SLCO4A1 expression is associated with activated inflammatory pathways in high-grade serous ovarian cancer.

Patients with high-grade serous ovarian cancer (HGSOC) have a very poor overall survival. Current therapeutic approaches do not bring benefit to all patients. Although genetic alterations and molecular mechanisms are well characterized, the molecular pathological conditions are poorly investigated. Solute carrier organic anion transporter family member 4A1 (SLCO4A1) encodes OATP4A1, which is an uptake membrane transporter of metabolic products. Its expression may influence various signaling pathways associated with the molecular pathophysiological conditions of HGSOC and consequently tumor progression. RNA sequencing of 33 patient-derived HGSOC cell lines showed that SLCO4A1 expression was diverse by individual tumors, which was further confirmed by RT-qPCR, Western blotting and immunohistochemistry. Gene Set Enrichment Analysis revealed that higher SLCO4A1 level was associated with inflammation-associated pathways including NOD-like receptor, adipocytokine, TALL1, CD40, NF-κB, and TNF-receptor 2 signaling cascades, while low SLCO4A1 expression was associated with the mitochondrial electron transport chain pathway. The overall gene expression pattern in all cell lines was specific to each patient and remained largely unchanged during tumor progression. In addition, genes encoding ABCC3 along with SLCO4A1-antisense RNA 1, were associated with higher expression of the SLCO4A1, indicating their possible involvement in inflammation-associated pathways that are downstream to the prostaglandin E2/cAMP axis. Taken together, increased SLCO4A1/OATP4A1 expression is associated with the upregulation of specific inflammatory pathways, while the decreased level is associated with mitochondrial dysfunction. These molecular pathophysiological conditions are tumor specific and should be taken into consideration by the development of therapies against HGSOC.

Determination of the influence of weather and air constituents on aortic aneurysm ruptures.

In this article, we present a method to determine the influence of meteorology and air pollutants on ruptured aortic aneurysm (rAA). In contrast to previous studies, our work takes into account highly resolved seasonal relationships, a time-lagged effect relationship of up to two weeks, and furthermore, potential confounding influences between the meteorological and air-hygienic variables are considered and eliminated using a cross-over procedure. We demonstrate the application of the method using the cities of Augsburg and Munich in southern Germany as examples, where a total of 152 rAA can be analyzed for the years 2010-2019. With the help of a Wilcoxon rank-sum test and the analysis of the atmospheric circulation, typical weather situations could be identified that have an influence on the occurrence of rAA in the southern German region. These are a rainy northwest wind-type in spring, humid weather in summer and warm southwest wind-type weather in autumn and winter.

Associations between Weather, Air Quality and Moderate Extreme Cancer-Related Mortality Events in Augsburg, Southern Germany.

While many authors have described the adverse health effects of poor air quality and meteorological extremes, there remain inconsistencies on a regional scale as well as uncertainty about the single and joint effects of atmospheric predictors. In this context, we investigated the short-term impacts of weather and air quality on moderate extreme cancer-related mortality events for the urban area of Augsburg, Southern Germany, during the period 2000-2017. First, single effects were uncovered by applying a case-crossover routine. The overall impact was assessed by performing a Mann-Whitney U testing scheme. We then compared the results of this procedure to extreme noncancer-related mortality events. In a second step, we found periods with contemporaneous significant predictors and carried out an in-depth analysis of these joint-effect periods. We were interested in the atmospheric processes leading to the emergence of significant conditions. Hence, we applied the Principal Component Analysis to large-scale synoptic conditions during these periods. The results demonstrate a strong linkage between high-mortality events in cancer patients and significantly above-average levels of nitrogen dioxide (NO2) and particulate matter (PM2.5) during the late winter through spring period. These were mainly linked to northerly to easterly weak airflow under stable, high-pressure conditions. Especially in winter and spring, this can result in low temperatures and a ground-level increase and the accumulation of air pollution from heating and traffic as well as eastern lateral advection of polluted air. Additionally, above-average temperatures were shown to occur on the days before mortality events from mid-summer through fall, which was also caused by high-pressure conditions with weak wind flow and intense solar radiation. Our approach can be used to analyse medical data with epidemiological as well as climatological methods while providing a more vivid representation of the underlying atmospheric processes.

Using virtual reality for forensic examinations of injuries.

The ability to accurately determine injury dimensions is an essential property of forensic documentation. The current standard for injury documentation is photography using a scale to approximate the injury dimensions in the image. The technical qualities of the photograph, such as orthogonality, depth of the field and sharpness of the desired area, are vital to obtaining a correct measurement. Adequate training of the forensic staff can reduce technical errors; nonetheless, there will always be some loss of information when visualizing an injury as a three-dimensional (3D) object on a two-dimensional (2D) photograph. The shortcomings of 2D photographs can be resolved by using 3D photogrammetry, which allows 3D documentation of persons and their injuries. A series of photographs has to be acquired and processed in photogrammetric software to create a photorealistic 3D model. In a prior study, a mannequin equipped with wound tattoos of known dimensions was documented with 3D photogrammetry using a multi-camera device. On the created 3D model, the dimensions of the injuries were then measured and compared to the dimensions approximated from standard forensic photographs. The results showed that the photogrammetric measurements in 3D are more accurate than the approximations performed with standard forensic photographs. In this subsequent study, the created 3D model was visualized and surveyed in virtual reality (VR), and the results were compared to the previous study. Our goal was to establish how accurately injuries can be measured in VR compared to the standard forensic photo documentation and photogrammetric method that is used on computer screens. We found that the measurements in VR are more accurate than the approximations from forensic photo documentation, but slightly less accurate than the photogrammetric measurements performed on a computer screen in dedicated software. In conclusion, photogrammetric software and virtual reality tools can both be used to make accurate size measurements of forensics-relevant injuries. Furthermore, 3D models can be visualized in varying ways allowing a much better understanding and review of injuries, even after the injury has healed.