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Transient receptor potential melastatin‐4 channel (TRPM4) dysregulation contributes to heart conditions, immune diseases, and cervical and prostate cancer. Up to now, the involvement of TRPM4 in colorectal cancer (CRC) pathophysiology remains unknown. Here, we investigated tumor tissue microarrays from 379 CRC patients and analyzed TRPM4 protein expression, tumor characteristics, and clinical outcome. High TRPM4 protein expression was associated with unfavorable tumor features characteristic for epithelial–mesenchymal transition and infiltrative growth patterns, that is, a high number of tumor buds and a low percentage in tumor border configuration. Compared to CRC cells representing early cancer stages, TRPM4 protein expression was the highest in cells representing late‐stage metastatic cancer. Investigation of CRC cell line HCT116 and five CRISPR/cas9 TRPM4 knockout clones demonstrated that TRPM4 exhibited large Na+ current densities (~ 60 pA/pF). In addition, CRISPR/cas9 TRPM4 knockout clones showed a tendency toward decreased migration and invasion, cell viability, and proliferation and exhibited a shift in cell cycle when compared to HCT116. Stable overexpression of TRPM4 (TRPM4 wild‐type) in two CRISPR/cas9 TRPM4 knockout clones rescued the decrease in cell viability and cell cycle shift. Stable overexpression of a nonconducting, dominant‐negative TRPM4 mutant (TRPM4 D894A) did not rescue the decrease in viability or cell cycle shift. Taken together, these findings pointed to TRPM4 ion channel conductivity as the underlying mechanism for decreased viability and cell cycle shift in the TRPM4 knockout clones. Together with previous findings, our present data suggest that TRPM4 plays a versatile role in cancer cell proliferation, cell cycle, and invasion.

Abstract Accurate variant calling and genotyping represent major limiting factors for downstream applications of single-cell genomics. Here, we report Conbase for the identification of somatic mutations in single-cell DNA sequencing data. Conbase leverages phased read data from multiple samples in a dataset to achieve increased confidence in somatic variant calls and genotype predictions. Comparing the performance of Conbase to three other methods, we find that Conbase performs best in terms of false discovery rate and specificity and provides superior robustness on simulated data, in vitro expanded fibroblasts and clonal lymphocyte populations isolated directly from a healthy human donor.

Background Stroke is one of the largest single-condition sources of the global burden of non-communicable disease in terms of disability-adjusted life-years and monetary costs, directly as well as indirectly in terms of informal care and productivity loss. The objective was to assess the population afflicted with ischaemic stroke in working age in the context of universal healthcare and social insurance; to estimate the levels of absence from work, the indirect costs related to that and to assess the associated patient characteristics.Methods This was a retrospective register-based study; all individuals registered with an ischaemic stroke during 2008–2011 in seven Swedish regions, covering the largest cities as well as more rural areas, were included. Individual-level data were used to compute net days of sick leave and disability pension, indirect costs due to productivity loss and to perform regression analysis on net absence from work to assess the associated factors. Costs related to productivity loss were estimated using the human capital approach.Results Women had significantly fewer net days of sick leave and disability pension than men after multivariable adjustment, and high-income groups had higher levels of sick leave than low-income groups. There were no significant differences for participants regarding educational level, region of birth or civil status. Indirect monetary costs amounted to €17 400 per stroke case during the first year, totalling approximately €169 million in Sweden.Conclusion The individual’s burden of stroke is heavy in terms of morbidity, and the related productivity loss for society is immense. Income-group differences point to a socioeconomic gradient in the utilisation of the Swedish social insurance.

Although potential urban green space accessibility is being discussed widely, specific barriers that affect accessibility are often under-estimated. They do not equate to limited or uneven accessibility nor are they exclusively related to physical settings. Rather, the range of barriers and their complex interactions, including people’s perceptions, personal conditions, and institutional frameworks, make this topic less clear cut and difficult to put into practice for planning purposes. Given the importance of barriers when people make decisions, we present a conceptual framework to capture the cumulative and interactive effects of different barriers on realizing recreational benefits of urban green spaces. The framework classifies physical, personal, and institutional barriers and highlights their interactions based on three case studies: Stockholm, Leipzig, and Lodz. We argue that constraints to the accessibility of urban green spaces are not so much the interactions between various physical, personal, and institutional barriers, but more the significance that beneficiaries assign to them as perceived barrier effects. Studying barriers seeks to improve the knowledge about the non-use of urban green spaces and to enable us to draw conclusions about the actual accessibility of recreational benefits. Deduced from the conceptual framework, three pathways are contrasted for improving accessibility to the recreational benefits of urban green spaces: the environment, knowledge, and engagement. We argue that these pathways should not be a diffuse objective, but a sensitive and scale-dependent re-balance of individual, physical, and institutional factors for considering justice in environmental and green space planning and management. Our systematic conceptualization and classification of multidimensional barriers enables a more comprehensive understanding of individuals’ decisions in terms of accessing recreational benefits.

Decision support tools for incentivizing environmentally sound decisions in building design, such as LCA (life cycle assessment), have been highlighted as an essential feature for enhancing the realization of more sustainable buildings. Nevertheless, the use of LCA to support decisions in building design is still limited in practice. A better understanding of the social dynamics and detailed contexts of the decisions leading up to a final building design is therefore critical for better integration of LCA-based information in the decision-making processes. This paper reports a qualitative, semi-structured interview study of single-family home producers in Sweden and their decision-making in relation to climate mitigation, with a particular focus on embodied carbon mitigation. By studying a specific branch of the building and construction sector, a more in-depth record can be obtained of the particularities of implementation contexts and decision-making situations in which LCA may, or may not, have a role in driving climate mitigation. Four primary decision contexts in which LCA may have an influential role to drive embodied carbon reduction include: (1) the development of building systems, (2) development and offering of house models, (3) the selection of construction products for the building system as well as for the offer of add-on products to customers, and (4) the dialogues in the individual house-buyer projects. Decision-making that affects sustainable outcomes in this part of the sector is very much dependent on a supporting regulatory context. Over the years, using building LCA in early design stages, for optimization towards low-impact final buildings, has been a repeatedly promoted recommendation both in academia and practice. This study, however, reveals that such a conclusion is too simplistic. The different overarching decision contexts identified for this particular branch display the variety of needs for life cycle-based information.