Browse Articles

Small-area spatio-temporal analysis of cancer risk to support effective and equitable cancer prevention

Cancer is rapidly increasing worldwide and urgent global action towards cancer control is required. Consistent with global trends, Canada is expected to experience a near doubling in new cases and cancer deaths between 2020–2040; population growth and ageing being the primary drivers. The projected increased cancer incidence and its associated costs is expected to further exacerbate socioeconomic inequities. Focused actions to prevent cancer, to detect it earlier when more treatable, and, to lower the risk of recurrence, must be prioritized. Almost half of all cancers are preventable, caused by risk factors that are potentially avoidable and modifiable. Integrating cancer prevention with care-based models is necessary and represents the most cost-effective and sustainable approach to control cancer. To be effective, prevention efforts must consider the cancers impacting local populations and understand how community and individual factors interact within the spatial and temporal contexts in which people live. This study is part of the Nova Scotia Community Cancer Matrix project which profiles the cancers impacting communities over time; measuring associations between cancer and socioeconomic status (SES); and determining how the joint spatial distribution of cancers can be used to address inequities, identify priority populations and strengthen prevention efforts. Using Bayesian inference to model spatio-temporal variations in 58,206 cases diagnosed in 301 communities between 2001–2017, across 10 preventable cancer types, we report significant disparities in cancer risk across communities based on sex and community SES. The work highlights the utility of small-area mapping to identify at-risk communities and understand how community-SES impacts risk. It also uncovers significant inequities rooted in the differential distribution of material and social capacity, operating beyond the control of individuals. The approach is implementable to other regions to inform and strengthen prevention efforts aiming at reducing the burden of cancer or that of other diseases.

Combining CD3/GD2 bispecific T cell engager with human Vγ9Vδ2 T cells facilitates neuroblastoma cell targeting and killing in vitro

Cancer immunotherapy, particularly T cell–based therapies, is considered to have strong potential for treating various types of cancer. A promising approach that has emerged is the use of γδ T cell-based strategies for cancer treatment. Neuroblastoma (NB), a solid tumor frequently found in childhood, is one of the more intriguing targets for immunotherapy. In this study, we report an alternative immunotherapy method for treating neuroblastoma by combining bispecific antibody with human Vγ9Vδ2 T cells. Initially, we screened for human scFv against CD3 epsilon using phage panning technology. Human scFv CD3 clone 18 demonstrated the highest ability to bind CD3 epsilon in an indirect ELISA assay. Consequently, we selected human scFv CD3 clone 18 to create a bispecific T cell engager antibody targeting both CD3 and disialoganglioside (GD2), called CD3/GD2 BiTE. This bispecific antibody was composed of human scFv CD3 clone 18 (VH-VL) and mouse scFv GD2 (VL-VH), linked by a flexible peptide linker. The interleukin-2 signal sequence and polyhistidine tag were added at the N- and C-termini for protein secretion and purification, respectively. CD3/GD2 BiTE was transiently produced in a mammalian cell expression system, which provided both high yield and quality. The CD3/GD2 BiTE folded naturally into a compact monomeric structure. Cell-based binding activity assays demonstrated that CD3/GD2 BiTE specifically binds to its target antigens on CD3-positive Jurkat cells and GD2-positive SH-SY5Y cells, but did not react with CD3-negative Raji cells and GD2-negative SK-N-SH cells. In subsequent in vitro experiments, the cytotoxicity of CD3/GD2 BiTE combined with human Vγ9Vδ2 T cells against neuroblastoma cells was evaluated. Human Vγ9Vδ2 T cells were primed with CD3/GD2 BiTE to improve the binding specificity and avidity against neuroblastoma cell lines before adding into SH-SY5Y cells. At concentrations of 180 and 360 nM, the CD3/GD2 BiTE significantly enhanced the killing ability of human Vγ9Vδ2 T cells against SH-SY5Y cells at an E:T ratio of 1:1. Moreover, CD3/GD BiTE armed with human Vγ9Vδ2 T cells enabled the killing of neuroblastoma cells using five- to ten-times fewer effector cells. The combination of CD3/GD2 BiTE and human Vγ9Vδ2 T cells also exhibited cytotoxic activity against a three-dimensional tumor spheroid model of SH-SY5Y GFP at an E:T ratio of 1:1. Consequently, CD3/GD2 BiTE enhances tumor-targeting and cytotoxic abilities of human Vγ9Vδ2 T cells against neuroblastoma cells in both two-dimensional and three-dimensional cell cultures. These results suggest that the combination of CD3/GD2 BiTE and human Vγ9Vδ2 T cells could represent an alternative immunotherapy strategy for treating neuroblastoma patients in the future.

Hepatic transcriptome profiling unveils candidate genes in cattle with liver abscesses under the influence of beef genetics in dairy cattle

Liver abscesses are a significant concern in cattle feeding, linked to visceral condemnation and carcass trimming; however, the molecular mechanism of development and progression of liver abscesses is unknown. This study aimed to evaluate the hepatic transcriptomic profile, immunohistochemistry, and IGF-I circulation in beef × dairy (Angus × Holstein) steers with and without liver abscesses. Samples were collected from twelve steers (final body weight of 719 ± 5.8 kg) originating from the same feedlot and were selected based on liver scores at harvest. The animals were divided into abscessed (n = 6) and healthy livers (n = 6). Blood samples were used to measure circulating insulin-like growth factor I (IGF-I) levels using an ELISA kit. Liver samples were divided into two portions; one portion was used for immunohistochemistry (IHC) to identify IGF-I receptor (IGF-IR) abundance, while the second portion was used for RNA extraction, library preparation, and sequencing (Illumina NovaSeq 6000 platform). Differentially expressed genes (DEGs) were identified with the DESeq2 R package, using an adjusted p-value ≤ 0.05 and fold change > 1.5. Sera IGF-I was not affected by liver condition; however, IGF-IR abundance was up-regulated in abscessed livers. A total of 568 DEGs were identified, with 372 up-regulated and 196 down-regulated in abscessed livers. Notably, the most highly up-regulated genes were FGF23, NXPH4, and CYP7A1, while EPHA6, CD70, and INHBA showed the most significant downregulation. Protein-protein interaction (PPI) network analysis identified THBS1 and COL1A2 as significant hub genes. The DEGs showed enrichment in biological processes related to angiogenesis, cell migration, adhesion, and extracellular matrix organization. Pathway analysis indicated activation in signaling pathways, including hepatic fibrosis, interleukin, and IGF-I signaling. These findings reveal candidate genes and pathways linked to inflammatory responses and tissue remodeling, offering valuable evidence that enhances our understanding of the progression of liver abscesses in cattle.

Prediction of testosterone deficiency using different screening indexes in adult American men: An NHANES cross-sectional study

Background Testosterone levels are closely associated with visceral obesity, insulin resistance, and lipid metabolism. The objective of this study was to investigate the associations among eight indicators related to visceral obesity, insulin resistance, lipid metabolism, and testosterone levels. Methods The data were obtained from a cross-sectional survey based on National Health and Nutrition Examination Survey (NHANES) 2013–2016. Logistic and linear regression were employed to assess the associations between these inicators and testosterone levels. Simultaneously, the receiver operating characteristic (ROC) curve was utilized to evaluate their predictive capacity for testosterone deficiency (TD). Results Data from a collective of 1514 individuals selected from NHANES were analyzed. After adjusting all potential confounders, a tight association was identified between these eight indexes and TD. The ROC curve analysis showed that the triglyceride-glucose waist-to-height ratio (TyG-WHtR)is the best predictor of testosterone deficiency (AUC: 0.7760, 95%CI: 0.7460–0.8060), with a cut-off value of 5.375. Further analyses indicated that participants with higher TyG-WHtR index exhibitrd a lower total testosterone level(β: −79.36,95%CI: −105.90, −52.82). Additionally, males in TyG-WHtR index tertile 3 had a higher risk of TD (OR: 6.61, 95%CI: 2.90,15.07), and lower total testosterone levels (β: −121.9, 95%CI: −186.82, −56.98). All the results remained stable in the subgroup analyses stratified by diabetes and hypertension. Conclusions We found that these indexses are tightly associated with testosterone levels in U.S. adult men. Moreover, the TyG-WHtR index demonstrates the most effective predictive performance in the population. However, more well-designed studies are still needed to validate their association.

Risk factors associated with adverse outcomes after cervical conization in patients with cervical adenocarcinoma in situ

Background Identifying high-risk groups for adverse outcomes after conization is crucial for developing targeted treatment plans for patients with cervical adenocarcinoma in situ (ACIS). This study aimed to analyze the clinical characteristics of patients with ACIS and identify risk factors associated with adverse outcomes. Methods Patients diagnosed with ACIS through colposcopic biopsy at the Affiliated Hospital of Qingdao University and Qilu Hospital between January 2012 and December 2022 were selected. After meeting the inclusion and exclusion criteria, we collected their clinical data. Chi-square (χ2) tests and logistic regression models were employed to determine independent risk factors. Results A total of 379 patients with ACIS were included in this analysis. About 26.1% of these patients tested positive on preoperative endocervical curettage (ECC), while 79.4% had a single lesion. Among the 334 patients who underwent cervical conization, 17.1% had positive surgical margins. Additionally, residual lesions were present in 53.6% of cases, and pathological upgrading occurred in 7.8% of patients. Multivariate analysis indicated that age (p < 0.001), preoperative histopathological results from ECC (p = 0.033), and the number of ACIS lesions (p < 0.001) were associated with positive surgical margins. Number of births (p = 0.011), preoperative histopathological results from ECC (p = 0.030), and surgical margin statuses at cervical conization (p < 0.001) were independent risk factors for residual lesions. Preoperative histopathological result of ECC (p = 0.035) was confirmed as a predictor of postoperative pathological upgrading. Conclusions Older, multiparous patients with ACIS and abnormal preoperative ECC results require deeper diagnostic excision. Patients with positive conization margins necessitate further treatment, particularly when accompanied by abnormal ECC results. For women who wish to preserve their fertility, a repeat conization may be appropriate; however, in older and multiparous women, a hysterectomy would be recommended.

The hepatic transcriptome is differentially regulated by a standardized meal in healthy individuals compared to patients with fatty liver disease

The human liver is dynamic organ with minute to hourly adaptions in response to feeding. Patients with non-alcoholic fatty liver disease (NAFLD) and cirrhosis have altered transcriptomic features compared to controls but how and if food intake affects such is unknown in humans. Our aim was to investigate the hepatic transcriptome at both fasting and postprandial states in patients with NAFLD, cirrhosis, and healthy controls and secondly to develop a browsable resource enabling easy and unrestricted access to such data. We hypothesized that hepatic transcriptome differed between groups, and this was also regulated by food intake. We obtained liver tissue by transjugular liver biopsies from patients with NAFLD (n = 9, mean age 49 (16 SD) y, BMI 35 (5) kg/m2), cirrhosis (n = 9, age 61 (11) y, BMI 32 (5) kg/m2) and healthy controls (n = 10, age 25 (3) y, BMI 23 (3) kg/m2). The hepatic transcriptome was sequenced using NGS and evaluated in bioinformatic analyses to assess differentially expressed genes (DEG) and gene ontology biological processes (GOBP). We identified 553 DEG between healthy controls and patients with NAFLD, 5527 DEG between healthy controls and patients with cirrhosis, and 3898 DEG in NAFLD compared with cirrhosis. A hitherto uncharacterized gene (MET proto-oncogene) was differentially expressed in human NAFLD and cirrhosis. The hepatic transcriptome changed significantly during a standardized meal and these changes were blunted in patients with NAFLD and cirrhosis. GOBP analyses revealed an increase in pro-inflammatory and pro-fibrotic genes in NAFLD and cirrhosis, as well as a decrease in genes related to metabolism. Data were made browsable using two web-based apps. The hepatic transcriptome is differentially regulated by a standardized meal in healthy individuals compared to patients with fatty liver disease.

The CLASS (Cerebral visual impairment Learning and Awareness for School Staff) Pilot Study: An evaluation of the awareness of CVI amongst teachers and comparative evaluation of two different educational resources on understanding

Cerebral visual impairment (CVI) is the leading cause of visual impairment in children in high income countries. Despite its prevalence, awareness of CVI among educators remains low, meaning that many affected children may not receive the support they need in school. While previous research has highlighted the challenges faced by children with CVI, few studies have systematically assessed teacher awareness and the effectiveness of targeted educational interventions in improving classroom practices. This study addresses this gap by evaluating: (1) teacher awareness of CVI, (2) existing classroom practices that may impact children with CVI, (3) the effectiveness of two CVI educational media formats (video and text) in increasing understanding, and (4) the changes teachers would be willing to implement following exposure to these resources. By comparing the impact of these two formats, this study provides insights into how best to deliver CVI training for teachers in a way that is both accessible and effective. A total of 111 teachers from primary, secondary, and special schools across the UK participated in a survey incorporating either a three-minute video simulation or a 1.5-minute text-based resource about CVI. Before exposure, 72% of participants had not heard of CVI, with awareness particularly low among mainstream teachers (98% of primary and 80% of secondary teachers were unaware). Teachers also reported inconsistent use of CVI-supportive practices, such as reducing classroom clutter and simplifying smart screen content. Both media formats significantly increased teachers’ willingness to implement changes (p < 0.0001). The text format showed a slightly greater increase in average Likert scores, and the Wilcoxon signed-rank test revealed a larger statistical effect for text (z = -12.91) compared to video (z = -8.90). However, the video format was also highly effective, producing a similarly strong impact, with both formats achieving an identical median increase of 1.0. These results suggest that while text may have led to slightly larger shifts in rank-based scores, the video format remained a powerful and engaging tool for increasing teachers’ willingness to implement CVI-supportive strategies. The findings suggest that small, manageable adaptations, such as reducing visual distractions and maintaining consistency in classroom layouts, are practical for teachers and may have a meaningful impact on children with CVI. This study highlights the potential of bite-size learning resources in raising awareness and encouraging evidence-based teaching adaptations. By providing concise, accessible materials, teachers can be equipped with strategies to support children with CVI while minimising additional workload demands. Future efforts should focus on scaling these resources to reach a wider audience, including families and caregivers, to foster a more inclusive understanding and response to CVI.

Measuring Child Labor: The Who’s, the Where’s, the When’s, and the Why’s

Measuring child labor accurately is a major challenge: parents’ and children’s reports tend to differ dramatically, and there is typically no way to verify whose reports are truthful (if any). To overcome this challenge, this paper uses novel data from a cocoa certifier in Côte d’Ivoire that draws on satellite imagery to minimize under-reporting. Concretely, aerial photos allow them to select remote and hard-to-reach communities—where parents typically have not been sensitized by government or NGOs, averting social desirability biases—and to visit these communities while cocoa is being harvested—precisely when children in employment are very visible, making it easier for enumerators to impute it if parents still fail to report it. We compare their figures with those obtained from business-as-usual surveys with parents and children in these regions, and find that (1) reporting inconsistencies between parents and their children in fact decrease with household remoteness; (2) adults dramatically under-report child labor relative to the certifier data, by a factor of at least 60%; and (3) in turn, children self-reports are statistically identical to the latter. Taking advantage of an experiment that randomly assigned a text-message campaign to discourage child labor, we further show that parents’ reports not only underestimate its prevalence, but can even lead to the wrong conclusions about the effects of policy interventions.

The joint effect of weight-adjusted waist index and physical activity on all-cause mortality in Chinese elderly patients with multimorbidity: A study based on the CLHLS from 2011 to 2018

Background The relationship between physical activity changes, weight-adjusted waist circumference index (WWI), and mortality risk among older Chinese adults with multimorbidity remains unclear. This study aimed to examine whether changes in physical activity and WWI modify the mortality risk by analyzing data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Method Our study was based on the 2011 ~ 2018 wave of the CLHLS, involving a study of 2,626 older adults with multimorbidity. Cox proportional hazards models were employed to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) and a stratified analysis was conducted to assess the combined impact of WWI and physical exercise on all-cause mortality in patients with multimorbidity. Result Patients with multimorbidity who engaged in regular physical activity exhibited a 41% reduction in all-cause mortality compared to those who had never been physically active (HR:0.59, 95% CI:0.49, 0.70). All-cause mortality was increased by 13% in patients with high WWI and multimorbidity compared to those with low WWI (HR:1.13, 95% CI:1.01, 1.27). Furthermore, WWI-stratified analyses revealed that varying physical activity profiles had a more pronounced protective or detrimental impact on all-cause mortality among multimorbidity patients in the high WWI group compared to the low WWI group. Conclusion This study demonstrates that both initiating and maintaining physical activity significantly reduce mortality risk in multimorbid older adults, even those with higher WWI. Our findings support integrating structured exercise interventions and routine WWI monitoring into clinical care to improve survival outcomes in this population.

Empowering safety managers to champion the implementation of smoking cessation services in the construction industry: Protocol for a sequential multiple assignment randomized trial

US construction workers (CWs) have the highest cigarette smoking rate among all occupations (27.2% vs. 15%), yet the lowest coverage of workplace smoking cessation services (14% vs. 29%). This study aims to empower safety managers to implement smoking cessation services in the construction industry. Using participatory research methods, this study aims to: 1) Develop multilevel strategies (MLIs) to implement adaptive smoking cessation programs delivered by the safety manager on construction sites, and 2) conduct a cluster-randomized, hybrid type 1 effectiveness-implementation, 2-phase sequential multiple assignment randomized trial (SMART) to test the programs (ClinicalTrials.gov: NCT06098144). The MLIs include: 1) creating the outer setting (research investigators, stakeholders) and inner setting facilitation (companies’ advisory committee, study champion), 2) conducting observational field assessments of workflows, 3) training safety managers to deliver the intervention, and 4) conducting implementation process evaluations. In SMART, 32 construction sites within 8 companies with 608 CWs will be enrolled. In Phase 1, sites will be randomized to A1 (referral to Tobacco Quitline -TQL) or B1 (referral to TQL + nicotine replacement treatment (NRT) + 1 group behavioral counseling session). In Phase 2, responders who quit smoking at 3 months continue with the assessment only, while non-responders will be re-randomized to C (4 counseling sessions + NRT; A1 + C, B1 + C) or an extra dose of Phase 1 treatment (A2, B2). Participants will receive 4 follow-up assessments at 3, 6, 9, and 12 months. Primary outcomes are the effectiveness (12-month biomarker-confirmed prolonged abstinence) and cost-effectiveness (cost/quit, cost/quality-adjusted life-year) of A1 + A2 vs. B1 + B2 and A1 + C vs. B1 + C. The secondary outcome is the feasibility of the program’s implementation. We hypothesize that B1 + B2 will outperform A1 + A2, and B1 + C will outperform A1 + C. This project will generate novel scientific evidence on the effectiveness, cost-effectiveness, and implementation feasibility of smoking cessation programs in the construction industry.

Variant evolution graph: Can we infer how SARS-CoV-2 variants are evolving?

The SARS-CoV-2 virus has undergone extensive mutations over time, resulting in considerable genetic diversity among circulating strains. This diversity directly affects important viral characteristics, such as transmissibility and disease severity. During a viral outbreak, the rapid mutation rate produces a large cloud of variants, referred to as a viral quasispecies. However, many variants are lost due to the bottleneck of transmission and survival. Advances in next-generation sequencing have enabled continuous and cost-effective monitoring of viral genomes, but constructing reliable phylogenetic trees from the vast collection of sequences in GISAID (the Global Initiative on Sharing All Influenza Data) presents significant challenges. We introduce a novel graph-based framework inspired by quasispecies theory, the Variant Evolution Graph (VEG), to model viral evolution. Unlike traditional phylogenetic trees, VEG accommodates multiple ancestors for each variant and maps all possible evolutionary pathways. The strongly connected subgraphs in the VEG reveal critical evolutionary patterns, including recombination events, mutation hotspots, and intra-host viral evolution, providing deeper insights into viral adaptation and spread. We also derive the Disease Transmission Network (DTN) from the VEG, which supports the inference of transmission pathways and super-spreaders among hosts. We have applied our method to genomic data sets from five arbitrarily selected countries — Somalia, Bhutan, Hungary, Iran, and Nepal. Our study compares three methods for computing mutational distances to build the VEG, sourmash, pyani, and edit distance, with the phylogenetic approach using Maximum Likelihood (ML). Among these, ML is the most computationally intensive, requiring multiple sequence alignment and probabilistic inference, making it the slowest. In contrast, sourmash is the fastest, followed by the edit distance approach, while pyani takes more time due to its BLAST-based computations. This comparison highlights the computational efficiency of VEG, making it a scalable alternative for analyzing large viral data sets.

“We’re here to help them if they want to come”: A qualitative exploration of hospital staff perceptions and experiences with outpatient non-attendance

Background Patient non-attendance remains a major challenge for health services. Few studies have examined how health service providers think about, potentially address, and prioritise non-attendance within the scope of their practice. This study aimed to (1) explore healthcare professionals’ perspectives, beliefs, and opinions about the impact of patient non-attendance within a publicly-funded outpatient physiotherapy clinic context; (2) explore perceived barriers and facilitators associated with the implementation of non-attendance mitigation strategies; and (3) identify health service staff generated solutions to address perceived barriers and enhance facilitators. Methods A focus group discussion and semi-structured interviews were conducted between June 2023 to January 2024 with 27 physiotherapy department clinic outpatient staff involved in operationalising clinic referral processing, appointment scheduling, or providing care to patients. Data was analysed using a hybrid inductive/deductive framework analysis approach. Results Participants indicated that non-attendance had predominantly negative implications for the health service, healthcare provider, and patient. The interconnected issue of non-attendance encompassed multiple areas and were broadly categorised into five inductively identified themes: impact of non-attendance, perceptions of value, material deprivation, service delivery and built environment, and professional role and identity. Non-attendance mitigation strategies generated by participants were deductively mapped to the theoretical domains framework (TDF) to explore behavioural determinants that may influence successful implementation. This included knowledge, reinforcement, goals, optimism, memory, attention and decision-making, environmental resources and context, and emotions. Conclusions Staff identified multiple strategies for reducing non-attendance; implementing many of these strategies would require additional resourcing. Research determining the effectiveness of such strategies both in the short-term and long-term following implementation into practice remains a priority for future investigation.

In silico analysis of quorum sensing modulators: Insights into molecular docking and dynamics and potential therapeutic applications

Quorum sensing (QS) regulates bacterial functions like virulence and biofilm formation, mediated by proteins such as LasI and QscR in Pseudomonas aeruginosa. This study investigates the structural dynamics of LasI and QscR proteins in complex with Sulfamerazine and Sulfaperin, using AiiA lactonase as a negative control, through molecular dynamics (MD) simulations to identify potential QS modulators. Molecular docking and MD simulations assessed binding affinity and structural dynamics, analyzing parameters like docking scores, root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), solvent-accessible surface area (SASA), radius of gyration (Rg), principal component analysis (PCA), and covariance analysis. Sulfamerazine exhibited the highest binding affinity for LasI based on docking scores, indicating strong ligand-protein interactions. MD simulations revealed stability in the LasI-Sulfamerazine complex, with lower RMSD compared to LasI-Sulfaperin and QscR complexes. RMSF analysis indicated greater flexibility in ligand-binding regions of LasI-Sulfaperin and QscR complexes, suggesting weaker binding. SASA showed a decrease in solvent-accessible surface area for the LasI-Sulfamerazine complex, supporting a compact structure. Rg values confirmed this, with the LasI-Sulfamerazine complex being more compact (~2.00 nm) than QscR-ligand complexes (2.10–2.30 nm). PCA revealed significant conformational changes in the LasI-Sulfamerazine complex, with PC1 explaining 57.26% variance. Covariance analysis indicated stronger residue coupling in the LasI-Sulfamerazine complex, suggesting higher rigidity, while LasI-Sulfaperin and QscR complexes exhibited flexible dynamics. AiiA lactonase was used as a negative control due to its established quorum quenching activity, which hydrolyzes AHL molecules and disrupts QS signaling. Unlike LasI and QscR, AiiA does not rely on small molecule binding for activation. However, a known LasI or QscR inhibitor would have served as a more appropriate positive control, which will be considered in future studies. These findings suggest the LasI-Sulfamerazine complex’s stability and rigidity make Sulfamerazine a promising QS modulator. Computational analyses highlight its potential to disrupt bacterial communication. Further experimental validation is needed to confirm its therapeutic implications.

Investigating methods to enhance interpretability and performance in cardiac MRI for myocardial scarring diagnosis using convolutional neural network classification and One Match

Machine learning (ML) classification of myocardial scarring in cardiac MRI is often hindered by limited explainability, particularly with convolutional neural networks (CNNs). To address this, we developed One Match (OM), an algorithm that builds on template matching to improve on both the explainability and performance of ML myocardial scaring classification. By incorporating OM, we aim to foster trust in AI models for medical diagnostics and demonstrate that improved interpretability does not have to compromise classification accuracy. Using a cardiac MRI dataset from 279 patients, this study evaluates One Match, which classifies myocardial scarring in images by matching each image to a set of labeled template images. It uses the highest correlation score from these matches for classification and is compared to a traditional sequential CNN. Enhancements such as autodidactic enhancement (AE) and patient-level classifications (PLCs) were applied to improve the predictive accuracy of both methods. Results are reported as follows: accuracy, sensitivity, specificity, precision, and F1-score. The highest classification performance was observed with the OM algorithm when enhanced by both AE and PLCs, 95.3% accuracy, 92.3% sensitivity, 96.7% specificity, 92.3% precision, and 92.3% F1-score, marking a significant improvement over the base configurations. AE alone had a positive impact on OM increasing accuracy from 89.0% to 93.2%, but decreased the accuracy of the CNN from 85.3% to 82.9%. In contrast, PLCs improved accuracy for both the CNN and OM, raising the CNN’s accuracy by 4.2% and OM’s by 7.4%. This study demonstrates the effectiveness of OM in classifying myocardial scars, particularly when enhanced with AE and PLCs. The interpretability of OM also enabled the examination of misclassifications, providing insights that could accelerate development and foster greater trust among clinical stakeholders.

Correction: Hyper-induction of IL-6 after TLR1/2 stimulation in calves with bovine respiratory disease

Cardiovascular disease risk among Australian unpaid carers – A survival analysis using 15 waves of the HILDA survey

Background Engaging in chronically stressful behaviours has been hypothesised to increase the risk of experiencing cardiovascular disease (CVD). Providing unpaid care is known to be a stressful activity, but it is not clear whether this caregiving is associated with CVD. This study filled a gap in the existing literature by examining the association between providing unpaid care and incident cardiovascular disease among a nationally representative sample of Australian adults. Methods 11,123 adult participants aged over 18 years from the Household Income and Labour Dynamics in Australia (HILDA) survey were followed for up to 14 years from baseline (2003) until 2017. Gender-stratified survival analysis models used self-reported caregiving and heart disease statuses as well as time-varying covariates, to assess the association between providing high-intensity or low-intensity unpaid care (to an elderly or disabled relative) and incident CVD in comparison with a non-caregiving control. Results Among females, there was weak evidence that CVD was associated with high-intensity unpaid care (HR = 1.27, 95% CI = [0.83, 1.95]) and no evidence for low-intensity unpaid care (HR = 0.79, 95% CI = [0.50, 1.26]) in comparison with non-carers after adjusting for confounders. There was no association between caregiving and incident CVD for high-intensity (HR = 0.82, 95% CI = [0.47, 1.42]) or low-intensity (HR = 0.84, 95% CI = [0.55, 1.28]) caregiving males in the adjusted models. Conclusions These findings do not provide strong evidence to reject the null hypothesis that providing unpaid care does not increase risk of developing CVD in the Australian population. Given that these findings are somewhat inconsistent with the extant literature from other populations, further research is necessary, both in Australia and internationally, to build on the findings of this study and improve understanding of the nature of the association between caregiving and incident CVD.

Utilizing Multi-omics analysis to elucidate the role of mitochondrial gene defects in Gastric cancer progression

Background Gastric cancer is a leading cause of cancer-related mortality worldwide, with poor survival outcomes despite advances in diagnostic and therapeutic methods. Mitochondrial autophagy, or mitophagy, is crucial for maintaining cellular homeostasis and has significant implications in tumor biology. DUSP1, a bispecific phosphatase regulating MAP kinase activity, has been associated with various cancers, but its role in GC remains unclear. Materials and methods In order to gain a deeper understanding of gastric cancer cells, this study utilized bulk RNA-seq data from TCGA and GEO, combined with the MSigDB database, to screen for mitophagy-related genes. Univariate Cox regression and LASSO analysis were employed to further identify key mitophagy-related genes. Single-cell RNA sequencing data from the database was analyzed using Seurat software to investigate the mitochondrial autophagy genes in each candidate gastric tissue. To clarify the functional pathways involved, enrichment analysis and differential gene expression analysis were conducted. The characteristics of the immune microenvironment were assessed using the CIBERSORT R package. Additionally, both the ssGSEA algorithm and the CIBERSORT algorithm were utilized to evaluate changes and effects in immunological characteristics during gastric cancer pathogenesis. Results We identified eight prognostic genes—STX10, CDC37, VPS35, RCAN1, TRIM25, DUSP1, SEC23A, and GLT8D1—using LASSO-Cox regression analysis. RCAN1 and DUSP1 are strongly positively correlated, while DUSP1 is strongly negatively correlated with TRIM25, and CDC37 is strongly negatively correlated with SEC23A. By incorporating mitochondrial autophagy scores and clinical characteristics, we established a prognostic model that accurately predicts the 3-year survival status of gastric cancer (GC) patients. Additionally, our single-cell analysis identified DUSP1 as a key mitophagy-related gene. Functional studies demonstrated that DUSP1 knockdown significantly inhibits GC cell proliferation and migration. Conclusion In this study, we developed a risk score based on eight mitochondrial autophagy-related genes and analyzed their expression across different cell types using single-cell analysis. DUSP1 stood out as a key player in gastric cancer progression, with higher expression in tumor tissues and a significant role in cell proliferation, apoptosis, and drug resistance. Our research also linked this risk score to tumor microenvironment immune cell infiltration and tumor mutational burden, revealing distinct high and low-risk groups in gastric cancer patients. This risk score holds potential for improving patient survival assessment and guiding personalized treatment, including enhancing immunotherapy efficacy.

Kinesthetic illusions induced by muscle tendon vibration: The orientation of the vibration motor as a new methodological factor?

Purpose/aim To investigate the impact of changing the rotational orientation of the vibrating motor on kinesthestic illusions. Materials and methods Twenty healthy individuals received vibration over the wrist flexor muscles of dominant and non-dominant sides (80 Hz, 1 mm, 10 seconds) using four conditions (3 trials/conditions) defined by the rotational direction of the vibrator’s eccentric rotating mass according to the anatomical position: (1) proximodistal, (2) distoproximal, (3) mediolateral and (4) lateromedial. Non-parametric statistical analyses were used to compare illusion characteristics across conditions. Results Lateromedial rotation created illusions that were more often in unexpected directions compared to the other rotational orientations. Distoproximal rotation was more likely to evoke kinesthetic illusions of wrist extension (76.8%) compared to lateromedial rotation (57.7%; p = 0.009). The latter led more frequently to complex/combined movement illusions (26.1%) especially with an ulnar deviation component (17.7%) compared to the other rotational directions. Conclusion Results from the present study demonstrated that the rotational orientation can influence illusory perceptions, but not to a great extent. Distoproximal rotation was more effective to elicit the expected illusions of wrist extension, compared to the lateromedial orientation that more often caused complex and variable perceptions of movement. Distoproximal rotation should thus be preferred if clear and reproducible perceptions are required and lateromedial might serve as a way of creating illusions more akin to everyday functional movements. Although the exact underlying mechanisms remain unclear, our work raises awareness on the importance of gaining a better understanding and control over methodological factors that could affect kinesthetic illusions.

A provably secure coercion-resistant e-voting scheme with confidentiality, anonymity, unforgeability, and CAI verifiability

Ensuring both cast-as-intended (CAI) verifiability and coercion-resistance in e-voting remains a critical challenge. The e-voting scheme proposed by Finogina and Herranz in 2023 represents the first notable advancement in reconciling these conflicting requirements. CAI verifiability allows voters to confirm that their intended vote has been correctly recorded, even without a secure channel to the election committee, while coercion-resistance prevents external influence and vote-selling. However, essential security properties such as confidentiality, anonymity, unforgeability, and double-voting prevention fall outside the scope of Finogina and Herranz’s e-voting scheme, leaving significant gaps in its security guarantees. To address this limitation, we propose a novel e-voting scheme that simultaneously achieves CAI verifiability, coercion-resistance, confidentiality, anonymity, unforgeability, and double-voting prevention while maintaining an asymptotic complexity of 𝒪(n). To the best of our knowledge, no existing scheme satisfies all these properties concurrently. Moreover, we establish that anonymity inherently implies CAI verifiability in e-voting schemes, a result of independent interest. By strengthening security and privacy guarantees, our work bridges existing gaps and provides a comprehensive security model that serves as a foundation for the design of future e-voting systems.

Enhanced Surveillance for Meningococcal Disease—United States, 2015–2019

Background High quality surveillance data are important to monitor U.S. epidemiology of meningococcal disease. Enhanced Meningococcal Disease Surveillance (EMDS) was established in 2015 to collect additional data and isolates from reported cases. Methods Epidemiologic information and isolates obtained through EMDS for meningococcal disease cases reported through the National Notifiable Diseases Surveillance System (NNDSS) during 2015–2019 were included in the analysis. Isolates were characterized by serogrouping and molecular typing using either Sanger sequencing or whole genome sequencing. Case fatality ratios (CFRs) were calculated using cases with known outcome as the denominator. Odds ratios (ORs) were calculated using logistic regression. Results A total of 1,806 meningococcal disease cases were reported during 2015–2019. The average annual incidence was 0.11 cases per 100,000 population. For key variables already collected through NNDSS, EMDS improved completeness over NNDSS by 21%-39% each year during 2015–2019. Completeness of key variables in EMDS improved over time by an average of 18%. Testing of isolates submitted through EMDS showed that serogroups B and C were predominant in all five years. For serogroup B, the most common clonal complex (CC) was CC32 in 2015–2017 and CC41/44 in 2018–2019; for serogroup C, CC11 was most common in 2015–2017 and CC103 in 2018–2019. The CFR was significantly lower for CC103 (6.7%) compared to other CCs (13.6%) (OR 0.44, 95% CI: 0.22–0.89). Conclusions U.S. incidence of meningococcal disease remained low during 2015–2019. Data and isolates obtained from EMDS supplement NNDSS and are critical to monitor U.S. meningococcal disease epidemiology.