Categories
Nevin Manimala Statistics

Predicting and classifying type 2 diabetes using a transparent ensemble model combining random forest, k-nearest neighbor, and neural networks

Sci Rep. 2025 Dec 19. doi: 10.1038/s41598-025-31562-5. Online ahead of print.

ABSTRACT

Diabetes is one of the major health challenges in today’s world, since chronic elevation of blood sugar can cause serious and sometimes irreparable damage to organs such as the heart, kidneys, and nervous system. Early detection of this disease plays a vital role in reducing its complications. However, machine learning and deep learning models often face distrust in medical settings due to their opaque, “black-box” nature. The aim of this study was to combine three machine learning algorithms using stacking and voting methods to propose a model for type 2 diabetes detection, and to increase transparency by using the explainability techniques LIME and SHAP to identify important features. This study used medical data from 768 Pima Indians Diabetes samples, including 8 features such as age, BMI, glucose, insulin, blood pressure, skin thickness, pregnancies, and family history. Data preprocessing included mean imputation for missing or zero values, Min-Max normalization, and classification into “Normal”, “Prediabetes”, and “Diabetes” based on fasting glucose thresholds. Feature selection was performed using Spearman correlation to retain the most relevant variables. A hybrid machine learning model was developed using three base models Neural Network (NN), k-Nearest Neighbors (KNN), and Random Forest (RF) with automated hyperparameter tuning. The outputs of these models were combined via stacking using a logistic regression (LR) meta-model and in parallel using a soft voting method. Nested cross-validation (5 outer and 5 inner folds) was applied to prevent data leakage and ensure robust evaluation. Model interpretability was assessed using LIME for local explanations and SHAP for global feature importance. Decision thresholds and influential feature regions were identified, and model calibration and decision curves evaluated clinical reliability. Models performance was evaluated using accuracy, precision, recall, specificity, F1-score, AUROC, Brier Score (1-B), and Expected Calibration Error (1-E). Statistical reliability was assessed using bootstrap resampling to compute 95% confidence intervals, as well as paired tests to compare the hybrid model with the base models and voting ensemble. Based on the evaluation metrics, the stacking ensemble achieved perfect performance for Class 0, with 100% accuracy, precision, recall, specificity, F1 score, and AUROC, alongside the highest calibration metrics (Brier Score: 99.9, ECE: 98.7). The Random Forest model also excelled, achieving 100% accuracy, precision, recall, specificity, and F1 score for Class 0 and Class 2. In contrast, the KNN model consistently underperformed, particularly for Class 0 (F1: 83.3, Precision: 83.3, Recall: 83.3). The Neural Network demonstrated strong recall for Class 0 (100%), while the voting ensemble showed balanced results but was slightly outperformed by the top ensemble methods. Explainable AI analyses using LIME and SHAP revealed that glucose was the most influential predictor for identifying the Pre-diabetes state. Both methods consistently identified a decision band between 0.35 and 0.47 (corresponding to 100-125 mg/dL) as the transition zone between “Normal” and “Prediabetes”, confirming the model’s alignment with WHO/ADA diagnostic criteria. The stacking model achieved perfect performance and superior calibration, outperforming all other models in type 2 diabetes prediction and classification. Explainability techniques (LIME and SHAP) identified glucose level, body mass index, and blood pressure as key predictive factors. This approach provides an accurate and interpretable tool for clinical decision support in healthcare systems.

PMID:41419964 | DOI:10.1038/s41598-025-31562-5

Categories
Nevin Manimala Statistics

Enhanced prediction of cholecystectomy using obesity-modified TyG indices: a machine learning and SHAP-based study

Eur J Med Res. 2025 Dec 19. doi: 10.1186/s40001-025-03680-3. Online ahead of print.

ABSTRACT

BACKGROUND: This study investigates the association between TyG-related composite indices and the risk of gallstones and the history of cholecystectomy, using logistic regression and machine learning models to evaluate predictive performance and clinical utility. Additionally, the study explores the relationship between TyG-derived obesity indices and the age at the history of cholecystectomy.

METHODS: A total of 3737 participants were analyzed. Logistic regression models were used to assess the relationship between TyG, TyG.BMI, TyG.WC, and TyG.WHtR with gallstone prevalence and the history of cholecystectomy. Performance metrics for 11 machine learning models, including XGB, logistic regression (LR), and gradient boosting machine (GBM), were evaluated using AUC-ROC, accuracy, sensitivity, and specificity. Decision curve analysis (DCA), calibration plots, and SHAP (Shapley additive explanations) analysis were used to assess clinical utility and interpretability. Additionally, De Long test was applied to compare the AUC-ROC values of the machine learning models to identify statistically significant differences.

RESULTS: Among 3737 participants, 395 (10.6%) had gallstones. Individuals with gallstones were older (median 59 vs. 51 years, P < 0.01), predominantly female, and had higher levels of TyG and TyG-related indices (all P < 0.01). Logistic regression analyses revealed that while TyG was not significantly associated with gallstones after full adjustment, composite indices incorporating obesity measures-TyG.BMI, TyG.WC, and TyG.WHtR-remained robustly associated with gallstone risk in the fully adjusted model. Participants in the highest quartile (Q4) of these indices had higher odds of gallstones compared to those in the lowest quartile (Q1). Further analysis revealed that TyG.BMI, TyG.WC, and TyG.WHtR were associated with younger age at the history of cholecystectomy, with threshold effects identified at TyG-BMI = 184.35 and TyG-WC = 776.69, above which the association with younger cholecystectomy age became significant. In predicting the history of cholecystectomy, XGB outperformed other models with an AUC-ROC of 0.83, accuracy of 0.89, and F1-score of 0.73, showing balanced sensitivity (0.72) and specificity (0.82). The De Long test indicated that XGB demonstrated statistically significant superior performance compared to all other models (P < 0.01 for pairwise comparisons), reaffirming its high predictive capability. Supplementary Fig. 2 presents ROC curves for all models, where XGB achieved the highest AUC-ROC (0.827), outperforming other models such as LR (AUC-ROC = 0.746) and GBM (AUC-ROC = 0.742).

CONCLUSIONS: TyG-derived composite indices, particularly TyG.WHtR, are strong predictors of both gallstone prevalence and the history of cholecystectomy. The XGB model demonstrated the best performance in predicting cholecystectomy risk, with the De Long test confirming its superior AUC-ROC compared to other models. The combination of strong predictive performance, good calibration, and high interpretability makes XGB a valuable tool for clinical decision-making in managing gallbladder disease risk.

PMID:41419963 | DOI:10.1186/s40001-025-03680-3

Categories
Nevin Manimala Statistics

Multi-omics study of molecular and genetic bases of orthostatic hypotension

Clin Epigenetics. 2025 Dec 19;17(1):202. doi: 10.1186/s13148-025-02019-3.

ABSTRACT

Orthostatic hypotension is a sharp decrease in blood pressure when an individual transitions from a supine to an upright position. OH affects at least 30% of older adults. It is attributed to the dysfunction of the autonomic innervation and decreased vascular bed capacity. Genomic (n = 2526), methylomic (n = 910), and transcriptomic (n = 391) data from centenarians aged 90 years and older were used to examine molecular and genetic factors for OH. No statistically significant genetic predictors of OH were identified. However, the study revealed numerous epigenetic markers of OH indicative of general aging, such as DNA hypomethylation. The predictive DNA methylation-based model for orthostatic hypotension demonstrated an average accuracy of 79%. The transcriptome analyses highlighted associations between OH and inflammation pathways, as well as other age-related biological processes. Integrated omics and clinical data have identified six key mechanisms associated with orthostatic hypotension: metabolic dysregulation, impaired muscle tone, altered cell proliferation, inflammation, humoral regulation, and neural regulation.

PMID:41419941 | DOI:10.1186/s13148-025-02019-3

Categories
Nevin Manimala Statistics

Genetic pleiotropy underlying obesity and autoimmune disorders: a large-scale cross-trait gwas analysis in European ancestry populations

J Transl Med. 2025 Dec 19. doi: 10.1186/s12967-025-07422-1. Online ahead of print.

NO ABSTRACT

PMID:41419940 | DOI:10.1186/s12967-025-07422-1

Categories
Nevin Manimala Statistics

Host PI3K inhibition via anti-cancer drug alpelisib influences Influenza A non-infectious particles and deletion-containing viral genomes

Cell Commun Signal. 2025 Dec 19. doi: 10.1186/s12964-025-02598-x. Online ahead of print.

ABSTRACT

RNA viruses can generate “defective” viral genomes during replication, which can interact with standard viral genomes affecting the course of infections. These non-standard viral genomes are related to milder clinical outcomes and are currently being tested as antivirals. Decades of research in influenza have focused on viral mechanisms affecting the production of deletion-containing viral genomes (DelVGs). Based on adaptations of influenza NS1 protein to manipulate host cell metabolism, we hypothesized host metabolic state could also alter the quantity and pattern of deletion-containing viral genomes and the particles that house them. To test this hypothesis, we manipulated host cell anabolic signaling activity and monitored the production of DelVGs and non-infectious particles by two influenza strains, using single-cell immunofluorescence and third-generation sequencing. We show that: 1) influenza infection activates PI3K signaling, with the A/H1N1 strain having roughly double the pAKT levels in single cells as the A/H3N2; 2) alpelisib, a PI3K receptor inhibitor, subverted the ability of both influenza strains to activate PI3K in a dose dependent manner; 3) DelVGs were increased roughly tenfold in polymerase complex segments and ~ 60% in the hemagglutinin segment of A/H1N1 at 20uM of alpelisib; and 4) the A/H3N2 strain did not show changes in DelVG production, but had a modest, statistically significant maximum increase of 11% in non-infectious particles. We find that host cell metabolism can increase the production of non-infectious particles and DelVGs during single rounds of infection, shifting potential interactions among virions. The differential results according to strain and alpelisib concentration suggest future directions examining strain differences in the NS1::p85β virus-host interaction and the specific metabolic state of the cell. Our study presents a new line of investigation into metabolic states associated with less severe flu infection and opens the possibility for potential induction of these states with metabolic drugs.

PMID:41419939 | DOI:10.1186/s12964-025-02598-x

Categories
Nevin Manimala Statistics

Electrophysiological evaluation of the auditory pathway in newborns and infants with peri-intraventricular hemorrhage and/or periventricular leukomalacia

Clinics (Sao Paulo). 2025 Dec 18;81:100853. doi: 10.1016/j.clinsp.2025.100853. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate and monitor, through electrophysiological assessment of hearing, the integrity of the peripheral and central auditory pathways in infants with Peri-intraventricular hemorrhage and/or Periventricular Leukomalacia (PIVH/PVL) who stayed in a Neonatal Intensive Care Unit (NICU), aiming to verify the occurrence of possible neural dysfunctions in this system.

MATERIAL AND METHODS: This prospective longitudinal study evaluated preterm Newborns (NBs) and infants at the time of hospital discharge and after 3- and 6-months. The Study Group (SG) had 12 females and 11 males, with gestational age between 25- and 33-weeks, and a mean gestational age of 29.82-weeks at birth. The Control Group (CG) had 26 healthy NBs, distributed in 13 females and 13 males, with gestational age between 27- and 33-weeks and a mean of 30.67-weeks of gestational age at birth. All participants underwent Auditory Brainstem Response (ABR) and Cortical Auditory Evoked Potentials (CAEP) P1, N1, P2, at the time of hospital discharge, and 3- and 6-months after discharge. Each group’s results were compared using statistical tests.

RESULTS: Evolutionary study of mean ABR and CAEP latencies in infants in the study and control group showed a similar pattern over the six months after hospital discharge.

CONCLUSION: The comparison of brainstem and cortical potentials showed that auditory function is symmetrical in the peripheral and central portions of the auditory pathway in both groups. The maturation of the ABR and CAEP waves in both groups developed in a very similar way over the six months after hospital discharge.

PMID:41418391 | DOI:10.1016/j.clinsp.2025.100853

Categories
Nevin Manimala Statistics

Different patterns of association between maternal mental health and infant negative affect subdomains: Findings from the Germina cohort

Infant Behav Dev. 2025 Dec 18;82:102174. doi: 10.1016/j.infbeh.2025.102174. Online ahead of print.

ABSTRACT

Negative affect (NA) is a central dimension of infant temperament and an early marker of risk for later psychopathology. While maternal mental health has been associated with increased infant NA, few studies have explored how maternal mental health symptoms relate to the specific subdomains of NA throughout infancy. This study examined longitudinal associations between maternal mental health and infant NA, comparing the general domain with its specific subdomains. We analyzed data from 557 mother-infant dyads enrolled in the Germina cohort in São Paulo, Brazil. Maternal symptoms of depression, anxiety, and stress, along with infant NA and its subdomains-sadness, fear, distress to limitations, and falling reactivity-were assessed at 3, 5-9, and 10-16 months postpartum. Longitudinal associations were examined using linear mixed-effects models with successive-differences contrasts, adjusting for sociodemographic covariates. Maternal stress consistently predicted higher NA and its subdomains-sadness, fear, and distress-across infancy, and was linked to reduced falling reactivity. Depression was associated with increased NA, distress, and decreased reactivity throughout infancy. Anxiety exhibited a time-varying association with distress, increasing from 3 to 9 months before declining, but showed no link with overall NA. Subdomain-specific analyses uncovered maternal mental health associations not evident in general NA models. Examining NA subdomains provides a more detailed understanding of their evolving, dynamic relationships with maternal mental health across infancy. These insights highlight the importance of integrating NA subdomains into screening and intervention strategies to more effectively support at-risk children.

PMID:41418383 | DOI:10.1016/j.infbeh.2025.102174

Categories
Nevin Manimala Statistics

Emotional freedom techniques-based counseling with breathing exercises in in vitro fertilization: effects on psychological distress and well-being

Eur J Obstet Gynecol Reprod Biol. 2025 Dec 13;318:114891. doi: 10.1016/j.ejogrb.2025.114891. Online ahead of print.

ABSTRACT

PURPOSE: To investigate whether psychosocial care during in vitro fertilization (IVF) treatment affects the emotional capacity and well-being of women undergoing fertility treatment.

METHODS: This randomized controlled, single-blind study was conducted between February 2020 and March 2021. A total of 112 women undergoing IVF were recruited based on predefined inclusion and exclusion criteria. After a 24.1 % loss to follow-up (n = 27), data from 85 participants (42 in the experimental group, 43 in the control group) were analyzed. The control group received routine care, while the intervention group attended a structured seven-session counseling program that included coping strategies such as Emotional Freedom Technique (EFT) and breathing exercises. Psychological outcomes were measured at three time points using Screening Tool on Distress in Fertility Treatment (SCREENIVF), Fertility Quality of Life Tool (FertiQol), COMPI Fertility Problem Stress Scales (COMPI-FPSS), and Subjective Units of Distress (SUD) scale. Group comparisons were analyzed with appropriate statistical methods.

RESULTS: Baseline characteristics did not differ between groups (p > 0.05). The experimental group had a higher positive hCG rate on day + 13 of IVF (42.9 % vs. 18.6 %, p = 0.015). Post-intervention, they showed greater reductions in anxiety (Cohen’s d = -0.72, 95 % CI [-1.15 to -0.28], p = 0.001) and helplessness (Cohen’s d = 1.26, 95 % CI [0.79-1.72], p < 0.001), and increased acceptance (p < 0.001), while depression decreased non-significantly (p = 0.167). Personal and social stress decreased (Cohen’s d = -0.99, 95 % CI [-1.43 to -0.54], p < 0.001; social domain p = 0.003), but marital stress did not (p = 0.619). FertiQOL total and Treatment Environment scores improved (Cohen’s d = -1.89, 95 % CI [-2.39 to -1.39], p < 0.001; Cohen’s d = -1.71, 95 % CI [-2.20 to -1.22], p < 0.001), whereas Treatment Tolerance did not differ (p = 0.001). SUD scores decreased after sessions 2, 4, and 5 (r = -0.62 to -0.63, 95 % CI [-0.77 to -0.46], p < 0.001). Effect sizes indicate medium to large clinical relevance. Participants at risk per SCREENIVF showed marked stress reduction and improved quality of life, with referrals to mental health services as needed.

CONCLUSION: Psychosocial care during IVF treatment appears to reduces psychological distress and enhances treatment-related well-being in women undergoing fertility procedures. These findings support the incorporation of psychosocial interventions into standard fertility care.

PMID:41418369 | DOI:10.1016/j.ejogrb.2025.114891

Categories
Nevin Manimala Statistics

Ecosystem response to mercury mitigation and forbidden fishing: A 20-year chronosequence of fish contamination in Baihua Reservoir

Ecotoxicol Environ Saf. 2025 Dec 18;309:119587. doi: 10.1016/j.ecoenv.2025.119587. Online ahead of print.

ABSTRACT

Environmental remediation including mercury (Hg) source closure, cage-farming prohibition, and sediment capping has been implemented at Baihua Reservoir (BHR) since 2007, which strongly influences Hg bioaccumulation in fish. In this study, total Hg (THg) and methylmercury (MeHg) concentrations were determined in abiotic matrices and fish in 2015-2016 and 2018-2019 and compared with data extracted from previous studies referring to 2002-2006 and 2008-2009. Following these remediation measures, the water quality improved, eutrophication declined, and environmental Hg levels dropped dramatically. By 2018-2019, the aqueous THg and MeHg decreased by 82 % and 89 %, and sediment THg and MeHg decreased by 99 % and 86 %, respectively, compared to 2002-2006 levels. However, prohibition of cage fish farming in BHR shifted fish diets toward plankton, slowing their growth rate and lengthening the food chain by one level. Paradoxically, average fish THg during 2008-2019 increased significantly by 73-168 %, whereas the increase in MeHg (33-137 %) was not statistically significant. The relative proportion of MeHg to THg (%MeHg) in fish transiently peaked at 56 ± 23 % in 2015-2016. The bioaccumulation factor for fish Hg was high, while the trophic magnification rates of Hg were lower and remained low compared to global averages, reflecting efficient initial uptake into the food web but constrained transfer efficiency. This unexpected rise in fish Hg is likely due to the dietary shift to Hg-rich plankton, reduced somatic growth dilution in wild fish, and enhanced Hg trophic transfer. Therefore, ongoing monitoring and updated fish consumption advisories are recommended to mitigate potential health risks.

PMID:41418362 | DOI:10.1016/j.ecoenv.2025.119587

Categories
Nevin Manimala Statistics

Morphological and textural descriptors analysis of digital mammograms with radiological findings to support breast cancer detection using artificial neural networks

Biomed Phys Eng Express. 2025 Dec 19. doi: 10.1088/2057-1976/ae2f65. Online ahead of print.

ABSTRACT

OBJECTIVE: To classify digital mammograms based on radiological findings using morphology and texture descriptors with artificial neural networks (ANN) for breast cancer detection.

APPROACH: The mammography dataset from High Specialty Regional Hospital of Oaxaca (HRAEO) (median patient age (mpa), 48 years [interquartile range (IQR), 41-54 years]) with radiological findings was retrospectively analyzed. All patients underwent breast biopsy and were not previously treated. External testing was performed using mammograms from the National Cancer Institute (INCAN) (mpa: 47 years [IQR, 37-62 years]). The morphology was analyzed using a circularity descriptor (), and the texture was analyzed using the mean height/width ratio of the extrema descriptor (). These results were compared with cancer/benign histopathology, which was binarily classified using ANNs. The F1-score, Cohen’s kappa (K), and area under the ROC curve (AUC) were employed as evaluation metrics, and the Wilcoxon rank-sum test was used for statistical analysis (h = 0, with p > 0.05, was considered as not statistically significant).

MAIN RESULTS: 216 raw mammograms from HRAEO and 33 mammograms from INCAN (95+16 breast cancer and 121+17 benign findings) were included. The best internal testing results were obtained with a one-hidden-layer ANN with 100 neurons, achieving a F1-score of 0.95, K of 0.91, and an AUC of 0.953 (95% confidence interval [CI]: 0.917, 0.977) (h=0, p>0.99). However, the external testing results were significantly lower: 0.38 F1-score, 0.02 K, and 0.509 AUC (95% CI: 0.344, 0.664) (h=0, p=0.14) due to not exactly meeting the inclusion criteria and possible demographic and spectrum bias, or domain-adaptation issues.

SIGNIFICANCE: The proposed morphology () and texture () descriptors show promise for detecting breast cancer in raw mammograms, with radiological findings, in a local context. However, their poor external performance highlights the need for substantial further work before this approach can be deemed suitable for broader diagnostic applications.

PMID:41418324 | DOI:10.1088/2057-1976/ae2f65