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Understanding tumor cell dynamics can improve prognosis and treatment but remains limited for lung adenocarcinoma in people who have never smoked (NS-LUAD). With RNA sequencing data from 684 NS-LUAD cases and validation in an independent dataset, we identified three subtypes with distinct phenotypic traits and cell compositions. Additional genomic and histologic data further characterized the subtypes. "Steady," marked by low proliferation, high alveolar cell fraction, moderate-to-well differentiation, and fewer driver gene alterations, is linked to prolonged survival and low immune evasion. "Proliferative" shows high proliferation markers, TP53 mutations, and gene fusions. "Chaotic," with high epithelial-to-mesenchymal transition markers, has the worst prognosis, even within stage I tumors. Lacking known molecular or histologic characteristics, this aggressive subtype is solely identified by transcriptomic data. A 60-gene signature recapitulates the classification and predicts survival even within subgroups based on tumor stage or known genomic features, emphasizing its potential for improving early-stage NS-LUAD prognostication in clinical settings. SIGNIFICANCE:The transcriptome of 684 NS-LUAD identifies three subtypes with different cellular dynamics and genomic and morphologic features. A 60-gene signature accurately stratifies subjects for mortality risk, even in stage I, offering a potential clinically applicable tool for treatment decision-making in patients with NS-LUAD. See related commentary by Azizi et al., p. 423.
This study investigated risk factors associated with HNC by subsite including oral cavity cancer (OCC), oropharyngeal cancer (OPC), and laryngeal cancer (LC) among former smokers in the International Head and Neck Cancer Epidemiology Consortium (INHANCE). Case-control study including former smokers from the pooled INHANCE data, with information on sociodemographic, smoking, and alcohol history. Associations were assessed using logistic regression with 95% confidence intervals (CI). The study included 2143 cases with HNC and 5799 controls. Cancer cases were categorized by their respective subsites: 954 LC (44.5%), 685 OPC (32.0%), 504 OCC (23.5%). The risk of developing OCC was 2.8-fold higher [CI: 1.9-4.1], LC 2.6-fold higher [CI: 1.9-3.5], and OPC 2.1-fold higher [CI: 1.5-2.8] in individuals who smoked > 50 pack-years, compared to < 10 pack-years. The risk of OCC/OPC/LC increased with tobacco consumption in North-America, whereas in Western/Southern-Europe and South-America the association plateaued beyond 31-50 pack-years. Cessation after age 55 increased the risk of LC by 3.0-fold [CI: 2.2-4.2], and OCC by 2.2-fold [CI: 1.4-3.3] versus cessation age ≤ 45 years. Consuming ≥ 5 drinks/day was associated with 5-fold higher risk of OPC [CI: 3.7-6.6], 4.4-fold higher risk of OCC [CI: 3.2-6.1] and 3.1-fold higher risk of LC [CI: 2.4-3.9] compared to 0-0.9 drinks/day. The risk of HNC among former smokers is not homogeneous across regions and that there were distinct patterns for OCC, OPC, and LC. The amount of tobacco and alcohol consumption are key risk factors, with alcohol being more important for OCC/OPC, and tobacco being more strongly associated with LC risk.
This study examined contextual factors influencing the uptake and use of the EMPOWER digital mental health platform, implemented in small and medium-sized enterprises and public agencies in Spain, Poland, Finland, and the United Kingdom. The platform was developed within an EU-funded project to promote workplace mental health and evaluated in a randomised controlled trial assessing its effectiveness and cost-effectiveness. A mixed-methods design was applied combining logistic regression analyses of baseline employee data with qualitative semi-structured interviews exploring barriers and facilitators to engagement. Results indicated that successful uptake was supported by strong employer involvement, a positive workplace culture, clear communication of benefits and data privacy, tailoring of content to employee needs, and available technical support. Barriers included insufficient communication, limited organisational support, lack of allocated time for use, unclear instructions, and concerns about anonymity. Employers often expressed reluctance to take responsibility for facilitating implementation, reflecting low organisational readiness. While the platform itself was generally regarded as user-friendly, its integration into daily workplace practices was inconsistent, with many employees using it outside of working hours. In conclusion, effective and sustainable implementation of digital workplace mental health interventions requires more active stakeholder engagement, clearer and sustained communication strategies, and alignment with organisational policies and structures. Addressing these contextual factors is essential for maximising uptake and ensuring that digital health platforms such as EMPOWER achiever their intended impact in supporting mental health at work.
OBJECTIVE:The association between occupational exposure to chlorinated solvents and lung cancer remains inconclusive. This study investigated this relationship using data from the internationally pooled SYNERGY study. METHODS:Data from 14 case-control studies conducted in 13 European countries and Canada were pooled, including 28 048 participants (12 329 cases and 15 719 controls). Lifetime occupational exposure to chlorinated solvents was assessed using the ALOHA+job-exposure matrix. ORs and 95% CIs were estimated using unconditional logistic regression, adjusted for study centre, age, sex, smoking (pack-years and cessation), cumulative exposure to five occupational lung carcinogens (asbestos, hexavalent chromium, polycyclic aromatic hydrocarbons, respirable crystalline silica and diesel engine exhaust), cumulative benzene exposure and employment in high-risk occupations ('List A' jobs). Associations were estimated across categories of exposure levels, durations and analyses stratified by smoking status and lung cancer subtypes. RESULTS:We found no evidence of an association between ever exposure to chlorinated solvents and lung cancer risk (OR 1.03; 95% CI 0.96 to 1.10). Among exposed individuals, a positive trend with cumulative exposure was observed (p=0.031), but not when non-exposed individuals were included (p=0.173). Positive trends were found with exposure duration (p=0.005 for exposed; p=0.048 overall); risks were modestly elevated (OR 1.11) in those exposed for 20 or more years. No increased risk was observed across smoking strata or lung cancer subtypes. CONCLUSIONS:This pooled analysis provides limited evidence of an association between occupational exposure to chlorinated solvents and lung cancer, though exposure-response trends were noted among exposed individuals.
Purpose Dose constraints (DC), as a tool of optimization, are still under research. This element of radiation protection seems to be essential, especially in interventional cardiology and radiology, where the occupational and public exposure doses may be relatively prominent. This article presents findings and insights to status of implementation the dose constraints in Europe. Materials and methods Questionnaire has been sent to two target groups in Europe – regulatory bodies representants and medical facilities’ workers, involved in establishing dose constraints and maintaining radiation protection e.g. radiation protection officers/experts or medical physicists. Collected data and analyze of answering show mainly that the dose constraints are implemented, both for occupational and public exposure, nevertheless there are differences in methods of implementation. Results The survey was fulfilled by 17 Regulatory Bodies (RB) from different European countries and by 50 Medical Facility Representants (MF) from 14 European countries. Using dose constraints as defined in the Basic Safety Standard document confirmed 82% of RBs and 76% of MF. Other, most important answers for questions targeted to both groups (RBs and MFs) as responsibility of setting DCs, also divided into two groups – occupational and public exposure, also with analysis are presented in this paper. Conclusions The need of preparing guidance is seen, especially for usage dose constraints in occupational exposure. What is more, respondents see the positive aspects of dose constraints, in terms of optimization, safer work environment and risk reduction.
