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Nevin Manimala Statistics

Risk-Stratified versus Cytology-Based Triage of Non-HPV 16/18-Positive for Detection of High-Grade Cervical Intraepithelial Neoplasia: Protocol of a Non- Inferiority Randomized Controlled Trial

Res Sq [Preprint]. 2026 Jul 25:rs.3.rs-10093990. doi: 10.21203/rs.3.rs-10093990/v1.

ABSTRACT

Background Human papillomavirus (HPV)-based screening is increasingly being adopted as the primary strategy for cervical cancer prevention due to its superior sensitivity compared with cytology. However, effective triage of women who test positive for high-risk HPV (hrHPV), particularly those infected with non-HPV16/18 genotypes, remains a significant challenge in low-resource settings. Cytology-based triage requires substantial laboratory infrastructure and technical expertise, which may limit its scalability. Risk-stratified triage approaches incorporating readily available clinical and demographic factors may offer a practical alternative for identifying women at highest risk of cervical precancer while reducing unnecessary referrals. Aim The ” STRAT-CIN Trial ” aims to determine whether a risk-stratified triage algorithm is non-inferior to standard cytology-based triage for the detection of high-grade cervical intraepithelial neoplasia (CIN2+) among women positive for non-HPV16/18 high-risk HPV types. Methods This protocol describes a two-arm, parallel, open-label, non-inferiority randomized controlled trial involving sexually active women aged 30-65 years who test positive for non-HPV16/18 high-risk HPV types during routine cervical cancer screening at the Lagos University Teaching Hospital (LUTH), Lagos, Nigeria, between June 2026 and January 2027. A total of 148 eligible women will be randomized in a 1:1 ratio to either a risk-stratified triage arm or a cytology-based triage arm. Participants in the intervention arm will be triaged using a composite algorithm incorporating age, HIV status, cigarette smoking, long-term oral contraceptive use, and multiple hrHPV genotype infections, while participants in the control arm will undergo reflex cytology according to the Bethesda 2014 classification. The primary outcome is the proportion of histologically confirmed CIN2 + lesions detected in each study arm. Secondary outcomes include diagnostic performance metrics, referral rates for colposcopy, colposcopic yield, and predictors of CIN2+. Analyses will follow the intention-to-treat principle. Differences in CIN2 + detection rates will be assessed using risk differences and corresponding 95% confidence intervals. Non-inferiority will be concluded if the lower bound of the confidence interval exceeds the pre-specified non-inferiority margin of – 10%. Logistic regression analyses will be used to identify independent predictors of CIN2+, and statistical significance will be set at P < 0.05. Discussion The ” STRAT-CIN Trial ” will evaluate whether a simplified risk-stratified triage approach can achieve diagnostic performance comparable to conventional cytology-based triage among women with non-HPV16/18 high-risk HPV infections. By integrating easily obtainable clinical and demographic risk factors into triage decision-making, this study has the potential to reduce unnecessary colposcopy referrals, improve screening efficiency, and support the implementation of context-appropriate cervical cancer prevention strategies in resource-constrained settings. The findings will contribute important evidence toward optimizing HPV-based cervical cancer screening programs in Nigeria and other low- and middle-income countries. Registration : PACTR202606895128487 (2nd June 2026).

PMID:42539082 | PMC:PMC13419630 | DOI:10.21203/rs.3.rs-10093990/v1

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Nevin Manimala Statistics

Endemic and epidemic human alphavirus infections in Eastern Panama; An Analysis of Population-based Cross-Sectional Surveys

medRxiv [Preprint]. 2026 Jul 24:2026.04.04.19007310. doi: 10.64898/2026.04.04.19007310.

ABSTRACT

BACKGROUND: Madariaga virus (MADV), has recently been associated with severe human disease in Panama, where the closely related Venezuelan equine encephalitis virus (VEEV) also circulates. In June 2017, a fatal MADV infection was confirmed in a community of Darien province.

METHODS: We conducted a cross-sectional outbreak investigation with human and mosquito collections in July 2017, where sera were tested for alphavirus antibodies and viral RNA. Additionally, by applying a catalytic, force-of-infection statistical model to two serosurveys from Darien province in 2012 and 2017, we investigated whether endemic or epidemic alphavirus transmission occurred historically.

FINDINGS: In 2017, MADV and VEEV IgM seroprevalence was 1.6% and 4.4%, respectively; IgG antibody prevalences were MADV: 13.2%; VEEV: 16.8%; Una virus (UNAV): 16.0%; and Mayaro virus (MAYV): 1.1%. Active viral circulation was not detected. Evidence of MADV and UNAV infection was found near households raising questions about its vectors and enzootic transmission cycles. Insomnia was associated with MADV and VEEV infection, depression symptoms were associated with MADV, and dizziness with VEEV and UNAV. Force-of-infection analyses suggest endemic alphavirus transmission historically, with recent increased human exposure to MADV and VEEV in some regions.

INTERPRETATION: The lack of additional neurological cases suggests that severe MADV and VEEV infections occur only rarely. Our results indicate that, over the past five decades, alphavirus infections have occurred at low levels in eastern Panama, but that MADV and VEEV infections have recently increased potentially during the past decade. Endemic infections and outbreaks of MADV and VEEV appear to differ spatially.

PMID:42539076 | PMC:PMC13419557 | DOI:10.64898/2026.04.04.19007310

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Nevin Manimala Statistics

Validation of the Ukrainian Prolonged Grief Assessment for Children (PGA‑C) in a Wartime Context

Res Sq [Preprint]. 2026 Jul 20:rs.3.rs-10008196. doi: 10.21203/rs.3.rs-10008196/v1.

ABSTRACT

Background : Prolonged grief reactions in children and adolescents are linked to marked emotional distress, social withdrawal, academic disruption, and impaired daily functioning. These difficulties may be intensified in contexts of chronic threat and instability, such as the ongoing war in Ukraine, where bereavement is widespread and support systems are disrupted. Valid, culturally adapted assessment tools are essential for identifying youth experiencing clinically significant grief responses. This study aimed to adapt and validate the Ukrainian version of the Prolonged Grief Assessment for Children (PGA‑C) in a sample of bereaved young people living under wartime conditions. Methods : A total of 129 bereaved children and adolescents (63.6% female; M age = 12.1, SD = 3.14) completed structured interviews. Analyses included descriptive statistics, internal consistency (Cronbach’s α), test-retest reliability over 4-5 weeks (ICC), exploratory factor analysis (EFA), confirmatory factor analysis (CFA), convergent validity testing, and regression analyses. Convergent/divergent validity was examined through associations with PTSD symptoms (CRIES‑8), anxiety and depression (RCADS‑25), and health‑related quality of life (KIDSCREEN‑27). Results : Internal consistency was excellent for the total PGA‑C scale (α = 0.92) and strong for both identified factors (α = 0.89 and 0.88). Test-retest reliability was high (ICC = 0.88, 95% CI [0.82-0.91], p < 0.001). PGA‑C scores showed strong negative associations with quality of life (r = -0.622, 95% CI [-0.729, -0.488]) and positive associations with depression (r = 0.480, 95% CI [0.330-0.620]) and PTSD symptoms (r = 0.438, 95% CI [0.273-0.585]). Correlations of PTSD (r = -0.333, 95% CI [-0.483, -0.162]) and depression (r = -0.350, 95% CI [-0.500, -0.190]) with components of quality of life were clearly weaker than those of PGA-C. No significant differences in PGA-C scores were found for sex, age, relationship to the deceased, or cause of death. EFA of the PGA-C supported a two-factor structure – Detachment/Avoidance and Yearning/Disbelief, yet CFA of the PGA-C showed limited fit of the data to this model (CFI < 0.90, RMSEA > 0.10). Strong internal consistency of the total scale and its concurrent/divergent validity support the use of the PGA-C total score. Conclusions : The Ukrainian PGA‑C demonstrates excellent internal consistency, strong test-retest reliability, and robust convergent and divergent validity. Findings support its use as a reliable tool for assessing prolonged grief among bereaved children and adolescents living in high‑adversity wartime contexts.

PMID:42539067 | PMC:PMC13419585 | DOI:10.21203/rs.3.rs-10008196/v1

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Nevin Manimala Statistics

Eccentricity-Constrained CNN Training Reveals Adaptive Information Coding Around the Visual Field

ArXiv [Preprint]. 2026 Jul 21:arXiv:2607.19316v1.

ABSTRACT

In the primate visual system, center-preferring cortical populations have higher spatial resolution and overlap face- and word-selective regions while periphery-preferring populations have lower spatial resolution and overlap scene-selective regions. This “eccentricity bias” may reflect differential task-relevance: central vision may better support fine-grained tasks like face recognition and reading, while peripheral vision may better support scene understanding. To test whether eccentricity-dependent coding can emerge from natural experience, we used egocentric video and eye-tracking data from the Visual Experience Dataset (VEDB). We trained ResNet-18 models using contrastive learning (SimCLR) on frames modified to isolate different eccentricities (gaze-contingent fovea-only crops, periphery-only crops, and periphery-only crops with a NeuroFovea transform applied). We evaluated downstream task performance and model alignment with human fMRI data (Natural Scenes Dataset; encoding models). In-domain VEDB frame classification showed systematic differences between fovea- and periphery-only models across categories, indicating differential informativeness across tasks. On downstream classification, VEDB-pretrained models generalized better to scene categorization (Places365) than face recognition (VGGFace2), with fovea-only models stronger on both. Across visual cortex, VEDB-pretrained models matched neural predictivity of models trained on mid-sized non-egocentric datasets (ImageNet-100), suggesting egocentric data supports emergence of cortically-aligned representations. In scene-selective cortex (PPA, RSC), periphery-only models held a small but consistent advantage in explained variance over fovea-only models, suggesting these regions are aligned with peripheral statistics. Together, these results suggest egocentric experience may adaptively constrain cortical information processing.

PMID:42539066 | PMC:PMC13419636

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Nevin Manimala Statistics

LocusBlend: Flexible multi-index regional visualization of genomic association signals

medRxiv [Preprint]. 2026 Jul 21:2026.07.15.26358129. doi: 10.64898/2026.07.15.26358129.

ABSTRACT

SUMMARY: It has become standard practice to visualize regional signals from genome-wide association studies (GWAS) using LocusZoom plots. Similarly, GWAS signals are compared to regionally matched quantitative trait loci (QTLs), i.e. variant-to-gene regulation data, using LocusCompare plots to aid assessment of candidate trait-related genes. Despite broad usage, these tools annotate variants by linkage disequilibrium (LD) to a single lead or index variant. This single-index representation has limitations for visualizing complex loci that contain multiple independent signals. We present LocusBlend, an interactive web application for multi-index LD-blended visualization of genomic loci. LocusBlend supports one or two genomic association summary-statistic datasets and one to three index variants, multi-index LocusZoom color-blended plots, and matching LocusCompare visualizations. Applications to Alzheimer’s disease GWAS and QTL signals illustrate LocusBlend enables visualization and separation of independent signals despite shared LD and high genomic complexity. Overall, LocusBlend is aimed at supporting researchers handle the continuously expanding complexity of human genomics findings.

AVAILABILITY AND IMPLEMENTATION: LocusBlend is freely available at https://locusblend.wustl.edu . Publication ready plots are generated in <1min. Source code, documentation, example datasets, input templates, and reproducibility instructions are available at https://github.com/Belloy-Lab/LocusBlend . LocusBlend is implemented in Python using Streamlit, Plotly, and PLINK.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:42539024 | PMC:PMC13419561 | DOI:10.64898/2026.07.15.26358129

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Nevin Manimala Statistics

Estimated global prevalence of metabolic syndrome: a proportional meta-analysis

Eur J Cardiovasc Nurs. 2026 Aug 1:zvag177. doi: 10.1093/eurjcn/zvag177. Online ahead of print.

ABSTRACT

AIM: Metabolic syndrome is a major global health burden. However, existing global prevalence estimates are largely based on studies conducted before the COVID-19 pandemic and do not fully account for contemporary epidemiological and structural determinants. This systematic review and meta-analysis updated global metabolic syndrome prevalence estimates and examined associated socioeconomic and healthcare system correlates using the most recent available evidence.

METHODS AND RESULTS: Six databases were searched from inception to October 27, 2025, for studies reporting crude metabolic syndrome prevalence among adults. Two reviewers independently screened the studies and extracted data. Random-effects proportional meta-analyses and meta-regression were performed to estimate the prevalence of metabolic syndrome and explore associated determinants, respectively. A total of 684 unique observational studies involving 44,979,527 participants were included in quantitative data synthesis. The global metabolic syndrome prevalence ranged from 19% (95% CI: 15%-24%) to 31% (95% CI: 30%-33%), with substantial heterogeneity across analyses. Subgroup analysis according to World Bank region indicated that studies conducted in South Asia (range: 30%-35%) and Latin America and the Caribbean (range: 33%-55%) reported higher prevalence rates than studies in other regions. A higher metabolic syndrome prevalence was significantly associated with an older age, higher proportion of females, greater income inequality, and higher Universal Health Coverage. Pre- and post-pandemic subgroup analyses showed no statistically significant difference in prevalence overall.

CONCLUSION: Metabolic syndrome remains a substantial global health challenge in the post-pandemic era. Beyond estimating prevalence, this review suggests that structural socioeconomic factors and health system coverage are meaningfully associated with prevalence patterns, supporting targeted prevention strategies in socioeconomically disadvantaged regions and populations.

PMID:42538574 | DOI:10.1093/eurjcn/zvag177

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Nevin Manimala Statistics

The perceived impact of the ANZAED Eating Disorder Credential: perspectives of individuals with eating disorder lived experience

J Eat Disord. 2026 Jul 31;13(Suppl 1):299. doi: 10.1186/s40337-026-01690-y.

ABSTRACT

BACKGROUND: In response to individual and systemic barriers hindering the timely and effective treatment of eating disorders (EDs), the Australia & New Zealand Academy for Eating Disorders (ANZAED) introduced an eating disorder credential for clinicians in June 2022. The Credential aims to enhance treatment access, quality, and outcomes. While the Credential has been well received by stakeholders, its effectiveness from the perspective of those with lived experience of an ED needs to be more fully understood. The current study aims to explore the experiences and perspectives of people living with an ED in relation to their treatment experiences provided by Credentialed Eating Disorder Clinicians (credentialed clinicians) and non-credentialed clinicians.

METHODS: An exploratory mixed-methods cross-sectional study was conducted involving 100 participants with personal lived experience of an ED. Participants were recruited via Australian eating disorder services and organisations, including the ANZAED and National Eating Disorders Collaboration (NEDC) membership databases, with recruitment information distributed through their email and social media platforms. Participants completed a survey with open- and closed-ended questions on their attitudes towards the Credential and experiences of treatment by a credentialed clinician or non-credentialed clinician. Descriptive statistics and Mann-Whitney U tests were used to examine differences in attitudes, treatment experiences, and helpfulness ratings between participants who had seen credentialed and non-credentialed clinicians, alongside inductive thematic analysis of open-ended survey responses.

RESULTS: Irrespective of their own clinicians’ credentialing status, participants valued the Credential; almost two thirds identified that their most helpful treatment experience was with a credentialed clinician. Three themes were generated from open-ended survey responses that explored the treatment experiences of those with lived experience of an ED: (1) Expertise, Accessibility, and Continuity of Care, (2) A Collaborative Approach, and (3) Personalised and Effective Treatment Delivered with Understanding, Compassion, and Respect.

CONCLUSIONS: The current study adds to the ED literature by highlighting the perceived value of the ANZAED Eating Disorder Credential by individuals with lived experience. Further, it supports existing research that identifies clinician’s expertise, a collaborative approach to treatment, and the provision of individualised treatment as key factors contributing to positive treatment outcomes. However, barriers to accessibility, including the cost of treatment and availability of credentialed clinicians, remain and need to be addressed for individuals to receive the full benefits of the Credential.

PMID:42538565 | DOI:10.1186/s40337-026-01690-y

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Nevin Manimala Statistics

Cancer treatment-related cardiovascular toxicity according to the ESC definition in patients receiving CAR T-cell therapy

Cardiooncology. 2026 Jul 30;12(1):103. doi: 10.1186/s40959-026-00544-5.

ABSTRACT

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy has substantially improved outcomes in refractory hematologic malignancies but may cause cardiovascular complications, particularly in the context of cytokine release syndrome (CRS). Real-world data on incidence, severity, and prognostic relevance of cancer therapy-related cardiovascular toxicity (CTR-CVT) defined by the 2022 ESC cardio-oncology guidelines remain in the context of CAR-T cell therapy limited.

METHODS: This retrospective single-center study includes 104 patients treated with CAR T-cells between 09/2019 and 02/2024 for acute lymphoblastic leukemia, non-Hodgkin lymphoma and multiple myeloma. The primary endpoint was new-onset CTR-CVT during hospital stay, defined as cancer therapy-related cardiac dysfunction (CTRCD), arrhythmia, myocardial infarction, cardiogenic shock, or cardiovascular death. Clinical characteristics, biomarkers, echocardiographic parameters, CRS/ICANS severity, and survival outcomes were analyzed.

RESULTS: Fifty-two patients (50%) met criteria for CTR-CVT, predominantly due to asymptomatic biomarker elevation. CTRCD occurred in 48.1%, whereas clinically significant events were rare: three patients developed symptomatic CTRCD, one experienced cardiogenic shock, and no myocardial infarctions or cardiovascular deaths were observed. Cardiovascular events occurred early and were associated with higher-grade CRS and ICANS, as well as elevated inflammatory markers. Reduced baseline left ventricular ejection fraction, elevated systolic pulmonary artery pressure, impaired performance status, and beta-blocker use were associated with increased CTR-CVT risk. Survival was numerically lower in patients with CTR-CVT but did not reach statistical significance.

CONCLUSION: Although half of patients fulfilled ESC criteria for CTR-CVT, clinically relevant cardiac events after CAR T-cell therapy were uncommon. These findings suggest potential overclassification driven by biomarker elevations and underscore the importance of emphasizing clinical relevance when assessing cardiotoxicity in CAR T-cell recipients.

PMID:42538564 | DOI:10.1186/s40959-026-00544-5

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Nevin Manimala Statistics

Distribution of transgene in the rodent choroid plexus after intracerebroventricular injection of adeno-associated virus

Fluids Barriers CNS. 2026 Jul 31;23(1):93. doi: 10.1186/s12987-026-00831-4.

ABSTRACT

Using adeno-associated virus to transfer genetic information to the choroid plexus has emerged as a promising route for long-term gene therapy in the brain for a variety of conditions. Overexpression of proteins has proved effective in small animal models but few attempts have been made to translate this technology to clinic, suppress the activity of a protein of interest, or further expand the limited capsid serotypes known to have choroid plexus tropism. We utilise transfer of green fluorescent protein to show choroid plexus epithelium tropism for novel AAV6 derived capsid ShH10Y445F in mouse, rat and porcine tissue explant cultures. In vivo tropism is shown in the mouse following stereotactic intracerebroventricular injection. We examined the distribution of viral transduction across the choroid plexus in all four ventricles following a single unilateral intracerebroventricular injection using both green fluorescent protein as a transgene, but also the CRISPR/Cas9 system to deliver permanent knockdown of apical water channel aquaporin-1. Quantitative immunofluorescence and SURVEYOR assay were used to statistically assess the magnitude and extent of choroid plexus knockdown across the ventricular system. We conclude that serotype ShH10Y445F targets choroid plexus epithelium in mouse, rat and pig; and when carrying the CRISPR/Cas9 system can reduce target protein expression in these cells. Transduced choroid plexus epithelial cells distribute unevenly with a bias toward the lateral ventricle on the injected side and a preferential infection of choroid plexus in the lateral over the third and fourth ventricles. Overcoming irregular distribution represents a challenge for clinical translation of this technology where clinical efficacy may require manipulation of the entire choroid plexus.

PMID:42538560 | DOI:10.1186/s12987-026-00831-4

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Introducing the TOP framework: a novel phenotyping solution for collaborative phenotype algorithm development and application

J Biomed Semantics. 2026 Jul 27;17(1):14. doi: 10.1186/s13326-026-00364-7.

ABSTRACT

BACKGROUND: Phenotyping, the comprehensive assessment of observable characteristics, is essential for advancing medical understanding and personalised healthcare. However, traditional phenotyping methods are often manual, time-intensive, and limited in scope. To address these challenges, this work introduces the TOP Framework, a software suite that leverages a structured approach. It provides tools for the formal definition of phenotypes, their organisation into ontological classes, the creation of phenotype models for disease-specific knowledge representation, and the generation of phenotype queries for automated data retrieval and analysis. A dynamic phenotype algorithm integrates these modules to efficiently identify individuals meeting complex phenotypic criteria. The Model for End-Stage Liver Disease (MELD) score serves as a running example to illustrate the framework’s capabilities. Furthermore, this paper presents a preliminary evaluation of the TOP Framework’s user experience by means of the User Experience Questionnaire (UEQ), assessing its usability and suitability for researchers and clinicians.

RESULTS: The TOP Framework includes a robust implementation of a reasoner model for deriving complex phenotypes and an automated testing module to ensure reliability. The user experience evaluation yielded generally positive results on a scale from -3 to 3 (n = 11), with mean scores and 95% confidence intervals as follows: attractiveness, 1.50 (CI = (1.07, 1.93)); pragmatic quality, 1.38 (CI = (1.00, 1.77)); and hedonic quality, 1.40 (CI = (0.76, 2.03)).

CONCLUSIONS: The TOP Framework offers a novel and automated approach to phenotyping, with the potential to enhance the efficiency, scalability, and reproducibility of phenotyping studies. This advancement contributes to a deeper understanding of disease and the progression of precision medicine.

PMID:42538550 | DOI:10.1186/s13326-026-00364-7