Content Analysis and Characterization of Medical Tweets During the Early Covid-19 Pandemic.

Objective The novel coronavirus disease 2019 (Covid-19) has infected millions worldwide and impacted the lives of many folds more. Many clinicians share new Covid-19-related resources, research, and ideas within the online Free Open Access to Medical Education (FOAM) community of practice. This study provides a detailed content and contributor analysis of Covid-19-related tweets among the FOAM community during the first months of the pandemic. Design, Setting, and Participants In this social media content analysis study, Twitter was searched from November 1, 2019, to March 21, 2020, for English tweets discussing Covid-19 in the FOAM community. Tweets were classified into one of 13 pre-specified content categories: original research, editorials, FOAM resource, public health, podcast or video, learned experience, refuting false information, policy discussion, emotional impact, blatantly false information, other Covid-19, and non-Covid-19. Further analysis of linked original research and FOAM resources was performed. One-thousand (1000) randomly selected contributor profiles and those deemed to have contributed false information were analyzed. Results The search yielded 8541 original tweets from 4104 contributors. The number of tweets in each content category were: 1557 other Covid-19 (18.2%), 1190 emotional impact (13.9%), 1122 FOAM resources (13.1%), 1111 policy discussion (13.0%), 928 advice (10.9%), 873 learned experience (10.2%), 424 non-Covid-19 (5.0%), 410 podcast or video (4.8%), 304 editorials (3.6%), 275 original research (3.2%), 245 public health (2.9%), 83 refuting false information (1.0%), and 19 blatantly false (0.2%). Conclusions Early in the Covid-19 pandemic, the FOAM community used Twitter to share Covid-19 learned experiences, online resources, crowd-sourced advice, and research and to discuss the emotional impact of Covid-19. Twitter also provided a forum for post-publication peer review of new research. Sharing blatantly false information within this community was infrequent. This study highlights several potential benefits from engaging with the FOAM community on Twitter.

Completeness of reporting for systematic reviews of point-of-care ultrasound: a meta-research study.

OBJECTIVES: Systematic reviews are often considered among the highest quality of evidence. Completely reported systematic reviews, however, are required so readers can assess for generalisability of the research to practice and risk of bias. The objective of this study was to assess the completeness of reporting for systematic reviews assessing the diagnostic accuracy of point-of-care ultrasound (POCUS) using the Preferred Reporting Items for Systematic Reviews and Meta-analyses for Diagnostic Test Accuracy (PRISMA-DTA) checklist that was published in 2018. DESIGN AND SETTING: In this meta-research study, MEDLINE, EMBASE and Cochrane Library databases were searched, with no date restriction, on March 1st, 2020 for systematic reviews assessing the diagnostic accuracy of POCUS. Adherence to PRISMA-DTA for the main text and abstract was scored independently and in duplicate using a modified checklist. Prespecified subgroup analyses were performed. MAIN OUTCOME MEASURES: The primary outcome was the mean PRISMA-DTA checklist adherence for the full-text and abstract. RESULTS: A total of 71 studies published from 2008 to 2020 met the inclusion criteria. The overall adherence for the full-text was moderate: 19.8 out of 26.0 items (76%) and for the abstract was 7.0 out of 11.0 items (64%). Although many items in the PRISMA-DTA checklist were frequently reported, several were r infrequently reported (<33% of studies), including item 5 (protocol registration), item D2 (minimally acceptable test accuracy) and item 14 (variability in target condition, index test and reference standards). Subgroup analyses showed a higher PRISMA-DTA mean adherence (SD) for high impact journals (20.9 (2.52) vs 18.9 (1.95); p<0.001), studies including supplemental materials (20.6 (2.48) vs 18.9 (2.28); p=0.004), studies citing adherence to PRISMA reporting guidelines (20.4 (1.95) vs 19.0 (3.00); p=0.038) and studies published in journals endorsing PRISMA guidelines (20.2 (2.47) vs 18.6 (2.37); p=0.025). There was variable adherence based on journal of publication (p=0.006), but not for study population (adult vs paediatric vs mixed) (p=0.62), year of publication (p=0.94), body region (p=0.78) or country (p=0.40). There was no variability in abstract adherence based on whether the abstract was structured with subheadings or not (p=0.25). A Spearman's correlation found moderate correlation between higher word counts and abstractand full-text adherence (R=0.45, p<0.001 and R=0.38, p=0.001), respectively. CONCLUSIONS: Overall, the reporting of POCUS diagnostic accuracy systematic reviews and meta-analyses was moderate. We identified deficits in several key areas including the preregistration of systematic reviews in an online repository, handling of multiple definitions of target conditions, index tests and reference standards and specifying minimally acceptable test accuracy. Prospective registration of reviews and detailed reporting as per PRISMA-DTA during the research process could improve reporting completeness. At an editorial level, word count and supplemental material limitations may impede reporting completeness, whereas endorsement of reporting guidelines on journal websites could improve reporting.

Discoidin domain receptor 1 deficiency in vascular smooth muscle cells leads to mislocalisation of N-cadherin contacts.

N-cadherin mediates cell-cell contacts in vascular smooth muscle cells (VSMCs), and regulates VSMC behaviours including migration and proliferation. Discoidin domain receptor 1 (DDR1) is a collagen binding receptor also implicated in these processes. Previous studies have shown that both N-cadherin and DDR1 are upregulated after vascular injury, but it is not known whether there is a relationship between the two molecules. In the current study we found that N-cadherin was mislocalised from cell-cell junctions in the absence of DDR1. This occurred in spite of the fact that there was no significant difference in total cell lysate levels of N-cadherin between DDR1+/+ and DDR1-/- VSMCs. Analysis of lipid raft fractions revealed decreased N-cadherin and associated junctional complex catenins in DDR1-/- compared to DDR1+/+ VSMCs. Treatment with cholesterol oxidase or methyl-ß-cyclodextrin to disrupt lipid rafts removed N-cadherin and DDR1 from the raft fractions. Reciprocal co-immunoprecipitations suggested the association of DDR1 and N-cadherin. Importantly, transfection of DDR1-/- cells with full-length DDR1b rescued the formation of N-cadherin junctions. Together, these data reveal that N-cadherin cell-cell contacts in VSMCs are regulated through interactions with DDR1 and both molecules are located in lipid rafts.

Biochemical characterization of human tissue kallikrein 15 and examination of its potential role in cancer.

OBJECTIVE: Human tissue kallikrein 15 (KLK15) is the last cloned member of the KLK-related gene family. Despite being implicated in multiple cancers, its pathophysiological role remains unknown. We aimed to biochemically characterize KLK15 and preliminarily study its role in cancer. DESIGN & METHODS: Recombinant KLK15 protein was produced, purified to homogeneity and quantified by mass spectrometry (parallel reaction monitoring analysis). We profiled the enzymatic activity of KLK15 using fluorogenic peptide substrates, and performed kinetic analysis to discover the cleavage sites. As KLK15 has mainly been associated with prostate cancer, we used a degradomic approach and subsequent KEGG pathway analysis to identify a number of putative protein substrates in the KLK15-treated prostate cancer cell line PC3. RESULTS: We discovered trypsin-like activity in KLK15, finding that it cleaves preferentially after arginine (R). The enzymatic activity of KLK15 was regulated by different factors such as pH, cations and serine protease inhibitors. Notably, we revealed that KLK15 most likely interacts with the extracellular matrix (ECM) receptor group. CONCLUSION: To our knowledge, this is the first study that experimentally verifies the trypsin-like activity of KLK15. We show here for the first time that KLK15 may be able to cleave many ECM components, similar to several members of the KLK family. Thus the protease could potentially be linked to tumorigenesis by promoting metastasis via this mechanism.