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Response was independent of the PD-1 inhibitor usedand also independent of the presence of distant metastases vs. locally advanced disease. Two predictive factors were found Patients with primaries located on the leg had a poorer therapy outcomeand patients with high lactate dehydrogenase serum levels at baseline. Treatment was overall tolerated well, with less than 10% of patients discontinuing therapy due to toxicity.
PD-1 inhibitors fulfill the need for an efficient systemic therapy for advanced cSCC and should be the new standard of care. With high RRs and durable disease control, neoadjuvant and adjuvant regimens should be evaluated.
PD-1 inhibitors fulfill the need for an efficient systemic therapy for advanced cSCC and should be the new standard of care. With high RRs and durable disease control, neoadjuvant and adjuvant regimens should be evaluated.Aquatic pollution is one of the greatest environmental problems, and therefore its control represents one of the major challenges in this century. In recent years, proteomics has emerged as a powerful tool for searching protein biomarkers in the field of pollution biomonitoring. For biomonitoring marine contamination, there is a consensus that bivalves are preferred organisms to assess organic and inorganic pollutants. Thus, the bivalve proteome was intensively studied, particularly the mussel. It is well documented that heavy metal pollution and organic chemicals altered the structural proteins causing degradation of tissues of molluscs. Also, it is well known that proteins involved in stress oxidative such as glutathione and enzymes as catalase, superoxide dismutase or peroxisomes are overexpressed in response to contaminants. Additionally, using bivalves, other groups of proteins proposed as pollution biomarkers are the metabolic proteins. Even though other marine species are used to monitor the pollution, the presence of proteomic tools in these studies is scarce. Concerning freshwater pollution field, a great variety of animal species (fish and crustaceans) are used as biomonitors in proteomics studies compared to plants that are scarcely analysed. In fish species, proteins involved in stress oxidative such as heat shock family or proteins from lipid and carbohydrate metabolism were proposed as candidate biomarkers. On the contrary, for crustaceans there is a lack of proteomic studies individually assessing the contaminants. Novel scenarios, including emerging contaminants and new threats, will require proteomic technology for a systematic search of protein biomarkers and a greater knowledge at molecular level of those cellular pathways induced by contamination.Air pollution can increase the risk of respiratory diseases, enhancing the susceptibility to viral and bacterial infections. Some studies suggest that small air particles facilitate the spread of viruses and also of the new coronavirus, besides the direct person-to-person contagion. However, the effects of the exposure to particulate matter and other contaminants on SARS-CoV-2 has been poorly explored. Here we examined the possible reasons why the new coronavirus differently impacted on Italian regional and provincial populations. With the help of artificial intelligence, we studied the importance of air pollution for mortality and positivity rates of the SARS-CoV-2 outbreak in Italy. We discovered that among several environmental, health, and socio-economic factors, air pollution and fine particulate matter (PM2.5), as its main component, resulted as the most important predictors of SARS-CoV-2 effects. We also found that the emissions from industries, farms, and road traffic - in order of importance - might be responsible for more than 70% of the deaths associated with SARS-CoV-2 nationwide. Given the major contribution played by air pollution (much more important than other health and socio-economic factors, as we discovered), we projected that, with an increase of 5-10% in air pollution, similar future pathogens may inflate the epidemic toll of Italy by 21-32% additional cases, whose 19-28% more positives and 4-14% more deaths. Our findings, demonstrating that fine-particulate (PM2.5) pollutant level is the most important factor to predict SARS-CoV-2 effects that would worsen even with a slight decrease of air quality, highlight that the imperative of productivity before health and environmental protection is, indeed, a short-term/small-minded resolution.Artificial light at night (ALAN) exposes us to prolonged illumination, that adversely affects female reproduction. However, it remains to be clarified how prolonged light exposure affects oocyte meiotic maturation and quality. To this end, we exposed female mice to a constant light (CL) of 250 lux for different durations. BC-2059 in vitro Our findings showed that CL exposure for 7 weeks reduced the oocyte maturation rate. Meanwhile, CL exposure caused greater abnormalities in spindle assembly and chromosome alignment and a higher rate of oocyte aneuploidy than the regular light dark cycle. CL exposure also induced oxidative stress and caused mitochondrial dysfunction, which resulted in oocyte apoptosis and autophagy. Notably, our results showed that CL exposure reduced the levels of α-tubulin acetylation, DNA methylation at 5 mC, RNA methylation at m6A and histone methylation at H3K4me2 but increased the levels of histone methylation at H3K27me2 in oocytes. In summary, our findings demonstrate that constant bright light exposure causes oocyte meiotic defects and reduces cytoplasmic quality. These results extend the current understanding of ALAN-mediated defects in female reproduction.The present study was aimed at investigating the effects of different acids and pH neutralizers applied to dredged marine sediment for the treatment of heavy metals, and the resulting influence on the sediment quality as a plant growth medium. The inspection of barley germination in the dredged marine sediment revealed that residual salts are critical plant stressors whose adverse effects exceed those exhibited by high-level heavy metals and petroleum hydrocarbons present in the sediment. Acid washing and pH neutralization reduced not only the heavy metal contents but also the sediment salinity (by factors of 6.1-9.5), resulting in 100% germination of barley. For acid-washed and calcium-oxide-neutralized sediment, the barley growth was comparable to that observed in untreated and water washed sediment despite factors of 5.2-8.0 greater sediment salinity in the former. This result represents the protective effect of residual calcium against sodium and chloride toxicity. Water washing of acid-washed and pH-neutralized sediments further enhanced barley growth owing to the reduction in osmotic pressure.