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Supplemental Material, sj-docx-1-cpa-10.1177_0706743720982428 for Suicide-related Twitter Content in Response to a National Mental Health Awareness Campaign and the Association between the Campaign and Suicide Rates in Ontario: Le contenu Lié au Suicide Sur Twitter en Réponse à Une Campagne Nationale de Sensibilisation à la Santé Mentale et à L’association Entre la Campagne et le Taux de Suicide en Ontario by David Côté, Marissa Williams, Rabia Zaheer, Thomas Niederkrotenthaler, Ayal Schaffer and Mark Sinyor in The Canadian Journal of Psychiatry

Supplemental material, Appendix_1 for The association between Twitter content and suicide by Mark Sinyor, Marissa Williams, Rabia Zaheer, Raisa Loureiro, Jane Pirkis, Marnin J Heisel, Ayal Schaffer, Donald A Redelmeier, Amy H Cheung and Thomas Niederkrotenthaler in Australian & New Zealand Journal of Psychiatry

Colorectal cancer (CRC) is a leading cancer globally; therefore, early diagnosis and surveillance of this cancer are of paramount importance. Current methods of CRC diagnosis rely heavily on endoscopy or radiological imaging. Noninvasive tests including serum detection of the carcinoembryonic antigen (CEA) and faecal occult blood testing (FOBT) are associated with low sensitivity and specificity, especially at early stages. DNA methylation biomarkers have recently been found to have higher accuracy in CRC detection and enhanced prediction of prognosis and chemotherapy response. The most widely studied biomarker in CRC is methylated septin 9 (SEPT9), which is the only FDA-approved methylation-based biomarker for CRC. Apart from SEPT9, other methylated biomarkers including tachykinin-1 (TAC1), somatostatin (SST), and runt-related transcription factor 3 (RUNX3) have been shown to effectively detect CRC in a multitude of sample types. This review will discuss the performances of various methylated biomarkers used for CRC diagnosis and monitoring, when used alone or in combination.

Supplemental material, supplementary_references for Media depictions of possible suicide contagion among celebrities: A cause for concern and potential opportunities for prevention by Mark Sinyor, Marissa Williams and Thomas Niederkrotenthaler in Australian & New Zealand Journal of Psychiatry

Malignant Pleural Mesothelioma (MPM) is an aggressive asbestos related malignancy. The global downregulation of microRNA (miRNA) expression is common in MPM, however, the mechanisms driving the downregulation of some tumour suppressor miRNAs, including the miR-15 family, are yet to be clarified. In this study, multiple mechanisms, including a combination of genomic deletion, DNA methylation and transcriptional repression, were demonstrated to lead to downregulation of miR-15a/16-1, miR-15b/16-2, miR-193a-3p, and miR-34c. The c-Myc oncogene was evidenced to transcriptionally repress expression of miR-15/16, predominately via association with the miR-15b/16-2 locus. The majority of MPM patients become refractory to the first-line treatment of pemetrexed and cisplatin chemotherapy due to chemo-resistance. MiRNAs belonging to the miR-15/16 and -34 families have been previously implicated in the development of drug resistance in other malignancies but their role in MPM chemo-resistance is largely unexplored. The expression of miR-15a/16-1 and miR-34a was downregulated in cell lines with acquired resistance to chemotherapy. Restoration of miRNA expression by mimic transfection led to the sensitisation of MPM cell lines to chemotherapy induced cytotoxicity and apoptosis, partly via repression of BCL2. Immune checkpoint inhibition of the PD-1/PD-L1 axis is an emerging therapeutic field in MPM. PD-L1 expression is upregulated and associated with poor prognosis in MPM, but the molecular mechanisms causing its dysregulation are poorly understood. In this study, reduced miRNA expression was related to elevated PD-L1 levels in the MPM patient panel. Restoration of miRNA expression led to downregulation of PD-L1 mRNA and protein expression via association with the 3’UTR region of the PD-L1 mRNA in MPM cell lines. Results from this study, and others, suggests that restoration of aberrant miRNA expression has the potential to improve, or lead to new targets for MPM therapy.

In light of the high incidence and mortality rates of cancer, early and accurate diagnosis is an important priority for assigning optimal treatment for each individual with suspected illness. Biomarkers are crucial in the screening of patients with a high risk of developing cancer, diagnosing patients with suspicious tumours at the earliest possible stage, establishing an accurate prognosis, and predicting and monitoring the response to specific therapies. Epigenetic alterations are innovative biomarkers for cancer, due to their stability, frequency, and noninvasive accessibility in bodily fluids. Epigenetic modifications are also reversible and potentially useful as therapeutic targets. Despite this, there is still a lack of accurate biomarkers for the conclusive diagnosis of most cancer types; thus, there is a strong need for continued investigation to expand this area of research. In this review, we summarise current knowledge on methylated DNA and its implications in cancer to explore its potential as an epigenetic biomarker to be translated for clinical application. We propose that the identification of biomarkers with higher accuracy and more effective detection methods will enable improved clinical management of patients and the intervention at early-stage disease.

Top 20 Enriched microRNA Families Extracted from the Four Gene Expression Datasets. Table S2. Pathway Enrichment Analysis of Gene Targets of the miR-17 family members. Table S3. Primers and TaqMan Assay IDs for RT-qPCR and siRNA and Mimic Sequences. Table S4. Characteristics of Patients Analyzed in Fig. 2h and i. Table S5. Individual P values for Fig. 3a, f and g. Figure S1. TGFBR2 mRNA down regulated followed miR-17-5p transfection. Figure S2. MPM cell viability was not affected by transfection with miR-17-5p mimic or siRNA. Figure S3. Effect of KCNMA1 down-regulation on cell cycle in MPM cells. Figure S4. KCNMA1 down-regulation and miR-17-5p did not induce MPM cell apoptosis. Figure S5. Migration of MPM cell lines treated with miR-17-5p mimic or KCNMA1 siRNAs. Figure S6. Invasion of MPM cell lines treated with miR-17-5-5p mimic or KCNMA1 siRNAs. Figure S7. Paxilline did not sensitize MPM cells to cisplatin or gemcitabine. (DOCX 10063 kb)