Future Screening Research Articles

Impact of Comorbid Polycystic Ovary Syndrome on Clinical and Laboratory Parameters in Female Adolescents with Metabolic Dysfunction-Associated Steatotic Liver Disease: A Cross-Sectional Study

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) and polycystic ovary syndrome (PCOS) share several pathophysiological mechanisms. While the prevalence of MASLD has been extensively studied in PCOS populations, the occurrence of PCOS among female adolescents with transient elastography (TE)-confirmed MASLD in pediatric hepatology settings remains poorly characterized. This cross-sectional study aims to address this knowledge gap and elucidate potential clinical and biochemical differences between female adolescents with MASLD and comorbid PCOS compared to those without PCOS. Methods: The study cohort included 45 female adolescents with TE-diagnosed MASLD. Comparative analyses of clinical and laboratory parameters were performed between those with (n = 19) and those without (n = 26) comorbid PCOS, diagnosed according to the Rotterdam criteria. Results: Adolescents with MASLD and comorbid PCOS exhibited significantly higher weight, lower height, and increased waist circumference compared to those without PCOS. Additionally, the prevalence of acanthosis nigricans was significantly higher in the PCOS group (68.4% versus 34.6%, p = 0.025). Regarding laboratory parameters, serum phosphorus levels and liver enzymes—including aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase—were significantly lower in adolescents with comorbid PCOS. However, no significant differences were observed in lipid profiles, glucose metabolism, or novel non-invasive biomarkers of MASLD. Conclusions: This study reveals distinct clinical and biochemical profiles in female adolescents with MASLD and comorbid PCOS compared to those without PCOS. These findings have the potential to inform and refine future screening protocols and diagnostic algorithms for these interrelated conditions, specifically tailored to pediatric hepatology settings.

Examining the relationships between pain, activities of daily living, and perceptions of overall health in older adults with breast cancer: Results from a brief geriatric screening.

273 Background: Geriatric assessment has been identified as an essential component to caring for patients with cancer who are over 65 years old. Prior research suggests that physical pain and illness perceptions each impact important health behaviors. This retrospective study utilized a brief geriatric screen to examine the relationships between pain levels, activities of daily living (ADLs), and perceptions of overall health for older adults with breast cancer. Implications for methods to improve the patient experience for this population are considered. Methods: The Senior Adult Oncology Program (SAOP) screening tool was administered to 429 patients age 65 or older at a breast oncology clinic. A total ADL score was computed by summing patient-reported responses to 13 ADL items, such as ability to dress oneself, feed oneself, and remember to take medications. A higher ADL score indicates greater difficulty with these responsibilities. Pain was assessed using a 10-point scale; scores were dichotomized to form a low-pain group (scores 0-4) and high-pain group (scores 5-10). Overall Health was assessed on a 1-10 scale, with higher scores indicating perceptions of greater health. Demographic and medical information was abstracted from patients’ electronic health records. Independent samples t-tests examined differences between the high-pain and low-pain groups in total ADL score and self-assessed Overall Health. Results: The average age of the sample was 76 years old (range = 65-89 years). Approximately half of the sample identified as White (48%); 20% identified as Black. In comparing the high-pain and low-pain groups, the high-pain group reported significantly greater difficulty with ADLs (M score = 3.25, 1.41, respectively; p=.026). Additionally, patients endorsing high pain levels reported significantly worse Overall Health as compared to patients endorsing low levels of pain (M= 7.50, 6.11, respectively; p=.001). Conclusions: Older adults with breast cancer experiencing high levels of pain demonstrated greater difficulty with ADLs and worse perceptions of overall health. It is critical that pain is assessed early and often for older adults with breast cancer. Early identification of high pain levels in this population could allow those in need to receive pharmacological and/or behavioral treatments for pain, which may maintain stability or promote improvement in ADLs and perceptions of one’s health. Incorporating brief pain assessments into future geriatric screening tools could improve the process of aging during and after breast cancer.

Analyzing high-throughput assay data to advance the rapid screening of environmental chemicals for human reproductive toxicity.

While high-throughput (HTP) assays have been proposed as platforms to rapidly assess reproductive toxicity, there is currently a lack of established assays that specifically address germline development/function and fertility. We assessed the applicability domains of yeast (S. cerevisiae) and nematode (C. elegans) HTP assays in toxicity screening of 124 environmental chemicals, determining their agreement in identifying toxicants and their concordance with reproductive toxicity in vivo. We integrated data generated in the two models and compared results using a streamlined, semi-automated benchmark dose (BMD) modeling approach. We then extracted and modeled relevant mammalian in vivo data available for the matching chemicals included in the Toxicological Reference Database (ToxRefDB). We ranked potencies of common compounds using the BMD and evaluated correlation between the datasets using Pearson and Spearman correlation coefficients. We found moderate to good correlation across the three data sets, with r = 0.48 (95 % CI: 0.28-1.00, p<0.001) and rs = 0.40 (p=0.002) for the parametric and rank order correlations between the HTP BMDs; r = 0.95 (95 % CI: 0.76-1.00, p=0.0005) and rs = 0.89 (p=0.006) between the yeast assay and ToxRefDB BMDs; and r = 0.81 (95 % CI: 0.28-1.00, p=0.014) and rs = 0.75 (p=0.033) between the worm assay and ToxRefDB BMDs. Our findings underscore the potential of these HTP assays to identify environmental chemicals that exhibit reproductive toxicity. Integrating these HTP datasets into mammalian in vivo prediction models using machine learning methods could further enhance their predictive value in future rapid screening efforts.

Cocrystal screening in minutes by solution-mediated phase transformation (SMPT): Preparation and characterization of ketoconazole cocrystals with nine aliphatic dicarboxylic acids

The rapid and efficient cocrystal screening, based on solution-mediated phase transformation (SMPT), was applied to the screening of cocrystals between ketoconazole (KTZ) and nine aliphatic dicarboxylic acids. Cocrystals formed successfully, in minutes, with a change of suspension characteristics, either a cake formation or the formation of large particles. Bulk cocrystals were characterized by powder X-ray diffraction, thermal analysis, and Raman spectroscopy. Single crystals were grown, and molecular structures were determined. Three previously reported cocrystals were reproduced, and six new cocrystals were discovered, including one that was reported as a failure in literature by solution or grinding method. Two hydrogen-bonded motifs are observed in these nine cocrystals: Most cocrystals form hydrogen bonded discrete tetramer with two KTZ and two acids molecules; while two cocrystals form infinite chain. This study demonstrated the high efficacy of cocrystal generation using the slurry screening method. It should be fully utilized in future cocrystal screening.

Cost-Effectiveness of Serum Pepsinogen as a Gastric Cancer Targeted Screening Strategy in the United States

Background and AimsCurrent gastric cancer (GC) screening modalities are invasive and expensive. Noninvasive screening for GC precursors with serum pepsinogen (PG) may improve early detection and prevention. Test characteristics of PG based on US prospective data was recently reported and used to study the cost-effectiveness of PG screening versus no screening in the US. MethodsA patient-level state transition microsimulation of gastric adenocarcinoma analyzed noninvasive screening versus no screening in a hypothetical cohort of average risk US individuals. Primary outcomes included life expectancy, quality-adjusted life years (QALYs), total costs, and incremental cost-effectiveness ratios (ICERs). Secondary outcomes included total GC incidence and mortality. Base-case PG sensitivity and specificity were 34.1% and 94.7%, respectively, with a wide range of PG performance characteristics also examined. ResultsOne-time serum PG screening at age 40 was cost-effective compared to no screening with an ICER of $4,913.29 per QALY. PG screening resulted in 10.9% relative reduction in lifetime GC incidence and 10.8% relative decrease in cumulative GC mortality. Localized stage at diagnosis increased from 30.5% to 33.6% and metastatic stage decreased from 40.8% to 37.4%. Sensitivity analysis showed PG screening was most sensitive to endoscopy costs, chronic atrophic gastritis quality of life, and PG prevalence. PG screening remained cost-effective across a wide range of test values. ConclusionPG screening is a cost-effective strategy to improve GC mortality, however, mortality benefit will depend on the test characteristics of the biomarker. Future blood-based screening tests that have better performance characteristics could further improve GC prevention.

Biophysical analysis of the membrane-proximal Venus Flytrap domain of ESAG4 receptor-like adenylate cyclase from Trypanosoma brucei

The protozoan parasite Trypanosoma brucei possesses a large family of transmembrane receptor-like adenylate cyclases (RACs), primarily located to the flagellar surface and involved in sensing of the extracellular environment. RACs exhibit a conserved topology characterized by a large N-terminal extracellular moiety harbouring two Venus Flytrap (VFT) bilobate structures separated from an intracellular catalytic domain by a single transmembrane helix. RAC activation, which typically occurs under mild acid stress, requires the dimerization of the intracellular catalytic domain. The occurrence of VFT domains in the RAC’s extracellular moiety suggests their potential responsiveness to extracellular ligands in the absence of stress, although no such ligands have been identified so far. Herein we report the biophysical characterization of the membrane-proximal VFT2 domain of a bloodstream form-specific RAC called ESAG4, whose ectodomain 3D structure is completely unknown. The paper describes an AlphaFold2-based optimisation of the expression construct, enabling facile and high-yield recombinant production and purification of the target protein. Through an interdisciplinary approach combining various biophysical methods, we demonstrate that the optimised VFT2 domain obtained by recombination is properly folded and behaves as a monomer in solution. The latter suggests a ligand-binding capacity independent of dimerization, unlike typical mammalian VFT receptors, as guanylate cyclase. In silico VFT2 genomic analyses shows divergence among cyclase isoforms, hinting at ligand specificity. Taken together this improved procedure enabling facile and high-yield recombinant production and purification of the target protein could benefit researchers studying trypanosomal RAC VFT domains but also any trypanosome domain with poorly defined boundaries. Additionally, our findings support the stable monomeric VFT2 domain as a useful tool for future structural investigations and ligand screening.

Machine learning models reveal how polycyclic aromatic hydrocarbons influence environmental bacterial communities

Polycyclic aromatic hydrocarbons (PAHs) are harmful and widespread pollutants in the environment, posing an ecological threat. However, exploring the influence of PAHs on environmental bacterial communities in different habitats (soil, water, and sediment) remains a major challenge. We collected and reanalyzed 1924 16S rRNA sequencing samples to determine the effects of PAHs on bacterial communities in different habitats and used machine learning to predict potential degrading bacteria. It was found that PAHs had substantial effects on the bacterial community, and that the bacterial community structure changed differently in different habitats. PAH contamination decreased the relative abundance of Proteobacteria in the soil (16.3 %) and sediment (10.1 %), whereas the abundance of Proteobacteria in water increased by 20.2 %. Among the tested models, the random forest model best identified the effects of PAHs on bacterial groups, with an accuracy of 99.51 % for soil, 97.72 % for sediment, and 100 % for water at the genus level. Using the random forest model, we identified 70 biomarkers that respond to PAHs, including potentially degrading microorganisms such as A4b, Bacillus, Flavobacterium and Polynucleobacter. Furthermore, PAH contamination did not significantly alter the functions of bacterial communities in the environment. This study provides a candidate strain set for future screening of PAH-degrading bacteria and contributes to the study of the adaptability of engineered PAH-degrading bacteria to the environment.

Comparative Analysis of HPV Detection Efficiency: Evaluating Cobas 8800 Performance in Vaginal Self-Sampling versus Clinician-Collected Samples at a Regional Thai Hospital

Background: This study, conducted at a regional Thai hospital, assesses the comparative efficacy of self-collected versus clinician-collected samples for HPV detection using the Cobas 8800 system among Thai women aged 30–60. Methods: Our methodology involved analyzing 1541 self-collected and 1398 clinician-collected samples. Results: The results show a statistically significant mean difference in cycle threshold (Ct) values favoring clinician-collected samples (1.53; 95% CI: 1.18–1.87, p &lt; 0.0001). This pattern was consistent across various age groups, with the most pronounced differences noted in the oldest cohort (50–59 years), suggesting higher detection efficiency in clinician-collected samples. The study further explored the correlation of Ct values with cytological and histological outcomes, where clinician-collected samples demonstrated superior diagnostic performance, particularly in identifying LSIL and HSIL conditions, evidenced by AUC values of 0.793 and 0.866, respectively. While self-sampling remains a viable method, with sensitivity reaching up to 48.84% for LSIL and 46.15% for HSIL, clinician collection proved more accurate, likely influencing future national screening policies. Conclusions: This work underscores the need for robust sample collection methods and the importance of ongoing enhancements to self-sampling assays and techniques to ensure their efficacy in cervical cancer screening programs.

Deciphering Chemical Rules for Drug Penetration into Strongyloides.

Background: Strongyloidiasis, a parasitic infection, presents a significant public health challenge in tropical regions due to the limited repertoire of effective treatments. The screening of chemical libraries against the therapeutically relevant third-stage larvae (L3) of the model parasite Strongyloides venezuelensis yielded meager success rates. This situation is reminiscent of Gram-negative bacteria, where drug entry is a limiting factor. Methods: Here, we set out to determine whether similar barriers are in place and establish whether structural and property requirements exist for anti-strongyloides drug discovery. We focused on dyes as their uptake and effects on viability can be independently assessed in the multicellular parasite, thus providing a means to study the possibility of similar entry rules. We tested different dyes in in vitro assays on L3s. Results: We found that staining was necessary to reduce parasite viability, with some dyes achieving anti-strongyloides effects at concentrations similar to those of the reference drug, ivermectin (IV). Some dyes also showed activity against female adults at concentrations well below that of ivermectin. Unfortunately, the most potent dye, Methylene Blue, was unable to prevent the infection in a preliminary in vivo mouse model assay, presumably due to fast dye clearance. Structural analysis showed that positive charges facilitated the access of the compounds to the L3 tissue, thus providing a structural tool for the introduction of activity. For female adults, low globularity is additionally required. As a proof of concept, we added a positive charge to an inactive compound of one of our chemical libraries and re-determined the activity. Conclusions: These findings allow us to establish structural rules for parasite entry that could be of interest for future drug screening or drug development campaigns. These rules might also be applicable to other related parasites.

Reactivities of N-Nitrosamines against Common Reagents and Reaction Conditions.

The knowledge of the reactivity of N-nitrosamines (NSAs) with common organic reagents in synthesis is essential in determining their presence in pharmaceutical products, if formed and retained during synthesis. In this study, we carried out a comprehensive survey of the Reaxys database for all reactions in which the NSA functional group is consumed. Very different reactivities for different classes of NSAs, e.g., N,N-dialkylnitrosamines and N,N-diphenylnitrosamine, were identified, suggesting substrates which should be included in any future reactivity screening. A classification of NSAs based on their reactivities, and corresponding reagents and transformations, was drawn up based on the data. Furthermore, the survey identified missing areas in the reported reactivities of NSAs with different reagents. This led to an experimental reactivity screening of 8 commercial NSAs with common synthetic reagents in the Mirabilis tool for purge assessment. The results showed Na2S2O4 in 1 M aqueous NaOH at 50 °C to be highly effective at destroying NSAs without damaging other organic compounds.

Adaptation and Validation of the Psychological Consequences of Screening Questionnaire (PCQ) for Cognitive Screening in Primary Care.

Context-specific measures with adequate external validity are needed to appropriately determine psychosocial effects related to screening for cognitive impairment. Two-hundred adults aged ≥65 y recently completing routine, standardized cognitive screening as part of their Medicare annual wellness visit were administered an adapted version of the Psychological Consequences of Screening Questionnaire (PCQ), composed of negative (PCQ-Neg) and positive (PCQ-Pos) scales. Measure distribution, acceptability, internal consistency, factor structure, and external validity (construct, discriminative, criterion) were analyzed. Participants had a mean age of 73.3 y and were primarily female and socioeconomically advantaged. Most had a normal cognitive screening result (99.5%, n = 199). Overall PCQ scores were low (PCQ-Neg: = 1.27, possible range 0-36; PCQ-Pos: = 7.63, possible range 0-30). Both scales demonstrated floor effects. Acceptability was satisfactory, although the PCQ-Pos had slightly more item missingness. Both scales had Cronbach alphas >0.80 and a single-factor structure. Spearman correlations between the PCQ-Neg with general measures of psychological distress (Impacts of Events Scale-Revised, Perceived Stress Scale, Kessler Distress Scale) ranged from 0.26 to 0.37 (P's < 0.001); the correlation with the World Health Organization-Five Well-Being Index was -0.19 (P < 0.01). The PCQ-Neg discriminated between those with and without a self-reported subjective cognitive complaint ( = 2.73 v. 0.89, P < 0.001) and was associated with medical visit satisfaction (r = -0.24, P < 0.001) on the Patient Satisfaction Questionnaire. The PCQ-Pos predicted self-reported willingness to engage in future screening ( = 8.00 v. 3.00, P = 0.03). The adapted PCQ-Neg is an overall valid measure of negative psychological consequences of cognitive screening; findings for the PCQ-Pos were more variable. Future studies should address measure performance among diverse samples and those with abnormal screening results. The PCQ scale is an overall valid measure of psychological dysfunction related to cognitive screening in older adults receiving normal screen results.PCQ scale performance should be further validated in diverse populations and those with abnormal cognitive screening results.The adapted PCQ may be useful to both health research and policy stakeholders seeking improved assessment of psychological impacts of cognitive screening.

Cancer Screening, Knowledge, and Fatalism among Chinese, Korean, and South Asian Residents of New York City.

Asian New York City residents have the lowest cancer screening uptake across race and ethnicity. Few studies have examined screening differences across Asian ethnic subgroups in New York City. Cross-sectional survey data were analyzed using multivariable logistic and multinomial regression analyses. Differences among Chinese, Korean, and South Asian adults in breast, cervical, and colorectal cancer screening uptake; breast and colorectal cancer screening knowledge; and cancer fatalism were examined. Associations between breast and colorectal cancer screening knowledge and their uptake were also assessed along with associations between cancer fatalism and breast, cervical, and colorectal cancer screening uptake. Korean women reported 0.52 times [95% confidence interval (CI), 0.31-0.89] lower odds of Pap test uptake compared with Chinese women; South Asian adults had 0.43 times (95% CI, 0.24-0.79) lower odds of colorectal cancer screening uptake compared with Chinese adults. Korean adults reported 1.80 times (95% CI, 1.26-2.58) higher odds of knowing the correct age to begin having mammograms compared with Chinese adults; South Asian adults had 0.67 times (95% CI, 0.47-0.96) lower odds of knowing the correct age to begin colorectal cancer screening compared with Chinese adults. Korean adults had 0.37 times (95% CI, 0.27-0.53) lower odds of reporting cancer fatalism compared with Chinese adults. Low cancer screening uptake among Asian American adults, low screening knowledge, and high cancer fatalism were found. Cancer screening uptake, knowledge, and fatalism varied by ethnic subgroup. Findings indicate the need for ethnicity-specific cultural and linguistic tailoring for future cancer screening interventions.

Association Between False-Positive Results and Return to Screening Mammography in the Breast Cancer Surveillance Consortium Cohort.

False-positive results on screening mammography may affect women's willingness to return for future screening. To evaluate the association between screening mammography results and the probability of subsequent screening. Cohort study. 177 facilities participating in the Breast Cancer Surveillance Consortium (BCSC). 3 529 825 screening mammograms (3 184 482 true negatives and 345 343 false positives) performed from 2005 to 2017 among 1 053 672 women aged 40 to 73 years without a breast cancer diagnosis. Mammography results (true-negative result or false-positive recall with a recommendation for immediate additional imaging only, short-interval follow-up, or biopsy) from 1 or 2 screening mammograms. Absolute differences in the probability of returning for screening within 9 to 30 months of false-positive versus true-negative screening results were estimated, adjusting for race, ethnicity, age, time since last mammogram, BCSC registry, and clustering within women and facilities. Women were more likely to return after a true-negative result (76.9% [95% CI, 75.1% to 78.6%]) than after a false-positive recall for additional imaging only (adjusted absolute difference, -1.9 percentage points [CI, -3.1 to -0.7 percentage points]), short-interval follow-up (-15.9 percentage points [CI, -19.7 to -12.0 percentage points]), or biopsy (-10.0 percentage points [CI, -14.2 to -5.9 percentage points]). Asian and Hispanic/Latinx women had the largest decreases in the probability of returning after a false positive with a recommendation for short-interval follow-up (-20 to -25 percentage points) or biopsy (-13 to -14 percentage points) versus a true negative. Among women with 2 screening mammograms within 5 years, a false-positive result on the second was associated with a decreased probability of returning for a third regardless of the first screening result. Women could receive care at non-BCSC facilities. Women were less likely to return to screening after false-positive mammography results, especially with recommendations for short-interval follow-up or biopsy, raising concerns about continued participation in routine screening among these women at increased breast cancer risk. National Cancer Institute.

Real-world first round results from a charity lung cancer screening program in East Asia.

Screening with low-dose computed tomography (LDCT) has been proven to potentially reduce the rate of mortality of lung cancer. Lack of real-world data outside of protocolized trials has been cited as an impediment to its more widespread implementation, especially in Asia. This report aims to provide such real-world data. A single round of LDCT was provided through a community-based charity program in Hong Kong, China to asymptomatic adults with a family history of lung cancer and/or smoking history. Anonymized data from this program were analyzed. LDCT was performed for 99 participants, including 98 (99%) who had one or more family members with history of lung cancer, and 70 (71%) who were never-smokers. After a single round of screening, a positive LDCT was noted in 47 participants (47%). A sister with a history of lung cancer (28% vs. 8%, P=0.01) and a multiplex family (MF) (47% vs. 23%, P=0.02) were factors associated with a positive LDCT. After a median period of 10 months (range, 5-16 months) following LDCT, lung cancer (all adenocarcinoma) was diagnosed as a direct consequence of positive LDCT findings in six participants (6%), of whom four had stage I disease and five received surgery with curative intent. In the 47 participants with a positive LDCT, having a sister with a history of lung cancer was associated with an increased risk of lung cancer (relative risk =5.23; 95% confidence interval: 1.09-25.21). Detected lesions categorized as Lung Imaging Reporting and Data System (Lung-RADS) 3 or above (odds ratio =12.08; 95% confidence interval: 1.27-114.64) or deemed by an experienced specialist to be suspicious (odds ratio =63.33; 95% confidence interval: 5.48-732.29) were significantly more likely to turn out to be a lung cancer. This real-world data demonstrates that a single round of LDCT screening at a community level in East Asia can detect potentially curable lung cancer at a rate comparable to those reported by protocolized trials. When considering future LDCT screening programs in East Asia, a family history of lung cancer may be a key factor indicating a person for screening, and how features of a LDCT-detected lesion should trigger further intervention warrant further definition.

764. PREDICTING AGE-SPECIFIC PREVALENCE OF BARRETT'S OESOPHAGUS IN AUSTRALIAN AND UNITED STATES

Abstract Background Barrett’s esophagus is the precursor to esophageal adenocarcinoma (EAC). EAC detected from endoscopic surveillance programs accounts for &amp;lt;10% of all EAC, suggesting a large number of patients with Barrett’s esophagus are likely unaccounted for. Several studies have estimated the observed prevalence of Barrett’s esophagus to be approximately 1%, but this may be an underestimate. The aim of this study is to use population incidence of EAC and rate of progression from Barrett’s esophagus from large cohort studies to estimate a realistic prevalence of Barrett’s esophagus. Methods A simple tree cohort model was created for progression to EAC from birth to death (100 years) for American and Australian population. Lifetime risk of esophageal cancer and adenocarcinoma were endpoints. This was then used to back-calculate age-specific and overall prevalence of Barrett’s esophagus using an optimisation algorithm. Results Lifetime risk of esophageal cancer and adenocarcinoma in US Whites is 0.56% and 0.36% respectively, while in Australian population is slightly higher at 0.81% and 0.61% (range 0.57% - 0.65%). Estimated overall prevalence of Barrett’s esophagus is ~3% (±0.3%) and ~5.4% (±0.6%) in US White and Australian populations, while in males is 5.3% (±0.6%) and 7.4% (±0.3%), respectively. Female cohorts were seen to have lower chance of developing esophageal cancer, adenocarcinoma, and Barrett’s esophagus. Conclusion Cohort studies of Barrett’s esophagus are likely to underestimate its prevalence of this silent disease. Computational models based on progression from Barrett’s esophagus to EAC accounting for undetected disease reveal higher estimates, which can help in future screening options.

O01 LISTEN TO YOUR HEART AND MIND: A FEASIBILITY STUDY ON COMBINED SCREENING OF RAISED BLOOD PRESSURE, ATRIAL FIBRILLATION, COGNITIVE IMPAIRMENT AND HEARING LOSS

Background and Objective. Detection rates of hypertension continues to be suboptimal worldwide. The risk of hypertension increases substantially in older adults aged ≥65 years, a group also at increased risk of atrial fibrillation (AF), cognitive decline and hearing loss—all factors associated with hypertension. This pilot study aimed to 1) implement a combined screening strategy for these health conditions, and 2) assess feasibility and acceptability of the combined screening. Methods. Adults aged ≥65 years without a prior diagnosis of cognitive impairment and dementia were invited to attend a combined screening appointment through advertisements posted in university and community group newsletters and noticeboards. Participants underwent blood pressure (BP) and AF screening using an oscillometric BP monitor with AF detection (Microlife WatchBP Office 2G), cognitive assessment (General Practitioner Assessment of Cognition, GPCOG), and audiometric testing. A subset of participants was invited to participate in a post-study process evaluation interview. Results. Of the 35 participants (age 73±6 years, 51% females), 26 (74%) had hypertension (on antihypertensive medication: n=20; measured: n=6; unaware: n=2; uncontrolled: n=4). Possible AF was detected in two participants and seven had possible cognitive decline (GPCOG score &lt;9). Hearing loss was detected in 13 participants. Interviews (n=16, 50% females) revealed that combined screening was acceptable and feasible as participants felt it was “convenient”, “saves time”, “a brilliant idea”, and that “… conditions are related and therefore appropriate to be together”. Most participants were already aware of their hypertension status, thus screening did not result in increased hypertension awareness except for one with uncontrolled hypertension who proceeded to purchase a home BP monitor. One participant with detected AF visited a cardiologist and confirmed non-AF arrhythmia. All interviewees found the appointment duration (approximately 60-75 minutes) was not too long nor too taxing. Conclusions. Combined screening in older adults with increased cardiovascular risk is feasible and acceptable and should be considered for future screening programs in older adults.

Genetic and Environmental Factors Co-Contributing to Behavioral Abnormalities in adnp/adnp2 Mutant Zebrafish.

Human mutations of ADNP and ADNP2 are known to be associated with neural developmental disorders (NDDs), including autism spectrum disorders (ASDs) and schizophrenia (SZ). However, the underlying mechanisms remain elusive. In this study, using CRISPR/Cas9 gene editing technology, we generated adnp and adnp2 mutant zebrafish models, which exhibited developmental delays, brain deficits, and core behavioral features of NDDs. RNA sequencing analysis of adnpa-/-; adnpb-/- and adnp2a-/-; adnp2b-/- larval brains revealed altered gene expression profiles affecting synaptic transmission, autophagy, apoptosis, microtubule dynamics, hormone signaling, and circadian rhythm regulation. Validation using whole-mount in situ hybridization (WISH) and real-time quantitative PCR (qRT-PCR) corroborated these findings, supporting the RNA-seq results. Additionally, loss of adnp and adnp2 resulted in significant downregulation of pan-neuronal HuC and neuronal fiber network α-Tubulin signals. Importantly, prolonged low-dose exposure to environmental endocrine disruptors (EEDs) aggravated behavioral abnormalities in adnp and adnp2 mutants. This comprehensive approach enhances our understanding of the complex interplay between genetic mutations and environmental factors in NDDs. Our findings provide novel insights and experimental foundations into the roles of adnp and adnp2 in neurodevelopment and behavioral regulation, offering a framework for future preclinical drug screening aimed at elucidating the pathogenesis of NDDs and related conditions.

Women’s experiences of risk-stratified breast cancer screening in the MyPeBS trial: a qualitative comparative study across two European countries

Objective Risk-stratification should improve the benefits-to-harms ratio for breast screening, whereby higher-risk women receive additional screening and low-risk women are screened less. This study investigated the effects of healthcare context by comparing how women in England and France experienced risk-based breast screening. Methods and measures Fifty-two women were purposively sampled from participants who underwent risk-based screening in the MyPeBS trial. Women received objectively-derived 5-year breast cancer risk estimates (low = < 1%, average = 1–1.66%, high = ≥ 1.67 to <6%, very-high-risk = ≥ 6%). This determined future trial-related screening schedules and prevention options. Semi-structured interviews were transcribed for thematic framework analysis. Results Two overarching themes were produced: the importance of supported risk communication and accessibility of risk management. Overall, risk-based breast screening was viewed positively. However, trial procedures, especially in risk estimate provision, differed across sites. Women at increased risk were more reassured when appointments were with specialist healthcare professionals (HCP). When absent, this resulted in reduced satisfaction with risk communication and greater uncertainty about its personal relevance. Low-risk women’s views on extended mammogram schedules seemed linked to how health services are organised differently. Conclusions Context is an important consideration regarding acceptability of healthcare innovations such as risk-stratified screening: it should not be assumed that findings from one country apply universally.

Explainable machine learning framework to predict the risk of work-related neck and shoulder musculoskeletal disorders among healthcare professionals.

This study aims to develop risk prediction models for neck and shoulder musculoskeletal disorders among healthcare professionals. A stratified sampling method was employed to select employees from medical institutions in Nanning City, yielding 617 samples. The Boruta algorithm was used for feature selection, and various models, including Tree-Based Models, Single Hidden-Layer Neural Network Models (MLP), Elastic Net Models (ENet), and Support Vector Machines (SVM), were applied to predict the selected variables, utilizing SHAP algorithms for individual-level local explanations. The SVM model excels in both Mean Absolute Error (MAE) and Root Mean Square Error (RMSE) and exhibits more stable performance when generalizing to unseen data. The Random Forest model exhibited relatively high overall performance on the training set. The MLP model emerges as the most consistent and accurate in predicting shoulder musculoskeletal disorders, while the SVM model shows strong fitting capabilities during the training phase, with occupational factors identified as the main contributors to WMSDs. This study successfully constructs work-related musculoskeletal disorder risk prediction models for healthcare professionals, enabling a quantitative analysis of the impact of occupational factors. This advancement is beneficial for future economical and convenient work-related musculoskeletal disorder screening in healthcare professions.

Examination of Firefighting as an Occupational Exposure Criteria for Lung Cancer Screening.

Firefighting is known to be carcinogenic to humans. However, current lung cancer screening guidelines do not account for occupational exposure. We hypothesize that firefighting is an independent risk factor associated with the development of high-risk lung nodules on low-dose CT (LDCT). Members of a firefighter's union underwent LDCT at a single institution between April 2022 and June 2023 within a lung cancer screening program. Results were interpreted by designated chest radiologists and reported using the Lung-RADS scoring system. Demographic and radiographic data were recorded, and summary statistics are reported. 1347 individuals underwent lung cancer screening, with a median age of 51years (IQR 42-58), including 56 (4.2%) females. Overall, 899 (66.7%) were never smokers, 345 (25.6%) were former smokers, and 103 (7.7%) were current smokers. There were 41 firefighters (3.0%) who had high-risk (Lung-RADS 3 or 4) nodules requiring intervention or surveillance, of which 21 (1.5%) were Lung-RADS 3 and 20 (1.5%) that were Lung-RADS 4. Of the firefighters with high-risk nodules, only 6 (14.6%) were eligible for LDCT based on current screening guidelines. There were 7 high-risk nodules (0.5%) that required procedural intervention, 6 (85.7%) of which were from the non-screening eligible cohort. There were also 20 never-smoking firefighters (57.1%) with high-risk nodules that were non-screening eligible. Firefighting, even in the absence of smoking history, may be associated with the development of high-risk lung nodules on LDCT. Carefully selected occupational exposures should be considered in the development of future lung cancer screening guidelines.