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LncRNA MHRT Stimulates Cardiac Fibrosis by way of miR-3185 Walkway Subsequent Myocardial Infarction.
What explanation is there when teams of researchers are unable to successfully replicate already established 'canonical' findings? One suggestion that has been put forward, but left largely untested, is that those researchers who fail to replicate prior studies are of low 'expertise and diligence' and lack the skill necessary to successfully replicate the conditions of the original experiment. Here we examine the replication success of 100 scientists of differing 'expertise and diligence' who attempted to replicate five different studies. Using a bibliometric tool (h-index) as our indicator of researcher 'expertise and diligence', we examine whether this was predictive of replication success. Although there was substantial variability in replication success and in the h-factor of the investigators, we find no relationship between these variables. The present results provide no evidence for the hypothesis that systematic replications fail because of low 'expertise and diligence' among replicators. ©2020 Protzko and Schooler.CD40-stimulating immunotherapy can elicit potent anti-tumor responses by activating dendritic cells and enhancing T-cell priming. Tumor vessels orchestrate T-cell recruitment during immune response, but the effect of CD40-stimulating immunotherapy on tumor endothelial cells has not been evaluated. Here, we have investigated how tumor endothelial cells transcriptionally respond to CD40-stimulating immunotherapy by isolating tumor endothelial cells from agonistic CD40 mAb- or isotype-treated mice bearing B16-F10 melanoma, and performing RNA-sequencing. Gene set enrichment analysis revealed that agonistic CD40 mAb therapy increased interferon (IFN)-related responses in tumor endothelial cells, including up-regulation of the immunosuppressive enzyme Indoleamine 2, 3-Dioxygenase 1 (IDO1). IDO1 was predominantly expressed in endothelial cells within the tumor microenvironment, and its expression in tumor endothelium was positively correlated to T-cell infiltration and to increased intratumoral expression of IFNγ. In vitro, endothelial cells up-regulated IDO1 in response to T-cell-derived IFNγ, but not in response to CD40-stimulation. Combining agonistic CD40 mAb therapy with the IDO1 inhibitor epacadostat delayed tumor growth in B16-F10 melanoma, associated with increased activation of tumor-infiltrating T-cells. CM 4620 manufacturer Hereby, we show that the tumor endothelial cells up-regulate IDO1 upon CD40-stimulating immunotherapy in response to increased IFNγ-secretion by T-cells, revealing a novel immunosuppressive feedback mechanism whereby tumor vessels limit T-cell activation. © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.Acute myeloid leukemia (AML) is a genetically heterogeneous clonal malignancy characterized by recurrent gene mutations. Genomic heterogeneity, patients' individual variability, and recurrent gene mutations are the major obstacles among many factors that impact treatment efficacy of the AML patients. With the application of cost- and time-effective next-generation sequencing (NGS) technologies, an enormous diversity of genetic mutations has been identified. The recurrent gene mutations and their important roles in acute myeloid leukemia (AML) pathogenesis have been studied extensively. In this review, we summarize the recent development on the gene mutation in patients with AML. © The Author(s) 2020.Detailed clinical and pathological features of placental mesenchymal dysplasia (PMD) complicated by preeclampsia (PE) are unknown. A 39-year-old nulliparous woman was referred at 19 weeks gestation. Ultrasound examination identified a fetus with severe growth restriction (-2.8 SD) and a markedly thickened placenta with many cystic structures suggestive of PMD. At 21 weeks, the patient developed severe hypertension (180/95 mm Hg) with marked proteinuria and an elevated serum soluble fms-like tyrosine-kinase-1 (sFlt-1) level (47,000 pg/L). The pregnancy was terminated to protect maternal health. Placental weight was 450 g and no histopathological findings of either proliferation or dysplasia were observed in the trophoblast. Villous chromosome examination revealed a 46XX karyotype, consistent with the diagnosis of PMD. In addition to the pathological findings of vascular endothelial dysfunction characteristic of the placenta in PE cases, enhanced expression of sFlt-1 in the syncytiotrophoblast of the enlarged villi was confirmed by immunohistochemistry as a novel finding in this condition. Monitoring of the serum sFlt-1 value is suggested to be a useful predictor of the pathological change associated with extremely early severe PE in PMD cases.Introduction Opioid-related adverse drug events (ORADEs) are an increasingly recognized complication associated with the common prescription of opioids after orthopedic surgery. In this study, we attempted to understand how potential ORADEs following hip replacement surgery in older patients affected hospital length of stay, hospital revenue, and their association with specific risk factors and clinically relevant diseases occurring during hospitalization. Methods We conducted a retrospective study using the Centers for Medicare and Medicaid Services Administrative Database to analyze Medicare discharges after hip replacement surgery to identify potential ORADEs. The impact of potential ORADEs on mean hospital length of stay (LOS) and hospital revenue was analyzed. Results The potential ORADE rate in patients who underwent hip replacement surgery was 8.6%. The mean LOS for discharges with a potential ORADE was 1.41 days longer than that for discharges without an ORADE. The mean hospital revenue per day with a potential ORADE was US$1708 less than without an ORADE. Potential ORADEs were also found to be strongly associated with poor patient outcomes such as pneumonia, septicemia, and shock. Discussion Potential ORADEs in hip replacement surgery in older patients are associated with longer hospitalizations, decreased hospital revenue per day, certain patient risk factors, and clinically relevant diseases occurring during hospitalizations. Our finding of an association between potential ORADEs and decreased hospital revenue per day may be attributed to the management of these adverse events, as a patient may need to undergo additional testing, may need additional treatment regimens, and may need a higher level of care. Conclusion By reducing the use of opioids and employing a multimodal analgesic approach, we may improve patient care, decrease hospital lengths of stay, and increase hospital revenue. © The Author(s) 2020.
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