No abstract

Uncharacterized and unannotated open-reading frames, which we refer to as novel open reading frames (nORFs), may sometimes encode peptides that remain unexplored for novel therapeutic opportunities. To our knowledge, no systematic identification and characterization of transcripts encoding nORFs or their translation products in cancer, or in any other physiological process has been performed. We use our curated nORFs database (nORFs.org), together with RNA-Seq data from The Cancer Genome Atlas (TCGA) and Genotype-Expression (GTEx) consortiums, to identify transcripts containing nORFs that are expressed frequently in cancer or matched normal tissue across 22 cancer types. We show nORFs are subject to extensive dysregulation at the transcript level in cancer tissue and that a small subset of nORFs are associated with overall patient survival, suggesting that nORFs may have prognostic value. We also show that nORF products can form protein-like structures with post-translational modifications. Finally, we perform in silico screening for inhibitors against nORF-encoded proteins that are disrupted in stomach and esophageal cancer, showing that they can potentially be targeted by inhibitors. We hope this work will guide and motivate future studies that perform in-depth characterization of nORF functions in cancer and other diseases.

Recent advances in proteogenomics indicate that protein or protein-like products can be encoded by previously uncharacterized Open Reading Frames (ORFs) that we define as Novel Open Reading Frames (nORFs) 1 , 2 . Although it is yet unclear if these protein or protein-like products could possess any significant biological function hopes have been raised to target them for anticancer and antimicrobial therapy 3,4 . In this study, we used computational tools to systematically investigate these novel protein sequences for their propensities toward structural disorder, post-translational modifications (PTM) and mutational densities. We found that these novel proteins have significantly higher disorder and similar PTM frequencies compared to known proteins. Although these regions were found to harbour deleterious mutations, we did not observe any correlation between the pathogenicity of mutations and their location (ordered/disordered) within these novel proteins. This study suggests that these nORFs encode an important class of proteins, that could undergo sequence, structural or regulatory changes during complex diseases, and hence warrant further study. Significance:Certain noncoding regions of the genome are known to make protein-like products. These protein-like products have significantly expanded the number of the cellular proteome but we dont know whether they are capable of performing biological functions. Here in this study, we have investigated all such putative protein-like products and analyzed whether they can form structures, whether hey harbour mutations, and whether they can be regulated by biochemical regulatory processes. Results from this study indicate that indeed these protein-like proteins can perform and be involved in all the above processes.

BackgroundThe number of female and black, Asian and minor ethnicity (BAME) healthcare professionals has significantly increased over the last few decades. While this highlights the National Health Service (NHS) workforce as diverse and inclusive, most senior managers and conference panellists remain mainly men from Caucasian backgrounds.MethodsWe reviewed all publicly available data for major Royal College conferences in the UK from 2015 to 2019 to examine how many of the panellists were men or women and how many were Caucasian or BAME.ResultsOur first finding was that publicly available data were available for only 20 out of 70 conferences (29%). At 60% (n=12) of conferences, there were a predominance of male speakers. The median percentage of female speakers remained between 35% and 46%. There were no all-male panels. At 20% (n=4) of conferences in the sample, there were no BAME speakers. The median percentage of BAME speakers remained between 9% and 18%.ConclusionConference panels do not yet reflect the diversity of the NHS workforce. We all have a duty to promote inclusivity and diversity in medicine. One way to do this is via conferences, through appropriate actions by conference organisers, panellists and delegates.

Results 40 paediatric staff members across all training grades participated in the well-being programme. Staff members provided feedback on the classes via an anonymised questionnaire. 100% of respondents 'strongly agreed' that the sessions improved team morale and bonding. All respondents either 'agreed' or 'strongly agreed' that they found the sessions beneficial. However, half of respondents either 'neither agreed or disagreed' or 'disagreed' that sessions helped reduce burnout. Key limitations of the project included, reduced attendance rate when classes occurred outside of normal working hours and difficulty ensuring consistency of classes (classes were run by trainees and so were dependent on their workload). Conclusions Exercise has a proven benefit in improving wellbeing and work related mental health problems. 4 This quality improvement project has shown a demand for introducing work-based activities and that it is beneficial and well regarded by paediatric staff. However, limitations regarding sustainability of such a programme need to be addressed in order to ensure longevity of the project and further work is needed to address whether this tackles the root cause of burnout.