Screening Strategies Research Articles

Strongly Coupled NiMo@Alloy‐LDH Interfaces with Low‐Barrier Schottky Junctions for Oxygen Evolution Reaction

AbstractThe main challenge in developing Schottky‐contact OER catalytic devices based on layered double hydroxides (LDHs) is to achieve metal–semiconductor junctions with low contact resistance and high charge transfer capacity. However, due to the presence of high potential barriers and Fermi pinning, conventional Schottky contacts are usually unsatisfactory, resulting in poor‐working electrode performance and high energy consumption. In this study, a new concept of “hindrance factor” is introduced to quantify the difficulty of electron transfer, and a low‐hindrance factor Schottky contact formed by strong coupling of semiconductor LDH and NiMo alloy clusters is designed. This interface guides charge redistribution, optimizes the bonding and orbital states of adsorption sites, and enhances the targeted adsorption of OH intermediates. The results show that the configured NiMo@NiFeCe‐LDH working electrode only needs 1.445 V (vs RHE) to drive the reaction and shows excellent durability in 400 h of testing. At the same time, based on this study, a strategy for screening high‐performance Schottky junctions is developed. This strategy provides a bridge for studying interface properties, orbital hybridization, and charge transfer, reveals the potential mechanism for reducing contact resistance, and has important guiding significance for screening high‐performance metal–semiconductor electrocatalysts and stability.

Management of chronic kidney disease: a Hong Kong consensus recommendation.

Chronic kidney disease (CKD) imposes a significant burden on healthcare systems worldwide, and diabetes is a major risk factor for CKD. There is currently no consensus in Hong Kong regarding the prioritisation of early identification and intervention for CKD. A comprehensive and Hong Kong-specific diabetes and CKD treatment guideline is also lacking. A multidisciplinary group of experts discussed issues surrounding the current management of CKD and reviewed evidence in the context of local experience to support recommendations. The experts used a modified Delphi approach to finalise recommendations. Consensus was regarded as ≥75% acceptability among all expert panel members. The panel members finalised 14 CKD-focused consensus statements addressing disease definition, screening, disease monitoring, lifestyle management, and treatment strategies. The recommendations provided are relevant to the Hong Kong healthcare setting and can be used as a guide by physicians across various specialties to facilitate the appropriate management of CKD.

Effectiveness of cascade screening for elevated lipoprotein(a), an underdiagnosed family disorder.

Elevated lipoprotein(a) [Lp(a)] is a prevalent, independent, genetic risk factor for cardiovascular disease. Though crucial for adequate risk assessment, detection of individuals at increased risk because of elevated Lp(a) is severely lacking in practice. In this light, several consensus statements have recommended familial cascade screening strategies to increase detection of elevated Lp(a). This review aims to synthesize findings from recent research into the effectiveness of cascade screening for elevated Lp(a). Cascade screening is an effective method for identifying individuals with elevated Lp(a) and is superior to opportunistic screening. Cascade screening identifies approximately one new case of elevated Lp(a) ≥ 125 nmol/L for every two first-degree relatives screened. The number needed to screen (NNS) ranged from 1.3 to 2.9, depending on Lp(a) threshold values and selected population. Cascade screening appears to be a promising strategy for identifying individuals with elevated Lp(a). However, several challenges persist regarding the implementation of this strategy in clinical practice. Deciding on threshold values for initiating cascade screening, considering the implications of ethnicity-related variability of Lp(a) levels, and further research into the clinical relevance of cascade screening are crucial steps. Understanding these factors will be essential for optimizing cascade screening protocols and enhancing its effectiveness in clinical practice. http://links.lww.com/COL/A31.

Selective Clearance of Circulating Histones Based on Dodecapeptide-Grafted Copolymer Material for Sepsis Blood Purification.

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Research indicates that circulating histones, as pathogenic factors, may represent a therapeutic target for sepsis. However, effectively clearing circulating histones poses a challenge due to their structural similarity to normal blood proteins, their low abundance in the bloodstream, and serious interference from other blood biomacromolecules. Here we design a dodecapeptide-based functional polymer that can selectively adsorb circulating histones from the blood. The peptide, named P1 (HNHHQLALVESY), was discovered through phage display screening and demonstrated a strong affinity for circulating histones while exhibiting negligible affinities for common proteins in the blood, such as human serum albumin (HSA), immunoglobulin G (IgG), and transferrin (TRF). Furthermore, the P1 peptide was incorporated into a functional polymer design, poly(PEGMA-co-P1), which was immobilized onto a silica gel surface through reversible addition-fragmentation chain transfer polymerization. The resulting material was characterized using solid nuclear magnetic resonance, thermogravimetric analysis, and X-ray photoelectron spectroscopy. This material demonstrated the ability to selectively and efficiently capture circulating histones from both model solutions and whole blood samples while also exhibiting satisfactory blood compatibility, good antifouling properties, and resistance to interference. Satisfactory binding affinity and efficient capture capacity toward histone were also observed for the other screened peptide P2 (QMSMDLFGSNFV)-grafted polymer, validating phage display as a reliable ligand screening strategy. These findings present an approach for the specific clearance of circulating histones and hold promise for future clinical applications in blood purification toward sepsis.

Development and Validation of Machine Learning Algorithms for Prediction of Colorectal Polyps Based on Electronic Health Records.

Colorectal Polyps are the main source of precancerous lesions in colorectal cancer. To increase the early diagnosis of tumors and improve their screening, we aimed to develop a simple and non-invasive diagnostic prediction model for colorectal polyps based on machine learning (ML) and using accessible health examination records. We conducted a single-center observational retrospective study in China. The derivation cohort, consisting of 5426 individuals who underwent colonoscopy screening from January 2021 to January 2024, was separated for training (cohort 1) and validation (cohort 2). The variables considered in this study included demographic data, vital signs, and laboratory results recorded by health examination records. With features selected by univariate analysis and Lasso regression analysis, nine machine learning methods were utilized to develop a colorectal polyp diagnostic model. Several evaluation indexes, including the area under the receiver-operating-characteristic curve (AUC), were used to compare the predictive performance. The SHapley additive explanation method (SHAP) was used to rank the feature importance and explain the final model. 14 independent predictors were identified as the most valuable features to establish the models. The adaptive boosting machine (AdaBoost) model exhibited the best performance among the 9 ML models in cohort 1, with accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and AUC (95% CI) of 0.632 (0.618-0.646), 0.635 (0.550-0.721), 0.674 (0.591-0.758), 0.593 (0.576-0.611), 0.673 (0.654-0.691), 0.608 (0.560-0.655) and 0.687 (0.626-0.749), respectively. The final model gave an AUC of 0.675 in cohort 2. Additionally, the precision recall (PR) curve for the AdaBoost model reached the highest AUPR of 0.648, positioning it nearest to the upper right corner. SHAP analysis provided visualized explanations, reaffirming the critical factors associated with the risk of colorectal polyps in the asymptomatic population. This study integrated the clinical and laboratory indicators with machine learning techniques to establish the predictive model for colorectal polyps, providing non-invasive, cost-effective screening strategies for asymptomatic individuals and guiding decisions for further examination and treatment.

Experiences and Perceptions of Cervical Cancer Screening Using Self-Sampling among Under-Screened Women in Flanders.

Primary Human Papillomavirus (HPV) screening on samples collected by women themselves has proven to be an effective strategy for cervical cancer screening (CCS) and may increase participation rates in women who do not partake (regularly) in screening. The aim of this study is to investigate reasons for non-participation and perceptions of CCS using self-sampling methods among under-screened women in Flanders. Individual interviews with 15 underscreened women aged 30-64 years were conducted. During the interviews, participants were given the opportunity to try out a urine and vaginal self-sampling kit. Thematic analysis was based on Ajzen's model of the Theory of Planned Behavior. The results showed that 14 out of 15 participants were more likely to participate in CCS if they had the option to self-sample. One of the main findings was a lack of knowledge on different aspects of cervical cancer. Most women had a positive attitude toward cancer screening and primary prevention such as HPV vaccination. Subjective norms were influenced by healthcare professionals, peers, and organized government initiatives. Informational, organizational, contextual, and emotional factors were mentioned as barriers as well as facilitators for participation. Additionally, high self-efficacy was considered to make self-sampling more convenient. All women showed the intention to use at least one method of self-sampling. We can conclude that women who do not participate in CCS would be more motivated to participate using self-sampling methods. Adequate education and guidance should be provided.

High-Throughput screening of TM1TM2/N6–1 (TM = Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Mo) as effective electrocatalysts for nitrogen fixation

The electrochemical nitrogen reduction reaction (NRR) is an emerging nitrogen fixation method in recent years. Double-atom catalysts compensate for the disadvantage of single-atom catalysts having only one active site, improving catalytic reaction activity. Herein, using a four-step high-throughput screening strategy with density functional theory (DFT) calculations, 45 homonuclear and heteronuclear catalysts, namely, transition metal dimers anchored on nitrogen-doped graphene (TM1TM2/N6–1, TM = Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Mo), were systematically studied to evaluate their catalytic performance for NRR. Our results showed that 16 catalysts stand out, among them, ScMo/N6–1 has an ultralow limiting potential of -0.09 V and a Faradaic efficiency of 100 %. This work provides a group of promising candidates and a reasonable high-throughput design strategy for NRR catalysts.

Breast Cancer Screening Using Mammography, Digital Breast Tomosynthesis, and Magnetic Resonance Imaging by Breast Density

Information on long-term benefits and harms of screening with digital breast tomosynthesis (DBT) with or without supplemental breast magnetic resonance imaging (MRI) is needed for clinical and policy discussions, particularly for patients with dense breasts. To project long-term population-based outcomes for breast cancer mammography screening strategies (DBT or digital mammography) with or without supplemental MRI by breast density. Collaborative modeling using 3 Cancer Intervention and Surveillance Modeling Network (CISNET) breast cancer simulation models informed by US Breast Cancer Surveillance Consortium data. Simulated women born in 1980 with average breast cancer risk were included. Modeling analyses were conducted from January 2020 to December 2023. Annual or biennial mammography screening with or without supplemental MRI by breast density starting at ages 40, 45, or 50 years through age 74 years. Lifetime breast cancer deaths averted, false-positive recall and false-positive biopsy recommendations per 1000 simulated women followed-up from age 40 years to death summarized as means and ranges across models. Biennial DBT screening for all simulated women started at age 50 vs 40 years averted 7.4 vs 8.5 breast cancer deaths, respectively, and led to 884 vs 1392 false-positive recalls and 151 vs 221 false-positive biopsy recommendations, respectively. Biennial digital mammography had similar deaths averted and slightly more false-positive test results than DBT screening. Adding MRI for women with extremely dense breasts to biennial DBT screening for women aged 50 to 74 years increased deaths averted (7.6 vs 7.4), false-positive recalls (919 vs 884), and false-positive biopsy recommendations (180 vs 151). Extending supplemental MRI to women with heterogeneously or extremely dense breasts further increased deaths averted (8.0 vs 7.4), false-positive recalls (1088 vs 884), and false-positive biopsy recommendations (343 vs 151). The same strategy for women aged 40 to 74 years averted 9.5 deaths but led to 1850 false-positive recalls and 628 false-positive biopsy recommendations. Annual screening modestly increased estimated deaths averted but markedly increased estimated false-positive results. In this model-based comparative effectiveness analysis, supplemental MRI for women with dense breasts added to DBT screening led to greater benefits and increased harms. The balance of this trade-off for supplemental MRI use was more favorable when MRI was targeted to women with extremely dense breasts who comprise approximately 10% of the population.

Cost-effectiveness of incorporating self-imaging optical coherence tomography into fundus photography-based diabetic retinopathy screening

Diabetic macular edema (DME) has emerged as the foremost cause of vision loss in the population with diabetes. Early detection of DME is paramount, yet the prevailing screening, relying on two-dimensional and labor-intensive fundus photography (FP), results in frequent unwarranted referrals and overlooked diagnoses. Self-imaging optical coherence tomography (SI-OCT), offering fully automated, three-dimensional macular imaging, holds the potential to enhance DR screening. We conducted an observational study within a cohort of 1822 participants with diabetes, who received comprehensive assessments, including visual acuity testing, FP, and SI-OCT examinations. We compared the performance of three screening strategies: the conventional FP-based strategy, a combination strategy of FP and SI-OCT, and a simulated combination strategy of FP and manual SD-OCT. Additionally, we undertook a cost-effectiveness analysis utilizing Markov models to evaluate the costs and benefits of the three strategies for referable DR. We found that the FP + SI-OCT strategy demonstrated superior sensitivity (87.69% vs 61.53%) and specificity (98.29% vs 92.47%) in detecting DME when compared to the FP-based strategy. Importantly, the FP + SI-OCT strategy outperformed the FP-based strategy, with an incremental cost-effectiveness ratio (ICER) of $8016 per quality-adjusted life year (QALY), while the FP + SD-OCT strategy was less cost-effective, with an ICER of $45,754/QALY. Our results were robust to extensive sensitivity analyses, with the FP + SI-OCT strategy standing as the dominant choice in 69.36% of simulations conducted at the current willingness-to-pay threshold. In summary, incorporating SI-OCT into FP-based screening offers substantial enhancements in sensitivity, specificity for detecting DME, and most notably, cost-effectiveness for DR screening.

Youth-derived Lactobacillus rhamnosus with prebiotic xylo-oligosaccharide exhibits anti-hyperlipidemic effects as a novel synbiotic

Changes in dietary patterns and living habits have led to an increasing number of individuals with elevated cholesterol levels. Excessive consumption of high-cholesterol foods can disrupt the body’s lipid metabolism. Numerous studies have firmly established the cholesterol-lowering effects of probiotics and prebiotics, with evidence showing that the synergistic use of synbiotics is functionally more potent than using probiotics or prebiotics alone. Currently, the screening strategy involves screening prebiotics for synbiotic development with probiotics as the core. However, in comparison to probiotics, there are fewer types of prebiotics available, leading to limited resources. Consequently, the combinations of synbiotics obtained are restricted, and probiotics and prebiotics are only relatively suitable. Therefore, in this study, a novel synbiotic screening strategy with prebiotics as the core was developed. The synbiotic combination of Lactobacillus rhamnosus S_82 and xylo-oligosaccharides was screened from the intestinal tract of young people through five generations of xylo-oligosaccharides. Subsequently, the cholesterol-lowering ability of the medium was simulated, and the two carbon sources of glucose and xylo-oligosaccharides were screened out. The results showed that synbiotics may participate in cholesterol-lowering regulation by down-regulating the expression of NPC1L1 gene, down-regulating ACAT2 and increasing the expression of ABCG8 gene in vitro through cell adsorption and cell absorption in vitro, and regulating the intestinal microbiota. Synbiotics hold promise as potential candidates for the prevention of hypercholesterolemia in humans and animals, and this study providing a theoretical foundation for the development of new synbiotic products.

Development and validation of optical coherence tomography (OCT) and OCT angiography prediction model for short-term vitreous haemorrhage secondary to polypoidal choroidal vasculopathy

AimsTo construct and validate an optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) image model for predicting the occurrence of short-term vitreous haemorrhage (VH) in polypoidal choroidal vasculopathy...

The Impact of Chemotherapy on Arterial Stiffness and Ventricular-Arterial Coupling in Women with Breast Cancer.

The cardiac toxicity of chemotherapy for breast cancer is not uncommon and has been associated with elevated morbidity and mortality. In the present study, we assessed the impact of chemotherapy on cardiovascular function by assessing the cardio-ankle vascular index (CAVI), global longitudinal strain (GLS) and ventricular-arterial coupling (VAC: CAVI/GLS ratio) in chemotherapy-treated women. This prospective study enrolled 78 women with breast cancer who were receiving anthracycline-based chemotherapy +/- anti-HER2 therapy (trastuzumab +/- pertuzumab). Forty-one age-matched healthy women served as controls. We comparatively evaluated left ventricular ejection fraction (LVEF), CAVI, GLS and VAC, between the chemotherapy and control groups. We also assessed their changes over time (baseline, 3-month and 6-month time point) and their independent association with the incidence of cancer therapy-related cardiovascular dysfunction (CTRCD) in the chemotherapy group. In comparison to healthy controls, women receiving chemotherapy presented with significantly higher GLS (from -21.02 ± 2.09% to -19.01 ± 2.81%, p < 0.001) and VAC (-0.36 ± 0.06 to -0.41 ± 0.11, p < 0.001). The presence of CTRCD was associated with a further increase in GLS and CAVI and a significant decline in LVEF and VAC compared to CTRCD-free women (p < 0.001). Baseline, CAVI, GLS and VAC were independently associated with CTRCD development during follow-up. Women with breast cancer undergoing chemotherapy displayed abnormal levels of CAVI, VAC and GLS, compared to healthy individuals. Those effects on VAC and CAVI were more exaggerated among women with CTRCD, implicating their potential use to refine screening and therapeutic strategies for this specific population.

SARS-CoV-2 Mpro inhibitor identification using a cellular gain-of-signal assay for high-throughput screening

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2, SARS2) is responsible for the COVID-19 pandemic and infections that continue to affect the lives of millions of people worldwide, especially those who are older and/or immunocompromised. The SARS2 main protease enzyme, Mpro (also called 3C-like protease, 3CLpro), is a bona fide drug target as evidenced by potent inhibition with nirmatrelvir and ensitrelvir, the active components of the drugs Paxlovid and Xocova, respectively. However, the existence of nirmatrelvir and ensitrelvir-resistant isolates underscores the need to develop next-generation drugs with different resistance profiles and/or distinct mechanisms of action. Here, we report the results of a high-throughput screen of 649,568 compounds using a cellular gain-of-signal assay. In this assay, Mpro inhibits expression of a luciferase reporter, and 8,777 small molecules were considered hits by causing a gain in luciferase activity 3x SD above the sample field activity (6.8% gain-of-signal relative to 100 µM GC376). Single concentration and dose-response gain-of-signal experiments confirmed 3,522/8,762 compounds as candidate inhibitors. In parallel, all initial high-throughput screening hits were tested in a peptide cleavage assay with purified Mpro and only 39/8,762 showed inhibition. Importantly, 19/39 compounds (49%) re-tested positive in both SARS2 assays, including two previously reported Mpro inhibitors, demonstrating the efficacy of the overall screening strategy. This approach led to the rediscovery of known Mpro inhibitors such as calpain inhibitor II, as well as to the discovery of novel compounds that provide chemical information for future drug development efforts.

Development of a new experimental NMR strategy for covalent cysteine protease inhibitors screening: toward enhanced drug discovery.

In the development of antiviral drugs, proteases and polymerases are among the most important targets. Cysteine proteases, also known as thiol proteases, catalyze the degradation of proteins by cleaving peptide bonds using the nucleophilic thiol group of cysteine. As part of our research, we are examining how cysteine, an essential amino acid found in the active site of the main protease (Mpro) enzyme in SARS-CoV-2, interacts with electrophilic groups present in ethacrynic acid (EA) and compounds 4, 6, and 8 to form sulfur-carbon bonds. Nuclear magnetic resonance (NMR) spectroscopy was used to monitor the reaction rate between cysteine and Michael acceptors. We found that the inhibitory activity of these compounds towards Mpro is correlated to their chemical reactivity toward cysteine. This approach may serve as a valuable tool in drug development for detecting potential covalent inhibitors of Mpro and other cysteine proteases.

Universal testing in endometrial cancer in Sweden

BackgroundThe aim of the study was to test a universal screening strategy on endometrial cancer to evaluate its effectiveness to find Lynch Syndrome (LS) cases to two established clinical criteria: Amsterdam II criteria, and the revised Bethesda criteria to select cases for prescreening with immunohistochemistry (IHC). Cases were subsequently screened for germline disease causing variants regarding the DNA mismatch repair (MMR) genes.MethodsIHC was performed on 221 endometrial cancer (EC) cases, using antibodies against the DNA mismatch repair proteins MLH1, PMS2, MSH2, and MSH6. MMR loss was found in 54 cases, and gene mutation screening was undertaken in 52 of those.ResultsIn this set of patients, the use of Amsterdam II criteria detected two (0.9%), the Bethesda criteria two (0.9%), and universal testing five (2.3%) cases of LS. The combination of universal testing and family history criteria resulted in detection of five patients (2.3%) with LS.ConclusionsBased on our results and other similar studies to date we propose a screening protocol for LS on EC tumors with prescreening using IHC for the four MMR proteins on all new EC cases diagnosed before 70 years of age, followed by mutation screening of all tumors with loss of MSH2 and/or MSH6 or only PMS2, plus consideration for mutation screening of all LS genes in cases fulfilling the clinical Amsterdam II criteria regardless of MMR status on IHC.

A Screening Strategy to Mitigate Vision Impairment by Engaging Adults Who Underuse Eye Care Services

Underuse of eye care services leads to underdiagnosed and undertreated eye disease. To assess the reasons for underuse of eye care and whether a novel, free eye disease screening program is engaging adults who are both at high risk of eye disease and were underusing eye care services. In a population-based cross-sectional study, adult participants from the first year of the Michigan Screening and Intervention for Glaucoma and Eye Health Through Telemedicine (MI-SIGHT) Program were included. The participants were recruited from primary care clinics serving 2 low-income communities. Recruitment occurred between June 28, 2020 and June 27, 2021 at the free clinic, and between January 27, 2021 and January 26, 2022 at a federally qualified health clinic. Data were analyzed from December 7, 2022, to May 29, 2024. Participants received comprehensive eye disease screening and completed surveys assessing health and prior eye care use. Risk factors for eye disease included age 65 years and older, diabetes, personal or family history of eye disease, and self-identifying as Black or African American individuals who were aged 50 years or older. Underuse of eye care was defined as no eye examination in 2 or more years. Percentage of participants who were at high risk of eye disease and underused eye care services before accessing this program. A total of 1171 MI-SIGHT participants were a mean (SD) age of 55 (14.5) years; 437 (38%) identified as male; 591 (54%) self-identified as Black or African American, 101 (10%) as Hispanic or Latino, and 371 (34%) as White; 492 (43%) had high school education or less, and 696 (70%) reported an annual household income of less than $30 000. Characteristics of participants reporting not having had an eye examination in 2 years or more included 23% (n = 151) of participants 65 years and over, 33% (n = 214) of participants who self-reported diabetes, 25% (n = 130) of participants reporting a family history of glaucoma, 3% (n = 14) of those with self-reported glaucoma; and 33% (n = 202) of Black or African-American participants aged 50 years and older. In participants who reported not having had an eye examination in 2 or more years, 21% (n = 137) screened positive for glaucoma, 20% (n = 129) for cataract, 6% (n = 38) for diabetic retinopathy, and 1% (n = 9) for age-related macular degeneration. Reported reasons for why participants had not had an eye examination included no insurance (175 of 627 [28%]), no reason to go (no problem) (135 of 627 [22%]), and cost of eye examination (101 of 627 [16%]). The findings of this study suggest that placing eye disease detection programs in primary care clinics in underserved areas may improve eye disease detection and treatment, possibly mitigating needless vision loss in the US.

Value of troponin and NT-proBNP to screen for cardiac amyloidosis after carpal tunnel syndrome surgery

BackgroundEarly diagnosis of cardiac amyloidosis (CA) is crucial due to the promising effect of disease-modifying treatment. This calls for screening strategies to identify CA patients with so-called “red flags”, such as carpal tunnel syndrome (CTS). ObjectivesThis study aims to assess Troponin-T (TnT) and N-terminal pro-B-type natriuretic peptide (NT-ProBNP) as predictors for CA in patients with a history of surgery for bilateral carpal tunnel syndrome, a population suitable for systematic screening. MethodsSubjects with a history of surgery for bilateral CTS 5–15 years prior, identified using national registries were investigated for CA as per international recommendations. Sensitivity, specificity, positive and negative predictive values were assessed, and receiver operating curves were generated using logistic regression. ResultsAmong the 250 participants, 12 were diagnosed with CA, all with wild-type transthyretin amyloidosis. Elevated TnT levels (≥13 ng/L) were found in all CA patients and 25.6% (±2.8) of non-CA patients. The negative predictive value (NPV) of TnT <13 ng/L was 100%. For NT-ProBNP the NPV was 99.1% when age dependent cutoff levels were used. A combination of both biomarkers yielded an NPV of 99.1% and sensitivity of 99.7%. Early disease (Mayo or NAC stage 1) was found in 83% of identified patients with CA. ConclusionThis study demonstrates the utility of TnT and NT-ProBNP as negative predictors to exclude CA in a screening population with a history of surgery for CTS.

Risk-stratified screening and colorectal cancer incidence and mortality: A retrospective study from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

ObjectiveTo determine whether risk stratification can optimize the benefits of flexible sigmoidoscopy (FSG) screening. MethodsThe Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial was conducted from 1993 to 2001 in the United States. A colorectal cancer (CRC) risk stratification tool was developed in the control arm (n = 64,207) from the PLCO cohort and validated in the UK Biobank (n = 270,726). PLCO participants (n = 130,021) were classified into low-, medium-, and high-risk groups. Cumulative incidence and mortality were estimated using the Kaplan-Meier method. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between screening and CRC incidence and mortality. ResultsThe CRC risk stratification tool was based on age, gender, body mass index, smoking status, family history of CRC, diabetes, regular use of aspirin, and CRC screening history. Compared with the control arm, FSG screening was significantly associated with a reduction in mortality in both the medium-risk (HR = 0.76, 95% CI = 0.63–0.92) and high-risk groups (0.58, 0.46–0.73), but not in the low-risk group (0.85, 0.61–1.19). FSG screening also reduced distal CRC incidence and mortality in the medium-risk and high-risk groups. Furthermore, it was associated with a reduction in incidence (0.74, 0.59–0.92) and mortality (0.59, 0.40–0.87) of proximal colon cancer in the high-risk group. ConclusionsFSG screening yielded more benefits for the high-risk group than for the low-risk and medium-risk groups, supporting the development of a risk-stratified CRC screening strategy.

Bioconjugates for Cancer Prevention: Opportunities for Impact.

Cancer prevention encompasses both screening strategies to find cancers early when they are likely to be most treatable and prevention and interception strategies to reduce the risk of developing cancers. Bioconjugates, here defined broadly as materials and molecules that have synthetic and biological components, have roles to play across the cancer-prevention spectrum. In particular, bioconjugates may be developed as affordable, accessible, and effective screening strategies or as novel vaccines and drugs to reduce one's risk of developing cancers. Developmental programs are available for taking novel technologies and evaluating them for clinical use in cancer screening and prevention. While a variety of different challenges exist in implementing cancer-prevention interventions, a thoughtful approach to bioconjugates could improve the delivery and acceptability of the interventions.

Construction of scalable multi-channel DNA nanoplatform for the combined detection of ctDNA biomarkers of ovarian cancer.

Single-level biomarker detection has the limitation of insufficient accuracy in cancer diagnosis. Therefore, the strategy of developing highly sensitive, multi-channel biosensors for high-throughput ctDNAdetermination is critical to improve the accuracy of early diagnosis of clinical tumors. Herein, in order to achieve efficient detection of up to ten targets for early diagnosis of ovarian cancer, a DNA-nanoswitch-based multi-channel (DNA-NSMC) biosensor was built based on the multi-module catalytic hairpin assembly-mediated signal amplification (CHA) and toehold-mediated DNA strand displacement (TDSD) reaction. Only two different fluorescence signals were used as outputs, combined with modular segmentation strategy of DNA-nanoswitch-based reaction platform; the multi-channel detection of up to ten targets was successfully achieved for the first time. The experimental results suggest that the proposed biosensor is a promising tool for simultaneously detecting multiple biomarkers for the early diagnosis of ovarian cancer, offering new strategies for the early screening, diagnosis, and treatment not only for ovarian cancer but also for other cancers.