Screening Results Research Articles

Exploring breast cancer screening fear through a psychosocial lens.

Breast cancer screening is crucial for early detection and treatment. Yet, underutilization persists due to various psychosocial factors. This manuscript delves into the multifaceted fears that hinder screening adherence. The literature provides a framework categorizing breast cancer screening fears into generalized cancer fear, fear of screening components, and fear of screening outcomes. In this review, we explore fear of screening components (concerns regarding radiation, discomfort, and pain) and fear of screening outcomes (disability and mortality apprehension, treatment fears, obligation anxiety, and financial concerns) as undesirable, and potentially addressable, aspects of breast cancer screening fear. False-positive results exacerbate these anxieties, prolonging distress and impacting patients' lives beyond the screening process. Addressing these concerns requires reframing current screening approaches to prioritize patient comfort, cultural sensitivity, and accessibility. To address current psychosocial challenges in breast cancer screening, this manuscript advocates for modifying breast cancer screening methods to improve adherence and patient well-being.

User-defined outcomes of the Danish cardiovascular screening (DANCAVAS) trial: A post hoc analyses of a population-based, randomised controlled trial.

The Danish cardiovascular screening (DANCAVAS) trial, a nationwide trial designed to investigate the impact of cardiovascular screening in men, did not decrease all-cause mortality, an outcome decided by the investigators. However, the target group may have varied preferences. In this study, we aimed to evaluate whether men aged 65 to 74 years requested a CT-based cardiovascular screening examination and to assess its impact on outcomes determined by their preferences. This is a post hoc study of the randomised DANCAVAS trial. All men 65 to 74 years of age residing in specific areas of Denmark were randomised (1:2) to invitation-to-screening (16,736 men, of which 10,471 underwent screening) or usual-care (29,790 men). The examination included among others a non-contrast CT scan (to assess the coronary artery calcium score and aortic aneurysms). Positive findings prompted preventive treatment with atorvastatin, aspirin, and surveillance/surgical evaluation. The usual-care group remained unaware of the trial and the assignments. The user-defined outcome was based on patient preferences and determined through a survey sent in January 2023 to a random sample of 9,095 men from the target group, with a 68.0% response rate (6,182 respondents). Safety outcomes included severe bleeding and mortality within 30 days after cardiovascular surgery. Analyses were performed on an intention-to-screen basis. Prevention of stroke and myocardial infarction was the primary motivation for participating in the screening examination. After a median follow-up of 6.4 years, 1,800 of 16,736 men (10.8%) in the invited-to-screening group and 3,420 of 29,790 (11.5%) in the usual-care group experienced an event (hazard ratio (HR), 0.93 (95% confidence interval (CI), 0.88 to 0.98; p = 0.010); number needed to invite at 6 years, 148 (95% CI, 80 to 986)). A total of 324 men (1.9%) in the invited-to-screening group and 491 (1.7%) in the usual-care group had an intracranial bleeding (HR, 1.17; 95% CI, 1.02 to 1.35; p = 0.029). Additionally, 994 (5.9%) in the invited-to-screening group and 1,722 (5.8%) in the usual-care group experienced severe gastrointestinal bleeding (HR, 1.02; 95% CI, 0.95 to 1.11; p = 0.583). No differences were found in mortality after cardiovascular surgery. The primary limitation of the study is that exclusive enrolment of men aged 65 to 74 renders the findings non-generalisable to women or men of other age groups. In this comprehensive population-based cardiovascular screening and intervention program, we observed a reduction in the user-defined outcome, stroke and myocardial infarction, but entail a small increased risk of intracranial bleeding. ISRCTN Registry number, ISRCTN12157806 https://www.isrctn.com/ISRCTN12157806.

ClassyPose: A Machine‐Learning Classification Model for Ligand Pose Selection Applied to Virtual Screening in Drug Discovery

Determining the target‐bound conformation of a drug‐like molecule is a crucial step in drug design, as it affects the outcome of virtual screening (VS), and paves the way for hit‐to‐lead and lead optimization. While most docking programs usually manage to produce at least a near‐native pose for a bioactive molecule inside its binding pocket, their integrated classical scoring functions (SFs) generally fail to prioritize this pose. Many studies have been carried out to tackle this SF problem, offering multiple pose refinement and/or classification methods, albeit with limitations. This study presents a new support vector machine model for pose classification, called “ClassyPose”, which predicts the probability that a receptor‐bound ligand conformation could be near‐native, without any additional pose optimization step. Trained on protein‐ligand extended connectivity features extracted from over 21 600 crystal and docking poses of diverse ligands, this model outperformed other machine‐learning algorithms and three existing SFs in terms of docking power, identifying the native ligand pose as top‐ranked solution for more than 90% of entries in two test sets. It also achieved high specificity (above 0.96), and improved VS performance when used for pose selection. This efficient, user‐friendly tool and all related data are available at https://github.com/vktrannguyen/Classy_Pose.

Impact of national health insurance and socioeconomic disparities on newborn hearing screening performance in South Korea: A nationwide population-based evaluation

ObjectivesThis study aimed to assess the impact of national health insurance coverage on newborn hearing screening (NHS) outcomes by analyzing hearing questionnaires from the National Infant Health Check-up Program (NIHCP) in South Korea. MethodsThis study evaluated the performance and referral rates of NHS using nationwide data from 814,875 infants enrolled in the 4-month NIHCP from January 2017 to December 2019. This period encompasses the periods before and after the National Health Insurance in South Korea began covering NHS expenses in October 2018. The study also investigated household income levels to determine their relationship with participation in the NIHCP and NHS outcomes. ResultsThe performance of NIHCP increased year-on-year, with NHS performance rates increasing from 88.5 % in 2017 to 91.5 % in 2019. Analysis by household income level revealed that the medical benefit recipients’ group had the lowest NHS performance rate of 81.9 % in 2019, whereas that of the higher income level group exceeded 90 %. The NHS referral rate remained consistent at 0.9 % nationally during the study period. ConclusionThe inclusion of NHS in national insurance coverage positively influenced its performance rates across South Korea. Nevertheless, the data indicate the need for more focused and customized support for low-income families to enhance early hearing detection and interventions in newborns and infants.

Screening and characterization of 133 physiologically-relevant environmental chemicals for reproductive toxicity

Reproduction is a functional outcome that relies on complex cellular, tissue, and organ interactions that span the developmental period to adulthood. Thus, the assessment of its disruption by environmental chemicals would benefit significantly from scalable and innovative approaches to testing using functionally comparable reproductive models such as the nematode C. elegans. We adapted a previously described low-throughput in vivo chromosome segregation assay using C. elegans predictive of reproductive toxicity and leveraged available public data sources (ToxCast, ICE) to screen and characterize 133 physiologically-relevant chemicals in a high-throughput manner. The screening outcome was further validated in a second, independent in vivo assay assessing embryonic viability. In total, 13 chemicals were classified as reproductive toxicants with the two most active chemicals belonging to the large family of Quaternary Ammonium Compounds (QACs) commonly used as disinfectants but with limited available reproductive toxicity data. We compared the results from the C. elegans assay with ToxCast in vitro data compiled from 700+ cell response assays and 300+ signaling pathways-based assays. We did not observe a difference in the bioactivity or in the average potency (AC50) between the top and bottom chemicals. However, the intended target categories were significantly different between the classified chemicals with, in particular, an over-representation of steroid hormone targets for the high Z-score chemicals. Taken together, these results point to the value of in vivo models that scale to high-throughput level for reproductive toxicity assessment and to the need to prioritize the assessment of QACs impacts on reproduction.

Screening for Cognitive Impairment in Bilinguals: What Is the Influence of the Language of Assessment?

Bilingualism's impact on cognitive assessment remains underexplored. This study analyzes the efficacy of the Mini-Mental State Examination (MMSE) as a screening tool for bilinguals, specifically examining the influence of language choice on balanced and unbalanced Lebanese bilinguals (Arabic-French) and its implications for diagnosing cognitive impairment. Ninety-three bilingual healthy controls (mean age = 67.99 ± 9.3) and 29 Alzheimer's disease patients (mean age = 77.2 ± 5.9), including 26 with mild and 3 with moderate dementia, underwent MMSE assessments in both Arabic and French. The study aimed to assess language impact on cognitive screening outcomes in different bilingual subtypes. Sensitivity in screening for cognitive impairment using the MMSE varied based on language and bilingualism subtype. For unbalanced bilinguals, using the prominent language increased sensitivity. Conversely, in balanced bilinguals, employing the societal majority language enhanced sensitivity. This suggests that the conventional use of the non-prominent language in cognitive screening for foreigners/immigrants may result in a subtle loss of MMSE sensitivity. This study emphasizes the critical role of language choice in cognitive assessment for bilinguals. The MMSE's sensitivity is influenced by language selection, with clinical implications for screening procedures. Recommendations include using the prominent language for cognitive screening in dominant bilinguals and the societal majority language for balanced bilinguals. This nuanced approach aims to improve the accuracy and cultural sensitivity of cognitive screening in bilingual populations, addressing the gap in current assessment practices.

Costs and Projected Effect of a Federally Qualified Health Center-Based Mailed Colorectal Cancer Screening Program in Texas.

Mailed stool testing for colorectal cancer (CRC) may improve screening uptake and reduce the incidence and mortality of CRC, especially among patients at federally qualified health centers (FQHCs). To expand screening programs it is important to identify cost-effective approaches. We developed a decision-analytic model to estimate the cost, effects on screening and patient outcomes (CRCs detected, CRCs prevented, CRC deaths prevented), and cost-effectiveness of implementing a state-wide mailed stool testing program over 5 years among unscreened, age-eligible (aged 50-75 y) patients at FQHCs in Texas. We compared various outreach strategies and organizational structures (centralized, regional, or a hybrid). We used data from our existing regional mailed stool testing program and recent systematic reviews to set parameters for the model. Costs included start-up and ongoing activities and were estimated in 2022 US dollars from the perspective of a hypothetical third-party payer. Cost-effectiveness was assessed by using both incremental and average cost-effectiveness ratios. Using either a statewide centralized or hybrid organizational configuration to mail stool tests to newly eligible FQHC patients and patients who have responded at least once since program inception is likely to result in the best use of resources over 5 years, enabling more than 110,000 additional screens, detecting an incremental 181 to 194 CRCs, preventing 91 to 98 CRCs, and averting 46 to 50 CRC deaths, at a cost of $10 million to $11 million compared with no program. A statewide mailed stool testing program for FQHC patients can be implemented at reasonable cost with considerable effects on CRC screening outcomes, especially when its structure maximizes program efficiency while maintaining effectiveness.

Abstract PS10-08: Validation of a clinical image-based AI-risk model for individualized breast cancer screening in a multi-national setting

Abstract Background: Image-derived AI risk models for breast cancer have shown high discriminatory performances compared with clinical risk models based on family history and lifestyle factors. However, little is known about their generalizability across different screening settings and clinical feasibility. Purpose: To investigate the predictive performance of a clinically used image-derived AI-based breast cancer risk model in multiple European screening populations. Methods: Four European mammographic screening populations in three countries screened between 2009-2020 for women aged 45-69 was used to perform a nested case-control study. In total, 739 women with incident breast cancers were included together with 7,812 controls matched to cases on year of study-entry. Mammographic features (density, microcalcifications, masses, left-right breast asymmetries of these features) for risk assessment were extracted using AI from full-field digital mammograms. Breast cancer occurrence was assessed after two years of follow-up. Absolute risks of breast cancer were predicted using the risk model from negative mammograms at study-entry. Adjusted Area Under the receiver operating characteristic Curves (aAUC) estimated discriminatory performance and, adjusted risk-ratios estimated the stratification performance of women at high/general risk per the clinical guidelines. Results: The overall aAUC of the AI risk model was 0.72 (95%CI 0.70-0.75), range 0.71 (95%CI 0.67-0.75) to 0.74 (95%CI 0.69-0.78) for breast cancers developed in four screening populations. In the 4.6% of women classified at high risk using the NICE guidelines thresholds, cancers were more likely diagnosed after 2 years follow-up, risk-ratio (RR) 6.7 (95%CI 5.6-8.0), compared with the 71% of women classified at general risk by the model. Similar risk-ratios were observed across tertiles of mammographic density. In the high-risk group, 22% of the 2-year future cancers were diagnosed, and 29% of stage 2 and higher cancers, p< 0.01. Conclusions: The AI risk model showed generalizable discriminatory performances across European populations and, captured ~30% of clinically relevant stage 2 and higher breast cancers in ~5% of high-risk women who were sent home with a negative mammogram. Similar results were seen in fatty and dense breasts. An image-derived AI model is feasible for personalized screening to improve screening outcomes. Citation Format: Mikael Eriksson, Marta Román, Axel Gräwingholt, Sylvia Heywang-Köbrunner, Paolo Rossi, Per Hall. Validation of a clinical image-based AI-risk model for individualized breast cancer screening in a multi-national setting [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS10-08.

Human Papillomavirus Vaccination Hesitancy, Screening Disparities, and Associated Factors Among Sexual and Gender Minority Women: A Systematic Review of Global Literature [ID 2683547

INTRODUCTION: Human papillomavirus (HPV) ranks as the most prevalent sexually transmitted infection globally, with a significant association with cervical cancer in cervix-having individuals. Understanding the epidemiological patterns of HPV vaccination rates and behaviors within the context of sexual and gender minority (SGM) women is essential in identifying factors hindering the initiation of HPV vaccination and screening. METHODS: A systematic review was conducted by searching five databases (PubMed, CINAHL, Embase, Web of Sciences, MedLine). Eligibility criteria included the following: reported HPV vaccination or screening outcomes, conducted among SGM women, data collected since 2010. All studies were independently screened and synthesized following PRISMA guidelines. Of 44 items, 13 studies met the criteria. RESULTS: Sexual and gender minority women reported substantial HPV vaccine hesitancy and decreased screening practices compared to their non-SGM peers, with the degree of vaccine hesitancy and delayed screening varying among bisexual, lesbian, and transgender individuals. Individual factors associated with HPV vaccine hesitancy and decreased screening include socioeconomic status, vaccination awareness, and SGM identity. Meanwhile, interpersonal and structural factors include community biases, family support, lack of provider LGBTQ+ health education, and structural racism. CONCLUSION: Sexual and gender minority women experience a substantial health care disparity surrounding HPV vaccination hesitancy and screening status. Results from this study substantiate the need for the standardization of health care practice, individual patient vaccine counseling, and the expansion of sexual and gender minority health training at all tiers of medical education. Furthermore, additional disaggregated research is needed to understand the unique health circumstances of bisexual, lesbian, and transgender individuals, as the current research landscape fails to capture the community’s health needs.

Investigation of the correlation between platelet antibodies and peripheral blood cytopenia in patients with hepatocellular carcinoma

The primary triggers that stimulate the body to generate platelet antibodies via immune mechanisms encompass events such as pregnancy, transplantation, and blood transfusion. Interestingly, our findings revealed that a subset of male patients with hepatocellular carcinoma (HCC), despite having no history of transplantation or blood transfusion, has shown positive results in platelet antibody screenings. This hints at the possibility that certain factors, potentially related to the tumor itself or its treatment, may affect antibody production. To delve the causes we initiated this study. We employed a case–control study approach to analyze potential influential factors leading to the positive results via univariate and multivariate regression analysis. We utilized Kendall’s tau-b correlation to examine the relationship between the strength of platelet antibodies and peripheral blood cytopenia. Antitumor medication emerged as an independent risk factor for positive results in HCC patients, and the strength of platelet antibodies positively correlated with the severity of anemia and thrombocytopenia. Without history of blood transfusion, transplantation, pregnancy, those HCC patients underwent recent tumor medication therapy are experiencing peripheral erythrocytopenia or thrombocytopenia, for them platelet antibody screenings holds potential clinical value for prevention and treatment of complications like drug-immune-related anemia and/or bleeding.

Outcomes of a Formal Hematopoietic Cell Transplantation Survivorship Program on Screening for Late Effects

Allogeneic hematopoietic cell transplantation (HCT) survivors may benefit from routine screening for post-transplant complications. However, the impact of formal survivorship efforts to promote screening adherence is uncertain. The effect of a formal HCT survivorship program to promote screening adherence was evaluated. We conducted a retrospective analysis of an academic formal HCT survivorship program with primary and specialty consult components. We included patients who underwent allogeneic HCT and were alive and relapse-free 1-year post-HCT. We excluded patients who died <2-year post-HCT or transferred care. We measured screening adherence to cardiovascular, pulmonary, ocular, secondary cancer, and endocrine evaluations. The primary outcome was proportion of patients completing ≥1 evaluation per screening domain prior to 2-year post-HCT. We examined screening adherence during 3 time periods: presurvivorship (2012 to 2014) and 2 postsurvivorship (2016 to 2018 and 2019 to 2021) using multivariate logistic and Cox proportional hazards regression. Four hundred ten patients (2012 to 2014: n = 136, 2016 to 2018: n = 153, 2019 to 2021: n = 121) were included. Compared to the presurvivorship period (16.9%), patients in 2016 to 2018 (47.7%, odds ratio [OR] = 4.9, P < .0001) and 2019 to 2021 (34.7%, OR = 2.7, P = .001) were more likely to complete ≥1 evaluation per screening domain. Except for pulmonary function tests in 2019 to 2021, median time to completion of survivorship evaluations was shorter in the survivorship periods compared to presurvivorship. Patients who completed a formal HCT survivorship consult in 2016 to 2018 and 2019 to 2021 were more likely to complete ≥1 evaluation per screening domain (OR = 5.1, P = .0004). Survivorship consult had similar effect on the primary screening outcome in 2016 to 2018 and 2019 to 2021 (consult × time interaction OR: 2.5, P = .2). However, patients who received a consult in 2019 to 2021 were more likely to complete all screenings (consult × time interaction: OR = 5.7, P = .03). Our HCT survivorship program with primary and specialty components improved screening adherence. Additional studies are needed to evaluate efficacy, dissemination, and implementation of formal HCT survivorship programs.

Clinical Outcomes from the Alaska Native Tribal Health Consortium Colorectal Cancer Control Program: 2009-2015.

The Alaska Native Tribal Health Consortium (ANTHC) participated in the United States Centers for Disease Control and Prevention Colorectal Cancer Control Program (CRCCP) from 2009 to 2015. We conducted a descriptive evaluation of ANTHC CRCCP demographics, quality measures, and clinical outcomes, including screening methods employed within the program and screening outcomes. There were 6981 program screenings completed, with the majority (81.3%) of people screened in the 50-75 year age group. Colonoscopy was the primary screening test used, accounting for 6704 (96.9%) of the screening tests. Quality of colonoscopy was high: adequate bowel preparation was reported in 98.2% of colonoscopies, cecal intubation rate was 98.9%, and the adenoma detection rate was 38.9%. A high proportion (58.9%) of colonoscopies had an initial finding of polyps or lesions suspicious for cancer; 41.2% of all colonoscopies had histological confirmation of either adenomatous polyps (40.6%) or cancer (0.5%). The ANTHC CRCCP successfully increased CRC screening among American Indian and Alaska Native peoples living in Alaska; this was achieved primarily through high-quality colonoscopy metrics. These data support a continued focus by the Alaska Native Tribal Health Consortium and its tribal health partners on increasing CRC screening and reducing cancer mortality among Alaska Native peoples.

A new neonatal BCG vaccination pathway in England: a mixed methods evaluation of its implementation

IntroductionThe introduction of a national evaluation of newborn screening for Severe Combined Immunodeficiency (SCID) in England triggered a change to the selective Bacillus Calmette-Guerin (BCG) vaccination programme delivery pathway, as this live attenuated vaccine is contraindicated in infants with SCID. The neonatal BCG vaccination programme is a targeted programme for infants at increased risk of tuberculosis and used to be offered shortly after birth. Since September 2021 the BCG vaccine is given to eligible infants within 28 days of birth, when the SCID screening outcome is available. We explore the experiences of those implementing the new pathway, and how they made sense of, engaged with, and appraised the change.MethodsA mixed-methods evaluation was conducted between October 2022 and February 2023. This involved national online surveys with BCG commissioners and providers and qualitative semi-structured interviews with commissioners, providers, and Child Health Information System stakeholders in two urban areas. Survey data was analysed using descriptive statistics and interview data was analysed thematically. The data was triangulated using Normalization Process Theory as a guiding framework.ResultsSurvey respondents (n = 65) and qualitative interviewees (n = 16) revealed that making sense of the new pathway was an iterative process. Some expressed a desire for more direction on how to implement the new pathway. The perceived value of the change varied from positive, ambivalent, to concerned. Some felt well-prepared and that improvements to data capture, eligibility screening, and accountably brought by the change were valuable. Others were concerned about the feasibility of the 28-day target, reductions in vaccination coverage, increased resource burden, and the outcome of the SCID evaluation. New collaborations and communities of practice were required to facilitate the change. Three main challenges in implementing the pathway and meeting the 28-day vaccination target were identified: appointment non-attendance; appointment and data systems; and staffing and resourcing. Feedback mechanisms were informal and took place in tandem with implementation.ConclusionThe new NHS neonatal BCG service specification has created an effective structure for monitoring and managing the BCG vaccination programme, but further work is required to support delivery of the 28-day vaccination target and improve uptake rates.

P088 Uveitis screening in Juvenile Idiopathic Arthritis: Are we following the guidelines?

Abstract Background/Aims Juvenile Idiopathic Arthritis (JIA) is the most common inflammatory arthritis in children. Uveitis is a common (8-30%) and potentially sight-threatening complication of JIA. Early detection and treatment of uveitis can prevent permanent visual impairment, making uveitis screening an essential part of the management of JIA patients. The purpose of this audit was to evaluate the referral and management of uveitis screening in JIA patients in our healthcare setting compared with Guidelines for Screening for Uveitis in Juvenile Idiopathic Arthritis (JIA) produced jointly by BSPAR and the RCOphth 2006. Methods The patients with a diagnosis of JIA at our District General Hospital (DGH) were reviewed retrospectively. The data was collected based on demographics, JIA diagnosis, subtypes, referral for uveitis screening, timing of uveitis screening, and screening outcome. Data was then analysed to assess if we met BSPAR and the RCOphth 2006 standards. Results A total of 42 patients were identified with a diagnosis of JIA between January 2021 and January 2023. Based on our criteria, four patients were excluded and the final analysis was done with 38 patients. 34 patients (89%) with JIA were referred for uveitis screening. 31 of those patients (91%) were referred within six weeks, while three patients (9%) were referred after six weeks of diagnosis. Only nine patients (24%) were seen for uveitis screening within the six weeks after initial referral as per BSPAR and the RCOphth 2006 standards. Uveitis was diagnosed in five patients(13%). One out of 38(2.6%) patients was diagnosed with Uveitis prior to diagnosis of JIA. Regarding the distribution of JIA subtypes, there were 15 cases of Polyarticular JIA, 14 instances of Oligoarticular JIA, six occurrences of Psoriatic JIA, two instances of Enthesitis-related JIA, and 1 case of Systemic JIA. Out of the five patients diagnosed with Uveitis, two had Polyarticular JIA, two had Oligoarticular JIA, and one presented with Psoriatic JIA. Furthermore, two of these patients tested positive for ANA, one tested negative, while the ANA status remained unknown for the remaining two individuals. Conclusion The results showed the need for improvement to be fully compliant with the guidelines for screening uveitis in JIA patients. We aim to ensure that all patients are referred and reviewed within 6 weeks for uveitis screening, as early detection and treatment of uveitis can prevent permanent visual impairment. We recommend collaborating with the ophthalmology unit to streamline the referral pathway and explore the idea of doing MDT clinics. Education should be arranged to raise awareness among all relevant healthcare staff. Disclosure J. Ahmad: None. A. Gupta: None. A. Bharadwaj: None. D. Olusanya: None.

Exploring Pyroptosis-related Signature Genes and Potential Drugs in Ulcerative Colitis by Transcriptome Data and Animal ExperimentalValidation.

Ulcerative colitis (UC) is an idiopathic, relapsing inflammatory disorder of the colonic mucosa. Pyroptosis contributes significantly to UC. However, the molecular mechanisms of UC remain unexplained. Herein, using transcriptome data and animal experimentalvalidation, we sought to explore pyroptosis-related molecular mechanisms, signature genes, and potential drugs in UC.Gene profiles (GSE48959, GSE59071, GSE53306, and GSE94648) were selected from the Gene Expression Omnibus (GEO) database, which contained samples derived from patients with active and inactive UC, as well as health controls. Gene Set Enrichment Analysis (GSEA), Weighted Gene Co-expression Network Analysis (WGCNA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed on microarrays to unravel the association between UC and pyroptosis. Then, differential expressed genes (DEGs) and pyroptosis-related DEGs were obtained by differential expression analyses and the public database. Subsequently, pyroptosis-related DEGs and their association with the immune infiltration landscape were analyzed using the CIBERSORT method. Besides, potential signature genes were selected by machine learning (ML) algorithms, and then validated by testing datasets which included samples of colonic mucosal tissue and peripheral blood. More importantly, the potential drug was screened based on this. And these signature genes and the drug effect were finally observed in the animal experiment.GSEA and KEGG enrichment analyses on key module genes derived from WGCNA revealed a close association between UC and pyroptosis. Then, a total of 20 pyroptosis-related DEGs of UC and 27 pyroptosis-related DEGs of active UC were screened. Next, 6 candidate genes (ZBP1, AIM2, IL1β, CASP1, TLR4, CASP11) in UC and 2 candidate genes (TLR4, CASP11) in active UC were respectively identified using the binary logistic regression(BLR), least absolute shrinkage and selection operator (LASSO), random forest (RF) analysis and artificial neural network (ANN), and these genes also showed high diagnostic specificity for UC in testing sets. Specially, TLR4 was elevated in UC and further elevated in active UC. The results of the drug screen revealed that six compounds (quercetin, cyclosporine, resveratrol, cisplatin, paclitaxel, rosiglitazone) could target TLR4, among which the effect of quercetin on intestinal pathology, pyroptosis and the expression of TLR4 in UC and active UC was further determined by the murine model.These findings demonstrated that pyroptosis may promote UC, and especially contributes to the activation of UC. Pyroptosis-related DEGs offer new ideas for the diagnosis of UC. Besides, quercetin was verified as an effective treatment for pyroptosis and intestinal inflammation. This study might enhance our comprehension on the pathogenic mechanism and diagnosis of UC and offer a treatment option for UC.

Marine litter weight estimation from UAV imagery: Three potential methodologies to advance macrolitter reports

In the context of marine litter monitoring, reporting the weight of beached litter can contribute to a better understanding of pollution sources and support clean-up activities. However, the litter scaling task requires considerable effort and specific equipment.This experimental study proposes and evaluates three methods to estimate beached litter weight from aerial images, employing different levels of litter categorization. The most promising approach (accuracy of 80 %) combined the outcomes of manual image screening with a generalized litter mean weight (14 g) derived from studies in the literature. Although the other two methods returned values of the same magnitude as the ground-truth, they were found less feasible for the aim.This study represents the first attempt to assess marine litter weight using remote sensing technology. Considering the exploratory nature of this study, further research is needed to enhance the reliability and robustness of the methods.

Cardiovascular screening outcomes in the Dutch survivorship care program for Hodgkin lymphoma survivors.

Hodgkin lymphoma (HL) survivors are at increased risk of cardiovascular disease (CVD) due to former lymphoma treatment. In 2013, cardiovascular screening for 5-year HL survivors according to national guidelines was implemented in Dutch survivorship clinics. We aim to assess the following: (1) adherence to screening guidelines and (2) the yield of (risk factors for) CVD in the screening program. The study population consisted of 5-year HL survivors who received survivorship care at three University Medical Centers from 2013 to 2016 through 2021. Patient characteristics, cardiovascular screening procedures, and outcomes were collected from the medical records. In 186 survivors eligible for cardiovascular screening (mean age 47.8years, 60.8% female), the following diagnostics were performed: complete blood tests (81.0%, median frequency: yearly instead of advised 5-yearly evaluation), electrocardiogram (93.0%), echocardiography (94.6%). Fifty-five percent of survivors had at least one modifiable cardiovascular risk factor (i.e., current smoking, overweight, new/insufficiently controlled hypertension, dyslipidemia, or diabetes). Screening detected ≥ 1 CVD in 31.1% of survivors. Among survivors with available echocardiography report (n = 106), screening detected new aortic and/or mitral valve dysfunction(s) in 51.0% (with grades 3-4 in 4.9%) and impaired left ventricular ejection fraction in 10.3%. Adherence to the screening guidelines in the Dutch HL survivorship care program was reasonable to good and a substantial number of actionable (risk factors for) CVD were diagnosed. Our findings inform HL survivors at high risk of late cardiotoxicity about cardiovascular screening findings and demonstrate appropriate therapeutic actions after diagnosis of (risk factors for) CVD.

Site-specific mutagenesis screening in KRASG12D mutant library to uncover resistance mechanisms to KRASG12D inhibitors

KRAS plays a crucial role in regulating cell survival and proliferation and is one of the most commonly mutated oncogenes in human cancers. The novel KRASG12D inhibitor, MRTX1133, demonstrates promising antitumor efficacy in vitro and in vivo. However, the development of acquired resistance in treated patients presents a considerable challenge to sustained therapeutic effectiveness. In response to this challenge, we conducted site-specific mutagenesis screening to identify potential secondary mutations that could induce resistance to MRTX1133. We screened a range of KRASG12D variants harboring potential secondary mutations, and 44 representative variants were selected for in-depth validation of the pooled screening outcomes. We identified eight variants (G12D with V9E, V9W, V9Q, G13P, T58Y, R68G, Y96W, and Q99L) that exhibited substantial resistance, with V9W showing notable resistance, and downstream signaling analyses and structural modeling were conducted. We observed that secondary mutations in KRASG12D can lead to acquired resistance to MRTX1133 and BI-2865, a novel pan-KRAS inhibitor, in human cancer cell lines. This evidence is critical for devising new strategies to counteract resistance mechanisms and, ultimately, enhance treatment outcomes in patients with KRASG12D-mutant cancers.

Outcomes of 10 years of PSA screening for prostate cancer in Norwegian men with Lynch syndrome.

Pathogenic germline variants in the mismatch repair (MMR) genes are associated with an increased risk of prostate cancer (PCa). Since 2010 we have recommended MMR carriers annual PSA testing from the age of 40. Prospective studies of the outcome of long-term PSA screening are lacking. This study aimed to investigate the incidence and characteristics of PCa in Norwegian MMR carriers attending annual PSA screening (PSA threshold >3.0 ng/mL) to evaluate whether our recommendations should be continued. This is a prospective observational study of 225 male MMR carriers who were recommended annual PSA screening by the Section of Inherited Cancer, Oslo University Hospital from 2010 and onwards. Incidence and tumor characteristics (age, PSA at diagnosis, Gleason score, TNM score) were described. IHC and MSI-analyses were done on available tumors. Standardized incidence ratio (SIR) was calculated based on data from the Cancer Registry of Norway. Twenty-two of 225 (9.8%) had been diagnosed with PCa, including 10/69 (14.5%) MSH2 carriers and 8/61 (13.1%) MSH6 carriers. Ten of 20 (50%) tumors had Gleason score ≥4 + 3 on biopsy and 6/11 (54.5%) had a pathological T3a/b stage. Eight of 17 (47.1%) tumors showed abnormal staining on IHC and 3/13 (23.1%) were MSI-high. SIR was 9.54 (95% CI 5.98-14.45) for all MMR genes, 13.0 (95% CI 6.23-23.9) for MSH2 and 13.74 for MSH6 (95% CI 5.93-27.08). Our results indicate that the MMR genes, and especially MSH2 and MSH6, are associated with a significant risk of PCa, and a high number of tumors show aggressive characteristics. While the impact of screening on patient outcomes remains to be more firmly established, the high SIR values we observe provide support for continued PSA screening of MSH2 and MSH6 carriers. Studies are needed to provide optimal recommendations for PSA-threshold and to evaluate whether MLH1 and PMS2 carriers should not be recommended screening.

Cervical cancer screening outcomes for HIV-positive women in the Lubombo and Manzini regions of Eswatini-Prevalence and predictors of a positive visual inspection with acetic acid (VIA) screen.

This study aimed to describe the prevalence and predictors of a positive VIA (visual inspection with acetic acid) cervical cancer screening test in women living with human immunodeficiency virus (HIV). We retrospectively analysed data from women aged ≥15 who accessed VIA screening from health facilities in the Lubombo and Manzini regions of Eswatini. Sociodemographic and clinical data from October 2020 to June 2023 were extracted from the client management information system (CMIS). VIA screening outcome was categorised into negative, positive, or suspicious. A logistic regression model estimated the adjusted odds ratio (AOR) of the predictors of a positive VIA screen at p<0.05 with 95% confidence intervals. Of 23,657 participants, 60.8% (n = 14,397) were from the Manzini region. The mean age was 33.3 years (standard deviation 7.0), and 33% (n = 7,714) were first-time screens. The prevalence of a positive VIA was 2.6% (95% CI: 2.2%, 3.0%): 2.8% (95% CI: 2.2%, 3.5%) in Lubombo and 2.4% (95% CI: 2.0%, 2.9%) in Manzini (p = 0.096). Screening at mission-owned (AOR 1.40; p = 0.001), NGO-owned (AOR 3.08; p<0.001) and industrial/workplace-owned health facilities (AOR 2.37; p = 0.044) were associated with increased odds of a positive VIA compared to government-owned health facilities. Compared to those aged 25-34, the odds of a positive VIA increased by 1.26 for those in the 35-44 age group (AOR 1.26; p = 0.017). Predictors with lower odds for a positive VIA test were: being on anti-retroviral therapy (ART) for 5-9 years (AOR 0.76; p = 0.004) and ≥10 years (AOR 0.66; p = 0.002) compared to <5 years; and having an undetectable viral load (AOR 0.39; p<0.001) compared to unsuppressed. Longer duration on ART and an undetectable viral load reduced the odds, while middle-aged women and screening at non-public health facilities increased the odds of a positive VIA screen.