Do help-seeking adolescents report more psychotic-like experiences than young adults on the 16-item version of the prodromal questionnaire (PQ-16)?

AIM: To compare psychotic-like experiences (PLEs) in adolescents and young adults referred to the Mental Health Services (MHSs). METHODS: Participants scored the 16-item Prodromal Questionnaire (PQ-16) as part of the intake procedure. Data on the Diagnostic and Statistical Manual of Mental Disorders (DSM) classification and demographic data were collected. RESULTS: The PQ-16 was completed by 13 783 respondents (mean age 24.63 years, SD = 6.09; 62.6% female). Overall, the scores on the PQ-16 were not higher for adolescents (11-17 years; m = 4.84, SD = 3.62) than for young adults (18-35 years; m = 5.47, SD = 3.85). On PQ-16 item level, adolescents reported seeing and hearing things more than adults did. Across all age groups, males scored lower on the PQ-16 than females. Specifically, adolescent males scored lower than other participants. For adolescents and young adults alike, PQ-16 scores were higher for participants with borderline personality disorder, PTSD, and mood disorder than for those with other DSM classifications. CONCLUSIONS: Although help-seeking adolescents did not score higher on the PQ-16 than help-seeking young adults, more of them reported perceptual anomalies. Irrespective of age, participants with borderline personality disorder, PTSD and mood disorder scored higher on the PQ-16 than those with other DSM classifications.

Leveraging cfDNA fragmentomic features in a stacked ensemble model for early detection of esophageal squamous cell carcinoma.

In this study, we develop a stacked ensemble model that utilizes cell-free DNA (cfDNA) fragmentomics for the early detection of esophageal squamous cell carcinoma (ESCC). This model incorporates four distinct fragmentomics features derived from whole-genome sequencing (WGS) and advanced machine learning algorithms for robust analysis. It is validated across both an independent validation cohort and an external cohort to ensure its generalizability and effectiveness. Notably, the model maintains its robustness in low-coverage sequencing environments, demonstrating its potentials in clinical settings with limited sequencing resources. With its remarkable sensitivity and specificity, this approach promises to significantly improve the early diagnosis and management of ESCC. This study represents a substantial step forward in the application of cfDNA fragmentomics in cancer diagnostics, emphasizing the need for further research to fully establish its clinical efficacy.

PSA screening for prostate cancer in the United States: 30 years of controversy.

In 1994, the United States approved the Prostate-Specific Antigen (PSA) test as a screening tool for prostate cancer. It did so despite the test's inherent weakness: not being prostate cancer specific. Subsequent randomized trials yielded conflicting results as to its benefits. Medical guideline organizations are concerned that PSA screening results in the diagnosis and treatment of clinically indolent prostate cancer. Nevertheless, PSA screening is prevalent in North America and Europe with PSA screening increasing in other regions. We provide a critical review of the major factors that led to the prevalence of PSA screening in the United States despite the debate about its benefits. Public advocacy in favor of the test and failure of the medical community to appreciate its inherent weakness led to widespread adoption. These factors persist today. Other countries need to carefully analyze the utility of the PSA test before adopting it.

Trends in Cancer-screening Rates in Korea: Findings from the National Cancer Screening Survey, 2004-2023.

Purpose: This study aimed to report the overall national trends in the rates of cancer screening based on recommendations and provide insights into the changing trends of these rates across different demographics. Materials and Methods: This study used data from the Korean National Cancer Screening Survey (KNCSS), which surveys nationwide cancer-screening rates and includes 4,500 individuals meeting the Korean National Cancer Screening Program (NCSP) protocol age criteria. Cancer-screening rates were assessed using structured questionnaires; yearly trends were analyzed for both lifetime cancer-screening rates and rates of screening based on recommendations, and subgroup analyses were performed based on age and sex. Results: The rates of cancer screening based on recommendations showed significant increments: the stomach cancer-screening rate increased from 39.2% in 2004 to 77.5% in 2023 (3.50% per year), the liver cancer-screening rate increased from 20.0% to 48.8% (4.30% per year), and the colorectal cancer, increased from 19.9% to 70.7% (5.15% per year). The breast cancer-screening rate increased from 33.2% to 72.7% (2.88% per year), and the cervical cancer, increased from 58.3% to 70.2% (1.08% per year). Despite some differences, particularly in relation to sociodemographic factors, screening rates increased significantly for all cancer types. Conclusion: Cancer-screening rates in Korea increased consistently from 2004 to 2023, demonstrating the effectiveness of the national cancer-screening program. However, the increments in breast, cervical and lung cancer-screening rates were relatively lower, indicating the need for additional efforts and strategies.

Early detection of multiple endocrine neoplasia type 1: A case report.

BACKGROUND: Multiple endocrine neoplasias (MENs) are a group of hereditary diseases involving multiple endocrine glands, and their prevalence is low. MEN type 1 (MEN1) has diverse clinical manifestations, mainly involving the parathyroid glands, gastrointestinal tract, pancreas and pituitary gland, making it easy to miss the clinical diagnosis. CASE SUMMARY: We present the case of a patient in whom MEN1 was detected early. A middle-aged male with recurrent abdominal pain and diarrhea was admitted to the hospital. Blood tests at admission revealed hypercalcemia and hypophosphatemia, and emission computed tomography of the parathyroid glands revealed a hyperfunctioning parathyroid lesion. Gastroscopy findings suggested a duodenal bulge and ulceration. Ultrasound endoscopy revealed a hypoechoic lesion in the duodenal bulb. Further blood tests revealed elevated levels of serum gastrin. Surgery was performed, and pathological analysis of the surgical specimens revealed a parathyroid adenoma after parathyroidectomy and a neuroendocrine tumor after duodenal bulbectomy. The time from onset to the definitive diagnosis of MEN1 was only approximately 1 year. CONCLUSION: For patients who present with gastrointestinal symptoms accompanied by hypercalcemia and hypophosphatemia, clinicians need to be alert to the possibility of MEN1.

The Chiraiya project: a retrospective analysis of breast cancer detection gaps addressed via mobile mammography in Jammu Province, India.

BACKGROUND: Breast cancer remains a pervasive threat to women worldwide, with increasing incidence rates necessitating effective screening strategies. Timely detection with mammography has emerged as the primary tool for mass screening. This retrospective study, which is part of the Chiraiya Project, aimed to evaluate breast lesion patients identified during opportunistic mammography screening camps in Jammu Province, India. METHODS: A total of 1505 women aged 40 years and older were screened using a mobile mammographic unit over a five-year period, excluding 2020 and 2021 due to the COVID-19 pandemic. The inclusion criterion was women in the specified age group, while the exclusion criterion was women with open breast wounds, history of breast cancer or a history of breast surgery. The screening process involved comprehensive data collection using a detailed Proforma, followed by mammographic assessments conducted within strategically stationed mobile units. Radiological interpretations utilizing the BI-RADS system were performed, accompanied by meticulous documentation of patient demographics, habits, literacy, medical history, and breastfeeding practices. Participants were recruited through collaborations with NGOs, army camps, village panchayats, and urban cooperatives. Screening camps were scheduled periodically, with each camp accommodating 90 patients or fewer. RESULTS: Among the 1505 patients, most were aged 45-50 years. The number of screenings increased yearly, peaking at 441 in 2022. The BI-RADS II was the most common finding (48.77%), indicating the presence of benign lesions, while the BI-RADS 0 (32.96%) required further evaluation. Higher-risk categories (BI-RADS III, IV, V) were less common, with BI-RADS V being the rarest. Follow-up adherence was highest in the BI-RADS III, IV, and V categories, with BI-RADS V achieving 100% follow-up. However, only 320 of 496 BI-RADS 0 patients were followed up, indicating a gap in continuity of care. The overall follow-up rate was 66.89%. Compared to urban areas, rural areas demonstrated greater screening uptake but lower follow-up rates, highlighting the need for tailored interventions to improve follow-up care access, especially in rural contexts. CONCLUSION: This study underscores the efficacy of a mobile mammographic unit in reaching marginalized populations. Adherence to screening protocols has emerged as a linchpin for early detection, improved prognosis, and holistic public health enhancement. Addressing misconceptions surrounding mammographic screenings, especially in rural settings, is crucial. These findings call for intensified efforts in advocacy and education to promote the benefits of breast cancer screening initiatives. Future interventions should prioritize improving access to follow-up care and addressing screening to enhance breast cancer management in Jammu Province.

Methodological Considerations in Evaluating Breast Cancer Screening Studies.

In evidence-based medicine frameworks, the highest level of evidence is derived from quantitative synthesis of double-masked, high-quality, randomly assigned controlled trials. Meta-analyses of randomly assigned controlled trials have demonstrated that screening mammography reduces breast cancer deaths. In the United States, every major guideline-producing organization has recommended screening mammography in average-risk women; however, there are controversies about age and frequency. Carefully controlled observational research studies and statistical modeling studies can address evidence gaps and inform evidence-based, contemporary screening practices. As breast imaging radiologists develop and evaluate existing and new screening tests and technologies, they will need to understand the key methodological considerations and scientific criteria used by policy makers and health service researchers to support dissemination and implementation of evidence-based screening tests. The Wilson and Jungner principles and the U.S. Preventive Services Task Force general analytic framework provide structured evaluations of the effectiveness of screening tests. Key considerations in both frameworks include public health significance, natural history of disease, cost-effectiveness, and characteristics of screening tests and treatments. Rigorous evaluation of screening tests using analytic frameworks can maximize the benefits of screening tests while reducing potential harms. The purpose of this article is to review key methodological considerations and analytic frameworks used to evaluate screening studies and develop evidence-based recommendations.

Implementation of remote general movement assessment using the in-motion instructions in a high-risk norwegian cohort.

BACKGROUND: General Movement Assessment (GMA) is recommended for early detection of risk for cerebral palsy but requires trained clinical experts. We aimed to implement home- and hospital-based filming for remote GMA in a Norwegian high-risk infant cohort, as well as evaluating parents' experiences in filming their infant at home. METHODS: This knowledge translational study used a prospective cohort design including participants referred to neurodevelopmental follow-up across three sites in the Central Norway Regional Health Authority. Two home films of the fidgety type of general movements were collected between 12+1-14+6 and 15+1-17+6 weeks after term by parents. An additional film was collected at the hospital between 12+1 and 17+6 weeks after term. The instructional guide for all filming was the In-Motion App standards. Videos were transferred to a remote GMA team and classified as either "GMA scorable" or "GMA not scorable" based on Prechtl's GMA standards. Parents responded to an online survey using a 5-point Likert scale to collect information about their perspectives, experiences, and possible worries by filming their infant at home. RESULTS: One-hundred-and-two infants from 95 families participated. Ninety-two (96.8%) families transferred 177 home-based videos. Eighty-four (92%) of these had 95 videos taken in their local hospital. All 177 home-videos were "GMA scorable" and three (3,1%) out of 95 hospital-based videos were classified as "GMA not scorable". Eight families did not respond to the survey and two families did not receive the survey due to a technical error. Seventy-eight (91.7%) respondents agreed or strongly agreed that it was easy to perform home filming and five (5.9%) agreed that they were more worried about their child`s development after filming at home. Almost 80% of respondents agreed that a video for GMA can be taken at home instead of in hospital. CONCLUSIONS: This study strengthens the clinical implementation of home filming by parents and remote GMA for early detection of CP in high-risk follow-up programs. The implementation of remote GMA has the potential to facilitate early intervention to improve function in children with CP in line with international recommendations. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04287166 Date of registration: 27/02/2020.

Use of Deep Neural Networks to Predict Obesity With Short Audio Recordings: Development and Usability Study.

BACKGROUND: The escalating global prevalence of obesity has necessitated the exploration of novel diagnostic approaches. Recent scientific inquiries have indicated potential alterations in voice characteristics associated with obesity, suggesting the feasibility of using voice as a noninvasive biomarker for obesity detection. OBJECTIVE: This study aims to use deep neural networks to predict obesity status through the analysis of short audio recordings, investigating the relationship between vocal characteristics and obesity. METHODS: A pilot study was conducted with 696 participants, using self-reported BMI to classify individuals into obesity and nonobesity groups. Audio recordings of participants reading a short script were transformed into spectrograms and analyzed using an adapted YOLOv8 model (Ultralytics). The model performance was evaluated using accuracy, recall, precision, and F1-scores. RESULTS: The adapted YOLOv8 model demonstrated a global accuracy of 0.70 and a macro F1-score of 0.65. It was more effective in identifying nonobesity (F1-score of 0.77) than obesity (F1-score of 0.53). This moderate level of accuracy highlights the potential and challenges in using vocal biomarkers for obesity detection. CONCLUSIONS: While the study shows promise in the field of voice-based medical diagnostics for obesity, it faces limitations such as reliance on self-reported BMI data and a small, homogenous sample size. These factors, coupled with variability in recording quality, necessitate further research with more robust methodologies and diverse samples to enhance the validity of this novel approach. The findings lay a foundational step for future investigations in using voice as a noninvasive biomarker for obesity detection.

A new antigen test device for rapid influenza A and B detection.

Introduction: Tests for detection of influenza must demonstrate high sensitivity and specificity, affordability, and rapidness. Methods: This study aimed to evaluate the performance of the LabOn-Time™ Influenza A + B Rapid test device (BMT Diagnostics, Ltd), as compared to Real-time polymerase chain reaction (RT-PCR), in identifying influenza A/B among 183 nasopharyngeal samples collected between February and April 2023 from patients with Influenza-like symptoms. Results: Out of 70 participants with a positive RT-PCR result, 53 (75.7 %) had a positive LabOn-Time result. The LabOn-Time kit had a sensitivity of 75.7 % and specificity of 100 %. The odds ratio for showing a false negative LabOn-Time result for influenza B, compared to influenza A was 5.24 (95%CI: 1.35-20.31). All false negative LabOn-Time samples had a RT-PCT cycle threshold ≥20. Mean time from symptom onset was significantly lower in the false negative LabOn-Time cases compared to the positive cases (36 ± 15.3 vs. 42.6 ± 10.1, respectively). The mean number of symptoms reported per patient was significantly higher in positive compared to negative LabOn-Time cases (2.5 ± 0.5 vs. 1.9 ± 0.4, p < 0.001). Conclusions: The LabOn-Time device, which is very simple and intuitive to operate, could significantly contribute to early detection of influenza A/B infection.

Ethnic inequalities in coverage and use of women's cancer screening in Peru.

OBJECTIVE: This study aimed to assess ethnic inequalities in the coverage and utilization of cancer screening services among women in Peru. METHODS: Data from the 2017-2023 Demographic and Family Health Survey in Peru were analyzed to evaluate ethnic disparities in screening coverage for breast and cervical cancer, including clinical breast examination (CBE), Pap smear test (PST), and mammography. Measures such as the GINI coefficient and Slope Index of Inequality (SII) were used to quantify coverage and utilization disparities among ethnic groups. RESULTS: The study included 70,454 women aged 30-69. Among women aged 40-69, 48.31% underwent CBE, 84.06% received PST, and 41.69% underwent mammography. It was found inequalities in coverage for any cancer screening (GINI: 0.10), mammography (GINI: 0.21), CBE (GINI: 0.19), and PST (GINI: 0.06), in 25 Peruvian regions. These inequalities were more pronounced in regions with larger populations of Quechua, Aymara, and Afro-Peruvian women. In rural areas, Quechua or Aymara women (SII: -0.83, -0.95, and - 0.69, respectively) and Afro-Peruvian women (SII: -0.80, -0.92, and - 0.58, respectively) experienced heightened inequalities in the uptake of CBE, mammography, and PST, respectively. Like Quechua or Aymara women (SII: -0.50, SII: -0.52, and SII: -0.50, respectively) and Afro-Peruvian women (SII: -0.50, SII: -0.58, and SII: -0.44, respectively) with only a primary education. CONCLUSION: Ethnic inequalities affect breast and cervical cancer screening coverage across regions in Peru. In Quechua, Aymara, and Afro-Peruvian women the uptake of mammography, CBE, and PST was less frequently than their white or mestizo counterparts. These inequalities are attributed to sociodemographic conditions such as lower education levels and residence in rural or non-capital areas.

Nonspecific Signs and/or Symptoms of Cancer: A Retrospective, Observational Analysis from a Secondary Care, US Community Oncology Dataset.

To help determine the unmet need for improved diagnostic tools to evaluate patients with nonspecific signs and/or symptoms (NSSS) and suspicion of cancer, we examined patient characteristics, diagnostic journey, and cancer incidence of patients with NSSS within The US Oncology Network (The Network), a secondary care community oncology setting. This retrospective, observational cohort study included patients aged ≥40 years with ≥1 NSSS in their problem list at their first visit within The Network (the index date) between 1 January 2016 and 31 December 2020. Patients were followed longitudinally with electronic health record data for initial cancer diagnosis, new noncancer diagnosis, death, end of study observation period, or 12 months, whichever occurred first. Of 103,984 patients eligible for inclusion, 96,722 presented with only 1 NSSS at index date; 6537/103,984 (6.3%) were diagnosed with 1 primary cancer within 12 months after the index date; 3825/6537 (58.5%) with hematologic malignancy, and 2712/6537 (41.5%) with solid tumor. Among patients diagnosed with cancer (n = 6774), the median time to cancer diagnosis after their first visit within The Network was 5.13 weeks. This study provides a real-world perspective on cancer incidence in patients with NSSS referred to a secondary care setting and highlights the unmet need for improved diagnostic tools to improve cancer outcomes.

Promising microRNAs in pre-diagnostic serum associated with lung cancer up to eight years before diagnosis: a HUNT study.

INTRODUCTION: Blood biomarkers for early detection of lung cancer (LC) are in demand. There are few studies of the full microRNome in serum of asymptomatic subjects that later develop LC. Here we searched for novel microRNA biomarkers in blood from non-cancer, ever-smokers populations up to eight years before diagnosis. METHODS: Serum samples from 98,737 subjects from two prospective population studies, HUNT2 and HUNT3, were considered initially. Inclusion criteria for cases were: ever-smokers; no known cancer at study entrance; 0-8 years from blood sampling to LC diagnosis. Each future LC case had one control matched to sex, age at study entrance, pack-years, smoking cessation time, and similar HUNT Lung Cancer Model risk score. A total of 240 and 72 serum samples were included in the discovery (HUNT2) and validation (HUNT3) datasets, respectively, and analysed by next-generation sequencing. The validated serum microRNAs were also tested in two pre-diagnostic plasma datasets from the prospective population studies NOWAC (n = 266) and NSHDS (n = 258). A new model adding clinical variables was also developed and validated. RESULTS: Fifteen unique microRNAs were discovered and validated in the pre-diagnostic serum datasets when all cases were contrasted against all controls, all with AUC > 0.60. In combination as a 15-microRNAs signature, the AUC reached 0.708 (discovery) and 0.703 (validation). A non-small cell lung cancer signature of six microRNAs showed AUC 0.777 (discovery) and 0.806 (validation). Combined with clinical variables of the HUNT Lung Cancer Model (age, gender, pack-years, daily cough parts of the year, hours of indoor smoke exposure, quit time in years, number of cigarettes daily, body mass index (BMI)) the AUC reached 0.790 (discovery) and 0.833 (validation). These results could not be validated in the plasma samples. CONCLUSION: There were a few significantly differential expressed microRNAs in serum up to eight years before diagnosis. These promising microRNAs alone, in concert, or combined with clinical variables have the potential to serve as early diagnostic LC biomarkers. Plasma is not suitable for this analysis. Further validation in larger prospective serum datasets is needed.

Protocol biopsy of kidney allograft enables early detection of BK virus nephropathy to preserve kidney allograft function.

BACKGROUND: The Banff Working Group has updated the histological classification of BK virus nephropathy (BKVN), highlighting the importance of early detection. However, an early detection strategy for BKVN using biopsy has not yet been established. Our investigation aimed to assess the efficacy of protocol biopsy for the diagnosis of BKVN. METHODS: We performed a retrospective cohort study of 314 patients who had undergone kidney transplantation between 2006 and 2021. Kidney allograft biopsies were performed as part of a protocol biopsy at 3 months and 1 year post-transplantation. Following the diagnosis of BKVN, the immunosuppressant dose was reduced. RESULTS: Twelve patients (3.8%) were diagnosed with BKVN by biopsy. Most diagnoses are established during the early stages of BKVN (polyomavirus nephropathy class 1 in six, class 2 in five, and class 3 in one). Following the reduction in immunosuppressant dose, kidney allograft function did not deteriorate in any patients. Additionally, test for BK virus DNA in the blood was negative. All but one patient demonstrated histological resolution of BKVN, and the other had a very slight positivity for the simian virus 40 large T antigen. The median follow-up time after BKVN diagnosis was 6 years. One patient developed de novo donor-specific antibody and subclinical acute antibody-mediated rejection that was successfully cured. CONCLUSIONS: Our analysis indicates that protocol biopsy may enable the early detection of BKVN, resulting in the preservation of kidney function.

Spatial extent as a sensitive amyloid-PET metric in preclinical Alzheimer's disease.

INTRODUCTION: Spatial extent-based measures of how far amyloid beta (Aß) has spread throughout the neocortex may be more sensitive than traditional Aß-positron emission tomography (PET) measures of Aß level for detecting early Aß deposits in preclinical Alzheimer's disease (AD) and improve understanding of Aß's association with tau proliferation and cognitive decline. METHODS: Pittsburgh Compound-B (PIB)-PET scans from 261 cognitively unimpaired older adults from the Harvard Aging Brain Study were used to measure Aß level (LVL; neocortical PIB DVR) and spatial extent (EXT), calculated as the proportion of the neocortex that is PIB+. RESULTS: EXT enabled earlier detection of Aß deposits longitudinally confirmed to reach a traditional LVL-based threshold for Aß+ within 5 years. EXT improved prediction of cognitive decline (Preclinical Alzheimer Cognitive Composite) and tau proliferation (flortaucipir-PET) over LVL. DISCUSSION: These findings indicate EXT may be more sensitive to Aß's role in preclinical AD than level and improve targeting of individuals for AD prevention trials. HIGHLIGHTS: Aß spatial extent (EXT) was measured as the percentage of the neocortex with elevated Pittsburgh Compound-B. Aß EXT improved detection of Aß below traditional PET thresholds. Early regional Aß deposits were spatially heterogeneous. Cognition and tau were more closely tied to Aß EXT than Aß level. Neocortical tau onset aligned with reaching widespread neocortical Aß.

Value of automated breast ultrasound in screening: Standalone and as a supplemental to digital breast tomosynthesis.

We aimed to determine the value of standalone and supplemental automated breast ultrasound (ABUS) in detecting cancers in an opportunistic screening setting with digital breast tomosynthesis (DBT) and compare this combined screening method to DBT and ABUS alone in women older than 39 years with BI-RADS B-D density categories. In this prospective opportunistic screening study, 3466 women aged 39 or older with BI-RADS B-D density categories and with a mean age of 50 were included. The screening protocol consisted of DBT mediolateral-oblique views, 2D craniocaudal views, and ABUS with three projections for both breasts. ABUS was evaluated blinded to mammography findings. Statistical analysis evaluated diagnostic performance for DBT, ABUS, and combined workflows. Twenty-nine cancers were screen-detected. ABUS and DBT exhibited the same cancer detection rates (CDR) at 7.5/1000 whereas DBT + ABUS showed 8.4/1000, with ABUS contributing an additional CDR of 0.9/1000. Standalone ABUS outperformed DBT in detecting 12.5% more invasive cancers. DBT displayed better accuracy (95%) compared to ABUS (88%) and combined approach (86%). Sensitivities for DBT and ABUS were the same (84%), with DBT + ABUS showing a higher rate (94%). DBT outperformed ABUS in specificity (95% vs. 88%). DBT + ABUS exhibited a higher recall rate (14.89%) compared to ABUS (12.38%) and DBT (6.03%) (p < .001). Standalone ABUS detected more invasive cancers compared to DBT, with a higher recall rate. The combined approach showed a higher CDR by detecting one additional cancer per thousand.

Prospective evaluation of the relevance of Epstein-Barr virus antibodies for early detection of nasopharyngeal carcinoma in Chinese adults.

BACKGROUND: Epstein-Barr virus (EBV) is a major cause of nasopharyngeal carcinoma (NPC) and measurement of different EBV antibodies in blood may improve early detection of NPC. Prospective studies can help assess the roles of different EBV antibodies in predicting NPC risk over time. METHODS: A case-cohort study within the prospective China Kadoorie Biobank of 512 715 adults from 10 (including two NPC endemic) areas included 295 incident NPC cases and 745 subcohort participants. A multiplex serology assay was used to quantify IgA and IgG antibodies against 16 EBV antigens in stored baseline plasma samples. Cox regression was used to estimate adjusted hazard ratios (HRs) for NPC and C-statistics to assess the discriminatory ability of EBV-markers, including two previously identified EBV-marker combinations, for predicting NPC. RESULTS: Sero-positivity for 15 out of 16 EBV-markers was significantly associated with higher NPC risk. Both IgA and IgG antibodies against the same three EBV-markers showed the most extreme HRs, i.e. BGLF2 (IgA: 124.2 (95% CI: 63.3-243.9); IgG: 8.6 (5.5-13.5); LF2: [67.8 (30.0-153.1), 10.9 (7.2-16.4)]); and BFRF1: 26.1 (10.1-67.5), 6.1 (2.7-13.6). Use of a two-marker (i.e. LF2/BGLF2 IgG) and a four-marker (i.e. LF2/BGLF2 IgG and LF2/EA-D IgA) combinations yielded C-statistics of 0.85 and 0.84, respectively, which persisted for at least 5 years after sample collection in both endemic and non-endemic areas. CONCLUSIONS: In Chinese adults, plasma EBV markers strongly predict NPC occurrence many years before clinical diagnosis. LF2 and BGLF2 IgG could identify NPC high-risk individuals to improve NPC early detection in community and clinical settings.

Electrochemical biosensors in early leukemia detection.

Leukemia, a type of blood cancer marked by an abnormal increase in white blood cells, poses a significant challenge to healthcare. The key to successful treatment lies in early detection. However, traditional methods often fall short. This review investigates the potential of electrochemical biosensors for a more accurate and earlier diagnosis of leukemia. Electrochemical biosensors are compact devices that transform biological interactions into electrical signals. Their small size, ease of use, and minimal sample requirements make them perfectly suited for point-of-care applications. Their remarkable sensitivity and specificity enable the detection of subtle biomolecular changes associated with leukemia, which is crucial for early disease detection. This review delves into studies that have utilized these biosensors to identify various types of leukemia. It examines the roles of electrodes, biorecognition elements, and signal transduction mechanisms. The discussion includes the integration of nanomaterials such as gold nanoparticles and nitrogen-doped graphene into biosensor design. These materials boost sensitivity, enhance signal amplification, and facilitate multi-analyte detection, thereby providing a more holistic view of the disease. Beyond technical advancements, the review underscores the practical benefits of these biosensors. Their portability makes them a promising tool for resource-constrained settings, enabling swift diagnosis in remote areas or at a patient's bedside. The potential for monitoring treatment effectiveness and detecting minimal residual disease to prevent relapse is also explored. This review emphasizes the transformative potential of electrochemical biosensors in combating leukemia. By facilitating earlier and more accurate diagnosis, these biosensors stand to revolutionize patient care and enhance treatment outcomes.

TOTEM: a multi-cancer detection and localization approach using circulating tumor DNA methylation markers.

BACKGROUND: Detection of cancer and identification of tumor origin at an early stage improve the survival and prognosis of patients. Herein, we proposed a plasma cfDNA-based approach called TOTEM to detect and trace the cancer signal origin (CSO) through methylation markers. METHODS: We performed enzymatic conversion-based targeted methylation sequencing on plasma cfDNA samples collected from a clinical cohort of 500 healthy controls and 733 cancer patients with seven types of cancer (breast, colorectum, esophagus, stomach, liver, lung, and pancreas) and randomly divided these samples into a training cohort and a testing cohort. An independent validation cohort of 143 healthy controls, 79 liver cancer patients and 100 stomach cancer patients were recruited to validate the generalizability of our approach. RESULTS: A total of 57 multi-cancer diagnostic markers and 873 CSO markers were selected for model development. The binary diagnostic model achieved an area under the curve (AUC) of 0.907, 0.908 and 0.868 in the training, testing and independent validation cohorts, respectively. With a training specificity of 98%, the specificities in the testing and independent validation cohorts were 100% and 98.6%, respectively. Overall sensitivity across all cancer stages was 65.5%, 67.3% and 55.9% in the training, testing and independent validation cohorts, respectively. Early-stage (I and II) sensitivity was 50.3% and 45.7% in the training and testing cohorts, respectively. For cancer patients correctly identified by the binary classifier, the top 1 and top 2 CSO accuracies were 77.7% and 86.5% in the testing cohort (n = 148) and 76.0% and 84.0% in the independent validation cohort (n = 100). Notably, performance was maintained with only 21 diagnostic and 214 CSO markers, achieving a training AUC of 0.865, a testing AUC of 0.866, and an integrated top 2 accuracy of 83.1% in the testing cohort. CONCLUSIONS: TOTEM demonstrates promising potential for accurate multi-cancer detection and localization by profiling plasma methylation markers. The real-world clinical performance of our approach needs to be investigated in a much larger prospective cohort.

Prostate-specific antigen screening for prostate cancer: Diagnostic performance, clinical thresholds, and strategies for refinement.

Prostate specific antigen (PSA) has transformed the diagnosis and treatment of prostate cancer by enabling early detection at global scale. Due to expression in both benign and malignant cells, PSA-based prostate cancer screening using single cut-points yields imperfect diagnostic performance and has led to the detection and over-treatment of low-grade prostate cancer. Additional challenges in the interpretation of PSA include substantial inter and intrapersonal variation, differences with age and prostate volume, and selection of standardized PSA value cutoffs for clinical application. In response, refinements to PSA including risk and age-based thresholds, age and genetic adjustments, PSA density, percentage free PSA, and PSA velocity have been proposed and extensively studied. In this review, we focus on the clinical role of PSA as a screening biomarker with a particular emphasis on its test characteristics, clinically actionable thresholds, and strategies to refine its clinical interpretation.