Multivalent interaction of ESCO2 with the replication machinery is required for sister chromatid cohesion in vertebrates.

The tethering together of sister chromatids by the cohesin complex ensures their accurate alignment and segregation during cell division. In vertebrates, sister chromatid cohesion requires the activity of the ESCO2 acetyltransferase, which modifies the Smc3 subunit of cohesin. It was shown recently that ESCO2 promotes cohesion through interaction with the MCM replicative helicase. However, ESCO2 does not significantly colocalize with the MCM complex, suggesting there are additional interactions important for ESCO2 function. Here we show that ESCO2 is recruited to replication factories, sites of DNA replication, through interaction with PCNA. We show that ESCO2 contains multiple PCNA-interaction motifs in its N terminus, each of which is essential to its ability to establish cohesion. We propose that multiple PCNA-interaction motifs embedded in a largely flexible and disordered region of the protein underlie the unique ability of ESCO2 to establish cohesion between sister chromatids precisely as they are born during DNA replication.

Evaluation of spin in the abstracts of systematic reviews and meta-analyses related to the treatment of proximal humerus fractures.

BACKGROUND: Research has shown that many physicians rely solely on abstracts to make clinical decisions. However, many abstracts have been shown to be misleading. The primary objective of this study was to identify the prevalence of spin - bias towards particular results - within the abstracts of systematic reviews and meta-analyses pertaining to the treatment of proximal humerus fractures, one of the most common osteoporotic fractures among elderly patients. METHODS: We systematically searched MEDLINE and Embase databases to identify systematic reviews and meta-analyses examining the treatment of proximal humerus fractures. Screening and data extraction occurred in a masked, duplicate fashion. The nine most severe types of spin that occur within abstracts were extracted along with study characteristics, including journal recommendations to adhere to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and year in which the review was performed, to identify potential associations. We subsequently explored the association between spin and the methodological quality of a systematic review using the revised A MeaSurement Tool to Assess systematic Reviews (AMSTAR 2) appraisal instrument. RESULTS: Our search retrieved 505 articles, of which 73 systematic reviews met inclusion criteria. We found that 34.2% (25/73) of the included systematic reviews contained spin. Spin type 3 (selective reporting of or overemphasis on efficacy outcomes or analysis favoring the beneficial effect of the experimental intervention) was the most common type identified (12/73, 16.4%). Three spin types were not identified in any of the abstracts. Spin was 3.2 (OR 3.2; 95% CI, 1.02-10.02) times more likely to be present in systematic reviews published in journals recommending adherence to PRISMA. Furthermore, the odds of an abstract containing spin was 1.25 (OR 1.25; 95% CI, 1.02-1.52) times more likely to be present in systematic reviews for each year after 2000. No other study characteristics were associated with spin. The methodological quality of 24 studies were rated as "critically low" (32.9%), 14 were "low" (19.2%), 28 were "moderate" (38.4%), and 7 were "high" (9.6%), but these findings were not associated with spin. CONCLUSION: Spin was present in systematic review abstracts regarding treatment of proximal humerus fractures. Measures such as education on the subject of spin and improved reporting standards should be implemented to increase awareness and reduce incidence of spin in abstracts. LEVEL OF EVIDENCE OF THE STUDY PERFORMED: Basic Science Study; Research Methodology.

Conflicts of Interest Among Authors of Systematic Reviews and Meta-analyses Investigating Interventions for Melanoma: Cross-sectional Literature Study.

BACKGROUND: Previous studies have highlighted the potential influence that industry relationships may have on the outcomes of medical research. OBJECTIVE: We aimed to determine the prevalence of author conflicts of interest (COIs) in systematic reviews focusing on melanoma interventions, as well as to determine whether the presence of these COIs were associated with an increased likelihood of reporting favorable results and conclusions. METHODS: This cross-sectional study included systematic reviews with or without meta-analyses focusing on interventions for melanoma. We searched MEDLINE and Embase for eligible systematic reviews published between September 1, 2016, and June 2, 2020. COI disclosures were cross-referenced with information from the CMS (Centers for Medicare & Medicaid Services) Open Payments database, Dollars for Profs, Google Patents, the United States Patent and Trademark Office, and previously published COI disclosure statements. Results were quantified using descriptive statistics, and relationships were evaluated by Fisher exact tests. RESULTS: Of the 23 systematic reviews included in our sample, 12 (52%) had at least one author with a COI. Of these 12 reviews, 7 (58%) reported narrative results favoring the treatment group and 9 (75%) reported conclusions favoring the treatment group. Of the 11 systematic reviews without a conflicted author, 4 (36%) reported results favoring the treatment group and 5 (45%) reported conclusions favoring the treatment group. We found no significant association between the presence of author COIs and the favorability of results (P=.53) or conclusions (P=.15). CONCLUSIONS: Author COIs did not appear to influence the outcomes of systematic reviews regarding melanoma interventions. Clinicians and other readers of dermatology literature should be cognizant of the influence that industry may have on the nature of reported outcomes, including those from systematic reviews and meta-analyses.