Unique and redundant roles of SOX2 and SOX17 in regulating the germ cell tumor fate

Embryonal carcinomas (ECs) and seminomas are testicular germ cell tumors. ECs display expression of SOX2, while seminomas display expression of SOX17. In somatic differentiation, SOX17 drives endodermal cell fate. However, seminomas lack expression of endoderm markers, but show features of pluripotency. Here, we use chromatin immunoprecipitation sequencing to report and compare the binding pattern of SOX17 in seminoma-like TCam-2 cells to SOX17 in somatic cells and SOX2 in EC-like 2102EP cells. In seminoma-like cells, SOX17 was detected at canonical (SOX2/OCT4), compressed (SOX17/OCT4) and noncomposite SOX motifs. SOX17 regulates TFAP2C, PRDM1 and PRDM14, thereby maintaining latent pluripotency and suppressing somatic differentiation. In contrast, in somatic cells canonical motifs are rarely bound by SOX17. In sum, only 12% of SOX17-binding sites overlap in seminoma-like and somatic cells. This illustrates that binding site choice is highly dynamic and cell type specific. Deletion of SOX17 in seminoma-like cells resulted in loss of pluripotency, marked by a reduction of OCT4 protein level and loss of alkaline phosphatase activity. Furthermore, we found that in EC-like cells SOX2 regulates pluripotency-associated genes, most likely by partnering with OCT4. In conclusion, SOX17 (in seminomas) functionally replaces SOX2 (in ECs) to maintain expression of the pluripotency cluster.     

The Effect of Homelessness on Patient Wait Times in the Emergency Department

BackgroundProlonged emergency department (ED) wait times could potentially lead to increased morbidity and mortality. While previous work has demonstrated disparities in wait times associated with race, information about the relationship between experiencing homelessness and ED wait times is lacking.ObjectivesThe purpose of this study was to explore the relationship between residence status (undomiciled vs. domiciled) and ED wait times. We hypothesized that being undomiciled would be associated with longer wait times.MethodsWe obtained data from the National Hospital Ambulatory Medical Care Survey from 2014 to 2017. We compared wait times in each triage category using t tests. We used multivariate linear regression to explore associations between residence status and wait times while controlling for other patient- and hospital-level variables.ResultsOn average, undomiciled patients experienced significantly longer mean ED wait times than domiciled patients (53.4 vs. 38.9 min; p < 0.0001). In the multivariate model, undomiciled patients experienced significantly different wait times by 15.5 min (p = 0.0002). Undomiciled patients experienced increasingly longer waits vs. domiciled patients for the emergent and urgent triage categories (+33.5 min, p < 0.0001, and +22.7 min, p < 0.0001, respectively).ConclusionsUndomiciled patients experience longer ED wait times when compared with domiciled patients. This disparity is not explained by undomiciled patients seeking care in the ED for minor illness, because the disparity is more pronounced for urgent and emergent triage categories.     

Knowledge of the Brain Death Concept in Dominican Immigration Residents in Spain and Florida

The Latin American population has a double way of immigration, one toward the United States by proximity and another toward Spain by sociocultural affinity. This population increase is affecting organ donation and transplantation in receiving countries.

Automatizing a nonscripting TPS for optimizing clinical workflow and reoptimizing IMRT/VMAT plans

The purpose of this study was to design a toolkit that interacts with the Monaco (Elekta AB, Stockholm, Sweden) treatment planning system (TPS) for optimization of intensity-modulated radiation therapy and volumetric-modulated arc therapy without the need for a dedicated application programming interface. Successful inverse planning of radiotherapeutic treatment depends on the tweaking of many parameters; a tool was thus needed to explore these parameters more exhaustively without significantly increasing planning time. The software that we used was based on an open-source library that mimics human interaction with Microsoft Windows applications. We developed a simple Autoflow software routine that analyzes and optimizes calculated plans by considering the relative impact of different cost functions and modifying constraints accordingly. It was also designed to change segmentation parameters to fit more complex treatments. The toolkit is publicly available for download at https://bitbucket.org/hgugmradiofisica/pymonaco/src/master/. A study of prostate cancer cases was conducted to compare automatically created plans with previously treated cases. The toolkit fully automated the radiotherapy planning procedure, allowing the TPS to calculate or optimize plans during nonworking hours. In the prostate study, the use of this tool reduced the dose to organs at risk with a negligible decrease in target coverage. This tool enables the efficient use of the TPS, allowing research and clinical applications to coexist without conflict. It provides consistency and efficiency throughout the treatment planning process, which may be of great value to clinics with few resources. The impact of this tool on clinical workflow is important, as it not only provides better efficiency, but also increases treatment quality.     

ANCA and anti-glomerular basement membrane double-positive patients: A systematic review of the literature

IntroductionDouble-positive patients (DPP) exhibiting anti-glomerular basement membrane (GBM) and anti-neutrophil cytoplasmic antibodies (ANCAs) belong to an entity that is newly and poorly described, mainly in short series. We aimed to better characterize the epidemiological features, clinical presentation and therapeutic outcomes of these patients through a systematic review.MethodsWe performed a systematic review of English-, German-, Spanish- and French-written publications from February 1987 to March 2020 reporting cases of DPP using the following databases: PubMed, Scielo, ScienceDirect, Google Scholar, The Cochrane Library, Open Grey, The Grey Literature Report, Clinicaltrials.gov and International Clinical Trial Registry Platform of the World Health Organization.ResultsIn total, 538 DPP were identified from 90 articles. Their clinical presentations were often severe, and the majority exhibited acute kidney failure (91.8%) with a median initial serum creatinine level of 873 μmol/L; 50.7% had alveolar haemorrhage. Other manifestations were present in 30.3% of DPP, mainly ear, nose, throat and articular manifestations. ANCAs were predominantly directed against MPO (n = 377/523; 72.1%) compared to PR3 (n = 107/523; 20.5%), with rare cases of triple positivity (n = 15/538; 2.9%). Although most patients received initial immunosuppressive therapy (n = 285/317; 89.9%), the one-year overall, renal and relapse-free survival rates were 64.8%, 38.7% and 71.1%, respectively.ConclusionDPP are associated with the characteristics of two eponymous vasculitis types, responsible for a poor overall and renal prognosis. Thus, simultaneous testing of both antibodies and systematic renal biopsy should be recommended in every patient with rapidly progressive glomerulonephritis to recognize this difficult-to-treat and rare disease.