Predicting early brain metastases based on clinicopathological factors and gene expression analysis in advanced HER2-positive breast cancer patients

The overexpression or amplification of the human epidermal growth factor receptor 2 gene (HER2/neu) is associated with high risk of brain metastasis (BM). The identification of patients at highest immediate risk of BM could optimize screening and facilitate interventional trials. We performed gene expression analysis using complementary deoxyribonucleic acid-mediated annealing, selection, extension and ligation and real-time quantitative reverse transcription PCR (qRT-PCR) in primary tumor samples from two independent cohorts of advanced HER2 positive breast cancer patients. Additionally, we analyzed predictive relevance of clinicopathological factors in this series. Study group included discovery Cohort A (84 patients) and validation Cohort B (75 patients). The only independent variables associated with the development of early BM in both cohorts were the visceral location of first distant relapse [Cohort A: hazard ratio (HR) 7.4, 95 % CI 2.4–22.3; p < 0.001; Cohort B: HR 6.1, 95 % CI 1.5–25.6; p = 0.01] and the lack of trastuzumab administration in the metastatic setting (Cohort A: HR 5.0, 95 % CI 1.4–10.0; p = 0.009; Cohort B: HR 10.0, 95 % CI 2.0–100.0; p = 0.008). A profile including 13 genes was associated with early (≤36 months) symptomatic BM in the discovery cohort. This was refined by qRT-PCR to a 3-gene classifier (RAD51, HDGF, TPR) highly predictive of early BM (HR 5.3, 95 % CI 1.6–16.7; p = 0.005; multivariate analysis). However, predictive value of the classifier was not confirmed in the independent validation Cohort B. The presence of visceral metastases and the lack of trastuzumab administration in the metastatic setting apparently increase the likelihood of early BM in advanced HER2-positive breast cancer

Diet of the grey wolf Canis lupus in Roztocze and Solska Forest, south-east Poland

The diet composition and prey selection of grey wolves (Canis lupus) inhabiting the Roztocze and Solska Forest (south-east Poland) was studied based on an analysis of scats collected in 2001-2002 (n = 84) and 2017-2020 (n = 302). In both periods, wolves preyed mainly on wild ungulates (96.5-96.7% of consumed biomass). Roe deer (Capreolus capreolus) was the most critical wolf prey accounting for 57.8% of consumed biomass in 2001-2002 and 49.2% and 2017-2020, but wolves positively select only wild boar (Jacob's selectivity index D = 0.213 in 2001-2002 and 0.710 in 2017-2020) and fallow deer (D = 0.588 only in 2017-2020). The largest species – moose Alces alces and red deer Cervus elaphus – were consumed less than expected from their share in the ungulate community. Predation on medium-sized wild mammals and domestic animals was low, 0.8-2.2% and 1.1-2.7% of the biomass consumed, respectively. The breadth of the wolf diet was very narrow and identical in both study periods (B = 1.07), while the similarity of diet composition was high (α = 0.999). This study indicated the stability of the wolf diet over two decades and the importance of wild boar as a food source for this carnivore

Community Assessment of the Predictability of Cancer Protein and Phosphoprotein Levels from Genomics and Transcriptomics.

Cancer is driven by genomic alterations, but the processes causing this disease are largely performed by proteins. However, proteins are harder and more expensive to measure than genes and transcripts. To catalyze developments of methods to infer protein levels from other omics measurements, we leveraged crowdsourcing via the NCI-CPTAC DREAM proteogenomic challenge. We asked for methods to predict protein and phosphorylation levels from genomic and transcriptomic data in cancer patients. The best performance was achieved by an ensemble of models, including as predictors transcript level of the corresponding genes, interaction between genes, conservation across tumor types, and phosphosite proximity for phosphorylation prediction. Proteins from metabolic pathways and complexes were the best and worst predicted, respectively. The performance of even the best-performing model was modest, suggesting that many proteins are strongly regulated through translational control and degradation. Our results set a reference for the limitations of computational inference in proteogenomics. A record of this paper's transparent peer review process is included in the Supplemental Information

Mammal responses to global changes in human activity vary by trophic group and landscape

Wildlife must adapt to human presence to survive in the Anthropocene, so it is critical to understand species responses to humans in different contexts. We used camera trapping as a lens to view mammal responses to changes in human activity during the COVID-19 pandemic. Across 163 species sampled in 102 projects around the world, changes in the amount and timing of animal activity varied widely. Under higher human activity, mammals were less active in undeveloped areas but unexpectedly more active in developed areas while exhibiting greater nocturnality. Carnivores were most sensitive, showing the strongest decreases in activity and greatest increases in nocturnality. Wildlife managers must consider how habituation and uneven sensitivity across species may cause fundamental differences in human–wildlife interactions along gradients of human influence.Peer reviewe

The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients

The cause of Huntington disease (HD) is a polyglutamine repeat expansion of more than 36 units in the huntingtin protein, which is inversely correlated with the age at onset of the disease. However, additional genetic factors are believed to modify the course and the age at onset of HD. Recently, we identified the V471A polymorphism in the autophagy-related gene ATG7, a key component of the autophagy pathway that plays an important role in HD pathogenesis, to be associated with the age at onset in a large group of European Huntington disease patients. To confirm this association in a second independent patient cohort, we analysed the ATG7 V471A polymorphism in additional 1,464 European HD patients of the “REGISTRY” cohort from the European Huntington Disease Network (EHDN). In the entire REGISTRY cohort we could not confirm a modifying effect of the ATG7 V471A polymorphism. However, analysing a modifying effect of ATG7 in these REGISTRY patients and in patients of our previous HD cohort according to their ethnic origin, we identified a significant effect of the ATG7 V471A polymorphism on the HD age at onset only in the Italian population (327 patients). In these Italian patients, the polymorphism is associated with a 6-years earlier disease onset and thus seems to have an aggravating effect. We could specify the role of ATG7 as a genetic modifier for HD particularly in the Italian population. This result affirms the modifying influence of the autophagic pathway on the course of HD, but also suggests population-specific modifying mechanisms in HD pathogenesis

Analysis of conclusions from technical opinions issued by the Military Institute of Armament Technology in Zielonka on conditions and possibilities of the safe use of some selected garrison target ranges

W artykule przedstawiono zasadnicze wnioski z opinii technicznych (ekspertyz) opracowanych przez Wojskowy Instytut Techniczny Uzbrojenia (WITU) w Zielonce dla wybranych strzelnic garnizonowych w kraju, w zakresie możliwości i warunków ich dalszego bezpiecznego użytkowania. Scharakteryzowano strzelnicę garnizonową w Dziwnowie jako typowy przykład analizowanych strzelnic i zaprezentowano kompleksowy sposób rozwiązania problemu zaproponowany przez dowództwo jednostki, celem wyeliminowania zagrożeń wynikających z jej eksploatacji w obecnej konfiguracji strzelnicy.Main conclusions from technical opinions developed by the Military Institute of Armament Technology in Zielonka for some selected garrison target ranges on their conditions and possibilities of the safe use are presented in the paper. The garrison shooting range in Dziwnowo is characterised in more details and a set of recommendations proposed by the command of the military unit to avoid threats existing at its current configuration is also presented

Some new types of add-on armours and screens protecting against blasts

W artykule przedstawiono wyniki prac prowadzonych w WITU w zakresie lekkich opancerzeń pojazdów oraz osłon antywybuchowych. Badania były prowadzone na próbkach materiałów pancernych zgodnie z wytycznymi normy STANAG 4569. Przedstawiono koncepcję zastosowania na lekkie opancerzenia pancernej blachy perforowanej w połączeniu z kompozytem aramidowym. Przeprowadzono badania osłon, min. na bazie materiałów polimerowych, chroniących obiekt przed skutkami detonacji ładunku wybuchowego.Some results of work carried out in the Military Institute of Armament Technology on the light add-on armours and anti-blast screens for vehicles are presented in the paper. Tests were carried out on the samples of armoured materials according to STANAG 4569. A concept is presented to use the perforated armour sheet combined with the aramide composite to get the light add-on armours. Tests of screens, made from polymer materials, were carried out to check protection against blasts