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Nevin Manimala Statistics

The relationship between uterine and fibroid volume with urinary symptoms as reported in the King’s Health Questionnaire

Eur J Obstet Gynecol Reprod Biol. 2026 Mar 2;321:115050. doi: 10.1016/j.ejogrb.2026.115050. Online ahead of print.

ABSTRACT

INTRO: Uterine fibroids are the most common benign genital tract tumours in women, causing a variety of symptoms including lower urinary tract symptoms (LUTS). The relationship between fibroid size and location, and LUTs is not well established. In this study we aim to understand the relationship between uterine volume and fibroid volume and location, with LUTs as self-reported using the King’s Health Questionnaire (KHQ).

MATERIAL AND METHODS: Women recruited to this study underwent Magnetic Resonance Imaging (MRI) performed with T2-weighted tri-planar MR images. The total uterine volume (TUV) and volume of the largest fibroid (VolFib) were calculated by Reportcard© software. Participants completed the KHQ, a validated questionnaire for LUTs and quality of life.

RESULTS: Linear regression analysis and ANOVA demonstrated that both TUV and VolFib have statistically significant relationships with multiple score domains of the KHQ. Mann Whitney U test showed that an anterior location of VolFib only had a statistically significant relationship with domain 8- sleep/energy score. However anterior fibroids > 500 cm3 showed a statistically significant relationship to the symptom severity score (p = 0.014).

CONCLUSIONS: Increasing uterine volume and fibroid volume was associated with worsening urinary symptom severity and a negative impact on quality of life. Our data demonstrated that the volume of the largest fibroid had the greatest impact on LUTs severity and quality of life. We found that anteriorly located dominant fibroids only had a statistically significant impact on symptom severity if they were > 500 cm3 in volume.

PMID:41795480 | DOI:10.1016/j.ejogrb.2026.115050

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Nevin Manimala Statistics

Statistical learning performance is impacted by a previous learning experience: A predictive eye-movement study

Cognition. 2026 Mar 6;272:106512. doi: 10.1016/j.cognition.2026.106512. Online ahead of print.

ABSTRACT

Statistical learning (SL), the ability to extract recurrent patterns from sensory input, plays an important role in a range of cognitive functions. While much research has studied SL in stable artificial environments, natural inputs are rarely fixed: regularities are often probabilistic and continuously changing. A key question, therefore, is how SL unfolds under such conditions and to what extent it is shaped by learners’ previous experiences. In the present study, we asked how trajectories of predictability ranging from highly structured to noisy sequences impact SL performance, and how learning in such conditions affects subsequent learning. To do so, we created a “Whack-a-Mole” game in which mole locations partially predicted subsequent mole locations, while the extent of predictability differed between blocks. In Experiment 1, predictability of mole locations increased across blocks in the first session and decreased in the second session, or vice versa. In Experiment 2, predictability followed the same trajectory in both sessions (either decreasing or increasing). Learning performance was measured using both reaction times and predictive eye movements toward target locations. Across studies, our findings reveal that learning in the second session was shaped by prior experience in the first session. Starting the second session with high predictability facilitated learning, whereas starting with low predictability hindered it, even when predictability later increased. These results suggest that learners are not passive absorbers of regularities but active information seekers, whose expectations about environmental structure impact learning. We discuss the implications of these findings for theories of SL in dynamic environments.

PMID:41795474 | DOI:10.1016/j.cognition.2026.106512

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Nevin Manimala Statistics

Mind the gap: Characterizing bias due to population mismatch in two-sample Mendelian randomization

Am J Hum Genet. 2026 Mar 5;113(3):483-493. doi: 10.1016/j.ajhg.2026.02.002.

ABSTRACT

Mendelian randomization (MR) is a statistical method for estimating causal effects using genetic variants as instrumental variables. In two-sample MR (2SMR), different study samples are used to estimate genetic associations with the exposure and outcome. For valid inference, these studies must include individuals from the same population. Using studies from different populations may bias the MR estimate due to differences in variant-exposure associations resulting from differences in linkage disequilibrium or genetic effects on the exposure trait. We show that violation of the same-population assumption leads to bias in the causal estimate toward zero on average and does not increase the rate of false positives when using the most common MR study design. We verify this result in a broad survey of MR estimates, comparing estimates made with matching and mismatching populations across 546 trait pairs measured in 2-7 ancestries. We find that most population-mismatched estimates are attenuated toward zero compared to their corresponding population-matched estimates and that increasing genetic distance between study populations is associated with greater shrinkage. We observe bias even when mismatched populations have the same continental ancestry. However, we also find that, in some cases, using a larger exposure study with mismatching ancestry can improve power by dramatically increasing precision. These results show that even intra-continental population mismatch can bias MR estimates but also suggest that there is potential to improve the power of MR in understudied populations by properly leveraging larger, mismatching study populations.

PMID:41795470 | DOI:10.1016/j.ajhg.2026.02.002

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Nevin Manimala Statistics

MetaGLIMPSE: Meta-imputation of low-coverage sequencing data for modern and ancient genomes

Am J Hum Genet. 2026 Mar 5;113(3):472-482. doi: 10.1016/j.ajhg.2026.02.004.

ABSTRACT

The advent of efficient and accurate imputation for low-coverage sequencing offers an unbiased alternative to SNP array imputation, increasing the accuracy of rare variant imputation across all populations. Since imputation accuracy generally increases with larger reference panels and closer ancestry match between target and reference samples, leveraging imputation from multiple reference panels improves imputation accuracy; however, individual reference panel genotypes are often privacy protected. Meta-imputation bypasses individual-level data by combining single-panel imputed genotypes through estimating panel- and marker-specific weights. We present a meta-imputation method, MetaGLIMPSE, that combines estimates from multiple reference panels for low-coverage sequencing imputation. Across all our scenarios, for both modern and ancient DNA samples, MetaGLIMPSE consistently outperforms the best single-panel imputation for coverages of 0.1×-8× and across all minor-allele frequencies, equaling the combined panel imputation for some parameters. Finally, MetaGLIMPSE is computationally efficient, meta-imputing 500 whole genomes in 16% of the time of GLIMPSE2.

PMID:41795469 | DOI:10.1016/j.ajhg.2026.02.004

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Nevin Manimala Statistics

Targeting the liver: Insights from a tertiary center on post-operative hepatic arterial oxaliplatin for metastatic colorectal cancer

Eur J Surg Oncol. 2026 Mar 3;52(4):111511. doi: 10.1016/j.ejso.2026.111511. Online ahead of print.

ABSTRACT

BACKGROUND: As the liver is the most common site of metastasis in colorectal cancer (CRC), and metastatic recurrence frequently occurs after resection of colorectal liver metastases (CRLM), hepatic arterial infusion chemotherapy (HAIC) has emerged as a promising treatment approach. This study investigates the feasibility, safety, and efficacy of postoperative HAIC with oxaliplatin following curative-intent resection of CRLM.

METHODS: A retrospective analysis was conducted on all patients with resected CRLM who received postoperative HAIC with oxaliplatin between 2008 and 2022 at a tertiary cancer center. The primary study endpoint were disease-free-survival (DFS) and overall survival (OS).

RESULTS: Overall, 119 patients (median age, 56 years; synchronous metastatic disease, 82%) received postoperative HAIC with oxaliplatin after complete resection of their CRLM (median number of metastases resected, 7). They received a median number of 6 HAIC cycles (range, 1-12), mostly combined with intravenous chemotherapy with 5-fluorouracil/leucovorin (n = 118, 99%) and irinotecan (n = 41, 34%). The median DFS was 10.2 months (95% CI 9-12.4) and the median intrahepatic DFS was 18.4 months (95% CI 12.4-29.7,12 months DFS rate, 60%). The median OS reached 55.5 months (95% CI, 50.0-86.6; 5-year OS rate, 46%). Grade 3-4 toxicities occurred in 45% of patients (neutropenia, 38%; peripheral neuropathy, 9%); 54% of patients experienced pain (mostly mild to moderate) during oxaliplatin infusion. HAI catheter-related complications included extrahepatic perfusion (30%) and catheter occlusion (11%).

CONCLUSIONS: HAIC with oxaliplatin is an effective, safe and feasible treatment option after resection/ablation of CRLM. These findings support the therapeutic relevance of postoperative HAIC in liver-limited metastatic CRC.

PMID:41795432 | DOI:10.1016/j.ejso.2026.111511

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Nevin Manimala Statistics

Multi-omic and immune landscapes of HPV-negative versus HPV-positive cervical cancer reveal implications for immunotherapy

Eur J Surg Oncol. 2026 Feb 4;52(4):111425. doi: 10.1016/j.ejso.2026.111425. Online ahead of print.

ABSTRACT

BACKGROUND: HPV-negative cervical cancer (3-8% of cases) presents distinct clinical challenges and poorer prognosis compared to HPV-positive disease. We aimed to conduct an exploratory study to characterize its unique tumor immune microenvironment (TIME) and molecular drivers to inform immunotherapy development.

METHODS: We analyzed 70 cervical cancer patients (50 HPV-positive/HPV-A, 20 HPV-negative/HPV-I) using targeted next-generation sequencing and multiplex immunofluorescence. Clinical features, mutational profiles, immune cell infiltrates, and prognostic factors were compared between groups. Strict FDR correction and effect size analysis (Cliff’s Delta) were applied to statistical comparisons.

RESULTS: HPV-I tumors showed significant association with gastric-type adenocarcinoma (p < 0.001) and higher CA125 levels (p = 0.011). Molecularly, HPV-I tumors were substantially enriched for TP53 mutations (46.2% vs 2.2%, OR = 0.030, p < 0.001), while PIK3CA mutations predominated in HPV-A tumors (41.3% vs 7.7%, OR = 7.78, p = 0.047), suggesting notable mutual exclusivity. Immunologically, HPV-A tumors showed substantially higher stromal M2 macrophage density (Cliff’s Delta = -0.51, Large Effect), while HPV-I tumors displayed significantly higher stromal immune cell ratios: M1/M2 (5.34 vs 0.87, p = 0.003), CD8+/M2 (13.65 vs 2.66, p = 0.004), and NK/M2 (8.43 vs 0.59, p = 0.012), revealing the paradox of favorable immune balance coexisting with immune exclusion. In HPV-I subgroup analysis, high CD8+/M2 ratio was associated with superior progression-free survival (16.7% vs 71.4% event rates, p = 0.014).

CONCLUSIONS: HPV-negative and HPV-positive cervical cancers represent distinct entities with unique molecular and immunological profiles. Our exploratory findings suggest that HPV-I tumors exhibit the paradox of favorable stromal immune cell ratios coexisting with immune-excluded phenotype, while HPV-A tumors show higher M2 macrophage infiltration. The prognostic significance of CD8+/M2 ratio in HPV-I patients may provide a valuable biomarker and suggest specific therapeutic strategies targeting immune exclusion and macrophage polarization based on HPV status.

PMID:41795431 | DOI:10.1016/j.ejso.2026.111425

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Nevin Manimala Statistics

Reweighting intersectionality: Statistical and epistemic alignment in intersectional MAIHDA

Soc Sci Med. 2026 Mar 4;397:119150. doi: 10.1016/j.socscimed.2026.119150. Online ahead of print.

ABSTRACT

Intersectionality offers a critical framework for understanding how multiple axes of social identity shape health outcomes. Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy (MAIHDA) has emerged as a popular method for operationalizing intersectionality in social epidemiology. By structuring individuals into intersecting social categories (strata), and modeling both within- and between-stratum variation, MAIHDA offers a way to quantify stratum-level heterogeneity while mitigating issues of sparse data through partial pooling. In this paper, we argue that the statistical structure of MAIHDA, and its subsequent interpretation, carries epistemic commitments that are rarely made explicit. First, shrinkage in MAIHDA induces an implicit reweighting of intersectional strata toward a population of equally sized groups. As a result, estimated between-stratum variation reflects a hypothetical target population rather than the empirical population distribution, raising questions about the interpretation of stratum-level effects. Second, we argue that the variance partition coefficient and proportional change in variance are the most informative metrics specifically with regards to intersectionality, and careful interpretation of these is required. In addition, observed heterogeneity is underdetermined by any single social theory, meaning that MAIHDA findings may be consistent with multiple explanatory frameworks beyond identity-based mechanisms, such as intersectionality. We conclude that MAIHDA is best understood as a descriptive tool that identifies stratified heterogeneity. This may provide empirical guidance for when intersectional explanations are relevant, but should remain open to alternative theoretical interpretations. This perspective encourages careful epistemic reflection on the assumptions and inferences made when applying MAIHDA to intersectionality-motivated research questions.

PMID:41795407 | DOI:10.1016/j.socscimed.2026.119150

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Nevin Manimala Statistics

Joint and independent associations of muscle and bone health with biological age acceleration in Chinese adults: Findings from the China National Health Survey

Maturitas. 2026 Mar 4;208:108900. doi: 10.1016/j.maturitas.2026.108900. Online ahead of print.

ABSTRACT

BACKGROUND: Population aging has intensified interest in identifying physiological determinants of biological age beyond chronological age. Muscle loss and bone deterioration are key features of age-related decline, yet their individual, joint, and sex-specific contributions to biological age acceleration remain insufficiently characterized in Asian populations.

METHODS: A total of 29,437 adults aged 20-80 years from the China National Health Survey conducted in 2023-2024 were included. Appendicular skeletal muscle mass was assessed by bioelectrical impedance analysis, handgrip strength by dynamometer, and bone mineral density by quantitative ultrasound. Biological age acceleration was estimated using the Klemera-Doubal method based on sex-specific biomarker panels. Logistic regression models evaluated associations of low muscle mass, low muscle strength, and sarcopenia with elevated biological age acceleration. Additive and multiplicative interactions between muscle indicators and bone mineral density were examined. Population-attributable fractions were calculated to quantify the contributions of muscle- and bone-related deficits.

RESULTS: Lower muscle mass and lower muscle strength were strongly and inversely associated with biological age acceleration in both sexes (all P < 0.0001). Individuals with low muscle mass, low muscle strength, or sarcopenia had approximately 30% to 80% higher odds of accelerated aging. Bone mineral density showed modest and sex-dependent associations, with a weak inverse relationship observed in men but no clear association in women. Joint effects of low bone mineral density and muscle deficits were observed in men and in postmenopausal women with osteoporosis defined as a T-score below -2.5. Population-attributable fraction analysis indicated that muscle-related deficits contributed substantially more to the risk of accelerated aging than low bone mineral density.

CONCLUSIONS: Muscle-related indicators are strongly associated with biological age acceleration, whereas the influence of bone mineral density is weaker. Clear combined effects were observed in men and in postmenopausal women with osteoporosis. Muscle-related deficits accounted for a substantially greater proportion of the risk of accelerated aging than low bone mineral density in both sexes.

PMID:41795347 | DOI:10.1016/j.maturitas.2026.108900

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Nevin Manimala Statistics

Optimization of 3D printing parameters for PLGA/HA scaffolds using the Taguchi method

J Mech Behav Biomed Mater. 2026 Feb 28;178:107385. doi: 10.1016/j.jmbbm.2026.107385. Online ahead of print.

ABSTRACT

PLGA/HA is a promising material for 3D printed bioresorbable bone scaffolds, but the effects of fused filament fabrication parameters on monotonic and cyclic mechanical performance of resulting structures are unknown. Furthermore, the evolution of mechanical properties and dimensional stability under prolonged exposure to temperature and cell culture immersion conditions is also poorly investigated. This study first applied a Taguchi L9 orthogonal array to evaluate the effects of layer height, nozzle temperature, print speed, and cooling fan speed on the flexural properties of 90:10 wt% PLGA/HA scaffolds. Statistical analysis revealed that flexural strength, modulus, and deflection at failure were significantly influenced by specific printing parameters, while energy absorption showed no significant dependence (p > 0.05). At 50% print porosity, flexural strength and modulus increased by 20% and 50%, respectively, under the optimal settings (0.12 mm layer height and 205 °C nozzle temperature), reaching 45.0 MPa and 1807.80 MPa. Differential scanning calorimetry revealed significant effects on second-cycle glass transition (p = 0.0029), first-cycle cold crystallization (p = 0.0086), second-cycle cold crystallization (p = 0.0177), and first-cycle crystallinity (p = 0.0177), with favorable transitions aligning with mechanical maxima. Fatigue samples were printed using parameters that provided maximum flexural strength, and tests in PBS at 37 °C showed an endurance limit of 1.2 MPa at 106 cycles. In-vitro degradation over 60 days caused swelling of the scaffold by more than 20%, while the strength and the modulus decreased by 76% and 65% respectively, still above lower levels for trabecular bone. Consequently, optimization of 3D print parameters resulted in attaining improved mechanical properties of PLGA/HA, making scaffolds printed under these conditions viable for partial load bearing bone tissue regeneration applications.

PMID:41795333 | DOI:10.1016/j.jmbbm.2026.107385

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Nevin Manimala Statistics

Diagnostic accuracy of donor-derived cell-free DNA for rejection following liver transplantation: a systematic review and meta-analysis

Transplant Rev (Orlando). 2026 Mar 3;40(3):101008. doi: 10.1016/j.trre.2026.101008. Online ahead of print.

ABSTRACT

BACKGROUND: Graft rejection following liver transplantation remains a major complication affecting long-term survival. Current monitoring strategies, which rely on liver function tests and invasive biopsies, have inherent limitations, creating a need for non-invasive biomarkers. Donor-derived cell-free DNA (dd-cfDNA) has shown promise for monitoring rejection in solid organ transplantation, but its diagnostic accuracy in liver transplantation requires systematic evaluation.

OBJECTIVE: To comprehensively assess the diagnostic accuracy of dd-cfDNA for rejection after liver transplantation via a systematic review and meta-analysis.

METHODS: A comprehensive literature search was conducted in PubMed, Web of Science, Embase, and the Cochrane Library for studies published up to November 26, 2025. Studies were selected based on predefined inclusion and exclusion criteria. Data were extracted, and study quality was assessed. Pooled sensitivity, specificity, and other diagnostic measures were calculated. A summary receiver operating characteristic curve (SROC) was constructed, and heterogeneity along with subgroup analyses were performed.

RESULTS: Eleven studies were included. The meta-analysis demonstrated that dd-cfDNA achieved a pooled sensitivity of 0.90 (95% CI 0.76-0.96) and a pooled specificity of 0.90 (95% CI 0.82-0.94) for diagnosing acute rejection, with an area under the SROC curve of 0.95.

CONCLUSIONS: Dd-cfDNA demonstrates promising diagnostic value as a complementary noninvasive biomarker for rejection after liver transplantation. However, significant heterogeneity in diagnostic thresholds exists across studies. Large-scale, multicenter studies are required in the future to validate its clinical utility.

PMID:41795313 | DOI:10.1016/j.trre.2026.101008