Geertsenrohde5894

Classification of cancer should lead to informative patients' stratification and selective therapeutic vulnerabilities. A pathway-based classification of glioblastoma uncovered a mitochondrial subtype with a unique sensitivity to inhibitors of oxidative phosphorylation. Precision targeting of cancer metabolism could provide therapeutic opportunities to a lethal neoplasm and be translated to other tumour types.Genomic DNA is folded into loops and topologically associating domains (TADs), which serve important structural and regulatory roles. It has been proposed that these genomic structures are formed by a loop extrusion process, which is mediated by structural maintenance of chromosomes (SMC) protein complexes. Recent single-molecule studies have shown that the SMC complexes condensin and cohesin are indeed able to extrude DNA into loops. In this Review, we discuss how the loop extrusion hypothesis can explain key features of genome architecture; cellular functions of loop extrusion, such as separation of replicated DNA molecules, facilitation of enhancer-promoter interactions and immunoglobulin gene recombination; and what is known about the mechanism of loop extrusion and its regulation, for example, by chromatin boundaries that depend on the DNA binding protein CTCF. We also discuss how the loop extrusion hypothesis has led to a paradigm shift in our understanding of both genome architecture and the functions of SMC complexes.It is commonly assumed that the strong sexual dimorphism of the human pelvis evolved for delivering the relatively large human foetuses. Here we compare pelvic sex differences across modern humans and chimpanzees using a comprehensive geometric morphometric approach. Even though the magnitude of sex differences in pelvis shape was two times larger in humans than in chimpanzees, we found that the pattern is almost identical in the two species. We conclude that this pattern of pelvic sex differences did not evolve de novo in modern humans and must have been present in the common ancestor of humans and chimpanzees, and thus also in the extinct Homo species. We further suggest that this shared pattern was already present in early mammals and propose a hypothesis of facilitated variation as an explanation the conserved mammalian endocrine system strongly constrains the evolution of the pattern of pelvic differences but enables rapid evolutionary change of the magnitude of sexual dimorphism, which in turn facilitated the rapid increase in hominin brain size.

Data on the association between visual difficulty and physical activity (PA) from low- and middle-income countries (LMICs) are scarce. Thus, the aim of the study was to investigate the association between visual difficulty and PA among adults from 36 LMICs, and to assess the mediators in this association.

Cross-sectional, community-based, predominantly nationally representative data from the World Health Survey were analysed. The final sample included 199,110 individuals aged ≥18 years [mean (SD) age 38.6 (16.1) years; 49.4% males]. Visual difficulty referred to having severe/extreme difficulties in seeing and recognizing a person that the participant knows across the road. Low PA was defined as not complying with PA recommendations of 150 min of moderate-vigorous PA per week. Multivariable logistic regression, meta-analysis, and mediation analysis were conducted to assess associations.

Meta-analysis based on country-wise multivariable logistic regression analysis showed that overall, visual difficulty is associated with a 1.53 (95% CI = 1.38-1.71) times higher odds for low PA. Particularly strong associations were observed in males (OR = 1.72; 95% CI = 1.45-2.05) and adults aged ≥65 years (OR = 1.95; 95% CI = 1.67-2.29). 6-Diazo-5-oxo-L-norleucine supplier Interpersonal activities, cognition, and sleep/energy explained >10% of the association between visual difficulty and low PA.

In conclusion, we found evidence that especially in the case of males and older adults with visual difficulties in LMICs, there were low levels of engagement with PA. Addressing issues such as interpersonal activities, cognition, and sleep/energy in people with visual difficulties may increase levels of PA.

In conclusion, we found evidence that especially in the case of males and older adults with visual difficulties in LMICs, there were low levels of engagement with PA. Addressing issues such as interpersonal activities, cognition, and sleep/energy in people with visual difficulties may increase levels of PA.Sensitive and robust outcome measures of retinal function are pivotal for clinical trials in age-related macular degeneration (AMD). A recent development is the implementation of artificial intelligence (AI) to infer results of psychophysical examinations based on findings derived from multimodal imaging. We conducted a review of the current literature referenced in PubMed and Web of Science among others with the keywords 'artificial intelligence' and 'machine learning' in combination with 'perimetry', 'best-corrected visual acuity (BCVA)', 'retinal function' and 'age-related macular degeneration'. So far AI-based structure-function correlations have been applied to infer conventional visual field, fundus-controlled perimetry, and electroretinography data, as well as BCVA, and patient-reported outcome measures (PROM). In neovascular AMD, inference of BCVA (hereafter termed inferred BCVA) can estimate BCVA results with a root mean squared error of ~7-11 letters, which is comparable to the accuracy of actual visual acuity assessment. Further, AI-based structure-function correlation can successfully infer fundus-controlled perimetry (FCP) results both for mesopic as well as dark-adapted (DA) cyan and red testing (hereafter termed inferred sensitivity). Accuracy of inferred sensitivity can be augmented by adding short FCP examinations and reach mean absolute errors (MAE) of ~3-5 dB for mesopic, DA cyan and DA red testing. Inferred BCVA, and inferred retinal sensitivity, based on multimodal imaging, may be considered as a quasi-functional surrogate endpoint for future interventional clinical trials in the future.