Tag: statistics

Anim Genet. 2025 Aug;56(4):e70037. doi: 10.1111/age.70037.

ABSTRACT

With advancing genomic technologies, single-nucleotide polymorphism (SNP) arrays and whole genome sequencing (WGS) have become essential tools in equine genetic research. In this study, we assessed the concordance in SNP calls and trait-mapping efficacy by comparing data of 21 horses both genotyped on the Equine 670 K SNP array and sequenced at either ~12× or ~30× depth. Our analysis revealed that higher sequencing depths were significantly associated with fewer discordant calls between platforms. Additionally, we investigated the most frequent no-call and discordant positions and identified positions that were indels or multiallelic in the WGS. To assess the effectiveness of the 670 K SNP array vs. WGS in trait association studies, we mapped the chestnut coat color. Both technologies showed a clear peak at the expected locus, although neither association had loci reaching Bonferroni-corrected statistical significance, which was not statistically possible in this small group of horses. The findings of this study provide valuable insights for making informed decisions when selecting between SNP arrays and WGS at varying sequencing depths for equine genomic research applications.

PMID:40817846 | DOI:10.1111/age.70037

J Clin Endocrinol Metab. 2025 Aug 16:dgaf461. doi: 10.1210/clinem/dgaf461. Online ahead of print.

ABSTRACT

OBJECTIVE: To study bone turnover markers (BTM) and sex steroids in relation to Trabecular Bone Score (TBS) in men.

MATERIAL AND METHODS: Longitudinal, population-based study in 465 healthy men, aged 25-45 years at baseline. Lumbar spine TBS was calculated with TBS iNsight® version 4 (v19.4.1, core module, Medimaps, Pessac, France), which adjusts for soft tissue thickness correction via DXA measurements. Sex hormone binding globulin (SHBG), C-terminal telopeptide and pro collagen type 1 N-terminal propeptide were measured using immunoassays. Total testosterone (T) and estradiol (E2) were determined by liquid chromatography-tandem mass spectrometry, free T and free E2 calculated. Statistical analyses were conducted via linear mixed-effects modelling.

RESULTS: At baseline, TBS was positively associated with free testosterone (p=0.01), free estradiol and total estradiol (both p<0.001), but not with total testosterone nor with BTM. Over a follow-up of 12.5 years, TBS declined by 1.43% (p<0.001). Higher baseline BMI and trunk fat were predictive of greater decreases in TBS (p=0.01 and p=0.02). Baseline levels of sex steroids and BTM nor changes therein were associated with changes in TBS.

CONCLUSIONS: TBS already decreases in young and middle-aged healthy men, corroborating earlier studies showing early decrease of trabecular bone volume and changes in trabecular microarchitecture. Although we identified some potentially contributing determinants, the underlying mechanisms of changes in TBS and trabecular bone in young men are yet to be fully elucidated.

PMID:40817832 | DOI:10.1210/clinem/dgaf461

J Vet Diagn Invest. 2025 Aug 16:10406387251357233. doi: 10.1177/10406387251357233. Online ahead of print.

ABSTRACT

Congestive heart failure (CHF) in feedyard cattle is of increasing concern among producers and can be difficult to diagnose definitively postmortem. In a cross-sectional observational study, we evaluated gross pathology findings, various heart measurements, and subjective heart scores (1-5 scale: 1 = normal, 5 = severely remodeled) to identify heart disease postmortem. In postmortem examinations of 346 feedyard deaths, we classified 106 (30.6%) cases as cardiac enlargement or misshapen ventricle (CEMV) when there was an abnormal heart shape or dilated ventricle(s), and no signs of infectious heart disease. CHF was defined as a CEMV case with chronic passive congestion of the liver (i.e., nutmeg liver) and ≥2 of the following lesions: serous or serosanguineous pleural, pericardial, or peritoneal effusion. Eleven of the 346 autopsied cattle were classified as having CHF. Descriptive statistics and multivariate models were used to identify statistical associations between objective heart measurements or subjective heart scores and the prevalence of CEMV or CHF. CEMV cases had significantly increased heart widths, thinner left ventricular free walls, and expanded right ventricular lumen areas (p <0.05). The CHF model did not converge because we had too few cases to be able to evaluate associations between CHF and variables of interest.

PMID:40817806 | DOI:10.1177/10406387251357233

Genet Med. 2025 Aug 13:101554. doi: 10.1016/j.gim.2025.101554. Online ahead of print.

ABSTRACT

PURPOSE: Through our implementation study providing rapid genomic sequencing (rGS) in safety-net Neonatal Intensive Care Units (NICUs), we investigated the feasibility and perceived usefulness of customized “Clinical Interpretive Reports” (CIRs) to help neonatal providers with interpreting, disclosing, and managing care based on rGS results.

METHODS: Enrolled infants received rGS through a clinically accredited vendor. We developed five CIR types to provide customized interpretation of rGS results and link results to clinical management considerations, research opportunities, and resources. We developed workflows to triage, create, and deliver CIRs within 3 business days. Providers received the vendor reports and CIRs, disclosed results, and completed post-disclosure surveys. We analyzed summary statistics for the first 100 cases.

RESULTS: We delivered 97/100 CIRs (97%) within our goal timeframe (average 1.3 days) and provided clinical management recommendations in 40/100 (40%). Neonatal providers completed the post-disclosure surveys for 86/100 disclosures (86%). Most reported using the CIR prior to disclosure (80/86, 93%) and finding it helpful at providing useful information beyond the vendor report (79/80, 99%).

CONCLUSIONS: It is feasible and useful to develop customized rGS reports to assist non-genetics providers in safety-net NICU settings. Similar approaches may hold promise for equitably advancing genomic care in other non-NICU settings.

PMID:40817795 | DOI:10.1016/j.gim.2025.101554

Stat Med. 2025 Aug;44(18-19):e70232. doi: 10.1002/sim.70232.

ABSTRACT

In this article, we consider the semiparametric transformation models with a shared frailty variable for the rate function of recurrent events, where a shared frailty model is imposed to enable a correlation between the recurrent event process and the censoring time. Unlike the commonly used shared-frailty proportional rate models, our models allow for the rate functions associated with any two sets of covariate values not to be proportional over time. The proposed estimating approaches are inspired by Wang and Huang, who decompose the rate function into shape and size components. We start with the inverse-rate weighting approach and subsequently introduce a novel generalized method of moments framework to improve estimation efficiency by combining the estimating procedures derived from the shape and size components, respectively. The proposed methods are robust because they do not require the assumption of a Poisson process for the recurrent events or distributional assumptions for the frailty and censoring times. The large sample properties of the proposed methods are established, and the finite sample properties are examined through the simulation studies. The proposed methods are applied to a real data set.

PMID:40817780 | DOI:10.1002/sim.70232

Stat Med. 2025 Aug;44(18-19):e70231. doi: 10.1002/sim.70231.

ABSTRACT

A functional multistate model is presented, which accommodates Markov processes governing disease transition in a finite set of states. Importantly, we consider a setting where the set of predictors contains a high-dimensional image with the goal of quantifying the association between the image and the transition of disease states. In the motivating application of breast cancer, women start from normal breast tissue, go through benign lesions, and then to the onset of DCIS/invasive cancer. As in the real data application, we consider the setting in which the individuals are observed intermittently and the transition times are interval censored. A score test is developed to test the nullity of the coefficient function for the image predictor at different transitions between states. The asymptotic distribution of the score statistic is provided. An application involving progression to the development of breast cancer with mammogram image data provides illustration. Our results demonstrate an important association between the mammogram image and the probability of transition in breast cancer.

PMID:40817779 | DOI:10.1002/sim.70231

J Toxicol Environ Health A. 2025 Aug 16:1-15. doi: 10.1080/15287394.2025.2542348. Online ahead of print.

ABSTRACT

Under the United States Environmental Protection Agency’s (U.S. EPA) CERCLA program, soils suspected of lead (Pb) contamination are evaluated to assess the impact of soil Pb exposure on blood Pb levels. The decision to remediate relies, in part, on whether the measured soil exposure point concentration (EPC) excee ds an action level. The U.S. EPA established data quality objectives (DQOs) to support data collection used to estimate the EPC and assess confidence in remediation decisions. To support DQO processes at sites where site-specific soil Pb relative bioavailability (RBA) is assessed, a statistical simulation model was developed that estimates false compliance/exceedance decision error probabilities based upon uncertainty in the RBA-adjusted EPC, employing model inputs defining (1) the sampling protocol being evaluated, (2) variability in total and bioavailable soil Pb across the assessed area, and (3) analytical measurement uncertainty. A framework for utilizing the simulation model is presented using a hypothetical site informed by concentration and soil Pb bioavailability distributions from an actual Pb-contaminated site. Pre-sampling, false compliance/exceedance decision error probabilities were predicted for various sampling protocols. A DQO-compliant sampling protocol was then selected, and accuracy and precision in the measured EPC were assessed relative to a specified risk-based action level.

PMID:40817761 | DOI:10.1080/15287394.2025.2542348

J Dent Res. 2025 Aug 16:220345251356437. doi: 10.1177/00220345251356437. Online ahead of print.

ABSTRACT

Oral frailty is a key factor in maintaining nutritional status, yet its impact on weight loss remains unclear. This study aimed to (1) evaluate the longitudinal association between oral frailty and the onset of weight loss among independent older adults and (2) explore how oral frailty components contribute to this association. Data were sourced from 2016 to 2022 of the Japan Gerontological Evaluation Study (JAGES). As a 6-y follow-up cohort study, the onset of >10% weight loss was used as the dependent variable, reflecting the significant threshold for older adults at ≥6-mo follow-up. Oral frailty was assessed as independent variables in 4 ways: (a) count score (sum of 5 components: fewer teeth, chewing difficulty, swallowing difficulty, dry mouth, and pronunciation difficulty), (b) individual 5 components, (c) a latent variable structured from 5 components, and (d) a refined latent variable incorporating additional paths from fewer teeth to chewing difficulty and pronunciation difficulty. Structural equation models (SEMs) were applied to examine the effect of oral frailty on weight loss, estimating standardized coefficients (SCs) and 95% confidence intervals (CIs). The construct validity of oral frailty was assessed using confirmatory factor analysis within the SEM framework. Model fit was evaluated using the standardized root mean squared residual (SRMR) and coefficient of determination (CD). Among 3,305 participants (47.4% women; mean age at baseline: 72.0 ± 4.9 y), 8.9% experienced >10% weight loss. Model d, which incorporated a refined latent structure of oral frailty, demonstrated the strongest association with weight loss (SC = 0.09; 95% confidence interval [CI] = 0.01; 0.16) among all models, with chewing difficulty showing the highest standardized factor loading (0.45; 95% CI = 0.35; 0.55). Model d also showed the best model fit (SRMR = 0.013; CD = 0.217), providing the high explanatory power and appropriateness of this model. Oral frailty significantly increases the risk of weight loss among independent older adults and its components have interrelationships.

PMID:40817757 | DOI:10.1177/00220345251356437

J Dent Res. 2025 Aug 16:220345251357588. doi: 10.1177/00220345251357588. Online ahead of print.

ABSTRACT

Canonical and noncanonical WNT signaling pathways are tissue specific and play roles in mineralized tissue development and repair. Here we characterize the activity of noncanonical WNT5B and canonical WNT10B in dental pulp stem cells (DPSCs) in osteo-/odontogenesis and target dentin-pulp complex regeneration using rWNT-loaded hydrogels. DPSCs in monolayers were treated with recombinant WNT10B (rWNT10B, 50 ng/mL), rWNT5B (50 ng/mL), or the canonical WNT pan-activator CHIR 99021 (10 nM). Gene expression of osteo-/odontogenic markers and Alizarin Red assay were performed. Collagen-based hydrogels were prepared from bovine type I collagen and loaded with rWNT10B, rWNT5B, or CHIR. A control group with no treatment was included. WNT release from hydrogels in phosphate-buffered saline was performed up to 14 d. The DPSC response to hydrogels was characterized by viability, morphology, gene expression, and alkaline phosphatase (ALP) activity. In vivo investigation was conducted using an ectopic model of pulp exposure in human tooth fragments implanted in mice for 4 wk. Hematoxylin and eosin, trichrome staining, and immunohistochemistry were performed. Statistical analysis was performed using analysis of variance and Tukey post hoc (α = 0.05). Our in vitro studies showed that rWNT5B significantly upregulated ALP, RUNX2, and DMP1 after 7 d. rWNTs and CHIR significantly enhanced mineralization. rWNTs were almost completely released from the hydrogels in 14 d, with 2 release peaks at 6 h and 4 d. rWNT-loaded hydrogels did not affect cell viability and morphology. rWNT10B-loaded hydrogels significantly increased the expression of ALP and RUNX2. The rWNT-loaded hydrogels significantly increased ALP activity. Our in vivo histological data indicate the presence of gel in the exposure area, the formation of pulp-like tissue in contact with the hydrogels, new blood vessels, and polarized cells adjacent to dentin tubules. Canonical WNT10B and noncanonical WNT5B appear to play specific roles in DPSC differentiation. WNT-loaded hydrogels are cytocompatible, increase the expression of osteo-/odontogenic markers and ALP activity, and induce pulp-like tissue formation.

PMID:40817756 | DOI:10.1177/00220345251357588

Int J Gynaecol Obstet. 2025 Aug 16. doi: 10.1002/ijgo.70466. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the potential reciprocal influences between in vitro fertilization (IVF) and the psychological states of patients.

MATERIALS AND METHODS: A prospective cohort study involved 180 couples who sought consultation for IVF. To monitor the fluctuations in the emotional states of the couples throughout the IVF process, questionnaires were administered on two separate occasions: the first was conducted immediately before the initiation of medication, and the second was administered promptly following the completion of embryo transfer. The BECK inventories for anxiety and depression were employed for evaluation. Pregnancy outcomes were exclusively analyzed for women who received high-quality blastocysts, with cleavage-stage embryo transfers being excluded from consideration.

RESULTS: Pregnancy rates did not significantly differ based on the presence of heightened anxiety and/or depression among couples. Notably, a correlation was identified between severe anxiety in women before IVF and diminished rates of fertilization, as well as lower blastocyst/oocyte and blastocyst/metaphase II (M2) ratios (8.7 ± 5.0 vs. 7.5 ± 6.1, P = 0.029; 0.284 ± 0.199 vs. 0.218 ± 0.209, P = 0.001; and 0.333 ± 0.209 vs. 0.272 ± 0.232, P = 0.016, respectively). In the male cohort, elevated anxiety scores, either pre- or post-IVF treatment, were found to be linked with a reduced mean oocyte count, as well as lower rates of M2, fertilization, blastocyst, and total embryo counts (P < 0.05).

CONCLUSIONS: Pregnancy rates were not affected by the presence of anxiety and depression, as they do not exert a significant impact on the implantation success of blastocysts. However, given that fertilization rates are statistically diminished in instances of severe anxiety, which consequently results in a reduced number of blastocysts and total embryos, a decline in cumulative pregnancy rates may be anticipated.

PMID:40817721 | DOI:10.1002/ijgo.70466