file - 322K, Supplemental Figure 1. Disease free survival (DFS) and distant metastasis free survival (DMFS) in breast cancer whole cohort (A), Lymph node negative (B) and lymphnode positive (C). Supplemental Figure 2. Disease free survival (DFS) and distant metastasis free survival (DMFS) in breast cancerlow risk, no adjuvant therapy (A), high risk, received endocrine therapy (B) and high risk, received CMF chemotherapy (C). Supplemental Figure 3. Disease free survival (DFS) and distant metastasis free survival (DMFS) in breast cancerER negative tumours (A), Triple negative tumours (B). Supplemental Figure 4. Clonogenic survival assay (A), Annexin-V FITC assay (B).

BLM m RNA and breast cancer (external validation cohort).

Supplementary Table S1: CDK12 expression in relation to clinicopathological parameters for the unselected TMA series; Supplementary Table S2: CDK12 expression in relation to clinicopathological parameters for the HER2-positive Herceptin treated series; Supplementary Table S3: CDK12 expression in relation to clinicopathological parameters for the METABRIC TMA series; Supplementary Table S4: Univariate and multivariate analysis of CDK12 in the TMA cohorts; Supplementary Table S5: CDK12 mutations in breast cancer. Taken from cBioportal (42,43); Supplementary Table S6: Correlations of CDK12 mutations, methylation, gene expression and ERBB2 copy number in primary breast cancers from TCGA; Supplementary Table S7: Correlations of CDK12 mutations and gene expression of DNA repair genes in primary tumors from METABRIC. P values from heteroscedastic 2-tailed, t-test; Supplementary Table S8: Correlations of CDK12 protein expression, and miRNA expression in primary tumors from METABRIC. Wilcoxon rank P values are corrected for multiple testing; Supplementary Table S9: Correlations of CDK12 protein expression and gene expression of DNA repair genes in primary tumors from METABRIC. Limma analysis corrected for multiple testing; Supplementary Table S10: Association of CDK12 absent and intermediate (0, 2-6) versus high (7-8) expression with DNA repair proteins in unselected and TNBC. P values from Fishers exact test.

Supplementary Tables S1-S9: Supplementary Table S1: Clinicopathological characteristics in the METABRIC cohort Supplementary Table S2: External validation cohorts (pooled n = 2413). Supplementary Table S3: Clinicopathological characteristics of Nottingham cohort Supplementary Table S4: Antigens, primary antibodies, clone, source, optimal dilution and scoring system used for each immunohistochemical marker Supplementary Table S5: BLM (nuclear protein expression) in breast cancer Supplementary Table S6: BLM (cytoplasmic protein expression) in breast cancer Supplementary Table S7: BLM (nuclear and cytoplasmic protein co-expression) in breast cancer Supplementary Table S8. BLM - Rad51 nuclear co-expression and breast cancer Supplementary Table S9: Multivariate analysis in Nottingham cohort.

<p>PDF file - 1391K, Supplemental Methods Fig. S1. Characterization of a polyclonal anti-SHON antibody raised in rabbits. Fig. S2. Specificity of the rabbit SHON polyclonal antibody. Fig. S3. Forced expression of SHON transforms normal human breast epithelial cells in vitro. Fig. S4. Immunocytochemistry with affinity purified SHON antibody. Fig. S5: Microphotographs of SHON expression in normal and breast cancer tissues. Fig. S6 and S7:: Kaplan-Meier survival curves. Fig. S8. SHON is an estrogen inducible gene. Fig. S9. The effects of endogenous SHON depletion significantly on growth in 3D Matrigel. Fig. S10. Depletion of SHON decreased BCL-2 and NF-kB transcription and protein in MCF-7 cells. Fig. S11. Depletion of endogenous SHON by a second SHON siRNA significantly reduced cell proliferation, anchorage independent growth and migration/invasion in MCF-7 cells. Fig. S12. Oncogenic properties of SHON in T47D mammary carcinoma cells. Fig. S13. BCL2 and NF-κB mediate SHON oncogenicity in T47D cells. Table S1. Primer sequences used to detect gene specific transcripts by RT-PCR. Table S2: The sequences of the primers used for real-time PCR. Table S3: Expression of genes in MCF7-SHON relative to MCF7-Vec cells. Table S4. The sequence of oligonucleotides used to construct SHON siRNA in pSilencer 2.1-U6 hygro vector. Table S5. Clinicopathological characteristics of the whole cohort (n=1650). Table S6: Antigens, primary antibodies, clone, source, optimal dilution and scoring system used for each immunohistochemical marker. Table S7: Association between SHON expression and other clinicopathologic variables. Table S8: Multivariate analysis using Cox regression analysis confirms that SHON protein expression is independent prognostic factor.</p>

Supplementary Table (S4). Antigens, primary antibodies, clone, source, optimal dilution and scoring system used for each immunohistochemical marker

Supplementary Table (S1). Clinico-pathological characteristics of early primary triple negative breast cancer (EP-TNBC; n=520)

BLM protein expression and survival.

Supplementary Figure S1: BLM m RNA and breast cancer (external validation cohort). Supplementary Figure S2: Western blots and immunohistochemistry. Supplementary Figure S3: BLM protein expression and survival. Supplementary Figure S4: BLM-Rad51 co-expression and survival. Supplementary Figure S5: BLM-Rad51 co-expression and survival in ER+ breast cancers.

Western blots and immunohistochemistry.

Supplementary Table (S3). Clinico-pathological characteristics of primary locally advanced triple negative breast cancer cohort (PLA-TNBC; n=110)

BLM-Rad51 co-expression and survival.

Supplementary Table (S2). Clinicopathological characteristics of triple negative breast cancer in the METABRIC cohort

<p>PDF file - 104K, Supplemental Table S1: Clinicopathological characteristics of whole breast cancer cohort Supplemental Table S2: Clinicopathological characteristics of validation setSupplementary Table S3: Antigens, primary antibodies, clone, source, optimal dilution and scoring system used for each immunohistochemical marker Supplementary Table S4: siRNA constructs for XRCC1 knockdown</p>

Supplementary Table (S5). ASCO/CAP Guide lines for scoring ER, PR and HER2.

Supplementary Table (S6). A list of the top 100 genes and pathways involved in the HAGE network. Created through the application of a non-linear, artificial neural network (ANN) modelling based, data mining approach applied to the TNBC cohort trial dataset (NCT00455533).