Electrochemical biosensors for early detection of breast cancer.

Breast cancer continues to be a significant contributor to global cancer deaths, particularly among women. This highlights the critical role of early detection and treatment in boosting survival rates. While conventional diagnostic methods like mammograms, biopsies, ultrasounds, and MRIs are valuable tools, limitations exist in terms of cost, invasiveness, and the requirement for specialized equipment and trained personnel. Recent shifts towards biosensor technologies offer a promising alternative for monitoring biological processes and providing accurate health diagnostics in a cost-effective, non-invasive manner. These biosensors are particularly advantageous for early detection of primary tumors, metastases, and recurrent diseases, contributing to more effective breast cancer management. The integration of biosensor technology into medical devices has led to the development of low-cost, adaptable, and efficient diagnostic tools. In this framework, electrochemical screening platforms have garnered significant attention due to their selectivity, affordability, and ease of result interpretation. The current review discusses various breast cancer biomarkers and the potential of electrochemical biosensors to revolutionize early cancer detection, making provision for new diagnostic platforms and personalized healthcare solutions.

Postpartum Psychosis as a Precursor to Schizophrenia: A Comprehensive Review.

Postpartum psychosis (PP) is a rare and severe mental health disorder occurring shortly after childbirth, characterized by symptoms such as delusions, hallucinations, and intense mood swings. This review examines the potential link between PP and the later development of schizophrenia, a chronic psychiatric condition that typically emerges in late adolescence or early adulthood. By reviewing existing literature and analyzing epidemiological and clinical data, this review aims to clarify whether PP can be a precursor to schizophrenia. Findings suggest that while the transition from PP to schizophrenia is not inevitable, there is an increased risk, with some studies indicating that a subset of women with PP may develop a chronic psychotic disorder later on. This underscores the importance of early detection, ongoing monitoring, and targeted interventions. The review emphasizes the need for improved diagnostic practices and preventive measures to better manage PP and its potential long-term effects. Enhanced understanding of this relationship can inform more effective treatment strategies and support better mental health outcomes for new mothers. Future research should focus on refining risk assessment tools, exploring underlying mechanisms, and developing comprehensive management approaches to address the challenges associated with PP and its potential progression to schizophrenia.

The efficacy of different biomarkers and endpoints to refine referrals for suspected prostate cancer: the TARGET study (Tiered integrAted tests for eaRly diaGnosis of clinically significant ProstatE Tumours).

BACKGROUND: The majority of men referred with a raised PSA for suspected prostate cancer will receive unnecessary tertiary investigations including MRI and biopsy. Here, we compared different types of biomarkers to refine tertiary referrals and when different definitions of clinically significant cancer were used. METHODS: Data and samples from 798 men referred for a raised PSA (≥ 3 ng/mL) and investigated through an MRI-guided biopsy pathway were accessed for this study. Bloods were acquired pre-biopsy for liquid biomarkers and germline DNA. Variables explored included PSA + Age (base model), free/total PSA (FTPSA), Prostate Health Index (phi), PSA density (PSAd), polygenic risk score (PRS) and MRI (≥ LIKERT 3). Different diagnostic endpoints for significant cancer (≥ grade group 2 [GG2], ≥ GG3, ≥ Cambridge Prognostic Group 2 [CPG2], ≥ CPG3) were tested. The added value of each biomarker to the base model was evaluated using logistic regression models, AUC and decision curve analysis (DCA) plots. RESULTS: The median age and PSA was 65 years and 7.13 ng/mL respectively. Depending on definition of clinical significance, ≥ grade group 2 (GG2) was detected in 57.0% (455/798), ≥ GG3 in 27.5% (220/798), ≥ CPG2 in 61.6% (492/798) and ≥ CPG3 in 42.6% (340/798). In the pre-MRI context, the PSA + Age (base model) AUC for prediction of ≥ GG2, ≥ GG3, ≥ CPG2 and ≥ CPG3 was 0.66, 0.68, 0.70 and 0.75 respectively. Adding phi and PSAd to base model improved performance across all diagnostic endpoints but was notably better when the composite CPG prognostic score was used: AUC 0.82, 0.82, 0.83, 0.82 and AUC 0.74, 0.73, 0.79, 0.79 respectively. In contrast, neither FTPSA or PRS scores improved performance especially in detection of ≥ GG3 and ≥ CPG3 disease. Combining biomarkers did not alter results. Models using phi and PSAd post-MRI also improved performances but again benefit varied with diagnostic endpoint. In DCA analysis, models which incorporated PSAd and phi in particular were effective at reducing use of MRI and/or biopsies especially for ≥ CPG3 disease. CONCLUSION: Incorporating phi or PSAd can refine and tier who is referred for tertiary imaging and/or biopsy after a raised PSA test. Incremental value however varied depending on the definition of clinical significance and was particularly useful when composite prognostic endpoints are used.

Resilience Gap in Gastrointestinal Endoscopy Activity during the COVID-19 Pandemic in South Korea.

This study assessed the impact of distancing measures during the COVID-19 pandemic on cancer diagnostic activities, including gastrointestinal endoscopy (GIE). It analyzed GIE volumes from 2020 to 2022 in comparison to 2018-2019, considering variations in resilience linked to socioeconomic status (SES). The analysis utilized data from the Korean Health Insurance Review and Assessment Services database, covering the entire population and medical facilities. Diagnostic GIE rates (2018-2022) in Gwangju Metropolitan City and Jeonnam province were examined, comparing age-standardized rates (ASRs) by area, gender, and SES. The results indicated a decline in ASRs for colonoscopy and endoscopic gastroduodenoscopy (EGD) in 2020 compared to 2018-2019, followed by an increase in 2021-2022, except for EGD in the medical aid population. SES based and rural-urban disparities were evident in the recovery of GIE rates. The findings suggest that equity-focused strategies are needed to ensure equitable healthcare access among different socioeconomic groups after pandemic.

Design of randomized controlled trials to estimate cancer-mortality reductions from multicancer detection screening.

BACKGROUND: Determining whether screening with multicancer detection (MCD) tests saves lives requires randomized controlled trials (RCTs). To inform RCT design, we estimated cancer-mortality outcomes from hypothetical MCD RCTs. METHODS: We used the Hu-Zelen model, previously used to plan the NLST, to estimate mortality reductions, sample-size, and power for 9 cancers for different RCT design parameters and MCD test parameters. RESULTS: Our base-case RCT with 5 yearly screens and 100,000 people ages 60-74 in each arm, who also undergo standard-of-care screens, has 87-89% power to detect an 9-10% mortality reduction (NNS = 578-724) over 7-9 years. The majority of prevented deaths were from lung-cancers (base-case (64-66%) and all sensitivity analyses), 8-10% from colorectal-cancer, and 26% from the other 7-cancers, mostly from stomach/ovary/esophagus (due to excellent stage-1 survival) and less from liver/pancreas (poor stage-1 survival) or head/neck-cancer/lymphoma (excellent stage-4 survival). There was limited power for mortality reductions at most individual cancer sites. Base-case findings were sensitive to test sensitivity, stage-shifts, and mean sojourn times in the preclinical state (especially for lung-cancer), but 90% power could be recovered by recruiting a substantially higher risk population. CONCLUSIONS: Large-scale MCD RCTs would have 89% power to detect a ∼10% cancer-mortality reduction over a relatively short 7-9 year timeframe from trial entry. The estimated NNS for MCD RCTs compares favorably to mammographic screening. Most prevented cancer-deaths in a well-powered MCD RCT would likely be from lung-cancer. Non-lung/CRC cancer sites could be a meaningful proportion of prevented cancer-deaths but power is insufficient to isolate non-lung-cancer mortality reductions.

GDF15 and LCN2 for early detection and prognosis of pancreatic cancer.

BACKGROUND: The prognosis of pancreatic ductal adenocarcinomas (PDAC) remains very poor, emphasizing the critical importance of early detection, where biomarkers offer unique potential. Although growth differentiation factor 15 (GDF15) and Lipocalin 2 (LCN2) have been linked to PDAC, their precise roles as biomarkers are uncertain. METHODS: Circulating levels of GDF15 and LCN2 were examined in human PDAC patients, heathy controls, and individuals with benign pancreatic diseases. Circulating levels of IL-6, CA19-9, and neutrophil-to-lymphocyte ratio (NLR) were measured for comparisons. Correlations between PDAC progression and overall survival were assessed. A mouse PDAC model was employed for comprehensive analyses, complementing the human studies by exploring associations with various metabolic and inflammatory parameters. Sensitivity and specificity of the biomarkers were evaluated. FINDINGS: Our results demonstrated elevated levels of circulating GDF15 and LCN2 in PDAC patients compared to both healthy controls and individuals with benign pancreatic diseases, with higher GDF15 levels associated with disease progression and increased mortality. In PDAC mice, circulating GDF15 and LCN2 progressively increased, correlating with tumor growth, behavioral manifestations, tissue and molecular pathology, and cachexia development. GDF15 exhibited highly sensitive and specific for PDAC patients compared to CA19-9, IL-6, or NLR, while LCN2 showed even greater sensitivity and specificity in PDAC mice. Combining GDF15 and LCN2, or GDF15 and CA19-9, enhanced sensitivity and specificity. INTERPRETATION: Our findings indicate that GDF15 holds promise as a biomarker for early detection and prognosis of PDAC, while LCN2 could strengthen diagnostic panels.

Clinical Perspectives on the Histomolecular Features of the Pancreatic Precursor Lesions: A Narrative Review.

Pancreatic cancer (PC) is a lethal cancer with poor prognoses. Identifying and characterizing pancreatic cystic lesions (PCLs) in the early detection and follow-up plans is thought to help detect pancreatic malignancy. Besides, the molecular features of PCLs are thought to unravel potentials for targeted therapies. We present a narrative review of the existing literature on the role of PCLs in the early detection, risk stratification, and medical management of PC. High-grade intraductal papillary mucinous neoplasms (IPMN) and pancreatic intraepithelial neoplasia (PanIN) stage III are high-risk lesions for developing PC. These lesions often require thorough histomolecular characterization using endoscopic ultrasound (EUS), before a surgical decision is made. EUS is also useful in the risk assessment of PCLs with tentative plans-for instance, in branch-duct IPMNs (BD-IPMN)- where the final decision might change. Besides the operative decisions, recent improvements in the application of targeted therapies are expected to improve survival measures. Knowledge of molecular features has helped develop targeted therapies. In summary, the histomolecular characterization of PCLs is helpful in optimizing management plans in PC. Further improvements are still needed for the broad application of this knowledge in the clinical setting.

Harnessing molecular probes for imaging of human epidermal growth factor receptor (HER) family.

The human epidermal growth factor receptor (HER) family plays a critical role in the development, migration, and invasion of various cancers. Currently, the FDA has approved numerous targeting therapies for the HER family consist of small molecule drugs, monoclonal antibodies and antibody-drug conjugates. To facilitate precision therapy using currently approved targeted agents, early detection and quantification of each HER receptor are essential for assessment, treatment, and prognostic purposes. This study provides a comprehensive review of the latest advancements in detection and quantification of HER receptors, including traditional biopsies, liquid biopsies, and non-invasive detection methods. Although traditional histological methods, such as immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), have yielded valuable insights, advancements in real-time and non-invasive detection technologies necessitate improved methods for the dynamic evaluation of HER status. This article also reviews several emerging real-time techniques for detecting and quantifying HER status in circulating tumor cells (CTCs) extracted from blood samples, as well as in vivo assessments using positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging. This review emphasizes the importance of continuous innovation in the application of HER receptor imaging technologies, with the goal of enhancing treatment outcomes and prognoses for cancer patients.

Epigenomic newborn screening for conditions with intellectual disability and autistic features in Australian newborns.

This study describes a protocol to assess a novel workflow called Epi-Genomic Newborn Screening (EpiGNs) on 100,000 infants from the state of Victoria, Australia. The workflow uses a first-tier screening approach called methylation-specific quantitative melt analysis (MS-QMA), followed by second and third tier testing including targeted methylation and copy number variation analyzes with droplet digital PCR, EpiTYPER system and low-coverage whole genome sequencing. EpiGNs utilizes only two 3.2 mm newborn blood spot punches to screen for genetic conditions, including fragile X syndrome, Prader-Willi syndrome, Angelman syndrome, Dup15q syndrome and sex chromosome aneuploidies. The program aims to: identify clinically actionable methylation screening thresholds for the first-tier screen and estimate prevalence for the conditions screened.

[Box: see text].

Development, validation, and visualization of a web-based nomogram for predicting chronic kidney disease incidence at health examination centers.

PURPOSE: To develop and validate a web-based nomogram for predicting new incident chronic kidney disease (CKD) within 4 years in a cohort undergoing routine physical examination from two health examination centers. METHODS: One center was utilized for training and internal validation of a nomogram model involving 6515 patients, while a separate center was employed for external validation with 3152 patients. Sixteen candidate predictors, including patient demographics, medical histories, physical examination, and laboratory test data, were included in this study to ascertain factors linked to new incident CKD. A nomogram was created to predict CKD risks using a logistic model. The nomogram's performance was assessed using the area under the receiver operating characteristic curve (AUC), calibration plot, and decision curve analysis. RESULTS: Out of the 9667 healthy individuals included in the study with mean age of 46 years, sex ratio (male/female) of 1.69 (6075/3592), 118 (2.59%), 51 (2.61%), and 60 (1.90%) individuals developed CKD in the training (n = 4563), internal validation (n = 1952), and external validation (n = 3152) datasets, respectively. Age, history of diabetes mellitus, systolic blood pressure, serum creatinine, albumin, and triglyceride levels were used to build the nomogram, which yielded excellent discrimination ability (training cohort, AUC = 0.8806, 95% confidence interval [CI] 0.8472-0.9141; internal validation cohort, AUC = 0.8506, 95% CI 0.7856-0.9156; external validation cohort, AUC = 0.9183, 95% CI 0.8698-0.9669). We further developed a web-based calculator for convenient application (https://luochuxuan.shinyapps.io/dynnomapp/). CONCLUSION: Our web-based nomogram accurately predicted CKD risks in Chinese health individuals and can be easily used in clinical settings.

Exploring circulating MiRNA signature for osteosarcoma detection: Bioinformatics-based analyzing and validation.

Early detection followed by efficient treatment still remain a considerable challenge for osteosarcoma (OS), indicating the importance of emerging innovative diagnostic methods. Circulating miRNAs offer a promising and non-invasive approach to assess the OS molecular landscapes. This study utilized RNAseq data from OS plasma miRNA expression profiles (PRJEB30542) and PCR Array data (GSE65071) from GEO and ENA databases. In total, 43 miRNAs demonstrated significant differential expression in OS samples of training dataset. A diagnostic model, including hsa-miR-30a-5p, hsa-miR-556-3p, hsa-miR-200a-3p, and hsa-miR-582-5p was identified through multivariate logistic regression analysis and demonstrated significant efficacy in differentiating OS patients from healthy controls in the validation group (AUC: 0.917, sensitivity: 1, specificity: 0.85). The result of target gene prediction and functional enrichment analyses revealed significant associations with terms such as epithelial morphogenesis, P53 and Wnt signaling pathways, and neoplasm metastasis. Further bioinformatics-based evaluations showed that the down-regulation of these miRNAs significantly correlates with poor prognosis and lower survival rate in OS patients and propose their tumor suppressor function in pathogenesis of OS. Furthermore, the study developed a miRNA-mRNA subnetwork that connects these miRNAs to the P53 and Wnt signaling pathways, which are critical pathways with oncogenic effects on OS progression. This comprehensive approach not only presents a promising diagnostic model but also proposes potential molecular markers for OS early diagnosis, making prognosis, and targeted therapy. The identified miRNA-mRNA functional axis holds promise as a valuable resource for further research in understanding OS pathogenesis and establishing therapeutic modalities.

The impact of non-structured PSA testing on prostate cancer-specific mortality on New Zealand Maori men.

OBJECTIVES: To assess the impact of differences in Prostate-Specific Antigen (PSA) testing rates on prostate cancer (PCa) diagnosis and PCa-specific mortality among Maori men in a New Zealand (NZ) population. PATIENTS AND METHODS: Maori men aged 40 years or older, without a history of PCa, with a PSA test between 2006 and 2018 were included. The cohort was divided into two groups; the "screened group" (ScG) consisting of men who had at least one PSA test every four years or less, and the "non-screened group" (non-SG). We measured the rate of cancer diagnoses and used competing risk analysis to assess survival. RESULTS: The study cohort included 63,939 Maori men, with 37,048 (58%) in the ScG. PCa was more frequently diagnosed in the ScG (3.7% vs. 3.0%, P < 0.001). A higher proportion of high-grade cancers were found in the non-SG (32.7% vs. 25.6%, P = 0.001). The 10-year cancer-specific survival was significantly higher in the ScG (99.4% vs. 98.5%, P < 0.001). In a multivariable risk model, PSA testing frequency was an independent predictor of PCa mortality. (HR 2.43, [95% CI 1.97-3.01], P < 0.001). CONCLUSIONS: In a cohort of only Maori men, lower PSA testing rates were associated with a higher risk of PCa-related death. Therefore, regular PSA testing for Maori could improve cancer-specific survival among Maori men. Regular PSA testing should be considered a priority area for improving PCa survival in this population.

Beyond the urban-rural divide: Exploring spatial variations in breast cancer outcomes in Queensland, Australia.

BACKGROUND: Breast cancer is the most commonly diagnosed cancer among women worldwide. While previous studies have reported urban and rural differences in breast cancer outcomes, the level of heterogeneity within these broad regions is currently unknown. METHODS: Population-level data from Queensland Cancer Register including 58,679 women aged at least 20 years who were diagnosed with breast cancer in Queensland, Australia, 2000-2019 were linked to BreastScreen Queensland and Queensland Hospital Admitted Patients Data Collection to estimate five breast cancer outcomes: incidence, proportion of localised disease and screen-detected cases (via public-funded program), surgical rates, and 5-year survival. Bayesian spatial models were used to smooth outcomes across 512-517 small areas in Queensland. RESULTS: The incidence of breast cancer was not proportionally distributed, with urban regions having higher rates. Less than half (47 %) of women were diagnosed with localised disease, 91 % had surgery, with five-year relative survival of 92 %. There was no evidence of geographic variation in the proportion of localised disease, surgical rates, or survival over Queensland. Publicly-funded screening detected 38 % of cases, with lower proportion of screen-detected cases observed in Queensland's urbanised south-east corner. CONCLUSION: Although the disparities in health outcomes faced by Australians living in rural areas have received increased attention, this study found limited evidence for spatial variation in breast cancer outcomes along the continuum of care across Queensland. These results suggest the detection and management practices for breast cancer may provide an achievable benchmark for other cancer types in reducing the geographical disparity in cancer outcomes.

Correlates of intention-to-attend and confirmed cervical screening attendance during the COVID-19 pandemic in Australia: Findings from Compass-PLUS, a prospective cohort study.

Objective: The coronavirus pandemic impacted health-seeking behaviour and access to primary care in Australia. We investigated factors associated with intention-to-attend and attendance of cervical screening during the pandemic, mainly in Victoria, Australia. Methods: We used questionnaire and attendance data (Aug 2020-Nov 2022) from Compass-PLUS, a sub-study of the Compass randomized-controlled trial of Human Papillomavirus-based vs cytology-based screening. Data was restricted to the HPV-screening arm for comparability to the national program. We investigated associations overall and for younger (25-39 years) and older (≥40 years) cohorts, between intention-to-attend/attendance, and socio-demographics, anxiety-related scores, and agreement with beliefs about screening during the pandemic (e.g. importance of screening, increased workload, working from home, risk of infection). Results: Among 2,226 participants, positive intention to attend screening was more likely among those with a family history of cancer (p = 0.030) or living outside major cities (p = 0.024). Increased attendance was associated with increasing age (p < 0.001), prior regular cervical screening history [adjusted relative risk (aRR) for 2 screens in 6 years vs none: 1.23 (95 %CI 1.09,1.40); p < 0.001], and part-time employment or retirement compared to full-time employment [aRR:1.08 (1.02,1.14); aRR:1.12 (1.03, 1.22); respectively]. Lower attendance was related to increased agreement with statements indicating screening de-prioritisation (p-trend < 0.05) and higher recent anxiety, specifically in the older cohort (p-trend = 0.002). Conclusions: Reduced priority of screening and heightened recent anxiety may partly explain indications of lower-than-expected cervical screening rates during the pandemic. It is important that catch-up of missed HPV screens is performed to prevent a possible increase in cancer diagnoses in the long term.

Epidemiological study of overall survivability of individuals diagnosed with lung and bronchus cancer in Michigan between the years 1996 and 2017.

INTRODUCTION: Lung and bronchus cancer is a leading cause of death in the United States. Compared with the national average, Michigan has an increased mortality rate and low early screening and treatment rates. This study aimed to explore the epidemiological trends and assess overall survival (OS) of patients diagnosed with lung cancer in Michigan from 1996 to 2017. METHODS: Data was acquired from the Michigan Cancer Surveillance Program (MCSP). Log-rank test was used to test OS among the time periods, univariate and multivariate cox regression models were employed to determine factors that significantly affected OS. We hypothesized that the introduction of more inclusive lung cancer screening guidelines in 2013 would improve OS for patients diagnosed after its implementation and that individual characteristics and tumor characteristics would both affect OS. RESULTS: Notably, 153 742 individuals met inclusion criteria: 54.22% male and 45.78% female. Mean age at diagnosis was 69 years. No significant difference in OS was found among the three time periods (p = 0.99). Univariate analyses identified four individual characteristics associated with reduced OS: age at diagnosis, male sex, American Indian race, and living in rural or urban area. Reduced OS was associated with primary sites tumors at main bronchus, lung base, or within overlapping lobes, and SEER stage 7. CONCLUSIONS: This study highlights several factors that influence OS. Consideration of these factors may be helpful as a community outreach tool to help increase early detection and reduce overall mortality.

Novel DNA methylation markers for early detection of gastric cardia adenocarcinoma and esophageal squamous cell carcinoma.

Gastric cardia adenocarcinoma (GCA) and esophageal squamous cell carcinoma (ESCC) present significant health challenges in China, often diagnosed at advanced stages with poor prognoses. However, effective biomarkers for early detection remain elusive. This study aimed to integrate methylome and transcriptome data to identify DNA methylation markers for the early detection of GCA and ESCC. In the discovery stage, we conducted Infinium MethylationEPIC array analysis on 36 paired GCA and non-tumor adjacent tissues (NAT), identifying differentially methylated CpG sites (DMCs) between GCA/ESCC and NAT through combined analyses of in-house and publicly available data. In the validation stage, targeted pyrosequencing and quantitative real-time RT-PCR were performed on paired tumor and NAT samples from 50 GCA and 50 ESCC patients. In the application stage, an independent set of 438 samples, including GCA, ESCC, high- and low-grade dysplasia (HGD/LGD), and normal controls, was tested for selected DMCs using pyrosequencing. Our analysis validated three GCA-specific, two ESCC-specific, and one tumor-shared DMCs, exhibiting significant hypermethylation and decreased expression of target genes in tumor samples compared with NAT. Leveraging these DMCs, we developed a GCA-specific 4-marker panel (cg27284428, cg11798358, cg07880787, and cg00585116) with an area under the receiver operating characteristic curve (AUC) of 0.917, effectively distinguishing between cardia HGD/GCA patients and cardia LGD/normal controls. Similarly, an ESCC-specific 3-marker panel (cg14633892, cg04415798, and cg00585116) achieved an AUC of 0.865 in distinguishing esophageal HGD/ESCC cases. Furthermore, integrating cg00585116, age, and alcohol consumption yielded a tumor-shared logistic model with good discrimination for two cancer/HGD (AUC, 0.767; 95% confidence interval, 0.720-0.813). The mean AUC of the model after 5-fold cross-validation was 0.764. In summary, our study identifies novel DNA methylation markers capable of accurately distinguishing GCA/ESCC and HGD from LGD and normal controls. These findings offer promising prospects for targeted DNA methylation assays in future minimally invasive cancer screening methods.

Digital cognitive assessments as low-burden markers for predicting future cognitive decline and tau accumulation across the Alzheimer's spectrum.

BACKGROUND: Digital cognitive assessments, particularly those that can be done at home, present as low-burden biomarkers for participants and patients alike, but their effectiveness in the diagnosis of Alzheimer's disease (AD) or predicting its trajectory is still unclear. Here, we assessed what utility or added value these digital cognitive assessments provide for identifying those at high risk of cognitive decline. METHODS: We analyzed >500 Alzheimer's Disease Neuroimaging Initiative participants who underwent a brief digital cognitive assessment and amyloid beta (Aß)/tau positron emission tomography scans, examining their ability to distinguish cognitive status and predict cognitive decline. RESULTS: Performance on the digital cognitive assessment was superior to both cortical Aß and entorhinal tau in detecting mild cognitive impairment and future cognitive decline, with mnemonic discrimination deficits emerging as the most critical measure for predicting decline and future tau accumulation. DISCUSSION: Digital assessments are effective at identifying at-risk individuals, supporting their utility as low-burden tools for early AD detection and monitoring. HIGHLIGHTS: Performance on digital cognitive assessments predicts progression to mild cognitive impairment at a higher proficiency compared to amyloid beta and tau. Deficits in mnemonic discrimination are indicative of future cognitive decline. Impaired mnemonic discrimination predicts future entorhinal and inferior temporal tau.

The serological diagnostic value of EBV-related IgA antibody panels for nasopharyngeal carcinoma: a diagnostic test accuracy meta-analysis.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is diagnosed relatively late and has a poor prognosis, requiring early detection to reduce the disease burden. This diagnostic test accuracy meta-analysis evaluated the serological diagnostic value of nine EBV-related IgA antibody panels (EBNA1-IgA, VCA-IgA, EA-IgA, Zta-IgA, EBNA1-IgA + VCA-IgA, VCA-IgA + EA-IgA, VCA-IgA + Rta-IgG, EBNA1-IgA + VCA-IgA + Zta-IgA and VCA-IgA + EA-IgA + Rta-IgG), aiming to identify suitable serological detection biomarkers for NPC screening. METHODS: PubMed, Embase, China National Knowledge Infrastructure and Chinese BioMedical Literature Database were searched from January 1st, 2000 to September 30th, 2023, with keywords nasopharyngeal carcinoma, IgA, screening, early detection, early diagnosis, sensitivity and specificity. Articles on the diagnostic value of serum EBV-related IgA antibody panels for NPC were included. Study selection, data extraction, and quality assessment were performed independently by two researchers, and a third researcher was consulted in the case of disagreement. Bivariate models were used for statistical analysis. The quality of included studies was evaluated through Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2). RESULTS: A total of 70 articles were included, involving 11 863 NPC cases and 34 995 controls. Among the nine EBV-related IgA antibody panels, EBNA1-IgA + VCA-IgA [0.928 (0.898, 0.950)], VCA-IgA + Rta-IgG [0.925 (0.890, 0.949)], EBNA1-IgA + VCA-IgA + Zta-IgA [0.962 (0.909, 0.985)] and VCA-IgA + EA-IgA + Rta-IgG [0.945 (0.918, 0.964)] demonstrated higher pooled sensitivity (95%CI). In terms of diagnostic odds ratio (DOR) (95%CI), EBNA1-IgA + VCA-IgA [107.647 (61.173, 189.430)], VCA-IgA + Rta-IgG [105.988 (60.118, 186.857)] and EBNA1-IgA + VCA-IgA + Zta-IgA [344.450 (136.351, 870.153)] showed superior performance. Additionally, the SROC curves for EBNA1-IgA + VCA-IgA and VCA-IgA + Rta-IgG were more favorable. However, publication bias was detected for VCA-IgA (P = 0.005) and EBNA1-IgA + VCA-IgA (P = 0.042). CONCLUSIONS: In general, parallel detection of serum EBNA1-IgA, VCA-IgA and Zta-IgA antibodies using ELISA demonstrates better pooled sensitivity and DOR among the studied panels. In the cases where fewer indicators are used, serum VCA-IgA and EBNA1-IgA/Rta-IgG antibody panel exhibits a comparable performance. TRIAL REGISTRATION: The International Prospective Register of Systematic Reviews registration number: CRD42023426984, registered on May 28, 2023.

Genomic-Based Early Detection Screening: A Literature Review of Prospective Trials and Emerging Strategies for Gastrointestinal Cancers.

Numerous genomic-based early detection screening tests are being developed. These tests have the potential to revolutionize current single-organ screening paradigms, especially in gastrointestinal cancers. In this review, we underscore the performance of these genomic-based early detection tests based on prospective clinical trials. Moreover, we discuss a professional advancement for gastroenterologists in the diagnostic assessment of individuals who are cancer signal positive.

Serum mRNA levels of cytokeratin-19 and vascular endothelial growth factor in oral squamous cell carcinoma and oral potentially malignant disorders using RT-PCR.

BACKGROUND: Oral cancers, which include tumors of the oral cavity, salivary glands, and pharynx, are becoming increasingly prevalent worldwide. Squamous cell carcinoma accounts for over 90% of malignant oral lesions, with oral squamous cell carcinoma (OSCC) being notably common in the Indian subcontinent and other regions of Asia. This is especially true in South-Central Asia, including Sri Lanka, where it is particularly prevalent among men. This study aims to evaluate the levels of Vascular Endothelial Growth Factor-A (VEGF-A) and Cytokeratin-19 (CK-19) mRNAs in whole blood as a potential method for the early detection of OSCC. METHODS: The study included 40 patients (each from OSCC, Oral Submucous Fibrosis (OSF), Oral Leukoplakia (OLK), Oral Lichen Planus (OLP), and 10 healthy controls. The expression levels of VEGF-A and CK-19 mRNAs were measured from extracellular RNA extracted from whole blood samples using real-time reverse transcription polymerase chain reaction (RT-PCR) with sequence-specific primers. Receiver operating characteristic (ROC) curve analysis was used to evaluate the effectiveness of these biomarkers in detecting OSCC. RESULTS: The results demonstrated a significant increase in blood transcripts of the candidate mRNAs CK-19 and VEGF-A in patients with OSCC, OSF, OLK, and OLP. The Wilcoxon signed-rank test revealed a p-value of 0.002 for each specific comparison between diseased patients and healthy controls (i.e., OSCC vs. HC, OSF vs. HC, OLP vs. HC, OLK vs. HC) for both CK-19 and VEGF-A. When these two biomarkers were used together, they provided a 60% predictive probability for patients with OSCC (p = 0.023). CONCLUSION: This study highlights the efficacy of blood mRNA transcriptome diagnostics in detecting OSCC. This innovative clinical approach has the potential to be a robust, efficient, and reliable tool for early cancer detection. Blood-based transcriptomes could be further explored for their effectiveness in various health contexts and for routine health monitoring.