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structures of the placenta and immunohistochemical signs of impaired immunological tolerance at the maternal-fetal interface. The data we obtained allow us to classify pregnancies under surrogate motherhood programs as a risk factor for the development of pregnancy complications with immune pathogenesis.Reliable modelling of the dynamics of cancer morbidity risk is important, not least due to its significant impact on healthcare and related policies. We identify morbidity trends and regional differences in England for all-cancer and type-specific incidence between 1981 and 2016. We use Bayesian modelling to estimate cancer morbidity incidence at various age, year, gender, and region levels. Our analysis shows increasing trends in most rates and marked regional variations that also appear to intensify through time in most cases. All-cancer rates have increased significantly, with the highest increase in East, North West and North East. The absolute difference between the rates in the highest- and lowest-incidence region, per 100,000 people, has widened from 39 (95% CI 33-45) to 86 (78-94) for females, and from 94 (85-104) to 116 (105-127) for males. Lung cancer incidence for females has shown the highest increase in Yorkshire and the Humber, while for males it has declined in all regions with the highest decrease in London. The gap between the highest- and lowest-incidence region for females has widened from 47 (42-51) to 94 (88-100). Temporal change in in bowel cancer risk is less manifested, with regional heterogeneity also declining. Prostate cancer incidence has increased with the highest increase in London, and the regional gap has expanded from 33 (30-36) to 76 (69-83). For breast cancer incidence the highest increase has occurred in North East, while the regional variation shows a less discernible increase. The analysis reveals that there are important regional differences in the incidence of all-type and type-specific cancers, and that most of these regional differences become more pronounced over time. A significant increase in regional variation has been demonstrated for most types of cancer examined here, except for bowel cancer where differences have narrowed.Purpose On June 13-14, 2019, the American Society for Radiation Oncology (ASTRO) and the Radiological Society of North America (RSNA) convened a workshop on the Treatment of Oligometastatic Disease in Washington, DC. The workshop was initiated because of several reasons. First, oligometastatic (OM) disease is of increasing academic and community interest, and has been identified by ASTRO membership as a top research priority. Second, emerging imaging and diagnostic technologies are more readily defining and detecting oligometastatic disease - making contemporary discussion of oligometastatic disease especially relevant. Third, radiosurgery and radiation in general are theorized to be ideal non-invasive therapy for the treatment of oligometastatic disease. Finally, innovations in targeted therapy and immune therapy have the potential to reverse widely disseminating disease into an oligometastatic state. Methods The workshop was organized into two keynote addresses, 6 scientific sessions, and three group discussions during an end of workshop breakout session. New scientific work was presented in the form of 4 oral presentations and a poster session. Workshop participants were charged with attempting to answer three critical questions 1) Can we refine the clinical and biological definitions of oligometastatic disease? 2) How can we better treat OM disease? And 3) What clinical trials are needed? Results Here, we present the proceedings of the workshop. Conclusions The clinical implications of improved treatment of oligometastatic disease are enormous and immediate. Radiation oncology and diagnostic radiology should rightly be at the forefront of the characterization and treatment of oligometastatic disease. Focused effort is required so that we can translate current efforts of large numbers of studies with few patients to larger studies of larger impact.Bosentan, an endothelin receptor antagonist, has been widely used as a first-line medication for the treatment of pulmonary arterial hypertension (PAH). However, liver dysfunction is a major side effect of bosentan treatment that could hamper the optimal management of patients with PAH. Previously, we demonstrated, using drug metabolism enzymes and transporters (DMET) analysis, that the carbohydrate sulfotransferase 3 (CHST3) and CHST13 alleles are significantly more frequent in patients with elevated amino-transferases during therapy with bosentan than they are in patients without liver toxicity. In addition, we constructed a pharmacogenomics model to predict bosentan-induced liver injury in patients with PAH using two single nucleotide polymorphisms (SNPs) and two non-genetic factors. The purpose of the present study was to externally validate the predictive model of bosentan-induced liver toxicity in Japanese patients. We evaluated five cases of patients treated with bosentan, and one presented with liver dysfunction. We applied mutation alleles of CHST3 and CHST13, serum creatinine, and age to our model to predict liver dysfunction. The sensitivity and specificity were calculated as 100% and 50%, respectively. Considering that PAH is a rare disease, multicenter collaboration would be necessary to validate our model.Reactive oxygen species (ROS) are chemically reactive species that are produced in cellular aerobic metabolism. They mainly include superoxide anion, hydrogen peroxide, hydroxyl radicals, singlet oxygen, ozone and nitric oxide, and are implicated in many physiological and pathological processes. Bilirubin, a cardinal pigment in the bile, has been increasingly investigated to treat cancer, diabetes, ischemia/reperfusion injury, asthma and inflammatory bowel diseases (IBD). selleck chemicals llc Indeed, bilirubin shown to eliminate ROS production, so it is now considered as a promising therapeutic agent for ROS-mediated diseases, and can be used for the development of anti-oxidative nanomedicines. This review summarizes the current knowledge of the physiological mechanisms of ROS production and its role in pathological changes, and focuses to discuss the anti-oxidative effects of bilirubin, and its application in the experimental studies of nanomedicines. Previous studies have shown that bilirubin was mainly used as a responsive molecule in the microenvironment of ROS overproduction in neoplastic tissues for the development of anti-cancer nanodrugs, however it could also exert powerful ROS scavenging activity in chronic inflammation and ischemia/reperfusion injury.