Purpose A major challenge in platinum-based cancer therapy is the clinical management of chemoresistant tumors, which have a largely unknown pathogenesis at the level of epigenetic regulation. Experimental Design We evaluated the potential of using global loss of 5-hydroxymethylcytosine (5-hmC) levels as a novel diagnostic and prognostic epigenetic marker to better assess platinum-based chemotherapy response and clinical outcome in high-grade serous tumors (HGSOC), the most common and deadliest subtype of ovarian cancer. Furthermore, we identified a targetable pathway to reverse these epigenetic changes, both genetically and pharmacologically. Results This study shows that decreased 5-hmC levels are an epigenetic hallmark for malignancy and tumor progression in HGSOC. In addition, global 5-hmC loss is associated with a decreased response to platinum-based chemotherapy, shorter time to relapse, and poor overall survival in patients newly diagnosed with HGSOC. Interestingly, the rescue of 5-hmC loss restores sensitivity to platinum chemotherapy in vitro and in vivo, decreases the percentage of tumor cells with cancer stem cell markers, and increases overall survival in an aggressive animal model of platinum-resistant disease. Conclusions Consequently, a global analysis of patient 5-hmC levels should be included in future clinical trials, which use pretreatment with epigenetic adjuvants to elevate 5-hmC levels and improve the efficacy of current chemotherapies. Identifying prognostic epigenetic markers and altering chemotherapeutic regimens to incorporate DNMTi pretreatment in tumors with low 5-hmC levels could have important clinical implications for newly diagnosed HGSOC disease.

Misinformation has been existed for centuries, though emerge as a severe concern in the age of social media, and particularly during COVID-19 global pandemic. As the pandemic approached, a massive influx of mixed quality data appeared on social media, which had adverse effects on society. This study highlights the possible factors contributing to the sharing and spreading misinformation through social media during the crisis. Preferred Reporting Items and Meta-Analysis guidelines were used for systematic review. Anxiety or risk perception associated with COVID-19 was one of the significant motivators for misinformation sharing, followed by entertainment, information seeking, sociability, social tie strength, self-promotion, trust in science, self-efficacy, and altruism. WhatsApp and Facebook were the most used platforms for spreading rumors and misinformation. The results indicated five significant factors associated with COVID-19 misinformation sharing on social media, including socio-demographic characteristics, financial considerations, political affiliation or interest, conspiracy ideation, and religious factors. Misinformation sharing could have profound consequences for individual and society and impeding the efforts of government and health institutions to manage the crisis. This SLR focuses solely on quantitative studies, hence, studies are overlooked from a qualitative standpoint. Furthermore, this study only looked at the predictors of misinformation sharing behavior during COVID-19. It did not look into the factors that could curb the sharing of misinformation on social media platforms as a whole. The study’s findings will help the public, in general, to be cautious about sharing misinformation, and the health care workers, and institutions, in particular, for devising strategies and measures to reduce the flow of misinformation by releasing credible information through concerned official social media accounts. The findings will be valuable for health professionals and government agencies to devise strategies for handling misinformation during public health emergencies.

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<div>Abstract<p><b>Purpose:</b> A major challenge in platinum-based cancer therapy is the clinical management of chemoresistant tumors, which have a largely unknown pathogenesis at the level of epigenetic regulation.</p><p><b>Experimental Design:</b> We evaluated the potential of using global loss of 5-hydroxymethylcytosine (5-hmC) levels as a novel diagnostic and prognostic epigenetic marker to better assess platinum-based chemotherapy response and clinical outcome in high-grade serous tumors (HGSOC), the most common and deadliest subtype of ovarian cancer. Furthermore, we identified a targetable pathway to reverse these epigenetic changes, both genetically and pharmacologically.</p><p><b>Results:</b> This study shows that decreased 5-hmC levels are an epigenetic hallmark for malignancy and tumor progression in HGSOC. In addition, global 5-hmC loss is associated with a decreased response to platinum-based chemotherapy, shorter time to relapse, and poor overall survival in patients newly diagnosed with HGSOC. Interestingly, the rescue of 5-hmC loss restores sensitivity to platinum chemotherapy <i>in vitro</i> and <i>in vivo</i>, decreases the percentage of tumor cells with cancer stem cell markers, and increases overall survival in an aggressive animal model of platinum-resistant disease.</p><p><b>Conclusions:</b> Consequently, a global analysis of patient 5-hmC levels should be included in future clinical trials, which use pretreatment with epigenetic adjuvants to elevate 5-hmC levels and improve the efficacy of current chemotherapies. Identifying prognostic epigenetic markers and altering chemotherapeutic regimens to incorporate DNMTi pretreatment in tumors with low 5-hmC levels could have important clinical implications for newly diagnosed HGSOC disease. <i>Clin Cancer Res; 24(6); 1389–401. ©2017 AACR</i>.</p></div>

<p>Western blot analysis of A2780, IF quantification, immunoblot quantification in human and murine cell lines</p>