Project description:BackgroundObstructive sleep apnea syndrome (OSAS) is a common chronic sleep disorder. OSAS is closely related to cardiovascular disease, metabolic disorders, cancer risk, and sudden death. This association has special significance in young people. Although it is known that OSAS has a great impact on physical health, it is estimated that 70-80% of patients with moderate-to-severe OSAS remain undiagnosed. Therefore, a new method for early diagnosis of the disease, the therapeutic effect of OSAS and prevention of complications to important.MethodsA total of 110 patients with moderate-to-severe OSAS diagnosed in the Sleep Disorders Diagnosis and Treatment Center of Peking University Shenzhen Hospital were selected. After excluding other diseases, 59 patients were finally selected as the OSAS group. In addition, 60 healthy people were selected as the control group. Serum RNA was then extracted. Eight RNA samples were randomly selected from the two groups for high-throughput miRNA sequencing. The 10 miRNAs with the greatest differences were selected as preselected markers from the results. Then, qRT-PCR was performed on the remaining RNA samples of the two groups to extract and verify the 10 miRNAs, and statistical analysis was performed between groups.ResultsA diagnostic panel was constructed by a stepwise logistic regression model combined with the expression data of miRNAs in the validation phase. A four-miRNA panel was identified to better predict OSAS, and the model was calculated using the following formula: Logit (P)= 0.77-1.65 × miR-486-5p - 4.56 × miR-148a-3p + 1.79 × miR-744-5p + 1.13 × let-7d-3p. The AUC for the four-miRNA panel was 0.955 (95% CI: 0.899 to 0.985; sensitivity = 91.38%, specificity = 91.38%). Gene Ontology (GO) annotation and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis was included in bioinformatic analysis.ConclusionA 4-miRNAs panel as a diagnostic biomarker for OSAS screening is feasible.
Project description:INTRODUCTION:University ranking systems and the publish-or-perish dictum, among other factors, are driving universities and researchers around the world to increase their research productivity. Authors frequently report multiple affiliations in published articles. It is not known if the reported institutional affiliations are real affiliations, which is when the universities have contributed substantially to the research conducted and to the published manuscript. This study aims to establish whether there is an empirical basis for author affiliation misrepresentation in authors with multiple institutional affiliations. METHODS AND ANALYSIS:This individual secondary data exploratory analysis on Scopus-indexed articles for 2016 will search all authors who report multiple institutional affiliations in which at least one of the affiliations is to a Chilean university. We will consider that misrepresentation of an affiliation is more likely when it is not possible to verify objectively a link between the author and the mentioned institution through institutional websites. If we cannot corroborate the author affiliation, we will consider this a finding of potential misrepresentation of the affiliation. We will summarise results with descriptive statistics. ETHICS AND DISSEMINATION:The study protocol was approved by the institutional ethics committee of Universidad de Santiago de Chile, Resolution No. 261, and dated January 15, 2018. Results will be submitted to the World Conference on Research Integrity, among other meetings on publication ethics and research integrity, and will be published in scientific, peer-reviewed journals.
Project description:BackgroundBy assessing the changes in concentration of soluble receptor activator of nuclear factor κ B ligand (RANKL) and osteoprotegrin (OPG) after initiation of combination antiretroviral therapy (cART) in treatment-naïve HIV-infected patients we aimed to evaluate whether the initial accelerated bone loss could be mediated by increased soluble RANKL (sRANKL) levels associated with CD4+ T cell recovery.MethodsWe used multiplex immunoassays to determine sRANKL and OPG concentrations in plasma from 48 HIV patients at baseline and 12, 24, 48 and 96 weeks after cART initiation.ResultsSoluble RANKL changed significantly over time (overall p = 0.02) with 25% decrease (95% CI: -42 to -5) at week 24 compared to baseline and stabilized at a lower level thereafter. We found no correlation between CD4+ T cell count increment and changes in sRANKL or between percentage change in BMD and changes in sRANKL.ConclusionIn this study there was no indication that the accelerated bone loss after cART initiation was mediated by early changes in sRANKL due to CD4+ T cell recovery. Future studies should focus on the initial weeks after initiation of cART.Trial registrationClinical-Trial.gov . id NCT00135460 , August 25, 2005. The study was approved by the Danish Data Protection Agency, Danish Medicines Agency and Regional Ethics Committee.
Project description:OBJECTIVE:To determine whether researchers are submitting manuscripts and peer reviews to BMJ journals out of hours and whether this has changed over time. DESIGN:Observational study of research manuscripts and peer reviews submitted between 2012 and 2019 for which an author's address could be geocoded. SETTING:Online BMJ submission systems for two large general medical journals. MAIN OUTCOME MEASURES:Manuscript and peer review submissions on weekends, on national holidays, and by hour of day (to determine early mornings and late nights). Logistic regression was used to estimate the probability of manuscript and peer review submissions on weekends or holidays. RESULTS:The analyses included more than 49?000 manuscript submissions and 76?000 peer reviews. Little change over time was seen in the average probability of manuscript or peer review submissions occurring on weekends or holidays. The levels of out of hours work were high, with average probabilities of 0.14 to 0.18 for work on the weekends and 0.08 to 0.13 for work on holidays compared with days in the same week. Clear and consistent differences were seen between countries. Chinese researchers most often worked at weekends and at midnight, whereas researchers in Scandinavian countries were among the most likely to submit during the week and the middle of the day. CONCLUSION:The differences between countries that are persistent over time show that a "culture of overwork" is a literal thing, not just a figure of speech.
Project description:BackgroundEnvironmental health and other researchers can benefit from automated or semi-automated summaries of data within published studies as summarizing study methods and results is time and resource intensive. Automated summaries can be designed to identify and extract details of interest pertaining to the study design, population, testing agent/intervention, or outcome (etc.). Much of the data reported across existing publications lack unified structure, standardization and machine-readable formats or may be presented in complex tables which serve as barriers that impede the development of automated data extraction methodologies.As full automation of data extraction seems unlikely soon, encouraging investigators to submit structured summaries of methods and results in standardized formats with meta-data tagging of content may be of value during the publication process. This would produce machine-readable content to facilitate automated data extraction, establish sharable data repositories, help make research data FAIR, and could improve reporting quality.ObjectivesA pilot study was conducted to assess the feasibility of asking participants to summarize study methods and results using a structured, web-based data extraction model as a potential workflow that could be implemented during the manuscript submission process.MethodsEight participants entered study details and data into the Health Assessment Workplace Collaborative (HAWC). Participants were surveyed after the extraction exercise to ascertain 1) whether this extraction exercise will impact their conducting and reporting of future research, 2) the ease of data extraction, including which fields were easiest and relatively more problematic to extract and 3) the amount of time taken to perform data extractions and other related tasks. Investigators then presented participants the potential benefits of providing structured data in the format they were extracting. After this, participants were surveyed about 1) their willingness to provide structured data during the publication process and 2) whether they felt the potential application of structured data entry approaches and their implementation during the journal submission process should continue to be further explored.ConclusionsRoutine provision of structured data that summarizes key information from research studies could reduce the amount of effort required for reusing that data in the future, such as in systematic reviews or agency scientific assessments. Our pilot study suggests that directly asking authors to provide that data, via structured templates, may be a viable approach to achieving this: participants were willing to do so, and the overall process was not prohibitively arduous. We also found some support for the hypothesis that use of study templates may have halo benefits in improving the conduct and completeness of reporting of future research. While limitations in the generalizability of our findings mean that the conditions of success of templates cannot be assumed, further research into how such templates might be designed and implemented does seem to have enough chance of success that it ought to be undertaken.
Project description:C/EBPα is an essential transcription factor involved in regulating the expression or function of certain cell-cycle regulators. However, little is known about the role of methylation in regulating the antiproliferation activity of C/EBPα. Here, we report that knockdown of protein arginine methyltransferases 1 (PRMT1) leads to cellular growth arrest accompanied by a decrease in Cyclin D1 gene expression in breast cancer cells. Furthermore, we reveal that C/EBPα is methylated by PRMT1 at three arginine residues (R35, R156, and R165), which impairs the interaction of C/EBPα with HDAC3 and modulates the transcription activity of C/EBPα and Cyclin D1 gene expression. PRMT1 is upregulated in human breast cancer, and elevated PRMT1 is correlated with cancer malignancy. Most importantly, a specific inhibitor of PRMT1 significantly impedes the growth of cancer cells from triple-negative breast cancer patients. Our data demonstrate that high expression of PRMT1 promotes the expression of Cyclin D1 through methylation of C/EBPα to interfere with the repressive function of HDAC3, which leads to rapid growth of tumor cells during the pathogenesis of breast cancer. This evidence that PRMT1 mediates C/EBPα methylation sheds light on a novel therapeutic pathway for breast cancer.
Project description:E-JOURNAL LINKED ABSTRACT URL http://www.current-oncology.com/index.php/oncology/article/view/840/ Pseudocirrhosis is a rare form of liver disease that causes clinical symptoms and shows radiographic signs of cirrhosis, but that has histologic features suggesting a distinct pathologic process. In the setting of cancer, hepatic metastases and systemic chemotherapy are suspected causes of pseudocirrhosis. We present the case of a 49-year-old woman with medullary thyroid carcinoma metastatic to the liver who developed pseudocirrhosis. The patient was initially enrolled in a phase i clinical trial of 5-fluorouracil, leucovorin, and oxaliplatin (folfox) in combination with sunitinib (NCT00599924). After this patient’s liver metastases regressed measurably, she was switched to sunitinib maintenance. After 4 months of combination therapy with folfox–sunitinib and 15 months of sunitinib maintenance, she developed abdominal bloating, early satiety, and right upper quadrant pain that increased with inspiration. Computed tomography of the abdomen revealed cirrhotic morphology changes in the liver, including the appearance of a nodular surface and capsular retraction. The patient had no risk factors for cirrhosis and laboratory testing for causes of liver disease were normal or negative. Core-needle liver biopsy demonstrated sheets and nests of epithelioid and spindle cells resembling the primary tumor; septal fibrosis and regenerative nodules typical of cirrhosis were not observed. The background hepatic plate architecture was intact. Laboratory studies showed increased aminotransferases, alkaline phosphatase, and international normalized ratio, and decreased albumin. Portal hypertension, esophageal varices, portal hypertensive gastropathy, and hepatic hydrothorax developed as a result of advanced liver disease. Because of disease progression, sunitinib was discontinued, and the patient was managed with sorafenib. Pseudocirrhosis has often been attributed to chemotherapeutic agents, particularly in the context of metastatic breast cancer. The toxicity profiles of folfox and sunitinib include hepatic steatosis and other forms of hepatotoxicity, but cirrhotic-like disease has not been reported. Considering the transformation of discrete hepatic metastases into a diffuse carcinomatous infiltrate and the unrelated toxicities of folfox and sunitinib, we diagnosed this patient with carcinomatous pseudocirrhosis secondary to metastatic medullary thyroid carcinoma. We discuss the diagnosis of pseudocirrhosis in this case and review the literature regarding pseudocirrhosis in cancer.
Project description:BACKGROUND: To assess how authors would describe their contribution to the submitted manuscript without reference to or requirement to satisfy authorship criteria of the International Committee of Medical Journal Editors (ICMJE), we analyzed responses of authors to an open-ended question "Why do you think you should be the author on this manuscript?". METHODS: Responses of authors (n=1425) who submitted their manuscripts (n=345) to the Croatian Medical Journal, an international general medical journal, from March 2009 until July 2010 were transcribed and matched to ICMJE criteria. Statements that could not be matched were separately categorized. Responses according to the number of authors or their byline position on the manuscript were analyzed using Mann-Whitney U test and Moses test of extreme reactions. RESULTS: The number of authors per manuscript ranged from 1 to 26 (median=4, IQR=3-6), with the median of 2 contributions per author (IQR=2-3). Authors' responses could be matched to the ICMJE criteria in 1116 (87.0%) cases. Among these, only 15.6% clearly declared contributions from all 3 ICMJE criteria; however, if signing of the authorship form was taken as the fulfillment of the third ICMJE criterion, overall fraction of deserving authorship was 54.2%. Non-ICMJE contributions were declared by 98 (7.6%) authors whose other contributions could be matched to ICMJE criteria, and by 116 (13.0%) authors whose contributions could not be matched to ICMJE criteria. The most frequently reported non-ICMJE contribution was literature review. Authors on manuscripts with more than 8 authors declared more contributions than those on manuscript with 8 or fewer authors: median 2, IQR 1-4, vs. median 2, IQR 1-3, respectively (Mann Whitney U test, p=0.001; Moses Test of Extreme Reactions, p<0.001). Almost a third of single authors (n=9; 31.0%) reported contributions that could not be matched to any ICMJE criterion. CONCLUSIONS: In cases of multi-author collaborative efforts but not in manuscripts with fewer authors open-ended authorship declaration without instructions on ICMJE criteria elicited responses from authors that were similar to responses when ICMJE criteria were explicitly required. Current authorship criteria and the practice of contribution declaration should be revised in order to capture deserving authorship in biomedical research.
Project description:OBJECTIVE:To conduct a time-cost analysis of formatting in scientific publishing. DESIGN:International, cross-sectional study (one-time survey). SETTING:Internet-based self-report survey, live between September 2018 and January 2019. PARTICIPANTS:Anyone working in research, science, or academia and who submitted at least one peer-reviewed manuscript for consideration for publication in 2017. Completed surveys were available for 372 participants from 41 countries (60% of respondents were from Canada). MAIN OUTCOME MEASURE:Time (hours) and cost (wage per hour x time) associated with formatting a research paper for publication in a peer-reviewed academic journal. RESULTS:The median annual income category was US$61,000-80,999, and the median number of publications formatted per year was four. Manuscripts required a median of two attempts before they were accepted for publication. The median formatting time was 14 hours per manuscript, or 52 hours per person, per year. This resulted in a median calculated cost of US$477 per manuscript or US$1,908 per person, per year. CONCLUSIONS:To our knowledge, this is the first study to analyze the cost of manuscript formatting in scientific publishing. Our results suggest that scientific formatting represents a loss of 52 hours, costing the equivalent of US$1,908 per researcher per year. These results identify the hidden and pernicious price associated with scientific publishing and provide evidence to advocate for the elimination of strict formatting guidelines, at least prior to acceptance.