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At least 19 recordsLinked to original sources
PubMed2026

Human-AI Interaction With AI-Assisted Tumor Overlays in Pediatric Whole-Body Magnetic Resonance Imaging: Exploratory Reader Study.

BACKGROUND: AI tools have the potential to enhance personalized clinical care, particularly in radiology. However, their integration into clinical workflows remains complex, especially in pediatric oncology, where early cancer detection is critical. Children with Li-Fraumeni syndrome (LFS), a rare cancer predisposition disorder, undergo regular surveillance whole-body magnetic resonance imaging (wbMRI), which presents an opportunity for AI-assisted tumor detection. OBJECTIVE: We evaluated the feasibility of an AI-assisted overlay for highlighting tumor-like regions in pediatric surveillance wbMRI and explored how access to the overlay influenced radiologist workflow, candidate-lesion marking behavior, follow-up recommendations, and perceived workload. METHODS: We developed a patch-based AI segmentation model trained on augmented 2D slices from 675 surveillance wbMRI volumes of pediatric patients with LFS. The model was designed to highlight regions with high tumor probability. A reader study was conducted with 2 radiologists who independently reviewed wbMRI cases both with and without AI assistance. We measured evaluation time, number and location of reader-marked candidate lesions, type of follow-up recommendation, and subjective feedback using structured questionnaires. RESULTS: AI assistance altered interpretation workflows for both radiologists, with mixed effects. On average, the time required to evaluate each case increased when using the AI tool for both radiologists. However, one radiologist had an increase in the number of candidate lesion locations selected with the tool, and one had a decrease in the number of candidate lesion locations selected with the tool. Subjective feedback indicated that one of the radiologists reported lower mental demand with the AI tool, while both radiologists reported lower stress with the AI tool. Interrater variability was evident, underscoring the need for personalized calibration of AI tools. CONCLUSIONS: AI-assisted wbMRI interpretation can improve tumor detection in pediatric cancer surveillance by reducing false negatives. However, its influence on workflow efficiency and interradiologist variability highlights the importance of careful implementation. Successful integration requires addressing challenges such as improving the predictive precision of AI models, offering intuitive end-user designs and instructions, and building trust in AI outputs. AI outputs can influence workflow and behavior in reader-specific ways. Clinical translation will require larger, randomized, multireader studies and model refinement to reduce false positives and quantify lesion-level reader performance. This can help ensure better patient outcomes in addition to reduced clinician burnout.

Humans↗
PubMed2025

Noninvasive detection and differentiation of gastric malignancy using cell-free DNA biomarkers.

INTRODUCTION: Gastric cancer remains a major global health burden, with high mortality driven by late-stage diagnoses that limit treatment options and reduce survival. Current diagnostic methods such as endoscopy and biopsy are invasive, resource-intensive, and impractical for large-scale early detection. OBJECTIVES: This study aimed to develop and validate an ensemble machine learning model integrating four cell-free DNA (cfDNA) fragmentomic feature classes derived from 5 × whole genome sequencing (WGS) data to non-invasively differentiate malignant gastric cancer from benign gastric lesions in high-risk or symptomatic patients. METHODS: A total of 681 plasma samples were prospectively collected, comprising 329 from patients with gastric cancer or high-grade intraepithelial neoplasia (HGIN) and 352 from individuals with benign gastric conditions. The dataset was divided into a training cohort (n = 333) and a temporally independent validation cohort (n = 348). An external validation cohort of 305 participants was also included. RESULTS: The ensemble model achieved an AUROC of 0.920 in cross-validation testing on the training cohort, 0.912 in the independent validation cohort, and 0.896 (95% CI 0.860-0.932) in the external cohort. At a pre-specified prediction threshold of 0.402, the model demonstrated 93.3% sensitivity and 71.9% specificity in the validation cohort, yielding a PPV of 71.3% and an NPV of 93.5%. In the external cohort, sensitivity and specificity were 91.7% and 69.1%, respectively (PPV 75.7%, NPV 88.8%). Model scores correlated with clinical stage, tumor grade, and histopathological subtype. Approximately 71% of non-cancer patients could have been spared unnecessary endoscopy. CONCLUSIONS: The cfDNA fragmentomics-based ensemble model enables accurate, non-invasive differentiation between gastric cancer and benign gastric lesions in high-risk or symptomatic patients. This approach demonstrates strong potential as a pre-endoscopy triage tool, supporting earlier detection and more efficient use of diagnostic resources.

Humans↗
PubMed1979

Cytostatic treatment of meningeal blastoses.

Intrathecal treatment with MTX was attempted in patients with diffuse meningeal blastoses. As a rule, symptoms and clinical findings improved rapidly. As objective parameters, the differential cell pictures of the CSF showed dissimilar results during therapy (25 mg MTX weekly i.t.). In leukoses (n = 10) and malignant lymphomas (n = 12), the CSF could be cleared with three exceptions which concerned differentiated tumors. The success was similarly good with meningeal dissemination of a seminoma. Meningeal carcinoses with mammary carcinoma (n = 7) and melanoma (n = 2) showed dissimilar results. No alteration of the cytograms of four bronchial carcinomas and one colon carcinoma was demonstrable. Besides the growth form, the degree of differentiation appears to be decisive for the success of therapy. The labeling index appears to be a useful indicator. Since symptoms and clinical findings often markedly improve even when a success cannot be objectively detected cytologically, an attempt at therapy is always to be recommended.

Breast Neoplasms↗
PubMed1978

Effect of CT noise on detectability of test objects.

Three types of test objects were superimposed on noisy backgrounds and observed by 58 subjects: large low-contrast disks to simulate tumors, small disks to simulate calcifications, and bars to simulate blood vessels. Three types of noise were used: random noise, CT noise (reconstructed random noise), and an actual water scan taken with an EMI CT1010 scanner. In addition, each image was smoothed by a factor of two, giving six test patterns altogether. Photographic images were presented to 25 lay observers, while 25 other lay observers and eight radiologists used a viewing console. The photographs produced a slightly lower true positive rate than the console, although the degree of confidence in the identifications was slightly greater. The anticorrelation property of CT noise gives it a "lumpy" structure, which aided the identification of bars but impeded the identification of small disks. Smoothing did not significantly affect the detectability with random noise, but with CT noise, smoothing improved the detectability of bars and large disks.

Humans↗
PubMed1978

Response variability in the mammalian auditory cortex: an objection to feature detection?

Research strategy in the auditory system has tended to parallel that in the visual system, where neurons have been shown to respond selectively to specific stimulus parameters. Auditory neurons have been shown to be sensitive to changes in acoustic parameters, but only rarely have neurons been reported that respond exclusively to only one biologically significant sound. Even at higher levels of the auditory system very few cells have been found that could be described as "vocalization detectors." In addition, variability in responses to artificial sounds have been reported for auditory cortical neurons similar to the response variability that has been reported in the visual system. Recent evidence indicates that the responses of auditory cortical neurons to species-specific vocalizations can also be labile, varying in both strength and selectivity. This is especially true of the secondary auditory cortex. This variability, coupled with the lack of extreme specificity in the secondary auditory cortex, suggests that secondary cortical neurons are not well suited for the role of "vocalization detectors."

Acoustic Stimulation↗
PubMed2026

Genomic characterisation of ST233 Pseudomonas aeruginosa co-producing KPC-2 and VIM-2 in Northeastern Brazil during the COVID-19 pandemic: Evidence of independent horizontal acquisition events.

BACKGROUND: Dual-carbapenemase-producing Pseudomonas aeruginosa poses a major therapeutic and epidemiological challenge worldwide, yet systematic data on KPC and VIM co-production in Brazil remain limited. The COVID-19 pandemic intensified antimicrobial use, a period temporally associated with increased carbapenemase detection globally. OBJECTIVES: To characterise the molecular epidemiology and resistance profiles of KPC and VIM co-producing P. aeruginosa isolates from Brazil (2019-2023). METHODS: Between 2019 and 2023, 1489 multidrug-resistant P. aeruginosa isolates were screened by multiplex PCR for carbapenemase-encoding genes. Co-producing isolates underwent pulsed-field gel electrophoresis (PFGE) for clonal profiling, followed by whole-genome sequencing (WGS) for high-resolution phylogenomic analysis. Antimicrobial susceptibility testing and plasmid characterisation using next-generation sequencing platforms were also performed. RESULTS: Forty-two isolates (2.8%) harboured both blaKPC-2 and blaVIM-2, with detection occurring exclusively between 2020 and 2023, temporally coinciding with the COVID-19 pandemic. PFGE identified eight distinct clonal groups, providing evidence for independent horizontal gene transfer (HGT) events, whilst WGS confirmed all isolates as the high-risk ST233 lineage. Chromosomally integrated blaVIM-2 within class 1 integrons predominated; 2 isolates carried dual chromosomal copies. Plasmid-borne blaKPC-2 was identified across heterogeneous replicons (43.3-430.1 kb), suggesting multiple independent acquisition events. All co-producing isolates displayed extensive drug resistance, retaining in vitro susceptibility only to cefiderocol and colistin. CONCLUSIONS: ST233 co-producing KPC and VIM, represents a high-risk resistance phenotype of epidemiological significance. Divergent genomic architectures suggest active horizontal dissemination across diverse genetic backgrounds rather than clonal expansion, highlighting the need for enhanced surveillance and infection control strategies.

Bacterial genomic characterisation↗
PubMed1979

Gamma-ray spectrometry of humans at the University of Utah.

A human total-body counter was designed and built with two 20 X 10 cm NaI (Tl) crystals suspended over an "isoresponse surface" upon which the subject reclines. This surface is curved from head to knee and from left to right, so that a gamma-ray emitting object is detected with equal efficiency when placed anywhere upon it. The positioner and detectors are housed in a low background enclosure constructed of steel 31 cm thick with a graded inner lining of lead + cadmium + copper. Calibration of the system was accomplished by administering trace amounts of various radionuclides to 48 human subjects of various sizes, ranging in age from 4--80 years. Counting rates per retained muCi at 0.53, 0.66, 1.53, and 2.75 MeV (83Rb, 137Cs, 42K, and 24Na) were determined as a function of body size and were compared with counting rates per muCi of corresponding emitters centered in a polyethylene cylinder of radius 10.3 cm. Limits of detection, corresponding to three times the standard deviation of a 50 min background, were 170 nCi 90Sr (via Bremsstrahlung X-rays), 0.78 nCi 131I, 0.48 nCi 83Rb, 0.52 nCi 137 Cs, 4.9 nCi 40K (or 5.8 g of natural potassium) and 1.7 nCi 222Rn.

Body Height↗
PubMed2026

Whole exome sequencing and cluster analysis reveal that EPB41L4A mutation may trigger tooth agenesis.

OBJECTIVE: To detect and analyze the correlation between commonly mutated genes and known genes associated with tooth agenesis in patients with non-syndromic tooth agenesis. The aim is to explore new genes that may be associated with tooth agenesis, to provide a genetic reference for its prevention as well as for the clinical diagnosis and treatment of tooth agenesis. METHODS: Genomic DNA was extracted from the peripheral blood of 18 congenitally edentulous subjects, and related gene mutations were identified by whole-exome sequencing. The genes related to maxillofacial development and the known pathogenic gene sequences of congenital tooth agenesis were selected for local alignment analysis of pairwise sequences, and the metric relationship of related sequences was determined. Hierarchical and fuzzy clustering methods were used for cluster analysis. RESULTS: Hierarchical clustering and fuzzy clusterings yielded consistent results. The EPB41L4A gene clustered with a large number of well-known and well-defined genes associated with tooth agenesis. From the perspective of cluster analysis, it can be inferred that the genes clustered together generally have similar functions. CONCLUSION: EPB41L4A, which is involved in the Wnt pathway, may be a candidate gene warranting further investigation.

Humans↗
PubMed2025

KRAS Mutations in Duodenal Lavage Fluid After Secretin Stimulation for Detection of Pancreatic Cancer.

OBJECTIVE: Although pancreatic ductal adenocarcinoma (PDAC) is still a devastating disease, the survival rate for surgically removed PDACs has significantly improved in recent years. Early detection is essential in managing PDAC. BACKGROUND: The presence of KRAS mutations in PDAC leads to the initial genetic abnormality and offers a significant timeframe for identifying resectable PDACs. A minimally invasive and highly specific PDAC screening test is necessary to prevent the need for invasive follow-up tests. METHODS: Between July 2021 and March 2023, 169 cases were enrolled in 7 institutions. By administering secretin before esophagogastroduodenoscopy (EGD), the excretion of pancreatic juice into the papillary fluid can be stimulated, creating a resource for testing. Washing fluid was collected using a specialized catheter from control individuals (n=75) and patients with resectable PDAC (n=89) at the initial diagnosis. A highly sensitive technique was employed to study KRAS gene mutations. RESULTS: This study obtained an AUC of 0.934 (95% CI: 0.904, 0.964) when using KRAS mutations in duodenal lavage fluid to differentiate between patients with resectable PDAC and healthy controls. The estimated sensitivities were calculated with specificity set at 100%, resulting in a sensitivity of 83.1% (95% CI: 71.7%, 91.2%). The McNemer test showed a significantly higher sensitivity for KRAS mutations than serum CEA and CA19-9 ( P <0.0001). CONCLUSIONS: We created a method to identify resectable PDACs by analyzing KRAS mutation levels in duodenal fluid collected during EGD with secretin stimulation of pancreatic juice secretion.

Humans↗
PubMed1978

On-line statistical detection of average evoked potentials: application to evoked response audiometry (ERA).

An objective method of EP detection in averaged EEG epochs is described which is based on the statistical properties of the averaged EEG in the absence of time-locked EP activity. The statistical properties of the subject's averaged background EEG are summarized by making a set of comparisons between two consecutive EEG epochs immediately preceding each stimulus presentation. After every stimulus presentation, a second set of comparisons is made between the post-stimulus EEG epoch and the immediately preceding pre-stimulus EEG epoch. These two sets of comparisons are then examined to determine whether the latter differ significantly from the former. The technique has been programmed for on-line use on a 12-bit minicomputer, validated on cooperative adult subjects and used for ERA threshold determinations in young children. Using response detection criteria yielding an empirically determined false positive error rate of between 1 and 4%, threshold estimates averaged about 10 dB higher than psychophysical thresholds. The efficiency with which such ERA thresholds may be obtained with this method is substantially greater than that of conventional ERA procedures employing subjective evaluation of averages. Further, the technique allows variation of detection criteria to suit non-audiometric needs and empirical determination of the false-positive error rate under any set of conditions.

Adult↗
PubMed2026

Detectable C-Peptide and Diabetic Ketoacidosis Risk in Type 1 Diabetes.

OBJECTIVE: To investigate whether detectable C-peptide levels in type 1 diabetes is associated with a lower risk of diabetic ketoacidosis (DKA). RESEARCH DESIGN AND METHODS: We analyzed the Diabetes Control and Complications Trial publicly available data repository for the association between detectable stimulated C-peptide (>0.2 nmol/mL, measured annually) and DKA incidence over an average 6.5-year follow-up. We used crude and adjusted Andersen-Gill models for recurrent DKA events with time-dependent covariates. RESULTS: Of the 1,441 participants (53% male, median age 27 years), 129 (9%) experienced 180 DKA events. Of these events, 179 (99.44%) occurred after C-peptide was &#x2264;0.2 nmol/L in the prior year and only 1 event occurred with C-peptide >0.2 nmol/L. C-peptide >0.2 nmol/L was associated with a DKA hazard ratio of 0.07 (95% CI 0.01-0.48; P = 0.007), consistent across adjusted models. CONCLUSIONS: Endogenous insulin production was significantly associated with lower DKA risk, suggesting that treatments preserving insulin production could decrease long-term DKA risk.

C-Peptide↗
PubMed2026

Optimizing prostate biopsy decision making - (MUSIC-screen): A 1:1 randomized controlled trial comparing micro-ultrasound versus multiparametric magnetic resonance imaging for prostate cancer diagnosis.

BACKGROUND: Micro-ultrasound (microUS) represents a potential alternative to multiparametric magnetic resonance (mpMRI) in guiding prostate biopsy, with level 1 evidence demonstrating non-inferiority to detect Grade Group &#x2265;2 (GG&#xa0;&#x2265;&#xa0;2) prostate cancer in biopsy-na&#xef;ve men. However, a critical gap remains in the screening pathway, in which imaging is needed to identify men at risk and determine whether biopsy is warranted. METHODS: MUSIC-Screen is a phase 3, open-label, noninferiority 1:1 randomized controlled trial evaluating microUS as an alternative imaging compared to mpMRI for determining the need for prostate biopsy in biopsy- and imaging- na&#xef;ve men at risk for GG&#xa0;&#x2265;&#xa0;2. A total of 1284 men will be randomized to undergo either microUS or mpMRI. Men with PRI-MUS 3-5 or PI-RADS 3-5 lesion will undergo targeted and systematic biopsy. Men with negative imaging and PSA density&#xa0;&#x2265;&#xa0;0.15 will undergo systematic biopsy, while those with PSA density&#xa0;<&#xa0;0.15 will defer biopsy. RESULTS: The primary outcome is GG&#xa0;&#x2265;&#xa0;2 detection in each study arm. The primary hypothesis is that microUS is non-inferior to mpMRI for screening and detection of GG&#xa0;&#x2265;&#xa0;2. Secondary objectives include comparison of GG&#xa0;&#x2265;&#xa0;2 detection rates in targeted cores among patients with PRI-MUS or PI-RADS scores of 3-5, proportion of men who defer biopsy but are diagnosed with GG&#xa0;&#x2265;&#xa0;2 within 8&#xa0;years, assessment of the negative predictive value of each imaging modality, and health economic analyses. CONCLUSION: MUSIC-Screen will determine whether microUS can be used as an imaging modality to inform biopsy decision making that is non-inferior to mpMRI for GG&#xa0;&#x2265;&#xa0;2 prostate cancer detection. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06626022.

Humans↗
PubMed2026

Exploring sex differences in endocannabinoid system biomarkers and their relationship with antidepressant treatment outcomes in major depressive disorder: a CAN-BIND 1 secondary analysis.

BACKGROUND: Sex differences in major depressive disorder (MDD) are well documented, but it remains unclear whether sex-related variation in peripheral endocannabinoid system (ECS)-related biomarkers is detectable in MDD. OBJECTIVES: To examine baseline sex differences in ECS-related mRNA expression, DNA methylation, and single nucleotide polymorphisms (SNPs) in MDD, and associations between baseline ECS markers and antidepressant outcomes in sex-stratified analyses. METHODS: Among 178 participants with MDD from CAN-BIND-1, all received escitalopram for 8 weeks; non-responders then received adjunctive aripiprazole from Weeks 8-16.Response was defined as &#x2265;&#x2009;50% reduction in MADRS score, and remission as MADRS&#x2009;&#x2264;&#x2009;10. ANCOVAs examined baseline sex differences and sex-stratified biomarker associations with percent MADRS reduction at Weeks 8 and 16, as well as categorical response and remission outcomes. Covariates included site, baseline MADRS, age, and ethnicity. False discovery rate correction was applied. RESULTS: Baseline sex differences in methylation were observed for CACNA1H, GABRB2, MAGL, and GABRR2, though none survived correction. No baseline sex differences in mRNA expression or SNPs were detected after correction. Lower baseline DAGLA mRNA in males was associated with greater Week 8 symptom improvement (FDR corrected). This association was not observed in females. No associations with response or remission at Weeks 8 or 16 survived correction. IMPLICATIONS: Baseline sex differences in peripheral ECS-related markers were not detected in this sample. Larger studies are needed to verify whether ECS-related biomarkers, particularly DAGLA, contribute to antidepressant outcomes in a sex-specific manner.

Humans↗
PubMed2026

Validation and refinement of a biomarker panel for frailty assessment and prediction of muscle weakness in older adults.

Frailty is a complex geriatric syndrome characterized by age-related declines in physiological function and cognitive reserve. To promote early prevention and intervention, minimally invasive and objective biomarkers that can detect frailty progression are required. We aimed to identify biomarkers associated with frailty progression and to elucidate their relevance to the Japanese version of the Cardiovascular Health Study (J-CHS) criteria, consist of five components (unintentional weight loss, self-reported exhaustion, muscle weakness, slow walking speed, and low physical activity). A total of 168 individuals (61 robust, 25 pre-frail, and 82 frail) enrolled in the NCGG (National Center for Geriatrics and Gerontology) Biobank were analyzed. Clinical information, blood-test data, aging-related factors, and gene-expression data were integrated for the analysis. First, linear regression identified one clinical factor, five aging-related factors, and 251 gene-expression factors associated with frailty. Subsequent logistic regression analyses examining each J-CHS components highlighted six candidate biomarkers. Cross-validation further suggested that three of these biomarkers-SMI, apelin, and GDF15-may represent potential biomarkers. Finally, retrospective and prospective analyses further demonstrated that those biomarkers were predictive of future muscle weakness, yielding a concordance index of 0.70. In conclusion, we validated and refined a biomarker panel consisting of SMI, apelin, and GDF15 that is associated with frailty, particularly muscle weakness (a major J-CHS component). These biomarkers may be useful for frailty assessment. Longitudinal analyses further suggested that they may be associated with the future development of muscle weakness in initially robust older adults, although validation in larger prospective cohorts is warranted.

Journal Article↗
PubMed2026

Circulating Methylated SEPT9 for Detection of Hepatocellular Carcinoma in Cirrhosis.

IMPORTANCE: Hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis remains suboptimal, with inadequate early-stage detection. &#x3b1;-Fetoprotein (AFP) demonstrates insufficient sensitivity. Circulating methylated septin 9 (SEPT9) has shown diagnostic promise. OBJECTIVE: To determine whether methylated SEPT9 improves detection of HCC when combined with AFP in patients with cirrhosis undergoing surveillance. DESIGN, SETTING, AND PARTICIPANTS: In this prospective, cross-sectional, diagnostic accuracy study, patients with cirrhosis undergoing routine HCC surveillance with ultrasonography and AFP were enrolled at 2 French academic centers from February 2018 through October 2024. HCC was diagnosed per international guidelines with centralized radiologic review, blinded to methylated SEPT9 results. Data were analyzed from October 2025 to January 2026. EXPOSURES: Plasma methylated SEPT9 was analyzed from 3 independent plasma aliquots and classified by number of positive replicates (single-positive, double-positive, or triple-positive). Serum AFP was evaluated at a threshold of 20 ng/mL. Biomarkers were evaluated individually and in combination using disjunction logic (tier 1; maximizing sensitivity) or conjunction logic (tier 2; maximizing specificity). MAIN OUTCOMES AND MEASURES: The primary outcome was the presence of HCC at enrollment. The primary end point was comparison of the area under the receiver operating characteristic curve (AUROC) between methylated SEPT9 and AFP. Secondary end points included diagnostic performance stratified by Barcelona Clinic Liver Cancer (BCLC) stage. RESULTS: Among 574 participants, 414 (72.1%) were male, and the median (IQR) age was 63 (57-70) years. A total of 118 had HCC, including 51 (43.2%) with BCLC stage 0-A. Methylated SEPT9 outperformed AFP (AUROC: 0.79 [95% CI, 0.74-0.84] vs 0.71 [95% CI, 0.66-0.76], respectively; P&#x2009;=&#x2009;.002; posterior probability of superiority >99.8%). Tier 1a (at least single-positive methylated SEPT9 or AFP >20 ng/mL) achieved 87.8% (95% CI, 81.6-93.5) sensitivity and a negative likelihood ratio of 0.2 (95% CI, 0.1-0.3). Among 64 HCC cases missed by AFP, tier 1a recovered 50 (78%). For BCLC 0-A disease, tier 1a sensitivity was 74.5% (95% CI, 62.2-86.5) vs 23.5% (95% CI, 12.5-35.8) for AFP, 3.2-fold increase. Tier 2 (triple-positive methylated SEPT9 and AFP >20 ng/mL) achieved 99.6% (95% CI, 98.9-100) specificity, a positive likelihood ratio of 76.0 (95% CI, 26.9-181.0), and a diagnostic odds ratio of 112.1 (95% CI, 37.8-294.7). CONCLUSIONS AND RELEVANCE: In this diagnostic study, combining methylated SEPT9 with AFP substantially improved HCC detection in patients with cirrhosis, particularly for early-stage disease amenable to curative treatment. Prospective studies are needed to determine whether improved detection translates into survival benefit.

Humans↗
PubMed2026

Epigenetic Profiling for Early Detection and Treatment Response Monitoring in Non-Small Cell Lung Cancer: Protocol for a Prospective Translational Biomarker Study.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide and continues to have poor survival outcomes, with most patients diagnosed at advanced stages of disease. In New Zealand, NSCLC contributes substantially to cancer inequities, with M&#x101;ori communities experiencing disproportionately high incidence and mortality rates. Although low-dose computed tomography screening can improve early detection, major limitations remain, including false-positive findings, overdiagnosis, high infrastructure costs, and limited accessibility for rural and underserved populations. Liquid biopsy approaches using circulating tumor DNA (ctDNA), particularly DNA methylation profiling, have emerged as promising, minimally invasive strategies for improving cancer detection, treatment monitoring, and precision oncology. OBJECTIVE: This study aims to establish integrated genomic and epigenomic predictive and prognostic biomarkers using ctDNA, tumor tissue, and transcriptomic profiling to improve early detection, risk stratification, treatment selection and response prediction, and longitudinal monitoring, with particular emphasis on identifying molecular mechanisms associated with treatment resistance and disease progression. METHODS: This prospective observational translational biomarker study is being conducted through the University of Otago and associated respiratory and oncology services in New Zealand. The study will recruit participants with NSCLC (including squamous and nonsquamous subtypes), individuals referred to fast-track lung nodule assessment clinics, and nonmalignant respiratory controls. Serial peripheral blood sampling will be performed in selected participants at predefined clinical follow-up time points to evaluate treatment response and disease progression. The availability of formalin-fixed paraffin-embedded archival tissues will be recorded, but will not be mandatory for enrollment. Genome-scale DNA methylation profiling will be performed using cell-free reduced representation bisulfite sequencing (cfRRBS), while targeted genomic profiling and transcriptomic analyses will be conducted using targeted sequencing panels and RNA sequencing. Integrative bioinformatic analyses will be used to identify molecular biomarkers associated with early-stage disease, advanced disease, treatment response, and therapeutic resistance. RESULTS: Ethics approval for the study has been obtained from the New Zealand Health and Disability Ethics Committee (2022 EXP 12566). This study commenced in 2022, and recruitment and biospecimen collection are ongoing. The study aims to recruit approximately 450 participants, including patients with NSCLC, individuals referred through respiratory diagnostic pathways, and nonmalignant controls. As of July 31, 2026, 205 participants have been recruited, with recruitment continuing until the target sample size is reached. Molecular and data analyses are ongoing, with additional publications expected as the cohort matures. CONCLUSIONS: This study will generate one of the first integrated genomic, epigenomic, and transcriptomic liquid biopsy datasets for NSCLC in New Zealand. The findings are expected to support the development of sensitive, accessible, and equitable blood-based biomarkers for NSCLC detection and treatment monitoring while also contributing to improved precision oncology approaches and reducing NSCLC inequities among M&#x101;ori populations.

Humans↗