Tag: statistics

Biol Trace Elem Res. 2025 Dec 18. doi: 10.1007/s12011-025-04949-8. Online ahead of print.

ABSTRACT

Unexplained recurrent spontaneous abortion (URSA) is a prevalent reproductive issue but its etiology remains obscure. Male exposure to environmental chemicals is suggested to elevate URSA risk in female partners. Herein, a case-control design set out to investigate associations between metal levels in human seminal plasma with URSA risk, plus to determine evidence of mediating effects by oxidative stress. Levels of 15 metal elements and oxidative stress marker malondialdehyde (MDA) in seminal plasma were measured in 125 male spouses of URSA cases compared to 108 male partners of women with successful pregnancy outcomes. The associations of single or mixed metals on URSA risk were analyzed using logistic regression and Bayesian kernel machine regression (BKMR), respectively. BKMR analyses reveal a joint effect of metal co-exposures on URSA risk. Through multiple statistical approaches, titanium (Ti), cadmium (Cd) or magnesium (Mg) were major contributors to metal mixtures elevating URSA risk. MDA was significantly and positively associated with URSA risk. Mediation analysis shows that the associations of Ti, Cd or Mg with URSA risk appear to be mediated by MDA at rates of 23.30%, 16.26% or 34.48%, respectively. In vitro experiments confirmed the seminal plasma relevant dose Ti, Cd or Mg exposure induced male mouse spermatocyte-derived GC-2 cells oxidative stress. Metal mixtures in seminal plasma are associated with increased URSA risk in female spouses, with Ti, Cd or Mg being significant contributors, potentially via oxidative stress, providing further insights into URSA etiology.

PMID:41410821 | DOI:10.1007/s12011-025-04949-8

Mol Neurobiol. 2025 Dec 18;63(1):308. doi: 10.1007/s12035-025-05628-4.

ABSTRACT

Epilepsy is a complex neural disorder that has an impact on over 50 million people around the world. Even though there are environmental factors that can be attributed to its occurrence, this disorder can also be associated with genetics. This work aimed to evaluate some known polymorphisms-CYP3A4*1B (rs2740574) and SLC6A11 (rs2304725). This case-control study consisted of 105 clinically diagnosed cases of epilepsy and 140 healthy controls. Genetic analysis was conducted using SYBR Green-based qRT-PCR with allele-specific primers. The relation of various genotypes with the risk of developing epilepsy was tested using logistic regression models. Stratified analyses were achieved based on the type of epilepsy, age of onset, and response to antiepileptic medication. Some participants were tested for gene expression analysis. Both polymorphisms were statistically associated with increased risk of developing epilepsy as the CYP3A4*1B GG genotype had a risk of 3.54-fold increase (95% CI: 1.35-9.27, p = 0.010) and the SLC6A11 TT genotype had an increase of risk by 3.00-fold (95% CI: 1.15-7.81, p = 0.024). The G-T allele combination of variant alleles conferred an even greater association (OR = 2.87, 95% CI: 1.78-4.62, p < 0.001). The association was found to be higher for generalized and early-onset epilepsy compared with focal and late-onset forms. The CYP3A4*1B GG genotype was significantly associated with drug resistance (OR = 4.44, 95% CI: 1.28-15.41, p = 0.019). Measurement of transcript expression showed a decrease of CYP3A4 and increased SLC6A11 with the variant genotypes. Genetic variants of CYP3A4*1B and SLC6A11 are relevant markers of sustained risk of acquiring epilepsy for the Iraqis population.

PMID:41410815 | DOI:10.1007/s12035-025-05628-4

Proc Natl Acad Sci U S A. 2025 Dec 23;122(51):e2523012122. doi: 10.1073/pnas.2523012122. Epub 2025 Dec 18.

ABSTRACT

Like human decision-making under real-world constraints, artificial neural networks may balance free exploration in parameter space with task-relevant adaptation. In this study, we identify consistent signatures of criticality during neural network training and provide theoretical evidence that such scaling behavior arises naturally from information-driven self-organization: a dynamic balance between the maximum entropy principle that promotes unbiased exploration and mutual information constraint that relates updates with task objective. We numerically demonstrate that the power-law exponent of updates remains stable throughout training, supporting the presence of self-organized criticality. Furthermore, we show that the loss landscape exhibits exponential ruggedness under small perturbations, transitioning to power-law ruggedness at larger scales, in the absence of mini-batch noise, indicating an intrinsic geometric landscape. We also observe a power-law distribution in the intervals between large updates, indicating an intermittent learning process. Together, these findings suggest that neural network learning reflects a nonequilibrium process governed by the fundamental trade-off between randomness and relevance, highlighting its dynamic nature and offering insights into the interpretability of AI systems.

PMID:41410766 | DOI:10.1073/pnas.2523012122

Eur J Appl Physiol. 2025 Dec 18. doi: 10.1007/s00421-025-06095-4. Online ahead of print.

ABSTRACT

PURPOSE: Fatigue can exacerbate gait abnormalities in unilateral transtibial amputees (TTA), but specific changes in walking patterns and compensatory strategies under fatigue remain unclear. This study aimed to investigate gait alterations in unilateral TTA following a fatigue-inducing protocol.

METHODS: Ten male unilateral TTA and ten age-matched able-bodied controls underwent three-dimensional gait analysis at self-selected speed under non-fatigued and fatigued conditions. Spatiotemporal parameters, joint kinematics, and ground reaction forces were measured. Two-way ANOVA was used for statistical comparisons.

RESULTS: Within the TTA group, the residual limb demonstrated a shorter stance phase (62.3 ± 2.4% vs. 65.1 ± 1.4%) and single support (34.7 ± 1.9% vs. 37.1 ± 2.8%), but greater step length (38.27 ± 2.49% vs. 35.76 ± 1.92%), peak hip flexion(35.0 ± 5.6° vs. 28.6 ± 3.0°) and knee flexion(67.3 ± 7.2° vs. 56.4 ± 5.6°) than the intact limb. Fatigue further increased step length (37.42 ± 2.41% vs. 36.61 ± 2.63%) and hip flexion (33.2 ± 5.3° vs. 30.5 ± 5.3°), while reducing hip extension (10.9 ± 4.8° vs. 12.8 ± 4.2°) and hip horizontal range of motion (17.5 ± 6.0° vs. 19.5 ± 6.6°). Compared to controls, TTA group had longer stride time (1.15 ± 0.04s vs. 1.08 ± 0.08s) and greater hip horizontal range of motion (18.5 ± 6.4° vs. 12.5 ± 3.0°), but lower cadence (105.1 ± 4.1 steps/min vs. 111.6 ± 8.1 steps/min).

CONCLUSION: Fatigue amplifies pre-existing gait asymmetries in unilateral TTA and elicits compensatory strategies, including increased reliance on the intact limb and greater proximal joint mobility. Targeted interventions to enhance residual limb function and hip flexor strength and endurance may help reduce fatigue-related asymmetry and fall risk.

PMID:41410758 | DOI:10.1007/s00421-025-06095-4

Eur J Trauma Emerg Surg. 2025 Dec 18;51(1):363. doi: 10.1007/s00068-025-03042-y.

ABSTRACT

PURPOSE: Post-traumatic pulmonary embolism (PE) may develop directly in the lungs, termed “de novo” pulmonary embolism (DNPE). Severe chest trauma has been identified as a potential risk factor for DNPE due to localized inflammation, occult vascular injury, and low-flow states (venous stasis). The primary outcome was to examine the association between DNPE and chest trauma, while the secondary outcome was to characterize patients in the DNPE group.

METHODS: We conducted a retrospective cohort study of patients with trauma aged ≥ 15 years admitted to Songklanagarind Hospital, a level 1 trauma center, from 2013 to 2023. All patients diagnosed with post-traumatic PE were reviewed for clinical parameters, imaging findings, and treatments. Patients without ultrasonographic evaluation for DVT were excluded.

RESULTS: Among 43,908 patients with trauma, PE was diagnosed in 78 (0.18%). After excluding four patients without DVT assessment, 74 patients remained. Of these, 49 (66%) were diagnosed with DNPE and 25 (34%) with PE + DVT. Compared with patients with PE + DVT (32%), patients with DNPE (38.8%) showed no significant difference in the incidence of chest trauma (p = 0.567). The location of PE significantly differed (p = 0.005) between the groups, with DNPE showing more peripheral involvement (79.6%) and PE + DVT showing more central emboli (52%). No patient in the DNPE group underwent pulmonary thromboembolectomy.

CONCLUSION: DNPE is more common among patients with trauma, but its association with chest trauma was not statistically significant. DNPE may result from undetected pelvic DVT or other mechanisms requiring further investigation.

PMID:41410754 | DOI:10.1007/s00068-025-03042-y

Pak J Biol Sci. 2025 Dec;28(9):576-586. doi: 10.3923/pjbs.2025.576.586.

ABSTRACT

&lt;b&gt;Background and Objective:&lt;/b&gt; Carvacrol, a naturally occurring phenolic monoterpenoid compound found in various essential oils, exhibits outstanding pharmacological characteristics, essentially anticancer, antiproliferative and pro-apoptotic effects. This study evaluates the therapeutic potential of carvacrol as a topical agent in preventing and treating DMBA-induced oral cancer in rats through &lt;i&gt;in vivo&lt;/i&gt; assessment of its anticancer efficacy and histopathological effects. &lt;b&gt;Materials and Methods:&lt;/b&gt; This study was designed to investigate the chemopreventive and therapeutic potential of topically applied carvacrol in a rat model of Oral Squamous Cell Carcinoma (OSCC) induced by 7,12-dimethylbenz[a]anthracene (DMBA). The expression of Proliferating Cell Nuclear Antigen (PCNA) and B-cell lymphoma/leukemia-2 (Bcl-2), markers of proliferation and apoptosis, respectively, was estimated by immunohistochemical staining. Data were analyzed using one-way ANOVA with Tukey’s &lt;i&gt;post hoc&lt;/i&gt; test and Pearson’s correlation, following normality confirmation (p>0.05), with results summarized using descriptive statistics. &lt;b&gt;Results:&lt;/b&gt; Noteworthy declines in both PCNA and Bcl-2 expression were noticed in groups treated with carvacrol, either concurrently with DMBA or following its application. The group receiving carvacrol alternately with DMBA showed the most noticeable suppression in both markers. &lt;b&gt;Conclusion:&lt;/b&gt; These results highlight carvacrol’s dual character in quashing carcinogenesis and stimulating apoptotic cell death, supporting its potential as a safe, natural therapeutic agent for OSCC intervention.

PMID:41410137 | DOI:10.3923/pjbs.2025.576.586

Biotechnol Bioeng. 2025 Dec 18. doi: 10.1002/bit.70128. Online ahead of print.

ABSTRACT

Extracellular vesicles (EVs), including exosomes, are abundant in bovine milk and Lactobacillus culture media but difficult to isolate with high efficiency and purity. In response, a micro-electro-mechanical systems (MEMS)-based membrane filter was developed to address these limitations. Under equivalent conditions, the developed filter outperformed commercial filters, achieving a 2.17-fold higher EV recovery rate compared to the commercial polyethersulfone (PES) membrane from a 5 mL high-concentration sample, and yielding a total of 50 mL of EV solution at a concentration of 5.52 × 10¹⁰ particles/mL. The membrane was engineered to achieve a minimum pore size of 32 nm and a minimum thickness of 290 nm through separate fabrication processes. Among these, the MEMS160 membrane, which features uniformly distributed 168 nm pores on a 318 nm thick structure, demonstrated enhanced performance by effectively reducing fouling, as confirmed by blocking-model assessments. Biological evaluations showed that EVs isolated using the developed filter retained notable purity and bioactivity. Specifically, milk-derived EVs increased the proliferation of human fibroblasts (Hs68) and human follicle dermal papilla cells (HFDPCs) by up to 25% and 50%, respectively, while Lactobacillus-derived EVs increased proliferation by up to 11% and 53% at certain concentrations. Furthermore, co-treatment with an anti-aging peptide (AIMP1-derived peptide) had a synergistic effect on both cell types. Similar trends were seen in canine and feline fibroblasts. Milk-derived EVs boosted proliferation by up to 25% in canine and 31% in feline cells, while Lactobacillus-derived EVs increased it by up to 46% and 34%, respectively. These effects reached statistical significance. These results show the filter’s potential for large-scale EV isolation and dermatological applications, requiring high purity and yield.

PMID:41410131 | DOI:10.1002/bit.70128

Biom J. 2025 Dec;67(6):e70104. doi: 10.1002/bimj.70104.

ABSTRACT

In the competing risks setting, the $t$ -year absolute risk for a specific time $t$ (e.g., 2 years), also called the cumulative incidence function at time $t$ , is often interesting to estimate. It is routinely estimated using the nonparametric Aalen-Johansen estimator. This estimator handles right-censored data and has desirable large sample properties, as it is the nonparametric maximum likelihood estimator (NPMLE). Inference for comparing absolute risks, via either a risk difference or a risk ratio, can therefore be done via usual asymptotic normal approximations and the delta method. However, the small sample performances of this approach are not fully satisfactory. Especially, (i) coverage of confidence intervals may be inaccurate and (ii) comparisons made using a risk ratio and a risk difference can lead to inconsistent conclusions, in terms of statistical significance. We, therefore, introduce an alternative empirical likelihood approach. One advantage of this approach is that it always leads to consistent conclusions when comparing absolute risks via a risk ratio and a risk difference, in terms of significance. Simulation results also suggest that small sample inference using this approach can be more accurate. We present the computation of confidence intervals and p-values using this approach and the asymptotic properties that justify them. We provide formulas and algorithms to compute constrained NPMLE, from which empirical likelihood ratios and inference procedures are derived. The novel approach has been implemented in the timeEL package for R, and some of its advantages are demonstrated via reproducible analyses of bone marrow transplant data.

PMID:41410124 | DOI:10.1002/bimj.70104

J Int Neuropsychol Soc. 2025 Dec 18:1-6. doi: 10.1017/S1355617725101732. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to explore the correlates of zero, one, and multiple performance validity test (PVT) failures on cognitive test performance in patients with various degrees of severity of traumatic brain injury.

METHOD: 306 participants completed the Trail Making Test as part of a neuropsychological evaluation within 1-36 months post-injury. They were assigned to zero, one, or ≥ two fail groups on the basis of at least two independent PVTs. Group differences in Trail Making Test performance were analyzed with analysis of variance, with post hoc contrasts with the Bonferroni correction for multiple comparisons. Groups were also compared on various background characteristics.

RESULTS: Participants who passed all PVTs had statistically significantly better performance on both parts of the Trail Making Test as compared to those who failed either one or multiple PVTs, with the latter two groups not differing statistically significantly from each other. PVT failure was relatively more common in participants who were female, had an uncomplicated mild TBI, were involved in financial compensation-seeking, and were seen at a longer time point since injury.

CONCLUSION: Failure of even only one PVT is associated with lower neuropsychological test performance in patients with traumatic brain injury, especially when empirically validated criteria are used that are stratified by injury severity. Such failure does not always reflect malingering but must be interpreted and addressed in the context of patient background characteristics.

PMID:41410118 | DOI:10.1017/S1355617725101732

Biom J. 2025 Dec;67(6):e70102. doi: 10.1002/bimj.70102.

ABSTRACT

Functional data analysis has received significant attention due to its frequent occurrence in modern applications, such as in the medical field, where electrocardiograms or electroencephalograms can be used for a better understanding of various medical conditions. Due to the infinite-dimensional nature of functional elements, the current work focuses on dimension reduction techniques. This study shifts its focus to modeling the conditional quantiles of functional data, noting that existing works are limited to quantitative predictors. Consequently, we introduce the first approach to partial dimension reduction for the conditional quantiles under the presence of both functional and categorical predictors. We present the proposed algorithm and derive the convergence rates of the estimators. Moreover, we demonstrate the finite sample performance of the method using simulation examples and a real dataset based on functional magnetic resonance imaging.

PMID:41410116 | DOI:10.1002/bimj.70102