scCircle-seq unveils the diversity and complexity of extrachromosomal circular DNAs in single cells.

Extrachromosomal circular DNAs (eccDNAs) have emerged as important intra-cellular mobile genetic elements that affect gene copy number and exert in trans regulatory roles within the cell nucleus. Here, we describe scCircle-seq, a method for profiling eccDNAs and unraveling their diversity and complexity in single cells. We implement and validate scCircle-seq in normal and cancer cell lines, demonstrating that most eccDNAs vary largely between cells and are stochastically inherited during cell division, although their genomic landscape is cell type-specific and can be used to accurately cluster cells of the same origin. eccDNAs are preferentially produced from chromatin regions enriched in H3K9me3 and H3K27me3 histone marks and are induced during replication stress conditions. Concomitant sequencing of eccDNAs and RNA from the same cell uncovers the absence of correlation between eccDNA copy number and gene expression levels, except for a few oncogenes, including MYC, contained within a large eccDNA in colorectal cancer cells. Lastly, we apply scCircle-seq to one prostate cancer and two breast cancer specimens, revealing cancer-specific eccDNA landscapes and a higher propensity of eccDNAs to form in amplified genomic regions. scCircle-seq is a scalable tool that can be used to dissect the complexity of eccDNAs across different cell and tissue types, and further expands the potential of eccDNAs for cancer diagnostics.

Interorganizational Communication at Mass Gatherings: Professionals' Perceptions during the Planning and Implementation Stage of Marathon Events.

INTRODUCTION: Mass gatherings (MGs) often bring together professionals and organizations that collaborate irregularly or have never engaged in joint working. They involve interaction and communication among multiple and diverse services, which can often prove challenging. Planning such an event is of paramount importance for its success, and interorganizational communication ranks among its most important aspects. Nonetheless, there is limited empirical evidence to support interagency communication in MGs. OBJECTIVE: This study used the 2017 Athens Marathon (Athens, Greece) as the empirical setting to examine how interorganizational communication was perceived among the multiple public health and safety professionals during the planning and implementation phase of the event. METHODS: Data comprised 15 semi-structured in-depth interviews with key informants, direct observations of meetings and the event itself, and documentary analysis. Open coding and thematic analysis were used to analyze the data. RESULTS: Findings indicated three key components of interorganizational communication in such an event: (1) shared situational awareness; (2) interorganizational understanding; and (3) implementing liaison officers. CONCLUSION: This study outlined the factors that influenced interorganizational communication before and during a MG. Practical implications arising from this study may inform the way organizers of marathons and other mass sporting events can engage in effective interorganizational communication.

Organizing Health Care Services for the 2017 "Athens Marathon, The Authentic:" Perspectives on Collaboration among Health and Safety Personnel in the Marathon Command Center.

INTRODUCTION: Mass gatherings pose unique challenges for interorganizational collaboration. The "Athens Marathon, The Authentic" is a 42,195m (26.2mile) race with approximately 18,000 runners that increases annually. On the same day, additional races take place and a grand total of more than 50,000 runners fill the city center of Athens, Greece. Responding effectively to unexpected incidents requires comprehensive planning, clear decision-making structure, and effective collaboration. Nonetheless, there is limited empirical evidence to support interagency collaboration in mass gatherings. PURPOSE: This study used the 2017 Athens Marathon and related races as the empirical setting to examine how interagency collaboration was perceived among the multiple public health and safety professionals involved in the marathon command center. METHODS: Data comprised 10 semi-structured, in-depth interviews with key informants, direct observations of meetings and the event itself, and documentary analysis. Open coding and thematic analysis were used to analyze the data. RESULTS: Findings indicated four key components of interagency collaboration in such an event: organizational culture, team synthesis, on-site spatial planning, and the usage of radio-amateurs. CONCLUSION: This study outlined the factors that shaped interagency collaboration in the context of a mass event. Practical implications arising from this study may inform the ways organizers of marathons and other mass sporting events can engage in effective partnerships and joint working.

Computational modelling of pathogenic protein spread in neurodegenerative diseases.

Pathogenic protein accumulation and spread are fundamental principles of neurodegenerative diseases and ultimately account for the atrophy patterns that distinguish these diseases clinically. However, the biological mechanisms that link pathogenic proteins to specific neural network damage patterns have not been defined. We developed computational models for mechanisms of pathogenic protein accumulation, spread and toxic effects in an artificial neural network of cortical columns. By varying simulation parameters we assessed the effects of modelled mechanisms on network breakdown patterns. Our findings suggest that patterns of network breakdown and the convergence of patterns follow rules determined by particular protein parameters. These rules can account for empirical data on pathogenic protein spread in neural networks. This work provides a basis for understanding the effects of pathogenic proteins on neural circuits and predicting progression of neurodegeneration.