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Abstract Restoring degraded peatlands is a promising strategy for mitigating carbon emissions. Large‐scale landscape transformations, such as rewetting of land used for intensive agriculture, often lead to conflicts. Elicitation of the relational values acting as barriers to landscape transformation may support the resolution or taming of such conflicts. This study aimed to explore the relational values associated with a transforming peatland site in Northern Germany. We focused on the value of living and non‐living peat landscape elements; cultural heritage values and identities; educational values; spiritual values; recreational values; and sensory, affective and cognitive experiences. Additionally, we sought to understand how past landscape changes have influenced these values. We conducted interviews with land managers and local residents. Using an art‐based research method, we created six thematic participant‐voiced poems that capture the diverse peatland values. Subsequent interpretation of these poems revealed three key observations: the importance of multisensory experiences; the significance of specific living elements; and the deep cultural and historical values linked to peat landscapes. Landscape changes impact peat landscape values, potentially weakening bonds between people and the peatland. Our study indicates that considering the cultural and historical significance of landscapes may prevent conflicts and foster support for peatland restoration. Ensuring the well‐being of those living and working in these areas requires value‐inclusive landscape planning that embraces a broader focus on relational values. This also involves the potential promotion of value shifts. Such an approach may cultivate a more sustainable and inclusive transformation of the landscape. Read the free Plain Language Summary for this article on the Journal blog.

Treatment with anaplastic lymphoma kinase (ALK) inhibitors significantly improves outcome for non‐small‐cell lung cancer (NSCLC) patients with ALK‐rearranged tumors. However, clinical resistance typically develops over time and, in the majority of cases, resistance mechanisms are ALK‐independent. We generated tumor cell cultures from multiple regions of an ALK‐rearranged clinical tumor specimen and deployed functional drug screens to identify modulators of ALK‐inhibitor response. This identified a role for PI3Kβ and EGFR inhibition in sensitizing the response regulating resistance to ALK inhibition. Inhibition of ALK elicited activation of EGFR, and subsequent MAPK and PI3K‐AKT pathway reactivation. Sensitivity to ALK targeting was enhanced by inhibition or knockdown of PI3Kβ. In ALK‐rearranged primary cultures, the combined inhibition of ALK and PI3Kβ prevented the EGFR‐mediated ALK‐inhibitor resistance, and selectively targeted the cancer cells. The combinatorial effect was seen also in the background of TP53 mutations and in epithelial‐to‐mesenchymal transformed cells. In conclusion, combinatorial ALK‐ and PI3Kβ‐inhibitor treatment carries promise as a treatment for ALK‐rearranged NSCLC.

Abstract Background Excess weight is convincingly associated with several cancers, but the association with ovarian cancer is insufficiently clarified, in particular regarding subgroups defined by menopausal status and ovarian cancer histologic type. Aims We carried out a comprehensive systematic review and meta‐analysis of overweight and obesity in relation to ovarian cancer with focus on different subgroups. Methods and Results We searched PubMed and Web of Science for relevant cohort and case–control studies published from inception to June 2021 in English language and using a clear definition of overweight and obesity. We combined maximally adjusted risk estimates using a random effects model. We analyzed data from 15 cohort and 26 case–control studies, including 28 471 ovarian cancer cases. The relative risk of ovarian cancer for overweight and obesity was 1.06 (95% confidence interval [CI] = 1.00–1.12) and 1.19 (95% CI = 1.11–1.28), respectively. Among premenopausal women, increased ovarian cancer risk was noted for overweight (RR 1.34; 95% CI = 1.03–1.75) and obesity (RR 1.51; 95% CI = 1.21–1.88). By comparison, among postmenopausal women no statistically significant association was found for overweight (RR 1.00; 95% CI 0.87–1.14) and obesity (RR1.03; 95% CI = 0.82–1.31). Increased risk was found for mucinous (RR 1.44; 95% CI = 1.03–2.01) and clear cell (RR 1.82; 95% CI = 1.11–2.99) ovarian cancer subtypes, but not for serous (RR1.12; 95% CI = 0.84–1.50;) and endometroid subtypes (RR1.24; 95% CI =0.96–1.60). Conclusions Obesity is associated with increased ovarian cancer risk. That relation is largely due to a positive association between adiposity and ovarian cancer among premenopausal but not postmenopausal women and among cases with mucinous and clear cell but not serous or endometrioid histology.

Abstract Objectives Both positive and negative including psychotic‐like cannabis intoxication effects are well‐established. Yet, consequences for consumption patterns, addictive behavior or psychotic developments are poorly researched in general, in Germany not at all. Thus, objective was to develop the first German‐language questionnaire operationalizing acute cannabis intoxication effects, based on the original “Cannabis Experience Questionnaire” (CEQ). Methods After expert translation of the CEQ, items related to acute intoxication effects were presented to a sample of 537 cannabis users. Four‐ and five‐factorial solutions of explorative factor analysis with a randomly split sub‐sample 1 were cross‐validated by confirmatory factor analysis on sub‐sample 2. Results After content review of factors and analysis of external validity, a 17 item four‐factorial model was approved. Factors are (1) “paranoia/dysphoria”, (2) “confusion/disorientation”, (3) “euphoria/creativity”, (4) “psychosis‐like/loss of reality”. Model fit is satisfactory (RMSEA = 0.058, SRMR = 0.065, CFI = 0.929, TLI = 0.914). Correlations with corresponding external measures support construct validity. Conclusions The present questionnaire is a time‐efficient, valid and reliable instrument. Thus, predictors of different cannabis intoxication effects can be analysed for the first time in German‐speaking area, as well as their significance for substance use or psychosis risk.

BackgroundAngiotensin‐converting enzyme (ACE) plays a major role in blood pressure regulation and cardiovascular homeostasis. Contrary to the assumption that ACE levels are stable, circulating ACE has been shown to be altered in obesity and weight loss. We sought to examine effects of a high‐saturated‐fat (HF) diet on ACE within the NUtriGenomic Analysis in Twins (NUGAT) study. Methods and ResultsForty‐six healthy and nonobese twin pairs initially consumed a carbohydrate‐rich, low‐fat diet over a period of 6 weeks to standardize for nutritional behavior prior to the study, followed by 6 weeks of HF diet under isocaloric conditions. After 6 weeks of HF diet, circulating ACE concentrations increased by 15% (P=1.6×10−30), accompanied by an increased ACE gene expression in adipose tissue (P=3.8×10−6). Stratification by ACE rs4343, a proxy for the ACE insertion/deletion polymorphism (I/D), revealed that homozygous carriers (GG) of the variant had higher baseline ACE concentrations (P=7.5×10−8) and additionally showed a 2‐fold increase in ACE concentrations in response to the HF diet as compared to non‐ or heterozygous carriers (AA/AG, P=2×10−6). GG carriers also responded with higher systolic blood pressure as compared to AA/AG carriers (P=0.008). The strong gene‐diet interaction was confirmed in a second independent, cross‐sectional cohort, the Metabolic Syndrome Berlin Potsdam (MeSyBePo) study. ConclusionsThe HF‐diet‐induced increase of ACE serum concentrations reveals ACE to be a potential molecular link between dietary fat intake and hypertension and cardiovascular disease (CVD). The GG genotype of the ACE rs4343 polymorphism represents a robust nutrigenetic marker for an unfavorable response to high‐saturated‐fat diets. Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT01631123.