Quantitative Electrochemical DNA Microarray on a Monolith Electrode with Ten Attomolar Sensitivity, 100% Specificity, and Zero Background

Circulating microRNA are promising diagnostic and prognostic biomarkers of disease in quantitative blood tests. A label-free, PCR-free, electrochemical microarray technology on a monolith electrode is described, with 10 attomolar (aM) sensitivity and responsiveness to binding of \u3c1 zeptomole of target to immobilized ssDNA probes with zero background. Specificity is 100% in a mixture with five nonspecific miRNA each with a 103-fold higher concentration. Direct measurement on plasma-derived miRNA without cDNA conversion and PCR demonstrated multiplexing and near-ideal quantitative correlation with an equivalent pure sample. The dynamic range is a target concentration ranging from 10–2 to 103 femtomolar (fM). This PCR-free novel technology can be applied as a test for cancer diagnosis/prognosis to detect 103 copies of a miRNA sequence in RNA extracted from 100 μL of plasma

An international multicenter retrospective analysis of patients with extranodal marginal zone lymphoma and histologically confirmed central nervous system and dural involvement

Marginal zone lymphoma of the central nervous system (CNS MZL) is rare. The clinical features, treatment, and prognosis are not well characterized. We performed a multicenter retrospective study of CNS MZL. Twenty-six patients were identified: half with primary and half with secondary CNS involvement. The median age was 59 years (range 26-78), 62% female and 79% with ECOG performance status ≤ 1. The most common disease site was the dura (50%). Treatment was determined by the treating physician and varied substantially. After a median follow up of 1.9 years, the estimated 2-year progression-free (PFS) and overall survival (OS) rates were 59% and 80%, respectively. Secondary CNS MZL was associated with 2-year OS of 58%. CNS MZL is rare, but relative to other forms of CNS lymphoma, outcomes appear favorable, particularly among the subset of patients with dural presentation and primary CNS presentation

H19 Noncoding RNA, an Independent Prognostic Factor, Regulates Essential Rb-E2F and CDK8-β-Catenin Signaling in Colorectal Cancer

The clinical significance of long noncoding RNAs (lncRNAs) in colorectal cancer (CRC) remains largely unexplored. Here, we analyzed a large panel of lncRNA candidates with The Cancer Genome Atlas (TCGA) CRC dataset, and identified H19 as the most significant lncRNA associated with CRC patient survival. We further validated such association in two independent CRC cohorts. H19 silencing blocked G1-S transition, reduced cell proliferation, and inhibited cell migration. We profiled gene expression changes to gain mechanism insight of H19 function. Transcriptome data analysis revealed not only previously identified mechanisms such as Let-7 regulation by H19, but also RB1-E2F1 function and β-catenin activity as essential upstream regulators mediating H19 function. Our experimental data showed that H19 affects phosphorylation of RB1 protein by regulating gene expression of CDK4 and CCND1. We further demonstrated that reduced CDK8 expression underlies changes of β-catenin activity, and identified that H19 interacts with macroH2A, an essential regulator of CDK8 gene transcription. However, the relevance of H19-macroH2A interaction in CDK8 regulation remains to be experimentally determined. We further explored the clinical relevance of above mechanisms in clinical samples, and showed that combined analysis of H19 with its targets improved prognostic value of H19 in CRC

Quantitative Electrochemical DNA Microarray on a Monolith Electrode with Ten Attomolar Sensitivity, 100% Specificity, and Zero Background

Circulating microRNA are promising diagnostic and prognostic biomarkers of disease in quantitative blood tests. A label-free, PCR-free, electrochemical microarray technology on a monolith electrode is described, with 10 attomolar (aM) sensitivity and responsiveness to binding of \u3c1 zeptomole of target to immobilized ssDNA probes with zero background. Specificity is 100% in a mixture with five nonspecific miRNA each with a 103-fold higher concentration. Direct measurement on plasma-derived miRNA without cDNA conversion and PCR demonstrated multiplexing and near-ideal quantitative correlation with an equivalent pure sample. The dynamic range is a target concentration ranging from 10–2 to 103 femtomolar (fM). This PCR-free novel technology can be applied as a test for cancer diagnosis/prognosis to detect 103 copies of a miRNA sequence in RNA extracted from 100 μL of plasma

Radiation Oncology Education Collaborative Study Group Annual Spring Symposium: Initial Impact and Feedback

The Radiation Oncology Education Collaborative Study Group (ROECSG) is an international collaborative network of radiation oncology (RO) professionals with the goal of improving RO education. This report summarizes the first two ROECSG annual symposia including an overview of presentations and analysis of participant feedback. One-day symposia were held in June 2018 and May 2019. Programs included oral and poster presentations, RO education leadership perspectives, and keynote addresses. Post-symposia surveys were collected. Research presentations were recorded and made available online. The 2018 symposium was had 36 attendees from 25 institutions in three countries. The 2019 symposium had 76 individuals from 41 institutions in five countries. Attendees represented diverse backgrounds including attending physicians (46%), residents (13%), medical students (14%), physicists (2%), nurses (1%), and program coordinators (1%). Fifty-five oral presentations were given with 53 released online. Ninety percent of attendees rated the symposium as improving their knowledge of RO educational scholarship, 98% felt the symposium provided the opportunity to receive feedback on RO education scholarship, and 99% felt that the symposium fostered the development of collaborative RO education projects. ROECSG was rated higher than professional organizations in fostering educational scholarship (p<0.001). All attendees felt that the symposium produced new RO education scholarship ideas and provided unique networking opportunities. The first two ROECSG symposia drew a diverse population of attendees and provided unique opportunities for presentation of RO education scholarship. Future ROECSG symposia will be designed to enhance opportunities to present RO education scholarship and to facilitate networking

The Impact of an Introductory Radiation Oncology Curriculum (IROC) for Radiation Oncology Trainees Across the United States and Canada

Despite interest from both radiation oncology residents and program directors, many residency training programs lack a formalized introductory curriculum to orient incoming radiation oncology residents to the specialty. Using the 6-step model for medical education curriculum development, a structured introductory radiation oncology curriculum (IROC) was created for incoming post-graduate year 2 (PGY-2) radiation oncology residents to address foundational concepts including patient simulation, contouring, and plan evaluation. The curriculum was distributed to 55 training programs across the United States and Canada at the start of the 2018 to 2019 and 2019 to 2020 academic years. Feasibility of curriculum dissemination was assessed via a survey of participating program directors. Curriculum effectiveness was assessed using an anonymous survey of participating residents administered pre- and postcurriculum and consisting of both subjective and objective knowledge-based questions. A total of 236 residents participated in IROC at the start of the 2018 to 2019 and 2019 to 2020 academic years. Of those, 228 of 236 (97%) completed both the pre- and postcurriculum surveys. Of participating residents, the median residency program size was 10 (range, 2-28), and the median number of residents in each program per year was 3 (range, 1-7). At baseline, most PGY-2s (142 of 228, 62%) reported being “not at all” or “slightly” prepared to function in the radiation oncology clinic, and after IROC most (188 of 228, 82%) felt “moderately,” “quite,” or “extremely” prepared. Objective knowledge improved pre- to postcurriculum on a multiple-choice test from 70% to 81% (P < .0001) correct, with improvements observed across all question items. Program directors also reported that the curriculum was easier to use and more effective than prior orientation materials. The implementation of an international introductory curriculum for PGY-2 radiation oncology residents is both feasible and effective. Similar strategies should be employed to enhance and standardize radiation oncology educational initiatives across training programs