BackgroundMany patients with incurable cancer are expected to live for a considerable period of time, yet with the knowledge of their disease's inevitable end-of-life outcome. This duality can lead to existential concerns. A single one-hour meaning-making conversation was developed in which a patient explores their sources of meaning together with a spiritual counselor.AimTo explore how patients experience and benefit from a conversation aimed at supporting meaning-making, in order to inform further refinement of this intervention.DesignWe conducted a formative mixed method pilot study. Evaluation interviews assessed patients' experience and reported benefits. A reflexive thematic analysis was conducted. Key themes were compared and contrasted by intervention timing and patients' experience of existential concerns. Validated questionnaires were administered to assess patients' existential wellbeing, problems, and needs pre- and post-intervention.Setting/ParticipantsTwenty-one patients with advanced solid malignancies and a prognosis >1 year participated at two different hospitals.ResultsAll patients experiencing existential concerns appreciated the meaning-making conversation and reported benefits, such as reflection, validation, insight and actions related to sources of meaning. Half of the those not experiencing existential concerns reported no benefits, and some reported a negative experience. Quantitative data suggest a decrease in most existential problems and needs post-intervention. Existential wellbeing increased post-intervention.ConclusionsA meaning-making conversation can support the process of meaning-making for patients living long-term with incurable cancer. Refinement of the intervention should focus on targeting patients experiencing existential concerns.

ObjectivesThis study aimed to compare serum leucine-rich repeat and fibronectin type III domain-containing protein-5 (LRFN5) and olfactomedin-4 (OLFM4) levels and aggregate index of systemic inflammation (AISI) values between hospitalized subjects with bipolar disorder (BD) experiencing acute manic episodes with psychotic features and healthy controls (HCs), and to examine their associations with clinical features and symptom severity.MethodsIn this cross-sectional study, participant characteristics and clinical features were assessed by structured clinical interviews. LRFN5 and OLFM4 levels were measured in the BD (n = 37) and HC (n = 35) groups using Enzyme-Linked ImmunoSorbent Assay kit.ResultsSerum LRFN5 (adjusted P = 0.0117) and OLFM4 (adjusted P = 0.0117) levels were significantly lower, whereas AISI (adjusted P = 0.0005) levels were significantly higher in the BD group compared with HCs, after adjusting for age, gender, body mass index, and smoking status. Within the BD group, a strong positive correlation was observed between LRFN5 and OLFM4 levels (r = 0.702, adjusted P = 0.006) and AISI showed a significant positive correlation with manic symptom severity score after controlling for age, gender, body mass index, and smoking status (r = 0.472, adjusted P = 0.030). In binary logistic regression analysis adjusted for age, gender, body mass index, and smoking status, lower OLFM4 levels (odds ratio (OR) = 0.970, P = 0.020, adjusted P = 0.003) and higher AISI values (OR = 1.008, P = 0.002, adjusted P = 0.001) were independently associated with BD status, alongside smoking status (OR = 19.213, P = 0.005, adjusted P = 0.001) (apparent area under the curve (AUC) = 0.914, optimism-corrected AUC = 0.884). After repeated stratified holdout validation, the mean and median test AUCs were 0.868 and 0.876, respectively.ConclusionsSubjects with BD experiencing acute manic episodes with psychotic features exhibited decreased circulating LRFN5 and OLFM4 levels alongside an increased systemic inflammatory burden, as reflected by AISI. AISI showed the strongest association with BD status and symptom severity and OLFM4 remained significant in adjusted analyses. Rather than indicating definitive diagnostic utility, the observed alterations may instead reflect underlying biological processes related to BD.

Work in eating disorder (ED) services presents unique challenges and rewards that may affect clinicians' work-related and personal wellbeing. However, research on ED clinician needs, views, and experiences is still sparse, despite major service changes since the COVID pandemic. This study aims to explore and conceptualise NHS ED clinicians' work-related experiences, challenges, and needs, in order to inform future clinicians wellbeing and service improvement strategies.

Clinicians working in ED services (N = 19) were interviewed using a semi-structured interview guide that probed their professional experiences, work-related needs, and views. Interviews were analysed using NVivo, following guidance from Braun and Clarke (2006) for reflexive thematic analysis.

A holistic ecological systems framework for ED services was created, comprised of five levels of influence: intrinsic, intra-personal, departmental, systemic, and societal. These levels contain nine themes: [1] clinician motivation for working in ED services [2], complexities of ED management [3], clinician personality and emotional disposition [4], team dynamics [5], supervision, management, and organizational support [6], service-level concerns [7], macro-level systemic concerns [8], broader societal challenges in ED care, and [9] COVID-related challenges. Key concerns included the chronic nature and risk of EDs, growing service demands amid limited resources, and regulation through guidelines and commissioning targets.

This presented framework illustrates the multifaceted array of complexities faced by ED clinicians. The interplay of personal, inter-personal, and systemic factors is explored, with clinicians' interest in and commitment to ED care at the core of the framework. These areas can be targeted to improve clinician job satisfaction and reduce burnout risk, with the goal to provide optimal patient care.

Emotion regulation is essential for adaptive behavior and mental health. Dominant theoretical frameworks, together with influential neuroscientific accounts, suggest that emotion regulation is closely linked to cognitive control processes; however, behavioral evidence supporting this link remains inconsistent. To quantify these associations, a comprehensive meta-analysis was conducted to examine the relationship between individual differences in cognitive control (updating, inhibition, shifting) and four emotion regulation strategies: reappraisal (k = 70 studies, N = 10,524), suppression (k = 45, N = 5,104), rumination (k = 109, N = 10,637), and worry (k = 36, N = 3,385). Individuals with stronger cognitive control abilities showed more frequent and more effective use of reappraisal and engaged less in rumination and worry, whereas suppression showed no consistent relation. Component-level analyses suggested associations with inhibition and updating, but not shifting, with stronger effects for regulation ability than for strategy use frequency. While all notable effects were conceptually consistent, their magnitudes (rs < |.15|) were small and substantially lower than those implied by prior theoretical frameworks and influential empirical studies. Moreover, the effects showed considerable heterogeneity and substantial uncertainty. Overall, these results challenge the widely held assumption that cognitive control and emotion regulation are closely linked, indicating instead that their associations are weaker and more specific than commonly assumed. They further suggest that dominant theoretical frameworks may overestimate the strength of this link at the behavioral level, highlighting the need for more ecologically valid assessments of both cognitive control and emotion regulation.

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality worldwide. Immune checkpoint inhibitors targeting the PD-1/PD-L1 and CTLA-4 axes have fundamentally transformed its treatment landscape. This narrative review traces the evolution of NSCLC immunotherapy, from advanced-stage monotherapy and chemoimmunotherapy to its critical expansion into early-stage disease, highlighting the paradigm shift brought by neoadjuvant, adjuvant, and perioperative strategies. We examine essential clinical challenges, including optimal treatment duration, management of brain metastases, immune-related adverse events, and mechanisms of primary and acquired resistance, with a focus on genomic alterations like KRAS co-mutations with STK11 and KEAP1. Furthermore, we critically evaluate the evolving biomarker landscape, moving beyond PD-L1 to encompass circulating tumour DNA, microbiome composition, and multiparametric approaches like T-cell receptor clonality. Finally, we provide an in-depth exploration of next-generation strategies, including bispecific antibodies, novel checkpoint targets, mRNA vaccines, antibody-drug conjugates, and advanced cellular therapies. While significant progress has been made, refining biomarker-driven selection and optimizing combination sequencing remain paramount. This thorough synthesis highlights promising future directions to overcome these hurdles and improve long-term survival in NSCLC.

Patients with locally advanced head and neck squamous cell carcinoma are receiving adjuvant radio(chemo)therapy as standard of care, according to national guidelines. However, patients with human papilloma virus (HPV) driven oropharyngeal squamous cell carcinoma (OPSCC), are shown to have superior locoregional control (LRC) rates, suggesting that they are likely being overtreated. To date it is unknown, if and to which extent adjuvant radiotherapy can be safely reduced.

The interventional multicentric DELPHI trial is investigating step-wise radiation dose reduction in patients with both p16-overexpressing and HPV16 DNA positive OPSCC. Depending on international clinical and histopathological risk factors, patients are being enrolled in the high-risk or intermediate-risk arm. Patients of the high-risk arm are receiving standard simultaneous chemotherapy with cisplatin. Patients with smoking history of at least 30 packyears are being treated in the observational arm. Primary endpoint of the DELPHI trial is LRC after 24 months. Secondary endpoints are acute and late toxicity, quality of life during and up to 24 months after the end of therapy as well as LRC and overall survival after 60 months.

Primary aim of the DELPHI trial is to show that radiation dose reduction is safe and therefore feasible in patients with HPV-positive OPSCC. Secondary objective is to show that radiation-dose reduction leads to less late toxicity compared with standard treatment and thus improves quality of life.

The DELPHI trial is registered at clinicaltrials.gov under the identifier NCT03396718.

RATIONALE AND OBJECTIVES: Remarkable intratumor heterogeneity of mitochondrial redox state was found in malignant tumors by optical redox imaging (ORI) of reduced nicotinamide adenine dinucleotide (NADH), oxidized flavoproteins (Fp) containing flavin adenine dinucleotide, and the optical redox ratio (ORR = Fp/(NADH + Fp)), with higher and lower ORR corresponding to more oxidative and more reductive redox status, respectively. Our previous reports suggested that ORR can be a biomarker for cancer aggressiveness or risk of progression. Our goal here is to explore the molecular basis of the ORR's biomarker value for breast cancer by investigating the expression and activity of PGC1α, a master regulator of mitochondrial metabolism and cancer progression. MATERIALS AND METHODS: Intratumor redox subpopulations were isolated from triple-negative breast cancer (TNBC) MDA-MB-231 mouse xenografts and grouped according to high, medium, and low levels of ORI indices (ORR, Fp, or NADH). Gene expression and associated gene networks were obtained by RNA sequencing and bioinformatics analysis, respectively. PGC1α gene expression was validated by RT-PCR. The role of PGC1α in TNBC progression was further investigated by knocking down PGC1α (validated by western blot and RT-qPCR) in MAD-MB-231 cells and measuring the changes in ORI indices and invasiveness in vitro. RESULTS: PGC1α was upregulated in the subpopulation with a high ORR compared to that with a medium ORR. A PGC1α associated gene network with 21 differentially expressed genes (DEGs) was also identified, implicating regulation of redox signaling, metabolism, and cancer progression. Important signaling regulating genes SIRT1 and FOXO1 were upregulated, whose activities influence the NAD⁺/NADH ratio or are influenced by the NAD⁺/NADH ratio. Decreased ORR and invasiveness were observed in vitro in PGC1α knockdown MDA-MB-231 cells, supporting the association of higher PGC1α expression with more oxidative redox status. CONCLUSION: ORI-based redox subpopulations in TNBC tumors exhibited differential expression of PGC1α gene that was associated with a gene network, providing a possible molecular basis underlying the potential value of ORR as a prognostic biomarker.

Following the publication of the above paper, and an Expression of concern statement (DOI: 10.3892/or.2025.9028), which notified the readers that the blots showing β‑actin mRNA expression in Fig. 1 on p. 1341 appeared to be similar to the β‑actin mRNA blots shown in Fig. 3 on p. 1342, albeit with some horizontal and vertical resizing, another reader has subsequently contacted the Editorial Office to explain that control western blot data featured in the same figures (Figs. 1 and 3) also appeared to be strikingly similar. We have again reached out to the authors, requesting an explanation for these apparent anomalies in the presentation of the data in this paper; however, up to this time, no response from them has been forthcoming. Owing to the fact that the Editorial Office has been made aware of additional potential issues surrounding the scientific integrity of this paper, we are issuing a second Expression of Concern to notify readers of these additional issues while the Editorial Office continues to investigate this matter. [Oncology Reports 19: 1339‑1345, 2008; DOI: 10.3892/or.19.5.1339].

COPD symptoms occur with day-to-day variation. An exacerbation of COPD is a symptom worsening that exceeds these fluctuations and requires systemic treatment. Differentiating the start of an exacerbation from day-to-day disease variation is an unmet research need. We sought to examine the evidence that monitoring daily variation in COPD can differentiate this from the onset of an exacerbation.

A systematic review was conducted across MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature, Institute of Electrical and Electronics Engineers and Cochrane databases, as well as a citation search, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eligible studies focused on monitoring daily symptoms and/or physiological parameters in stable COPD. Quality assessments were conducted using the Newcastle-Ottawa Scale and the Cochrane Risk of Bias tool. Findings were qualitatively synthesised, considering essential components.

22 studies were included in the review. The definitions of exacerbation were diverse across studies. 14 (64%) of the included studies demonstrated that day-to-day variation in symptoms (e.g. Chronic Airways Assessment Test score), vital signs (heart rate, respiratory rate and peripheral oxygen saturation) and lung function (peak expiratory flow, forced oscillatory technique), alone and in combination, showed promise in differentiating the onset of exacerbations. Daily monitoring provided earlier detection of exacerbation, up to 7 days before the day of onset. Baseline and threshold settings were identified as crucial factors. Continuous monitoring was more effective than once-daily assessments.

This review summarises evidence on how day-to-day variation differs from the start of an exacerbation in COPD. The combination of continuous monitoring, reliable measurement tools and a refined algorithm, with personalised baseline and threshold values, yields promising results.

Diagnosing asthma in children and young people (CYP) remains challenging. Oscillometry is a promising tool and is feasible from 2 years of age. European Respiratory Society (ERS) technical standards and bronchodilator response (BDR) oscillometry thresholds have been published, but diagnostic accuracy is not established.

We systematically reviewed studies comparing oscillometry and spirometry in CYP under investigation for asthma. Reference standards were positive BDR or positive methacholine challenge test (MCT). Primary aims were to investigate the sensitivity and specificity of current ERS oscillometry thresholds (>40% decrease in resistance at 5 Hz (R ₅), >50% increase in reactance at 5 Hz (X ₅) or >80% decrease in the area under the reactance curve); secondary aims were to identify oscillometry threshold values optimising both sensitivity and specificity.

11 studies were included; six (n=992 CYP) utilised BDR and five (n=531 CYP) MCT as reference standard. Meta-analysis was not possible due to heterogeneity of results reported. In two studies using current ERS BDR thresholds, zero sensitivity and high specificity (>85%) were observed. In weighted regression analyses of BDR studies, a 17.0% decrease in resistance at 5-6 Hz had sensitivity and specificity of 71.6% (95% CI 69.7-73.7%); a 20.2% increase in X ₅ had sensitivity and specificity of 68.6% (95% CI 66.6-70.8%). Similarly, 27.7% increase in R ₅ had sensitivity and specificity of 73.6% (95% CI 71.9-75.3%) for MCT.

Currently recommended ERS thresholds for oscillometry BDR have low sensitivity. Proposed thresholds for defining positive BDR and MCT by oscillometry require prospective validation and adoption of standards for measuring and reporting oscillometry parameters in future diagnostic comparative studies.