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Purpose: All patients living with cancer, including those with metastatic cancer, are encouraged to be physically active. This paper examines the secondary endpoints of an aerobic exercise intervention for men with metastatic prostate cancer. Methods: ExPeCT (Exercise, Prostate Cancer and Circulating Tumour Cells), was a multi-centre randomised control trial with a 6-month aerobic exercise intervention arm or a standard care control arm. Exercise adherence data was collected via heart rate monitors. Quality of life (FACT-P) and physical activity (self-administered questionnaire) assessments were completed at baseline, at 3 months and at 6 months. Results: A total of 61 patients were included (69.4 ± 7.3 yr, body mass index 29.2 ± 5.8 kg/m2). The median time since diagnosis was 34 months (IQR 7–54). A total of 35 (55%) of participants had > 1 region affected by metastatic disease. No adverse events were reported by participants. There was no effect of exercise on quality of life (Cohen’s d = − 0.082). Overall adherence to the supervised sessions was 83% (329 out of 396 possible sessions attended by participants). Overall adherence to the non-supervised home exercise sessions was 72% (months 1–3) and 67% (months 3–6). Modelling results for overall physical activity scores showed no significant main effect for the group (p-value = 0.25) or for time (p-value = 0.24). Conclusion: In a group of patients with a high burden of metastatic prostate cancer, a 6-month aerobic exercise intervention did not lead to change in quality of life. Further exercise studies examining the role of exercise for people living with metastatic prostate cancer are needed. Trial Registration: The trial was registered at clinicaltrials.gov (NCT02453139) on May 25th 2015. [ABSTRACT FROM AUTHOR]

During extravehicular activities (EVAs), astronauts are heavily dependent on the Mission Center (MCC) and their Intra-Vehicular Astronaut (IVA) counterparts. Each procedure step in a mission is relayed to the astronaut through a real-time voice loop, and emergency procedures are written on cuff checklists that astronauts must read from their spherically shaped helmet. In all situations, crew members heavily rely on IVA or MCC support, especially when they do not understand a procedure or need help with a specific problem. However, it can be hard to communicate procedures effectively due to a lack of visual diagrams and situational awareness between the two parties. To improve EVA efficiency, we investigated the use of a virtual whiteboard on a heads-up display during a lunar surface EVA task with virtual reality (VR). The virtual whiteboard allows MCC to send additional visual guidance (e.g., drawings and annotations) overlayed on the astronaut's visual field of view to better assist with mission tasks. We conducted a between-subjects experiment where 21 participants were asked to accomplish a rover repair procedure, with (n = 11) and without (n = 10) the virtual whiteboard, using a VR lunar environment with support of a research proctor acting as MCC. The whiteboard group completed the rover procedure 39.1% faster than the non-whiteboard group, and this difference was statistically significant (p = 0.017). The total number of words exchanged during the experimental sessions was not statistically different between groups (p = 0.99). However, participants in the whiteboard group showed a tendency to talk less than their counterparts, while the research proctor in the whiteboard group showed a tendency to speak more. Finally, analysis of the spatial locations during the experiment indicated that whiteboard participants stayed closer to the rover, showing a better focus on the task at hand and therefore short completion times. The results of this experiment inform future development of AR spacesuit technologies for future planetary exploration EVA operations. [ABSTRACT FROM AUTHOR]

CAG-expanded ATXN7 has been previously defined in the pathogenesis of spinocerebellar ataxia type 7 (SCA7), a polyglutamine expansion autosomal dominant cerebellar ataxia. Pathology in SCA7 occurs as a result of a CAG triplet repeat expansion in excess of 37 in the first exon of ATXN7, which encodes ataxin-7. SCA7 presents clinically with spinocerebellar ataxia and cone-rod dystrophy. Here, we present a novel spinocerebellar ataxia variant occurring in a patient with mutations in both ATXN7 and TOP1MT, which encodes mitochondrial topoisomerase I (top1mt). Using machine-guided, unbiased microscopy image analysis, we demonstrate alterations in ataxin-7 subcellular localization, and through high-fidelity measurements of cellular respiration, bioenergetic defects in association with top1mt mutations. We identify ataxin-7 Q35P and top1mt R111W as deleterious mutations, potentially contributing to disease states. We recapitulate our mutations through Drosophila genetic models. Our work provides important insight into the cellular biology of ataxin-7 and top1mt and offers insight into the pathogenesis of spinocerebellar ataxia applicable to multiple subtypes of the illness. Moreover, our study demonstrates an effective pipeline for the characterization of previously unreported genetic variants at the level of cell biology. Neurodegenerative disease: Finding new mutations associated with ataxia Two genetic mutations combine to cause a novel variant of spinocerebellar ataxia (SCA), a rare neurodegenerative disease. SCA affects the cerebellum, a brain region that controls movement, causing progressive coordination problems. Presented with a patient with an atypical form of SCA, Ray Truant at McMaster University in Hamilton, Canada, and co-workers used whole-genome sequencing to identify mutations in two genes: ATXN7, involved in cytoskeleton maintenance, and TOP1MT, in mitochondria, the cellular powerhouses. Unable to see differences in the affected tissues using routine microscopy, the researchers used computer-guided microscopy image analysis to determine that the altered ATXN7 protein was mis-located in cells. High-fidelity measurements of cell metabolism showed that mitochondria with altered TOP1MT produced insufficient energy. These results clarify the genetics of ataxia, and offer new ways to identify the effects of rare mutations. [ABSTRACT FROM AUTHOR]

Metastatic prostate cancer (mPC) comprises a spectrum of diverse phenotypes. However,the extent of inter- and intra-tumor heterogeneity is not established. Here we use digital spatial profiling (DSP) technology to quantitate transcript and protein abundance in spatially-distinct regions of mPCs. By assessing multiple discrete areas across multiple metastases, we find a high level of intra-patient homogeneity with respect to tumor phenotype. However,there are notable exceptions including tumors comprised of regions with high and low androgen receptor (AR) and neuroendocrine activity. While the vast majority of metastases examined are devoid of significant inflammatory infiltrates and lack PD1, PD-L1 and CTLA4,the B7-H3/CD276 immune checkpoint protein is highly expressed, particularly in mPCs with high AR activity. Our results demonstrate the utility of DSP for accurately classifying tumor phenotype, assessing tumor heterogeneity, and identifying aspects of tumor biology involving the immunological composition of metastases. [ABSTRACT FROM AUTHOR]

Whole exome sequencing (WES) can be used to efficiently identify de novo genetic variants associated with genetically heterogeneous conditions including intellectual disabilities. We have performed WES for 4102 (1847 female; 2255 male) intellectual disability/developmental delay cases and we report five patients with a neurodevelopmental disorder associated with developmental delay, intellectual disability, behavioral problems, hypotonia, speech problems, microcephaly, pachygyria and dysmorphic features in whom we have identified de novo missense and canonical splice site mutations in CSNK2A1, the gene encoding CK2α, the catalytic subunit of protein kinase CK2, a ubiquitous serine/threonine kinase composed of two regulatory (β) and two catalytic (α and/or α′) subunits. Somatic mutations in CSNK2A1 have been implicated in various cancers; however, this is the first study to describe a human condition associated with germline mutations in any of the CK2 subunits. [ABSTRACT FROM AUTHOR]

Coffin-Siris and Nicolaides-Baraitser syndromes (CSS and NCBRS) are Mendelian disorders caused by mutations in subunits of the BAF chromatin remodeling complex. We report overlapping peripheral blood DNA methylation epi-signatures in individuals with various subtypes of CSS (ARID1B, SMARCB1, and SMARCA4) and NCBRS (SMARCA2). We demonstrate that the degree of similarity in the epi-signatures of some CSS subtypes and NCBRS can be greater than that within CSS, indicating a link in the functional basis of the two syndromes. We show that chromosome 6q25 microdeletion syndrome, harboring ARID1B deletions, exhibits a similar CSS/NCBRS methylation profile. Specificity of this epi-signature was confirmed across a wide range of neurodevelopmental conditions including other chromatin remodeling and epigenetic machinery disorders. We demonstrate that a machine-learning model trained on this DNA methylation profile can resolve ambiguous clinical cases, reclassify those with variants of unknown significance, and identify previously undiagnosed subjects through targeted population screening. [ABSTRACT FROM AUTHOR]