Category: Statistics

J Oral Rehabil. 2025 Oct 4. doi: 10.1111/joor.70068. Online ahead of print.

ABSTRACT

AIM: Systematically evaluate the previous literature on the association between insomnia and sleep bruxism (SB) in adults.

METHODS: Advanced searches were performed in different databases (PubMed, Embase, LILACS, Scopus and Web of Science) and grey literature until March 2025. Two trained reviewers independently conducted all stages of the review to identify observational studies evaluating the association between insomnia and SB in adults. Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS). A narrative synthesis summarised the main characteristics of the included studies. Meta-analyses were performed to obtain pooled estimates separately for self-reported and polysomnography (PSG)-based SB. Available data on insomnia and SB were converted into odds ratio (OR) with corresponding 95% confidence intervals (CIs).

RESULTS: Of the 1135 records initially identified, 931 were screened by title and abstract, and 23 were assessed in full text. Eight studies met the inclusion criteria for the systematic review, and six were eligible for meta-analysis, comprising a total sample of approximately 6990 adults. The meta-analysis of four studies investigating the association between insomnia and self-reported SB found no statistically significant association under the random-effects model (OR 1.17; 95% CI 0.79-1.72). Likewise, the pooled analysis of studies assessing PSG-based SB also showed no significant association with insomnia (OR 0.91; 95% CI 0.43-1.95).

CONCLUSION: Our findings indicate a lack of consistent evidence for a significant association between insomnia and SB. This conclusion is further limited by the small number of included studies, the moderate risk of bias in some studies, and the observed heterogeneity.

PMID:41044999 | DOI:10.1111/joor.70068

Pediatr Int. 2025 Jan-Dec;67(1):e70209. doi: 10.1111/ped.70209.

ABSTRACT

BACKGROUND: Epilepsy often begins in childhood or adolescence, a period marked by significant hormonal changes. Antiepileptic drugs (AEDs) like valproic acid (VPA) and levetiracetam (LEV) are commonly used, but VPA is associated with notable endocrine side effects, particularly in adolescent girls. This raises concerns about drug choice during puberty.

OBJECTIVE: To compare the effects of VPA and LEV monotherapy on pubertal hormone profiles, menstrual characteristics, physical development, and gynecologic ultrasound findings in adolescent girls with primary epilepsy.

METHODS: This prospective, cross-sectional study included 61 adolescent girls (16 on VPA, 15 on LEV, 30 controls) at a tertiary hospital from January 2018 to January 2019. Participants underwent anthropometric measurements, hormonal evaluations (FSH, LH, estradiol, testosterone, SHBG, TSH, 17-OH progesterone, DHEASO₄), menstrual assessments, and pelvic ultrasound. Statistical analysis was performed with a significance level of p < 0.05.

RESULTS: VPA users had significantly higher TSH levels than LEV users and controls (p = 0.036), suggesting possible subclinical thyroid dysfunction. They also had lower 17-OH progesterone and DHEASO₄ levels (p = 0.008 and p = 0.022, respectively). No significant differences were observed between groups in weight, height, BMI, pubertal hormone levels, menstrual cycle characteristics, or ultrasound findings. Treatment duration did not significantly affect hormone levels.

CONCLUSION: VPA appears to negatively impact thyroid and adrenal hormones in adolescent girls, whereas LEV has a safer endocrine profile. Given the hormonal sensitivity during puberty, LEV may be a safer alternative for adolescent girls with epilepsy to reduce potential endocrine disturbances.

PMID:41044995 | DOI:10.1111/ped.70209

Orthod Craniofac Res. 2025 Oct 3. doi: 10.1111/ocr.70038. Online ahead of print.

ABSTRACT

OBJECTIVE: Temporomandibular disorders (TMDs) are heterogeneous conditions of unclear aetiology involving the temporomandibular joint, masticatory muscles and neural tissues. Limited understanding of their pathogenesis hampers accurate diagnosis and targeted treatment. Therefore, this study aimed to identify salivary microRNA (miRNA) signatures associated with TMDs to support future diagnostic, therapeutic and prognostic applications.

MATERIALS AND METHODS: Unstimulated cell-free saliva (5 mL) was collected from 9 adult female TMD subjects (using Diagnostic Criteria/TMD) and eight healthy female controls of similar ages. Total RNA was extracted, small RNA libraries were prepared, and sequencing was performed using Illumina NovaSeq 6000. Reads were aligned to the human genome (GRCh38) via STAR. Differential expression analysis was conducted using DESeq2, followed by functional enrichment via miEAA 2.1.

RESULTS: A total of 187 salivary miRNAs were significantly differentially expressed between TMD and control groups (adjusted p < 0.05; log2-fold change > +1 or < -1), with 125 upregulated and 62 downregulated in TMD subjects. Several differentially expressed miRNAs were linked to the negative regulation of cadherin-mediated cell-cell adhesion, neurogenesis and chemokine production. Some overlapped with miRNAs implicated in rheumatoid arthritis and osteoarthritis, suggesting shared mechanisms. While no clear association was found between miRNA and TMD phenotypes, 5 miRNAs were strongly (R = 0.67-0.77) and significantly (p < 0.05) correlated with pain intensity and chronic pain grade.

CONCLUSIONS: Salivary miRNA profiling offers promise as a non-invasive diagnostic tool for TMDs, with the potential to uncover molecular endotypes and disease mechanisms not evident through clinical evaluation. Future studies with larger, more diverse cohorts are needed to validate these findings and assess their clinical utility.

PMID:41044994 | DOI:10.1111/ocr.70038

J Orthop Res. 2025 Oct 3. doi: 10.1002/jor.70077. Online ahead of print.

ABSTRACT

Unicompartmental knee arthroplasty (UKA) may enable improved functional outcomes compared to total knee arthroplasty (TKA). This randomized controlled trial assessed pre- and postoperative patient reported outcome measures (PROMs) and knee joint gait biomechanics for UKA and TKA patients. Patients were allocated to UKA (Oxford Partial Knee, Biomet, USA) and TKA (Persona CR Knee System, Zimmer, USA) study arms. Patients completed the Oxford Knee Score (OKS) and Western Ontario & McMaster University Arthritis Index (WOMAC), as well as instrumented gait analysis before and 1-year after surgery. Measures of interest: OKS scores; WOMAC sub-scores; Patient-specific correlations and root mean squared errors (RMSE) of stance phase sagittal and coronal knee angles. Statistical analysis included linear mixed-effects models (PROMs; α = 0.0125) and multivariate analysis of variance (gait biomechanics; α = 0.05). A total of 38 patients were recruited (UKA n = 17; TKA n = 21). All PROMs improved significantly following surgery (n = 37, p < 0.001), regardless of surgical technique. A significant effect of surgical technique on gait biomechanics was observed (n = 30, F_4,25, p = 0.010), where UKA patients displayed greater sagittal plane correlations [median(Q1,Q3) UKA 0.985 (0.967, 0.991), TKA 0.955 (0.942, 0.973)]; p = 0.018] and lower coronal plane RMSEs [UKA 3.6 (2.4,5.0)°, TKA 8.6 (5.1, 11.5)°; p = 0.002]. Although patient-reported outcomes improved similarly following UKA and TKA, UKA more closely preserved native knee kinematics as indicated by the greater similarity of sagittal gait patterns shapes and lower magnitude of coronal angle changes. CLINICAL SIGNIFICANCE: Greater preservation of patient-specific knee kinematics with UKA supports its use in appropriately selected patients and informs the design of targeted, functionally oriented rehabilitation protocols.

PMID:41044992 | DOI:10.1002/jor.70077

J Appl Toxicol. 2025 Oct 4. doi: 10.1002/jat.4952. Online ahead of print.

ABSTRACT

This study investigates the in vitro effects of florasulam, a widely used herbicide with known environmental impact, on bull epididymal sperm and primary testicular cells. Epididymal spermatozoa were collected from the cauda epididymis attached to one testis of a paired set obtained from a local abattoir and diluted to a concentration of 1 × 10⁸ spermatozoa/mL. The other testis was used to isolate testicular cells, which were then seeded onto 12-well and 96-well plates at the concentration of 5 × 10⁵ and 5 × 10⁴ cells per well, respectively. Sperm samples were exposed to various concentrations of florasulam (0-1000 μg/mL) for 2 h and evaluated for motility (M), plasma membrane integrity (PMI), acrosome integrity (AI), and mitochondrial membrane potential (MMP). Likewise, testicular cells were treated with different concentrations of florasulam for 48 h and assessed for cytotoxicity, apoptosis, steroidogenesis, and MMP. Statistical analyses were performed using ANOVA followed by Duncan’s multiple range test. The results showed that florasulam exposure significantly reduced sperm motility and MMP at concentrations of 100-1000 μg/mL. Additionally, 10 μg/mL florasulam stimulated cell proliferation, whereas 10, 100, and 500 μg/mL inhibited steroid secretion in testicular cells. Apoptosis was significantly increased at 500 and 1000 μg/mL, and MMP was negatively affected at 1000 μg/mL (p ≤ 0.05). These findings provide the first evidence that florasulam, even at sub-toxic concentrations, can impair male reproductive function by reducing sperm motility and mitochondrial activity, and by inducing apoptosis and hormonal disruption in testicular cells. This highlights its potential risk to cattle fertility and broader environmental reproductive health.

PMID:41044991 | DOI:10.1002/jat.4952

J Prim Care Community Health. 2025 Jan-Dec;16:21501319251380623. doi: 10.1177/21501319251380623. Epub 2025 Oct 3.

ABSTRACT

BACKGROUND: Previous publications have demonstrated the benefits of pharmacist involvement in hypertension management, including in rural health care settings. Unlike many of the previous studies that evaluated pharmacist interventions occurring in collaboration with physicians, this study uniquely assessed the impact of pharmacist-led interventions under a collaborative practice agreement (CPA) on hypertension outcomes in a rural, medically underserved federally qualified health center (FQHC) in the southeastern U.S.

OBJECTIVES: To evaluate the effectiveness of direct pharmacist intervention under a CPA compared to physician-only standard care in achieving blood pressure (BP) control. Secondary outcomes included all-cause hospitalization rates and adherence to antihypertensive medications.

METHODS: This retrospective, single-center observational study included adult patients with hypertension seen by either a clinical pharmacist or a primary care provider over a 3-month period. Primary outcomes were the proportion of patients reaching target systolic and/or diastolic BP and the median time in days to control. Secondary outcomes included all-cause hospitalizations and changes in antihypertensive medication adherence, measured by proportion of days covered (PDC).

RESULTS: Among 159 patients, those managed by pharmacists achieved significantly faster BP control (SBP: 49 days vs 182 days, P < .0001; DBP: 146 days vs 160 days, P = .0061). Combined SBP/DBP control was also achieved more quickly (160 days, P < .0001), despite higher initial BP levels. Notably, 0% of patients in the pharmacist group were hospitalized, compared to 10% in the physician-only group (P = .0065). Medication adherence improved, with average PDC rising from 72.5% to 80.2%, and 70.4% of patients reaching ≥80% adherence by study end.

CONCLUSIONS: Pharmacist-led hypertension management under a CPA significantly improves BP control, time to goal, medication adherence, and reduces hospitalizations compared to physician-only care in a rural, underserved FQHC setting.

PMID:41044881 | DOI:10.1177/21501319251380623

Biophys J. 2025 Oct 3:S0006-3495(25)00651-4. doi: 10.1016/j.bpj.2025.09.049. Online ahead of print.

ABSTRACT

MicroRNAs (miRNAs) are ubiquitous short RNAs regulating gene expression in many organisms, including humans. How the secondary structure (SS) of a mature miRNA affects its regulatory function remains an open question. Here we investigate this question through computational SS predictions of miRNA point mutants. We explore the mutational neighborhoods of miRNAs with association to human diseases, including cancer. We focus on possible SS changes independent of target-site complementarity, by leaving the seed region unchanged. We formulate metrics of the SS differences between such mutants and their wild types (WTs), and test whether disease-associated mutations tend to differ from others in terms of these metrics by comparing our results with the miRNASNP-v3 database. We find that disease-related mutants tend to have a higher probability of being fully unfolded than their WT; this and other SS-related measures are statistically significant at the database level. This is confirmed when we restrict the analysis to the better-validated miRNAs encoded by genes that appear in the manually curated MiRGeneDB database. With the same approach, we identify a subset of individual miRNAs for which SS changes are most likely to be related to disease. These are hsa-miR-1269b, hsa-miR-4537, hsa-miR-4477b, hsa-miR-4641, and hsa-miR-6821-3p; when focussing on the higher-confidence MiRGeneDB miRNAs, we find that hsa-miR-485-5p and hsa-miR-1908-3p are the ones for which SS changes are most likely to be linked to disease. In addition, we show that there are pairs of known miRNA WTs differing only by disease-related point mutations outside the seed region and exhibit very different SS. These pairs include hsa-miR-1269a-hsa-miR-1269b, and hsa-miR-3689a-3p-hsa-miR-3689b-3p.

PMID:41044879 | DOI:10.1016/j.bpj.2025.09.049

Genome Biol. 2025 Oct 3;26(1):333. doi: 10.1186/s13059-025-03776-3.

ABSTRACT

Most population-scale genomic datasets collected to date consist of “bulk” samples obtained from heterogeneous tissues, reflecting mixtures of different cell types. We introduce Unico, a Unified cross-omics computational method designed to deconvolve standard two-dimensional bulk matrices (samples by features) into three-dimensional tensors (samples by features by cell types). Unico is the first principled model-based deconvolution method that is theoretically justified for any tissue-level genomic data. By deconvolving bulk gene expression and DNA methylation datasets, we demonstrate Unico’s superior performance compared to existing methods, enhancing the ability to conduct powerful, large-scale genomic studies at cell-type resolution.

PMID:41044605 | DOI:10.1186/s13059-025-03776-3

BMC Med Educ. 2025 Oct 3;25(1):1350. doi: 10.1186/s12909-025-07931-z.

ABSTRACT

BACKGROUND: The aim of the study was to identify whether differences existed in the aesthetic perception of anatomical variations of the face and teeth among dental students, based on factors such as education level, gender, and the presence of a dentist in the family.

METHODS: The study was carried out with dental students using the Google Forms platform. A young female model was selected for the survey, with no aesthetic-compromising restorations or pathologies in her maxillary anterior teeth. Standard facial and smile reference photographs were digitally manipulated to alter specific aesthetic features using professional image-editing software (Adobe Photoshop v.20.0.0, Adobe Inc., San Jose, California, USA). Participants evaluated these photographs, focusing on components such as facial symmetry, gingival position, buccal corridor, and occlusal plane angulation. Preclinical and clinical students rated the original and manipulated images on a scale from 1 to 5, with 5 representing the most aesthetically acceptable image and 1 representing the least pleasing one. Statistical analysis comprised Shapiro-Wilk test, Levene test, Mann-Whitney U test.

RESULTS: In the research, 493 students participated, including 240 clinical students; 312 were female, and 89 had a dentist in their family. The overall aesthetic perception score was high (82.63 ± 8.5). Clinical students demonstrated significantly better perceptions of midline diastema, occlusal plane inclination, clinical crown height, and dental modifications compared to preclinical students (p < 0.05). Female students scored higher in lower facial height perception than males (p = 0.014). The presence of a dentist in the family did not significantly influence aesthetic perception (p > 0.05).

CONCLUSION: Clinical training positively impacted students’ ability to critically analyze aesthetics while maintaining function and naturalness. It can be suggested that, as the academic level increases in dental education, students’ aesthetic judgment skills also improve.

PMID:41044602 | DOI:10.1186/s12909-025-07931-z

Genome Biol. 2025 Oct 3;26(1):331. doi: 10.1186/s13059-025-03802-4.

ABSTRACT

BACKGROUND: Over 1100 independent signals have been identified with genome-wide association studies (GWAS) for bone mineral density (BMD), a key risk factor for mortality-increasing fragility fractures; however, the effector gene(s) for most remain unknown.

RESULTS: We execute a CRISPRi screen in human fetal osteoblasts (hFOBs) with single-cell RNA-seq read-out for 89 non-coding elements predicted to regulate osteoblast gene expression at BMD GWAS loci. The BMD relevance of hFOBs is supported by heritability enrichment from stratified LD-score regression involving 98 cell types grouped into 15 tissues. Twenty-three genes show perturbation in the screen, with four (ARID5B, CC2D1B, EIF4G2, and NCOA3) exhibiting consistent effects upon siRNA knockdown on three measures of osteoblast maturation and mineralization. Lastly, additional heritability enrichments, genetic correlations, and multi-trait fine-mapping unexpectedly reveal that many BMD GWAS signals are pleiotropic and likely mediate their effects via non-bone tissues.

CONCLUSIONS: Our results provide a roadmap for how single-cell CRISPRi screens may be applied to the challenging task of resolving effector gene identities at all BMD GWAS loci. Extending our CRISPRi screening approach to other tissues could play a key role in fully elucidating the etiology of BMD.

PMID:41044600 | DOI:10.1186/s13059-025-03802-4