Wiley最新文献

Clinical trials have shown that low-dose computed tomography (LDCT) screening reduces lung cancer mortality among selected groups of ever-smokers. Nordic countries have yet to implement lung cancer screening programs in part due to limited evidence on the associated health and economic consequences. This study evaluated the cost-effectiveness of LDCT screening compared with no screening for Norwegian individuals aged 50-74 years who ever smoked, using the Dutch-Belgian NELSON screening-eligibility criteria and trial outcomes. In addition, we evaluated the potential need and value of additional research to improve decision-making about LDCT screening implementation. We developed a probabilistic simulation model reflecting the Dutch-Belgian NELSON trial outcomes and Norwegian epidemiological, cost, and health-related quality-of-life data to evaluate long-term (discounted) health and economic consequences from an extended healthcare perspective. Model outputs included sex-stratified clinical and economic outcomes. Cost-effectiveness was summarized using incremental cost-effectiveness ratios (ICERs). Compared with no screening, NELSON-like LDCT screening provided an additional 0.043 quality-adjusted life-years (QALYs) per screened man for an additional $1286, yielding an ICER of $30,672 per QALY gained. For women, screening yielded greater health benefits and therefore a lower ICER (i.e., $22,249 per QALY gained), though there was greater uncertainty around health benefits. Additional analyses indicated potential value in collecting further evidence on screening-related outcomes to reduce decision uncertainty, particularly for women. Given Norwegian benchmarks for good value and achieving similar mortality benefits to the NELSON trial, LDCT lung cancer screening for individuals who ever smoked under "NELSON-like" criteria may be considered cost-effective for both men and women in Norway.

To what extent environmental factors are associated with liver diseases and liver cancer among individuals with varying levels of genetic predisposition remains unknown. In 353,703 UK Biobank participants, a validated polygenic risk score (PRS) for liver steatosis (PNPLA3, TM6SF2, MBOAT7, GCKR, and HSD17B13 variants) and an environmental risk score (ERS) from six known risk factors (obesity, type 2 diabetes mellitus, smoking, frequent alcohol intake, physical inactivity, and infrequent coffee intake) were calculated. Incident outcomes were identified from hospital records and cancer registries. The genetics by environment (G × E) interactions and population attributable risks (PARs) for each ERS tertile were calculated, stratified by PRS tertile. We identified 3801 MASLD, 3458 liver cirrhosis, and 674 liver cancer in a median 13.6-year follow-up. PRS contributes 13.3% (95%CI: 10.8-15.9%) for MASLD, 8.2% (5.5-10.9%) for cirrhosis, and 14.7% (8.6-20.7%) for liver cancer. ERS contributes 34.1% (32.1-36.1%) for MASLD, 25.6% (23.1-28.1%) for cirrhosis, and 25.4% (19.2-31.5%) for liver cancer. Significant G × E interactions (p-interaction <.05) were found for liver cirrhosis and liver cancer where risk attributed to ERS was greater in the high versus the low PRS tertile. For liver cancer, PAR of the high versus low ERS was 36.5% (27.3-45.0%) in the high PRS tertile, compared to 16.5% (4.7-27.9%) in the low PRS tertile. High environmental risk showed greater contributions among participants with high genetic risk for liver cirrhosis and liver cancer. These stronger G × E interactions in clinically severe liver diseases underscore the importance of risk stratification and precision medicine.

Background and aims: Despite multiple interventions, national-level trends of buprenorphine prescription use plateaued during a period of increasing opioid overdose deaths in the United States; county-level use trends may provide additional insights. We aimed to analyze county-level trends in buprenorphine treatment for opioid use disorder (OUD) and determine factors associated with trends.

Design: In this retrospective study, we used an iterative hierarchical cluster analysis to group counties with similar buprenorphine prescription use trends and then compared characteristics between clusters.

Setting: Retail pharmacy dispensing in the United States from 2018 to 2022.

Participants: Data on prescriptions dispensed for buprenorphine medications labeled to treat OUD.

Measurements: We analyzed standardized mean differences (SMD) and 95% confidence intervals (CI) of county-level characteristics between counties with varying trends in buprenorphine utilization.

Findings: Prescriptions dispensed for buprenorphine significantly increased in 924 counties (28% of US population) from 2018 to 2022 but declined in 839 counties (50%) from 2021 to 2022. Counties with decreasing (versus increasing) use had significantly higher opioid overdose death rates (SMD = -0.23; 95% CI = -0.34 to -0.13) and unemployment (SMD = -0.36; 95% CI = -0.46 to -0.27). Counties with increasing trends had higher percentages of residents in rural areas (SMD = 0.26; 95% CI = 0.16-0.35) and prescribing by nurse practitioners (SMD = 0.39; 95% CI = 0.29-0.48).

Conclusions: From 2018 to 2022, buprenorphine use as treatment for opioid use disorder increased in some United States counties, notably counties with more residents living in rural areas and counties with more prescriptions written by nurse practitioners. However, declining use in other US counties suggest challenges persist in increasing access to medication for treament of opioid use disorder, hindering progress in addressing the opioid crisis.

This study investigated the mechanisms of cadmium (Cd) tolerance and root exudate-mediated soil activation in mulberry (Morus alba L.), a promising species for phytoremediation. Hydroponic experiments with Cd-tolerant seedlings exposed to 5 and 50 mg/L Cd revealed a biphasic concentration-dependent response. Low Cd induced negligible biological effects, whereas high Cd triggered substantial disturbances across multiple biological levels, including morphological alterations, physiological dysregulation and disrupted elemental accumulation patterns. Metabolomic profiling indicated that Cd stress significantly altered the secretion patterns of 17 root exudate metabolites in mulberry, exemplified by the upregulation of sucrose, lactose and 4-acetylbutyric acid, and the downregulation of β-alanine and myo-inositol. Further pathway enrichment analysis linked these differential metabolites to 17 metabolic pathways, with carbohydrate and amino acid metabolism as the main Cd-responsive pathways, suggesting their core role in mediating mulberry's Cd resistance. Root exudates enhanced soil Cd mobilisation in a positive concentration-dependent yet negative time-dependent manner. Consequently, mulberry adapts to Cd stress via metabolic reprogramming of root exudates-a strategic trade-off that serves a dual role by enhancing plant tolerance while simultaneously increasing Cd bioavailability in the soil. This insight provides a foundational framework for phytoremediation, centred on exudate management and the selection of stress-tolerant varieties.

Fruit peel colour is a critical quality trait in chayote, directly influencing its commercial value. However, the molecular mechanisms underlying peel colour variation remain poorly understood. In this study, we observed higher chlorophyll content in deep green peel (DGP), green peel (GP), and light green peel (LGP) compared to white peel (WP). Additionally, WP exhibited reduced chloroplast number and structural disorganisation, with metabolomics confirming the reduction of galactolipids (DGDG and MGDG) essential for membrane stability. Integrated transcriptomic, resequencing, and WGCNA analyses identified SeAPRR2 as a candidate gene controlling peel colour, with a ~ 13-kb deletion in WP responsible for the white phenotype. This deletion triggered downregulation of DEGs related to chlorophyll biosynthesis and photosynthesis pathways. DAP-Seq revealed that SeAPRR2 binds to the cis-element (AAT(G/C)ATT) in promoters. Through Y1H, DLR, GUS activity, EMSA, and molecular docking assays, we confirmed that SeAPRR2 activates the transcription of SeHEMA1 and SeLHCB4 via promoter binding. Heterologous overexpression of SeAPRR2, SeHEMA1, and SeLHCB4 in tomato significantly elevated chlorophyll content and increased chloroplast number. Collectively, this study establishes SeAPRR2 as a master regulator of peel colour through the SeAPRR2-SeHEMA1/SeLHCB4 module. The large-fragment deletion mechanism provides novel genetic insights for breeding colour traits in cucurbit crops.

For the vast majority of the evolutionary history of Homo sapiens, a range of natural environments defined the parameters within which selection shaped human biology. Although human-induced alterations to the terrestrial biosphere have been evident for over 10,000 years, the pace and scale of change has accelerated dramatically since the onset of the Industrial Revolution in the late 18th century. Industrialisation has profoundly transformed our various natural habitats, driving rapid urban expansion, increasing reliance on fossil fuel energy and causing environmental contamination, ecosystem degradation and biodiversity loss. Today, most of the world's population resides in highly industrialised urban areas. These new primary human habitats differ fundamentally from our ancestral natural habitats, creating novel environmental challenges while, simultaneously, lacking key natural features linked to health and function. Although the adaptive capacity of humans has enabled survival in diverse and fluctuating environmental conditions, this capacity is limited. It is possible that the rapid industrialisation of our habitat is outpacing our adaptive capacity and is imposing selective pressures that threaten our evolutionary fitness. A growing body of observational and experimental evidence suggests that industrialisation negatively impacts key biological functions essential for survival and reproduction and, therefore, evolutionary fitness. Specifically, environmental contamination arising directly from industrial activities (e.g. air, noise and light pollution, microplastic accumulation) is linked to impaired reproductive, immune, cognitive and physical function. Chronic activation of the stress response systems, which further impairs these biological functions, also appears more pronounced in industrialised areas. Here, we consider whether the rapid and extensive environmental shifts of the Anthropocene have compromised the fitness of Homo sapiens. We begin by contrasting contemporary and ancestral human habitats before assessing the effects of these changes on core biological functions that underpin evolutionary fitness. We then ask whether industrialisation has created a mismatch between our primarily nature-adapted biology and the novel challenges imposed by contemporary industrialised environments - a possibility that we frame through the lens of the Environmental Mismatch Hypothesis. Finally, we explore experimental approaches to test this hypothesis and discuss the broader implications of such a mismatch.

Traits that affect organismal fitness are often highly genetically variable. This genetic variation is vital for populations to adapt to their environments, but it is also surprising given that nature - after all - 'selects' the best genotypes at the expense of those that fall short. Explaining the extensive genetic variation of fitness-related traits is thus a longstanding puzzle in evolutionary biology, with cascading implications for ecology, conservation, and human health. Balancing selection - an umbrella term for scenarios in which natural selection maintains genetic variation - is a century-old explanation to resolve this puzzle that has gained recent momentum from genome-scale methods for detecting it. Yet evaluating whether balancing selection can, in fact, resolve the puzzle is challenging, given the logistical constraints of distinguishing balancing selection from alternative hypotheses and the daunting collection of theoretical models that formally underpin this debate. Here, we track the development of balancing selection theory over the last century and provide an accessible review of this rich collection of models. We first outline the range of biological scenarios that can generate balancing selection. We then examine how fundamental features of genetic systems - non-random mating between individuals, ploidy levels, genetic drift, linkage, and genetic architectures of traits - have been progressively incorporated into the theory. We end by linking these theoretical predictions to ongoing empirical efforts to understand the evolutionary processes that explain genetic variation.

The biological effects of weak magnetic fields have long been a subject of scientific inquiry, with increasing evidence supporting their influence on biochemical, physiological, and behavioural processes. This review describes three primary mechanisms of magnetoreception that have been identified in migrating animals: use of magnetite in sensitive cells, sensitive electroreceptors, and spin dynamics in cryptochrome radical pairs. It also critically examines the potential of the radical-pair mechanism to serve as a universal explanation for the diverse non-sensory biological effects of weak magnetic fields, including extremely low-frequency magnetic fields, static magnetic fields, and hypomagnetic conditions. Understanding how weak magnetic fields influence radical-pair processes could revolutionize our approach to bioelectromagnetic interactions and provide new avenues for development of medical and technological applications. Future research should focus on direct real-time monitoring of radical-pair-mediated biochemical reactions, evaluating the interplay between magnetic fields, light exposure, and temperature, and refining theoretical models to bridge the gap between quantum-scale interactions and macroscopic biological effects. Addressing these questions will be essential in determining whether the radical-pair mechanism can serve as a unifying principle in magnetobiology.