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.

Chronic obstructive pulmonary disease (COPD) is a leading cause of global morbidity and mortality. Emerging evidence suggests disparities in COPD outcomes between rural and urban populations, but no prior review has synthesised these differences globally. Five databases (Medline, Embase, Emcare, CINAHL and Cochrane Central) were searched in May 2025. Eligible peer-reviewed studies directly compared rural and urban populations in at least one of four measures of COPD burden: prevalence, symptom burden, exacerbations or mortality. Study quality was assessed and narrative synthesis was conducted due to heterogeneity in outcome measures. Of 1339 screened studies, 32 met inclusion criteria, spanning 13 countries. COPD prevalence was higher rurally in 83% (15/18) of studies, with 11/15 demonstrating statistical significance. This pattern was consistent across geographical distributions. Total exacerbation rates were higher rurally in 60% (3/5) of studies, although hospitalisations varied significantly. 50% (6/12) of studies reported higher hospitalisation rates in urban areas and 5/12 studies reporting higher rates in rural areas. 86% (6/7) of studies demonstrated higher mortality rurally and symptom burden was higher amongst rural residents in 67% (4/6) of studies; however, the majority of these were conducted in the USA. This review highlights consistent rural-urban inequalities in COPD prevalence and outcomes, reflecting the impact of healthcare inequities, socioeconomic deprivation and environmental exposures on COPD burden in rural areas. Targeted interventions promoting equitable healthcare access, health education, transition to cleaner fuels and rural access to smoking cessation and pulmonary rehabilitation services are essential to mitigate these disparities and improve outcomes in rural populations.

Ventilator-induced lung injury continues to limit outcomes in patients with acute respiratory failure despite established lung-protective strategies.Mechanical power, the rate of energy transfer from the ventilator to the respiratory system, has emerged as an integrative index of ventilator-induced stress. Experimental studies indicate that cumulative and dissipated energy, rather than isolated pressures or volumes, drive lung injury. Observational and registry data consistently link higher mechanical power with increased mortality in acute respiratory distress syndrome and mixed intensive care unit populations, with thresholds of ∼16-18 J·min^-1 associated with increased risk. Normalised indices (e.g. mechanical power per predicted body weight or per compliance) often outperform absolute mechanical power as predictors of outcome. Strategies to minimise mechanical power include individualised positive end-expiratory pressure titration, driving pressure limitation, and an optimised respiratory rate. Complementing traditional physiological analysis, this review highlights the emerging role of technological integration, specifically closed-loop ventilation and artificial intelligence-driven prediction models, as essential tools to bridge the gap between theoretical mechanical power concepts and bedside application.Mechanical power provides a unifying physiological framework that integrates volume, pressure, flow and frequency into a single descriptive measure of ventilatory load. While higher mechanical power is consistently associated with worse outcomes, current evidence does not support titrating ventilation to pre-defined numerical power thresholds, and prospective randomised trials are required to determine whether mechanical power-informed strategies improve patient-centred outcomes. Mechanical power should therefore be regarded as a contextual physiological descriptor rather than a standalone therapeutic target.

In the United States, post-COVID-19, Mental and Behavioral Health (MBH) related Emergency Department (ED) visits, specifically for young adults, have increased. This article presents a review of 29 peer-reviewed articles on technological ED interventions to improve the safety and care experiences of patients with MBH conditions. The key findings indicate improved MBH identification for patients, improved access to care with telepsychiatry, enhanced communication through standardized documentation and alerts, and high acceptability of crisis management interventions. Further research needs to be conducted to enhance intervention design, acceptability, and adoption of screening, remote consultation, and crisis management interventions, and reduce staff documentation workload.

Postpartum depression (PPD) is a common childbirth complication that impairs the mother-infant relationship and contributes to long-term developmental challenges among children. Although PPD treatment reduces depressive symptoms, it is not necessarily sufficient to improve maternal-infant interaction. In addition, several barriers preclude timely access to care including mental health stigma, limited specialized providers, and challenges with navigating the healthcare system and securing necessary childcare and transportation. Our team developed a 12-session patient- and clinician-facing digital platform, MommaConnect that combines evidence-based therapies-- Mother Baby Interaction Therapy and Interpersonal Psychotherapy-- to improve PPD symptoms and mother-infant interaction, address barriers to care, and provide support between therapy sessions. The purpose of this article is to describe the translation of our in-person approach to treating PPD and improving mother-baby interaction to our MommaConnect digital platform that integrates core psychotherapy components into a user-centered platform.

Our methods were guided by the PRECEDE-PROCEED Model and three stages of a nine-stage digital platform development process. In stage 1, we conducted focus groups to understand the needs of postpartum mothers who had experienced PPD and in-depth interviews to understand the concerns of perinatal mental health clinicians. We analyzed the qualitative data with thematic content analysis. In stage 2, we used component mapping to translate treatment modalities into the digital platform. Finally in stage 3, we used co-design, prototyping, and user-interface design to build the MommaConnect prototype.

Results from the focus groups identified four themes including (1) barriers to accessing care, (2) preferences and needs in mental health care delivery, (3) feedback on the MommaConnect App, and (4) broader challenges and experiences. The in-depth interviews with the clinicians resulted in six themes including (1) assessment and early intervention, (2) barriers to care, (3) role of technology in treatment, (4) building a therapeutic alliance, (5) community and social support, and (6) addressing comorbid conditions. Additionally, the team translated the in-person treatment modality to a 12-session format and designed the current version of the MommaConnect prototype, which has both patient-facing and clinician-facing components.

MommaConnect offers an innovative, accessible approach that combines Mother Baby Interaction Therapy and Interpersonal Psychotherapy to treat PPD and improve the quality of mother-infant interaction. Its digital adaptation provides a treatment platform for mothers and clinicians to work together in real time and communicate between sessions. MommaConnect may expand access, reduce barriers to care, and inform the broader translation of evidence-based behavioral interventions into scalable, technology-enabled formats. This work has the potential to transform access to perinatal mental health care, improve maternal and infant outcomes, and reduce the long-term sequelae associated with untreated PPD and disrupted early relational experiences for infants.