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Nevin Manimala Statistics

Metabolic Dysfunction-Associated Fibrosis 5 Score and the Risk of Liver-Related Events in the General Population

Gut Liver. 2026 Jun 22. doi: 10.5009/gnl250626. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: The metabolic dysfunction-associated fibrosis 5 (MAF-5) tool has been proposed for identifying individuals at high risk of liver fibrosis, but its ability to predict liver-related events (LREs) remains unknown. We aimed to evaluate the ability of MAF-5 to predict LREs and assess whether modifications could enhance its predictive capacity.

METHODS: A retrospective cohort of 62,625 adults without cancer, organ transplantation, chronic viral hepatitis, or heavy alcohol intake was followed for LREs (hepatocellular carcinoma and/or liver cirrhosis complications). The MAF-5 score was calculated and compared with other non-invasive liver fibrosis biomarkers. We also assessed whether modifying the MAF-5 score could improve LRE prediction.

RESULTS: During a median follow-up of 11.2 years, 147 patients developed LREs. The MAF-5 scores were used to stratify participants by LRE risk into low-, intermediate-, and high-risk categories, with incidence rates of 0.108, 0.576, and 1.520 cases per 1,000 person-years, respectively. Age was identified as an independent risk factor for LREs, and therefore, we developed an age-modified MAF-5 (aMAF-5) score, which showed improved performance (C-index: 0.870 vs 0.818; integrated area under the curve: 0.858 vs 0.784). Within the same MAF-5 category, LRE risk varied according to the aMAF-5 score. The use of “either positive” criteria improved sensitivity (from 0.412 to 0.765) and decreased specificity (from 0.944 to 0.830), while “both positive” criteria improved specificity and reduced sensitivity. Both scores performed well regardless of age, sex, or metabolic syndrome status.

CONCLUSIONS: The MAF-5 score allows effective stratification of LRE risk. The aMAF-5 score further improves risk stratification. These scores identify individuals at risk of LREs who may benefit from enhanced surveillance.

PMID:42325012 | DOI:10.5009/gnl250626

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Nevin Manimala Statistics

Implementing a Neonatal and Paediatric Flexible Endoscopic Evaluation of Swallowing (FEES) Service in a Tertiary Children’s Hospital in the United Kingdom: A Retrospective Clinical Audit

Int J Lang Commun Disord. 2026 Jul-Aug;61(4):e70278. doi: 10.1111/1460-6984.70278.

ABSTRACT

BACKGROUND: Flexible endoscopic evaluation of swallowing (FEES) is internationally recognised as an important instrumental assessment for paediatric dysphagia. Evidence supports its feasibility and safety in infants and children, but UK specific data remain limited. No published UK report describes a jointly delivered speech and language therapist (SLT) and paediatric otolaryngologist (ENT) FEES model applied across both neonatal and paediatric cohorts.

OBJECTIVE: To describe the implementation of a neonatal and paediatric FEES service delivered jointly by SLTs and ENT surgeons, and to evaluate clinical characteristics, FEES findings and subsequent changes to management.

METHODS: A retrospective audit included all children undergoing FEES between January 2024 and January 2025. Extracted data included demographics, comorbidities, referral indications, secretion management, penetration and aspiration events, swallow physiology, procedural tolerance and pre and post FEES feeding plans. Descriptive statistics were used to describe results. Governance approval was obtained through the hospital’s information governance office. (IG 2024-890).

RESULTS: Thirty-three children aged 4 days to 8 years underwent FEES. Comorbidities associated with dysphagia were present in 31/33 participants. Penetration or aspiration occurred in 21/33 participants, and secretion management difficulties occurred in 14/33 participants. Following FEES, 30/33 participants had a change to their feeding management plan compared with the plan developed based on a clinical feeding evaluation. No major adverse events occurred. One brief episode of mild epistaxis resolved spontaneously. The joint SLT and ENT model supported efficient scope passage and likely contributed to high procedural tolerance.

CONCLUSION: A neonatal and paediatric FEES service can be safely implemented in a UK tertiary hospital using a joint SLT and ENT model. Simultaneous upper airway examination alongside FEES provided clinically meaningful information that frequently changed management. Findings support further multicentre work to establish national paediatric FEES pathways.

WHAT THIS PAPER ADDS: What is already known on this subject FEES is a well-established instrumental assessment for paediatric dysphagia, providing objective insights into swallow function and airway protection. While widely used in countries like the U.S., Australia, and Canada, there is limited research describing paediatric or neonatal FEES in the United Kingdom or broader European context. Existing literature focuses primarily on feasibility and diagnostic accuracy, but does not address its implementation in UK public health systems or its integration with ENT services. What this study adds to the existing knowledge This is the first known study to describe the implementation of a joint ENT-SLT led paediatric FEES service within an NHS hospital. It identifies a high incidence of laryngomalacia during FEES, suggesting a potential association with oropharyngeal dysphagia even in the absence of classic airway symptoms. The study also demonstrates substantial variation in oral feeding plans post-FEES compared to bedside assessment, raising concerns about the standalone reliability of non-instrumental evaluations in neonates and infants. What are the potential or actual clinical implications of this work? The study supports routine inclusion of ENT in paediatric FEES, particularly for neonates, due to the frequency of structural airway anomalies such as mild laryngomalacia. It highlights critical limitations of bedside swallow evaluations as sole diagnostic tools and underscores the need for expanded access to FEES within the NHS. These findings reinforce the urgency for standardized UK-specific protocols and training pathways for neonatal and paediatric FEES to ensure accurate diagnosis and safe feeding management.

PMID:42324950 | DOI:10.1111/1460-6984.70278

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Nevin Manimala Statistics

Beyond Heuristics: A Model-Agnostic Framework for Uncertainty Quantification in QSAR via Adaptive Conformal Prediction

Chem Res Toxicol. 2026 Jun 22. doi: 10.1021/acs.chemrestox.6c00065. Online ahead of print.

ABSTRACT

Reliable quantification of uncertainty is critical for the interpretation and regulatory use of the QSAR models. Applicability domain (AD) assessment was introduced precisely for this purpose─the original OECD guidance defines AD in terms of prediction reliability─yet in practice AD metrics output heuristic similarity scores without statistically guaranteed confidence estimates. We present conformal prediction as a calibration layer that retrofits any QSAR models into a confidence predictor, producing prediction intervals for regression and prediction sets for classification at a user-specified nominal confidence level (e.g., 90%), with statistically guaranteed coverage, without retraining, using only model predictions and a calibration set. The guarantee holds under the exchangeability assumption─that calibration and test compounds are drawn from the same input space─and follows as a mathematical consequence of the rank-based calibration procedure. When the assumption is violated, coverage may fall below the nominal level─signaled by widening intervals and shrinking singleton rates. The framework uses auxiliary models trained on molecular fingerprints as nonconformity scores, a role that most existing AD indices can equally fulfill; a novel ordinal distance strategy extends the approach to hard-label classifiers by generating pseudoproabilities compatible with standard conformal methods. Applied to over 100 VEGA QSAR models spanning physicochemical properties, toxicity, and environmental endpoints (https://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/technical-overview-ecological-risk-assessment-risk), the framework consistently achieves nominal coverage across all models and endpoint types. Conformal efficiency metrics─prediction interval width for regression and singleton rate for classification─correlate strongly with AD indices, demonstrating that CP formalizes and quantifies what AD heuristics approximate: the relationship between structural novelty and prediction reliability, successfully transforming heuristic chemical similarity into statistically valid prediction intervals or label sets. Large-scale application to the EPA CompTox chemical inventory demonstrates practical deployment at a regulatory scale. An open-source pipeline facilitates application to any QSAR/QSPR platform, enabling an improved transparency and reliability assessment.

PMID:42324899 | DOI:10.1021/acs.chemrestox.6c00065

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Nevin Manimala Statistics

Mismatch Between Vaccine Targets and Endemic HPV Genotypes in Sarawak, East Malaysia: Implications for Cervical Cancer Prevention

J Med Virol. 2026 Jun;98(6):e71010. doi: 10.1002/jmv.71010.

ABSTRACT

Cervical cancer remains a major public health concern in Sarawak, East Malaysia, which reports the highest incidence in the country. Prophylactic human papillomavirus (HPV) vaccination programme currently uses bivalent (2 v) and quadrivalent (4 v) vaccines targeting HPV16 and 18 (and additional low-risk HPV6 and 11 for 4 v). However, the alignment of these vaccines with locally circulating high-risk HPV (hrHPV) genotypes is poorly understood. We conducted a serial cross-sectional study involving 1,108 women in Sarawak, Malaysia from 2018 to 2024. Self-collected high vaginal swabs were analyzed using the Anyplex™ II HPV HR Detection Kit for 14 hrHPV genotypes. Demographic data and vaccination status were collected. Descriptive statistics and Chi-square tests were used to evaluate associations between hrHPV positivity and demographic variables. The overall hrHPV prevalence was 10.2% (95% CI: 8.6-12.1%). Among positive cases, 87.6% had single, 10.6% dual, and 1.8% triple genotype infections. The most frequent genotypes were HPV18 (19.2%), HPV52 (16.9%), HPV39 (14.6%), and HPV51 (10.0%). Genotypes covered by the 2 v/4 v vaccines (HPV16/18) accounted for 25.4% of infections, and those included in the nonavalent (9 v) vaccine extended coverage to 56.2%. Notably, 43.8% of infections were due to non-2v/4 v/9 v vaccine genotypes. No significant associations were found between HPV positivity and age group, ethnicity, geographic division, or vaccination status. Our findings indicate a mismatch between current HPV vaccines and the prevalent hrHPV genotypes in Sarawak. While the 9 v vaccine offers improved coverage, a substantial proportion of infections are due to non-vaccine types. Strengthening molecular surveillance, improving access to screening, and addressing vaccine-derived complacency are critical to achieving cervical cancer elimination in this region.

PMID:42324898 | DOI:10.1002/jmv.71010

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Nevin Manimala Statistics

Understanding food insecurity and its relationship with health, psychosocial, and behavioral variables among the Latine population in the North Carolina High Country

Ethn Health. 2026 Jun 21:1-20. doi: 10.1080/13557858.2026.2688761. Online ahead of print.

ABSTRACT

BACKGROUND: The Latine population is at least two times more likely to be food insecure compared to the non-Hispanic white population. Challenges in accessing sufficient, culturally preferred, and healthy foods, particularly for those in rural areas, include limited financial resources and transportation difficulties. Additionally, this population commonly has low enrollment in food assistance programs, an effective method in reducing food insecurity (FI). Obesity, diabetes, cardiovascular diseases (CVD), and depression are frequently associated with FI; the Latine population carries a disproportionately high burden or risk of these diseases.

OBJECTIVES: We aimed to understand the prevalence of FI, FI as a predictor and outcome variable, and health conditions associated with FI among the Latine population in rural, western North Carolina.

METHODS: We conducted a cross-sectional survey in community settings using purposive sampling. Data were analyzed using descriptive statistics, bivariate analysis, and multivariable binary logistic regressions.

RESULTS: Among 193 participants, 47% reported FI. Those identifying as food insecure were more likely to report a household income under $35,000 (OR 5.49, 95% CI: 1.37, 22.06), low educational attainment (OR 3.85, 95% CI: 1.23, 12.04), and being unmarried (OR 3.53, 95% CI: 1.01, 12.20). When modeled as a predictor, FI was associated with higher odds of reporting symptoms of CVD (OR 3.95, 95% CI: 1.43, 12.14) and depression (OR 5.01, 95% CI: 1.45, 21.52).

CONCLUSION: Our study demonstrates a high prevalence of FI and significant relationships between FI and a myriad of variables in a region of rural, western NC and contributes to a dearth of literature about the experience of FI among the Latine population. Understanding the predictors of FI in this context can better support efforts to increase food security among this population.

PMID:42324865 | DOI:10.1080/13557858.2026.2688761

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Nevin Manimala Statistics

ReinVar: A model-free paradigm-based reinforcement learning approach to detect copy number variation

J Bioinform Comput Biol. 2026 Jun;24(3):2650006. doi: 10.1142/S021972002650006X. Epub 2026 Jun 11.

ABSTRACT

Copy number variation (CNV) is one of the most imperative forms of structural variations that can span over the coding and non-coding regulatory regions of an individual’s genome. Copy number variations (CNV) can significantly impact the genotype and phenotype traits by altering the gene dosage, consequently affecting the gene expression landscape concerning various cellular functions and are the cause behind complex diseases in an individual. Exceptionally fast advancement in Next Generation Sequencing (NGS) technology has led to massive growth of DNA-seq data, which contains both Whole Genome Sequence (WGS) and targeted Exome Sequence data of various species including H.sapiens, and precise detection of the DNA region affected by CNV enables the copy number profiling of a genome, thereby understanding our genome. This work has proposed a methodology named ReinVar, which can accurately determine and analyze the underlying copy number profile of the whole genome by adopting a model-free reinforcement learning paradigm. The methodology involves a novel approach to model the problem of identifying CNV as a Markov decision process (MDP), followed by determination of CNV under Reinforcement Learning framework. ReinVar also adopted a Map-Reduce programming paradigm to provide a big data solution to address the issue of exponential growth of NGS read sequence data. ReinVar has shown strong performance in detecting CNV gains and losses across diverse ethnic groups, with a high number of shared variant calls. ReinVar’s ability to accurately identify both CNV gains and losses, coupled with consistent detection across ethnic groups and strong ROC characteristics, underscores ReinVar’s effectiveness as a robust and sensitive CNV detection method.

PMID:42324820 | DOI:10.1142/S021972002650006X

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Nevin Manimala Statistics

When pipelines run but coordinates fail: A simple spatial specificity check for false locality in post-GWAS analysis

J Bioinform Comput Biol. 2026 Jun;24(3):2671003. doi: 10.1142/S0219720026710034. Epub 2026 Jun 12.

ABSTRACT

Some post-GWAS analysis software can run to completion without reporting an error while producing results that are not biologically valid. We call this failure false locality: a result appears to be local to a gene or protein because it was produced from a regional window, but the window or its metadata points to the wrong genomic address. We identify three mechanisms. First, a genome-build address mismatch occurs when GRCh38 protein-QTL coordinates are used with GRCh37 outcome files; in our 91-sentinel audit, 66 coordinates moved by more than 100[Formula: see text]kb and 54 moved by more than 200[Formula: see text]kb after remapping. Second, non-specific regional noise occurs when significant P values persist after the analysis window is deliberately moved to a zero-overlap variant set. Third, location-label blindness occurs when software returns the same output after the declared coordinate label is changed while the SNP table is unchanged; in an official SMR/HEIDI CXCL10 test, the top SNP, SMR P value, and HEIDI P value remained identical across correct, wrong, and shifted labels. We propose a simple Change Test: a result should not be treated as local evidence unless the numerical output changes, weakens, or disappears when the analysis window or coordinate label is intentionally moved to a biologically wrong location. This standard turns software execution from a passive success signal into an explicit spatial-specificity check.

PMID:42324819 | DOI:10.1142/S0219720026710034

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Nevin Manimala Statistics

Determinants of adult height and BMI in a sample of Polish physical education students: parental stature, birth size, and family socioeconomic environment

Anthropol Anz. 2026 Jun 19. doi: 10.1127/anthranz/2006. Online ahead of print.

ABSTRACT

Adult height and body mass index (BMI) are among the fundamental somatic characteristics of humans and are shaped by the interplay of biological, familial, and environmental factors. An increasing body of research indicates the long-term importance of early-life conditions for traits observed in adulthood. This study aimed to assess the contribution of selected biological and family-related environmental determinants to variation in adult height and BMI among physical education students. An additional exploratory aim was to analyse potential correlates of age at menarche in women. The study included 267 physical education students (180 men and 87 women). Body height and body mass were measured, and data on birth parameters and family characteristics were collected, with the data obtained at the beginning of the 2025/2026 academic year. Statistical analyses were performed using descriptive statistics and multiple linear regression models. Adult height was significantly associated with the stature of both parents as well as with birth length and birth weight, with the high proportion of explained variance being partly attributable to the inclusion of sex in the models. BMI was associated with sex, birth weight, and maternal educational level, with a moderate degree of explained variance. No significant associations were found between age at menarche and the predictors included in the analysis. The findings highlight the importance of familial and early-life determinants for adult height in young adults, as well as the limited role of socioeconomic environmental factors in the population studied. Interpretation of the results for BMI requires consideration of the specific characteristics of a physically active population.

PMID:42324814 | DOI:10.1127/anthranz/2006

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Nevin Manimala Statistics

Estimating the Joint Probability Density for Index Construction: Some Simplifications Using the TWEAK as Example

Int J Methods Psychiatr Res. 2026 Jun;35(2):e70081. doi: 10.1002/mpr.70081.

ABSTRACT

BACKGROUND: Index construction using the joint probability density (JPD) method is extremely robust and, unlike confirmatory factor analysis (CFA) or item response theory (IRT), puts few restrictions on underlying data. When input variables’ numbers are large, however, JPD estimation can be difficult.

OBJECTIVE: To assess two simplifications of JPD estimation using the TWEAK, a well validated screener for problematic drinking, and to compare these against the fully estimated JPD, the conventionally scored TWEAK, and TWEAK scores estimated through CFA and IRT.

METHODS: Mailed survey of a nationally representative panel of 410 gender-stratified, post-9/11 Veterans with pending disability claims for posttraumatic stress disorder.

RESULTS: Summary statistics for the TWEAK’s fully estimated JPD and the two simplifications were very similar, and Spearman’s correlations were 0.97-1.00 (ps < 0.001). Spearman’s correlations across the remaining scoring approaches were -0.84 to -0.90 (ps < 0.001). All 6 scoring approaches identified differences in men’s TWEAK scores by alcohol use diagnosis (ps ≤ 0.02); the 3 JPD approaches did not reach statistical significance in the women. IRT analysis identified local dependence issues.

CONCLUSIONS: Our simplified estimations of JPD score were very similar to the fully estimated JPD and much easier to calculate. All 3 JPD estimations were highly concordant with more traditional scoring approaches.

PMID:42324792 | DOI:10.1002/mpr.70081

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Nevin Manimala Statistics

Paired serological testing of rubella IgG: monitoring antibody stability over time

Infect Dis (Lond). 2026 Jun 21:1-9. doi: 10.1080/23744235.2026.2689018. Online ahead of print.

ABSTRACT

BACKGROUND: Rubella immunity plays a key role in preventing congenital rubella syndrome, but longitudinal data on antibody stability remain limited.

OBJECTIVE: To evaluate rubella IgG seroprevalence, seroconversion, and changes in rubella IgG concentrations over time.

METHODS: We conducted a retrospective cohort study of 2,022 consecutive individuals from Region Zealand, Denmark, each with at least two serum samples submitted for routine rubella IgG testing between 11 September 2018 and 30 May 2025. Pairedsamples from each individual were analysed.

RESULTS: At baseline, 88.6% of participants were seropositive, increasing to 90.6% at follow-up. The cohort was predominantly female (99.4%) and mean age at first sample was 29.8 years. Among initially seronegative individuals, 75 seroconverted, while 34 individuals initially seropositive seroreverted. Median IgG levels among seroconverts were 23.5 IU/mL (range 10-350 IU/mL). Individuals who remained seropositive showed a modest yet statistically significant median decrease of 8.4% between the first and second samples (Hodges-Lehmann ratio = 0.92, 95% CI: 0.91-0.93, p < 0.0001), with minimal association between antibody change and time interval (Spearman’s ρ = -0.058, p = 0.015).

CONCLUSIONS: In this cohort of routinely tested individuals, rubella IgG levels remained broadly stable, indicating sustained rubella seropositivity over time. Seroconversion and seroreversion occurred in a small subset of individuals, supporting the continued monitoring of rubella immunity, particularly among women of reproductive age. Maintaining high vaccination coverage remains important to sustain rubella elimination and prevent congenital rubella syndrome.

PMID:42324788 | DOI:10.1080/23744235.2026.2689018