Category: Statistics

Differentiation. 2026 Jan 23;148:100936. doi: 10.1016/j.diff.2026.100936. Online ahead of print.

ABSTRACT

Micro-CT has become the standard for the assessment of malformations in mouse embryos because it allows the visualisation of internal structures in the context of the intact embryo. Statistical comparison of volume differences is possible via manual segmentation of organs of interest from micro-CT scans, but this process is slow and laborious. Automated registration-based methods now exist that make the volumetric analysis of all organs feasible. Here, we expand the available atlases for use with the LAMA registration and analysis pipeline to include high-resolution population averages derived from phosphotungstic acid-stained C57BL/6J embryos and corresponding manually segmented atlases at embryonic stage (E) 12.5, E15.5, and E17.5. We report application of these population averages and atlases with the LAMA phenotyping pipeline to Wbp11 heterozygous null embryos, identifying defects previously reported in the cervical vertebrae, brain, nasal cavity, palate, liver and kidneys as well as a right aortic arch defects missed by manual analysis, and volume differences in the eyes and spinal cord. Finally, we report a high-resolution isolated E18.5 mouse heart population average and corresponding atlas that when applied to the Wbp11 line identified significant differences. These findings highlight the advantages of unbiased, volumetric and quantitative approaches in the analysis of mouse models of human disease.

PMID:41621112 | DOI:10.1016/j.diff.2026.100936

Neurosurg Focus. 2026 Feb 1;60(2):E7. doi: 10.3171/2025.11.FOCUS25913.

ABSTRACT

OBJECTIVE: Stroke is a leading cause of long-term disability, with conventional rehabilitation often failing to achieve substantial motor recovery, particularly in patients with severe paresis or in chronic stages. Brain-computer interfaces (BCIs) offer a novel rehabilitation approach by translating neural signals into real-time external feedback. The authors performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of noninvasive BCIs for poststroke motor rehabilitation.

METHODS: A systematic literature review was performed based on the PRISMA guidelines using 3 databases. Eligible RCTs enrolled stroke patients receiving noninvasive BCI-assisted motor rehabilitation compared with conventional therapies. The primary outcome was the Fugl-Meyer Assessment for Upper Extremity (FMA-UE) improvement. Secondary outcomes included the Action Research Arm Test (ARAT), Motor Activity Log (MAL), Modified Barthel Index (MBI), and Modified Ashworth Scale (MAS). Effect sizes were pooled using random-effects models and expressed as mean differences (MDs), standardized MDs (SMDs), or odds ratios, each with corresponding 95% confidence intervals (CIs).

RESULTS: Thirty-two RCTs comprising 1187 patients were included with no heterogeneity or significant imbalances in baseline characteristics across groups. A BCI was significantly superior in FMA-UE score improvement compared with controls (MD 3.85, 95% CI 2.84-4.86; p < 0.01), with benefits sustained at follow-up. Within-group analyses revealed greater improvement in the BCI arm from follow-up to baseline (MD 8.18, 95% CI 5.77-10.60; p < 0.01). A BCI was also associated with higher ARAT (MD 7.18, 95% CI 2.4-12.0; p < 0.01) and MAL (SMD 0.59, 95% CI 0.34-0.85; p < 0.01) scores, although between-group differences for these endpoints were not statistically significant. For the MBI, a subgroup analysis did not demonstrate significant differences, but a sensitivity analysis revealed a significant improvement in the BCI group (p = 0.042). There were no significant differences in the within- and between-group analyses of the MAS. A subgroup analysis suggested a synergistic benefit with the BCI combined with neuromuscular electrical stimulation. Adverse events were infrequent and generally mild; 2 withdrawals in the BCI group were reported due to seizure and electrode allergy. Notably, all heterogeneity was successfully resolved through sensitivity analyses, supporting the robustness of the findings.

CONCLUSIONS: Noninvasive BCI-assisted rehabilitation is a safe and effective adjunct to conventional therapy, enhancing motor recovery after stroke. While all included RCTs evaluated noninvasive systems, the potential value and efficacy of invasive and minimally invasive BCIs may require further consideration.

PMID:41621102 | DOI:10.3171/2025.11.FOCUS25913

Environ Toxicol. 2026 Feb 1. doi: 10.1002/tox.70046. Online ahead of print.

ABSTRACT

This study investigates how phthalate exposure contributes to uterine fibroid (UF) development by studying the effects of the Mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), a metabolite of Di(2-ethylhexyl) phthalate, on myometrial stem cells (MMSCs). MMSCs from normal (MYON) and at-risk (MYOF) uterine tissues were cultured in 3D organoids and treated with 1.6 μM MEHHP for 48 h. Functional assays investigated cell viability, apoptosis, and mitochondrial activity, whereas RT-PCR, immunohistochemistry (IHC), and RNA sequencing evaluated markers of proliferation, apoptosis, extracellular matrix (ECM), and oxidative stress (OS). Cytokines and growth factors secretion were analyzed using a multiplex ELISA. Results showed that MEHHP exposure significantly increased cell viability and inhibited apoptosis in MYOF compared to MYON organoids. Proliferation markers (PCNA, Ki67), anti-apoptotic markers (BCL2/BAX ratio), and ECM markers (fibronectin and COL1A1) were significantly upregulated, whereas pro-apoptotic markers (Caspase-3) were downregulated in MYOF organoids. MEHHP-treated MYOF organoids exhibited elevated secretion of pro-inflammatory cytokines (e.g., TNF-α, IL-6, IL-8) and growth factors (e.g., PDGF, VEGF, TGFβ1), indicative of impaired tissue repair and fibrosis. RNA sequencing identified increased OS in MYOF organoids, validated by differential expression of genes such as CA9 and GPX3. Mitochondrial analysis revealed enhanced oxidative phosphorylation (OXPHOS) and elevated oxygen consumption rates, implicating mitochondrial dysfunction as a driver of cytokine release and UF pathogenesis. In conclusion, MEHHP was shown to promote the transformation of MYOF organoids into a UF phenotype by driving proliferation, inhibiting apoptosis, and inducing cytokine-mediated inflammation via mitochondrial dysfunction. These findings related to MYOF-specific effects, as compared to MYON, emphasize that these differences are statistically significant and relevant to UF risk. It can shed insight on how phthalates exposures may impact UF pathogenesis and provide a basis for exploring targeted therapeutic strategies.

PMID:41621087 | DOI:10.1002/tox.70046

J Biomater Sci Polym Ed. 2026 Feb 1:1-18. doi: 10.1080/09205063.2026.2624425. Online ahead of print.

ABSTRACT

Resveratrol is a polyphenol with potent antioxidant activity; however, its application in topical formulations is limited by low aqueous solubility and poor stability. Polymeric nanoparticles represent an attractive strategy to overcome these limitations. Poly(D,L-lactic acid) (PLA) nanoparticles coated with poly(arginine) were prepared by nanoprecipitation and loaded with resveratrol at 5%, 10%, and 15% (w/w). The systems were characterized in terms of particle size, morphology, zeta potential, encapsulation efficiency, antioxidant activity, thermal stability, chemical structure, and cytocompatibility using L929 fibroblasts and HaCaT keratinocytes. The nanoparticles exhibited spherical morphology and mean diameters in the range of 100-150 nm, with high colloidal stability maintained for up to six months. Encapsulation efficiency decreased with increasing drug loading, from 84% at 5% to 62% at 15%. FTIR analysis indicated physical incorporation of poly(arginine) and resveratrol without detectable chemical interactions, while TGA confirmed adequate thermal stability of the systems. Antioxidant activity ranged within similar levels for free and encapsulated resveratrol, with no statistically significant differences among formulations in the DPPH assay. All formulations demonstrated excellent cytocompatibility, with cell viabilities exceeding 95%. Poly(arginine)-coated PLA nanoparticles constitute an effective platform to enhance the physicochemical stability of resveratrol while maintaining its antioxidant activity and biocompatibility. Among the evaluated systems, the 5% and 10% formulations exhibited the most balanced overall performance.

PMID:41621063 | DOI:10.1080/09205063.2026.2624425

Appl Neuropsychol Adult. 2026 Feb 1:1-12. doi: 10.1080/23279095.2025.2611308. Online ahead of print.

ABSTRACT

Picture naming performance, including accuracy and reaction time (RT) for living and nonliving objects, may provide sensitive markers of cognitive and functional status in older adults. The authors examined whether naming measures differentiate individuals with mild cognitive impairment (MCI) from healthy older adults (HOAs) and relate to global cognition and daily functioning. Twenty-three participants with MCI and twenty-five HOAs completed a 120-item picture naming task and assessments including the Montreal Cognitive Assessment (MoCA), Instrumental Activities of Daily Living (IADL), and Geriatric Depression Scale. Participants with MCI were significantly slower and less accurate than HOAs, with both groups showing better performance for nonliving items. Logistic regression classified 89.1% of participants correctly. In the MCI group, accuracy for living items predicted MoCA scores, whereas RT for living items predicted MoCA scores in HOAs. Partial correlations in the MCI group further indicated that slower RTs for living items and lower accuracy for nonliving items were associated with reduced IADL scores. The authors showed that picture naming, particularly accuracy and speed for living items, provides clinically meaningful information about cognitive integrity and subtle functional decline. The authors showed that naming measures may enhance the early detection of MCI.

PMID:41621050 | DOI:10.1080/23279095.2025.2611308

Eur Radiol. 2026 Feb 1. doi: 10.1007/s00330-025-12164-1. Online ahead of print.

ABSTRACT

OBJECTIVES: Microvascular invasion is a strong prognostic factor in hepatocellular carcinomas. The aim of our study was to assess the diagnostic value of mechanical parameters measured with compression MR elastography to detect microvascular invasion in hepatocellular carcinomas.

MATERIALS AND METHODS: In this prospective preoperative MR elastographic study, consecutive patients with hepatocellular carcinomas, scheduled for tumor surgical resection, were included. The tumor parameters assessed with MR elastography were the basal visco-elastic parameters (storage modulus, loss modulus, and phase angle, reflecting elasticity, viscosity and visco-elastic ratio) during expiration and inspiration, and the tumor stiffening slope during compression induced by respiration, reflecting non-linear elasticity. Microvascular invasion was determined with histopathological examination of resected tumors. Diagnostic performance of MR elastography was assessed with area under the receiver operating curve (AUC) analysis.

RESULTS: The final study group consisted of 53 patients with complete surgical resection, MR elastography and histological data, including 31 patients with microvascular invasion. Compression stiffening slope and storage modulus difference between inspiration and expiration were significantly higher in hepatocellular carcinomas without than with microvascular invasion (p < 0.001 and p = 0.03, respectively). Among clinical, morphological and biomechanical imaging features, the MR elastography compression stiffening slope (p = 0.004) and histological WHO differentiation (p = 0.02-0.03) were the only independent determinants of hepatocellular carcinoma microvascular invasion. In contrast to basal biomechanical parameters, the compression stiffening slope had high diagnostic performance for detecting microvascular invasion (AUC_{compression stiffening} = 0.83, p < 0.001).

CONCLUSION: Our results suggest that the compression stiffening slope at MR elastography is useful to diagnose microvascular invasion in patients with hepatocellular carcinomas.

KEY POINTS: Question Because non-invasive imaging markers of hepatocellular microvascular invasion are lacking, the development of new MRI markers is advisable. Findings In our MR elastography study, respiration-induced tumor stiffening, in contrast to basal visco-elastic parameters, had good accuracy for diagnosing hepatocellular carcinoma microvascular invasion. Clinical relevance Our results in patients with hepatocellular carcinomas suggest that the non-invasive measurement of MR elastography tumor compression stiffening slope may assess microvascular invasion.

PMID:41621038 | DOI:10.1007/s00330-025-12164-1

Ambio. 2026 Feb 1. doi: 10.1007/s13280-025-02333-3. Online ahead of print.

ABSTRACT

The recovery of large carnivore populations in Europe often leads to conflicts with the primary sector. Compensation for livestock and agricultural losses is a common mitigation tool, but its impact on tolerance and support for conservation remains unclear. We investigated brown bear damage to apiaries in the Polish Carpathians by surveying beekeepers in areas of bear presence. Using statistical modelling, we examined how emotional and cognitive responses to damage and compensation experiences shape tolerance and behavioural intentions towards bear conservation. We found that experiencing damage and receiving compensation was associated with higher risk perceptions and greater trust in the management administration. Whereas negative intentions were more likely when tolerance was low and fear was high, conservation support was positively associated with tolerance and perceived control. These findings suggest that conservation authorities can improve coexistence by relying on non-lethal strategies that minimize risk, build trust and foster a sense of control.

PMID:41621030 | DOI:10.1007/s13280-025-02333-3

Qual Life Res. 2026 Feb 1;35(3):54. doi: 10.1007/s11136-026-04166-3.

ABSTRACT

PURPOSE: Obstructive Sleep Apnea (OSA) impairs children’s quality of life (QoL), but the impact of air pollution and heat wave on pediatric OSA-related QoL remains unclear. This retrospective cross-sectional study investigated associations between short-term air pollutant (PM_2.5, PM₁₀, SO₂, and NO₂) exposure, heat wave, and QoL in children with OSA, including pollutant lag effects.

METHODS: A retrospective cross-sectional study was conducted at Henan Provincial Children’s Hospital (2021-2023). Eligible participants were ≤ 14-year-old Henan residents with confirmed OSA (OAHI > 1) via polysomnography. QoL was assessed by the OSA-18 Scale. Air pollutant and heat wave data were from national monitoring networks. Generalized Linear Regression Models (GLMs) analyzed continuous QoL outcomes, with sensitivity analyses performed.

RESULTS: 1943 children were included. The statistical analysis results showed that PM_2.5 lag03-lag07; PM₁₀ lag0-lag6, lag01-lag07; SO₂ lag0-lag2, lag01-lag07; NO₂ lag7, lag05-lag07 were statistically correlated with the impact on the QoL of pediatric patients. The maximum effect values OR were 1.042 (95% CI 1.006, 1.079), 1.030 (95% CI 1.016, 1.045), 1.774 (95% CI 1.279, 2.462), and 1.101 (95% CI 1.013, 1.197), respectively. Additionally, heat wave was associated with worse QoL (OR:1.537, 95% CI 1.021, 2.313). Sensitivity analyses confirmed result stability.

CONCLUSIONS: Air pollutants (especially SO₂ and NO₂) and heat waves reduce QoL in children with OSA, highlighting the need for targeted environmental interventions.

PMID:41621022 | DOI:10.1007/s11136-026-04166-3

Orv Hetil. 2026 Feb 1;167(5):180-187. doi: 10.1556/650.2026.33484. Print 2026 Feb 1.

ABSTRACT

INTRODUCTION: The diagnostic work-up of patients presenting to the emergency department with chest pain remains a major clinical and health-economic challenge worldwide. Although most cases are caused by benign, non-cardiopulmonary conditions, the primary goal of emergency care is the timeous, but safe exclusion of life-threatening disorders – mainly acute coronary syndrome and pulmonary embolism. Excessive diagnostic testing increases both healthcare costs and emergency department overcrowding. Preliminary observations suggest that previously unrecognized spinal asymmetry or scoliosis is more prevalent among ambulatory adults presenting with pleuritic or musculoskeletal-type chest pain, potentially predisposing to costosternal or costovertebral subluxation as a mechanical pain generator.

OBJECTIVE: The planned prospective, multicenter study aims to assess the prevalence and clinical significance of spinal asymmetry among ambulatory, low-risk adults presenting with chest pain, and to develop/validate a novel musculoskeletal chest pain clinical prediction model.

METHODS: Primary outcome variables include pulmonary embolism and major cardiac events (non-ST-elevation myocardial infarction, unstable angina). Based on power calculations by Peduzzi et al. (1996), a total of 2,500 patients will provide adequate statistical power to avoid Type II error. Patients will be followed up at 30, 90, and 365 days for complications, recurrent visits, major adverse cardiac events, and mortality. Data will be analyzed using bootstrapping techniques for internal validation of the derived score.

EXPECTED RESULTS: We hypothesize that spinal asymmetry independently correlates with acute musculoskeletal chest pain but does not confer an increased risk of short- or long-term mortality. The newly developed musculoskeletal chest pain clinical prediction model may facilitate early recognition and safe management of musculoskeletal chest pain in the emergency department setting.

CONCLUSION: This study is expected to refine diagnostic algorithms for low-risk chest pain, reduce unnecessary investigations, improve cost-effectiveness, and enhance patient satisfaction. Orv Hetil. 2026; 167(5): 180-187.

PMID:41621021 | DOI:10.1556/650.2026.33484

Discov Oncol. 2026 Feb 1. doi: 10.1007/s12672-026-04459-6. Online ahead of print.

ABSTRACT

BACKGROUND: Trifluridine/Tipiracil (TAS-102) is an effective agent for the late-line treatment of metastatic colorectal cancer (mCRC). Combining TAS-102 with bevacizumab improves outcomes but may increase adverse events. We conducted a real-world, retrospective, exploratory comparison of two dosing schedules (bi-weekly vs. four-weekly) to describe efficacy, safety, and potential molecular and clinical correlates.

METHODS: We analyzed patients with mCRC who were treated with TAS-102 in combination with bevacizumab as late-line therapy from January 2020 to February 2023. Regimen assignment followed physician-patient shared decision-making based on clinical factors and local practice changes after emerging evidence, not randomization. Endpoints included progression-free survival (PFS), overall survival (OS), adverse events (AEs). Analyses were exploratory and hypothesis-generating, with multivariable Cox models for selected covariates.

RESULTS: A total of 92 patients were enrolled in this study. Median PFS was 3.2 months (bi-weekly) vs. 3.7 months (four-weekly), and median OS was 10.0 vs. 9.3 months, with no statistically significant differences. KRAS mutation was associated with inferior OS (7.7 vs. 11.8 months; P = 0.018), whereas TP53 was not. Eastern Cooperative Oncology Group performance status (ECOG-PS) = 2 independently predicted shorter PFS and OS; prior bevacizumab exposure correlated with shorter PFS but not OS. Common adverse events in patients were neutropenia (63.0%), leukopenia (67.0%), anemia (44.6%), malaise (55.4%), nausea (45.7%), anorexia (31.5%), and diarrhea (23.9%).

CONCLUSION: In this retrospective, real-world study, the two regimens demonstrated comparable disease control, and the bi-weekly regimen appeared to be better tolerated, representing a reasonable potential alternative. Nevertheless, these findings should be interpreted as exploratory, and future prospective studies are warranted.

PMID:41621001 | DOI:10.1007/s12672-026-04459-6