Category: Statistics

Epigenetics Chromatin. 2026 Jun 19. doi: 10.1186/s13072-026-00685-y. Online ahead of print.

ABSTRACT

BACKGROUND: Asthma is a clinically heterogeneous airway disorder characterized by complex interactions between environmental exposures, immune activation, and molecular regulatory programs, whose underlying mechanisms are not fully elucidated by known genetic loci. DNA methylation serves as a mechanistic interface bridging genetic predisposition and environmental influences; however, most epigenetic studies remain confined to isolated CpG sites, lacking robust biological interpretability.

METHODS: We developed a cross-tissue, multi-cohort, and mechanistically interpretable epigenetic framework to delineate pathway-level methylation mechanisms underlying asthma. Leveraging data from 908 participants across one combined training cohort and three independent validation cohorts, we constructed a linear support vector classifier based on pathway-derived methylation scores. Additionally, SHapley Additive exPlanations (SHAP) were applied to quantify the contributions of individual pathways. To assess the statistical significance of pathway contributions, one-sample t-tests were performed for each pathway’s SHAP values against zero, followed by Benjamini-Hochberg false discovery rate (FDR) correction to obtain adjusted p values.

RESULTS: The model exhibited reproducible and cross-tissue performance, achieving area under the curve (AUC) values of 0.792 (95% CI: 0.782-0.799; GSE65163) and 0.980 (95% CI: 0.974-0.990; GSE201872) in two airway epithelial cohorts, and 0.736 (95% CI: 0.690-0.771; GSE104471) in peripheral blood samples. Pathway interpretability analyses identified dominant roles of amino acid metabolism, epithelial and mesodermal developmental programs, metabolic-immune transport pathways, and neuroimmune signalling in shaping asthma-associated methylation patterns. Mediation analyses further revealed that these pathways influence asthma both directly and indirectly via eosinophil activity, epithelial proliferative dynamics, and nitric oxide-linked airway inflammation. Notably, pathways annotated by GO:0061205 and GO:0098727 exerted significant direct effects independent of immune intermediates.

CONCLUSIONS: This study describes a pathway-level methylation model designed for biological interpretability that shows associations with both clinical severity and latent molecular heterogeneity. It provides statistical evidence contributing to the understanding of epigenetic, immune, and metabolic signatures in asthma, offering a potential framework warranting further validation for precision respiratory medicine.

PMID:42321852 | DOI:10.1186/s13072-026-00685-y

Cancer Imaging. 2026 Jun 20. doi: 10.1186/s40644-026-01069-x. Online ahead of print.

ABSTRACT

Hypoxia is associated with poor outcomes in soft tissue sarcoma (STS) and is linked to increased expression of hypoxia-inducible factor 1-alpha (HIF-1α), carbonic anhydrase IX (CAIX), and lysyl hydroxylase 2 (PLOD2). These factors are potential therapeutic targets. This exploratory study aimed to investigate the correlation between ¹⁸F-fluoromisonidazole (¹⁸F-FMISO) positron emission tomography (PET) imaging, a marker of hypoxia, and the expression of these biomarkers in STS. This imaging phase II clinical trial (NCT #03730077) recruited 5 patients with suspected soft tissue sarcoma (STS) and imaged these patients with ¹⁸F-Fluorodeoxyglucose (¹⁸F-FDG) and ¹⁸F-FMISO within 2 weeks of each other. STS tissue was analyzed for HIF-1α, CAIX, and PLOD2 expression using immunohistochemistry and western blotting. Collagen formation was assessed by Masson’s trichrome. In this small sample, a correlation was found between STS size and PLOD2 expression (r = 0.996, P = 0.004). STS grade correlated positively with ¹⁸F-FMISO T/M (tumor/muscle) SUVmax (r = 0.894, P = 0.041). ¹⁸F-FDG correlated positively with ¹⁸F-FMISO SUVmax (r = 0.994, P = 0.006). Positive but non-significant associations were noted between ¹⁸F-FMISO T/M SUVmax and CAIX (r = 0.95, P > 0.05) and PLOD2 (r = 0.93, P > 0.05). These preliminary observations in a small sample are hypothesis-generating at best and must be interpreted with substantial caution due to the extremely limited number of patients, which precludes robust statistical inference and generalizability. No definitive conclusions can be drawn regarding the relationship between 18F-FMISO uptake and hypoxia biomarker expression. Larger, adequately powered prospective studies are essential to validate these findings, clarify potential correlations, and determine the clinical utility of 18F-FMISO PET/CT as a noninvasive hypoxia biomarker in STS.

PMID:42321847 | DOI:10.1186/s40644-026-01069-x

Head Face Med. 2026 Jun 19. doi: 10.1186/s13005-026-00630-0. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to evaluate the in vitro effects of commercially available teething gels with different formulations on epithelial barrier integrity and cellular viability.

MATERIALS AND METHODS: Six commercially available teething gels were tested at concentrations of 0.1%, 20%, 50%, and 80%. Cellular viability was assessed using the MTT assay in human gingival mesenchymal stem cells after 72 h of exposure. Epithelial barrier integrity was evaluated by measuring transepithelial electrical resistance (TEER) in HaCaT keratinocyte cells cultured on transwell inserts at 24, 48, and 72 h. Statistical analyses were performed using IBM SPSS Statistics 27, applying mixed-design and two-way ANOVA with appropriate post hoc tests, with significance set at p < 0.05.

RESULTS: TEER values differed significantly according to gel type, concentration, and exposure time (p < 0.05). At 0.1%, significant intergroup differences were observed at 24 h (p = 0.001) and 72 h (p = 0.017), with Dentinox showing significantly lower TEER values than Gengigel, Aftamed, Buccotherm, and Jack N’Jill. At 20%, 50%, and 80% concentrations, Dentinox consistently exhibited reduced TEER levels at 24-72 h (p = 0.001), whereas Gengigel showed higher TEER values mainly at 24 h (20%) and 72 h (50%), and Buccotherm at 48 h across higher concentrations. MTT analysis revealed significant gel- and concentration-dependent differences at 20%, 50%, and 80% (p = 0.001). Jack N’Jill exhibited higher cell viability at 20%, while both Jack N’Jill and Buccotherm showed higher viability at 50% and 80%.

CONCLUSIONS: Teething gels exert formulation, concentration, and time-dependent effects on epithelial barrier integrity and cellular viability, emphasizing the need for careful evaluation of products intended for infant use.

CLINICAL RELEVANCE: This study demonstrates that teething gels with different formulations and concentrations can differentially affect epithelial barrier integrity and cellular viability. These findings highlight the clinical importance of carefully evaluating teething gel composition and concentration, particularly for products intended for use in infants and young children.

PMID:42321842 | DOI:10.1186/s13005-026-00630-0

Harm Reduct J. 2026 Jun 20. doi: 10.1186/s12954-026-01479-x. Online ahead of print.

ABSTRACT

BACKGROUND: People who inject drugs (PWID) are at increased risk of infective endocarditis (IE). While opioid injection is a major risk factor for IE, the risk associated with specific prescription opioids, such as hydromorphone, remains unclear and is inconsistently reported, despite a hypothesized pathway whereby the insolubility of controlled-releaseformulations may promote injection equipment reuse and bacterial contamination. Therefore, we estimated and compared the 1-year incidence rates of IE among PWID reporting injection of hydromorphone versus non-hydromorphone opioid medications and versus other opioids/drugs.

METHODS: Baseline questionnaire data on PWID in the Ontario Integrated Supervised Injection Services cohort (November 2018-March 2020) were linked to health administrative databases. IE incidence was calculated over 1-year post-baseline. Participants were followed until first of IE, death, or 1-year censoring. Exposure was self-reported recent (past 6 months) injection of: hydromorphone, non-hydromorphone opioid medications of interest, or other opioids/drugs. Cox regression estimated associations, adjusting for age, gender, ethnicity, injection drug use, and prior injection-related infections.

RESULTS: Among the 514 participants included, 191 reported recent injection of hydromorphone, 32 non-hydromorphone opioid medications of interest, and 291 other opioids/drugs. IE incidence rates were low across groups: 1.6, 3.3, and 1.8 per 100 person-years. Adjusted hazard ratio comparing recent hydromorphone injection versus non-hydromorphone opioid medications of interest was 0.64 (95% confidence interval (CI) 0.06-6.53); versus other opioids/drugs was 0.82 (95% CI 0.19-3.51).

CONCLUSIONS: In this cohort of PWID, no clear association was found between hydromorphone injection and IE when compared to non-hydromorphone opioid medications or to other opioids/drugs. Due to low event rates and the resulting wide CIs, the findings are limited by low statistical precision. Further research with larger cohorts is warranted to quantify IE risk of specific injected drugs among PWID.

PMID:42321840 | DOI:10.1186/s12954-026-01479-x

Reprod Health. 2026 Jun 20. doi: 10.1186/s12978-026-02386-x. Online ahead of print.

ABSTRACT

BACKGROUND: Home delivery continues to be a significant factor contributing to maternal mortality in Africa, particularly among rural women with limited access to skilled birth attendants and healthcare facilities. Factors influencing home delivery operate at individual, household, and community levels. Therefore, this study aimed to examine the prevalence and risk factors of home delivery among rural women in 28 African countries.

METHODS: This retrospective cross-sectional study analyzed the most recent Demographic and Health Surveys (2011-2024) from 28 African countries. The weighted sample included 103,011 rural women of reproductive age. We performed descriptive analysis, chi-square tests, and binary logistic regression. Results are presented as frequencies, percentages, and odds ratios (ORs) with 95% confidence intervals (CIs). Statistical significance was set at p < 0.05.

RESULTS: The overall prevalence of home delivery among rural women in Africa was 34.01% [95% CI: 23.33%-35.26%], ranging from 5.91% in Rwanda to 85.19% in Chad. Women with mistimed pregnancy [aOR = 0.79, 95% CI = 0.76-0.82] and those with unwanted pregnancy [aOR = 0.86, 95% CI = 0.81-0.92] had lower odds of home delivery. Risk factors included having four or more births [aOR = 2.04, 95% CI = 1.91-2.17], no/other religion [aOR = 2.41, 95% CI = 2.24-2.56] and those in Central Africa [aOR = 2.09, 95% CI = 1.98-2.19].

CONCLUSION: This research reveals that home delivery remains prevalent among rural women in Africa, with significant between-country disparities. Key risk factors include high parity, no/other religion, and Central African residence. Programs should prioritize multiparous women and expand maternal health services across all religious groups. Additionally, context-specific policies and targeted investments are needed in Central Africa to address regional disparities.

PMID:42321838 | DOI:10.1186/s12978-026-02386-x

J Cardiothorac Surg. 2026 Jun 19. doi: 10.1186/s13019-026-04476-0. Online ahead of print.

ABSTRACT

BACKGROUND: Pectus excavatum (PE) is commonly associated with spinal abnormalities. However, the effect of the Nuss procedure on thoracic scoliosis remains unclear. This study therefore aimed to characterize the dynamic changes in the thoracic Cobb angle (tCA) among adult PE patients undergoing Nuss procedure.

METHODS: A total of 186 Patients with PE who underwent the Nuss procedure and subsequent bar removal (BR) were retrospectively analyzed. Clinical data were collected, including serial tCA measurements from posteroanterior chest radiographs taken preoperatively, at 1 month, 3-6 months, and 1 year postoperatively, as well as 1 day before and 1 week after BR for analysis. Subgroups were stratified by sex, Haller index (≥ 4 vs. <4), bar number (1-3), bar orientation (oblique vs. horizontal), bar flipping within 3 months, and preoperative tCA (≥ 10° vs. <10°).

RESULTS: Compared to the preoperative mean tCA, the tCA increased significantly at 1 month postoperatively (5.4 ± 4.2° vs. 5.9 ± 4.4°, p < 0.001). It then decreased significantly by 1 day before BR (5.4 ± 4.2° vs. 4.9 ± 3.9°, p < 0.001) and further at 1 week after BR (5.4 ± 4.2° vs. 4.4 ± 4.0°, p < 0.001). All subgroup analyses demonstrated a significant reduction in the tCA following BR.

CONCLUSIONS: The Nuss procedure induced a temporary increase in tCA at 1 month postoperatively, followed by gradual improvement during the bar maintenance period and a net reduction below the preoperative level after bar removal. Notably, patients with mild thoracic scoliosis also experienced a reduction in tCA after complete PE correction. While this reduction was not clinically meaningful, it still indicates that the procedure does not worsen thoracic spinal alignment and may offer some improvement.

PMID:42321835 | DOI:10.1186/s13019-026-04476-0

J Cardiothorac Surg. 2026 Jun 19. doi: 10.1186/s13019-026-04414-0. Online ahead of print.

ABSTRACT

BACKGROUND: This study aims to evaluate residual apical space (RAS) as a predictor of pneumothorax recurrence in patients undergoing video-assisted thoracoscopic surgery (VATS) for primary spontaneous pneumothorax (PSP) and to assess its impact by surgical treatment type.

METHODS: Data of 463 patients undergoing VATS for PSP at three Italian high-volume thoracic surgery centers (January 2012-March 2023) were retrospectively reviewed. Exclusions included secondary pneumothorax, patients < 18 years, and those undergoing thoracotomy. Four surgical approaches were analyzed, with RAS measured using the Collins method (4.2% equivalent to 0 cm RAS) on chest X-ray before discharge. The primary outcome of interest was the recurrence rate stratified by surgical procedure. Statistical analyses were performed to correlate RAS, clinical and surgical variables with pneumothorax recurrence.

RESULTS: The overall recurrence rate was 6.9% (32 patients). The mean hospitalization was 6.5 ± 3.5 days, with an average RAS before discharge of 9.7 ± 5.4%=1.15 cm. Mechanical pleurodesis alone had an higher recurrence risk (*p* = 0.0027), while apicectomy with chemical pleurodesis significantly reduced recurrence risk (*p* < 0.0001). Increased RAS (> 9.7%) was associated with a higher recurrence rate (*p* = 0.063). Multivariate analysis confirmed that increased RAS significantly predicts recurrence (*p* = 0.002), particularly in patients aged > 34 years. Stratifying by type of surgery, an increased RAS value was associated to higher rate of recurrence (*p* = 0.001) in patients who underwent apicectomy combined to mechanical pleurodesis.

CONCLUSIONS: Apicectomy combined with chemical pleurodesis is still the most protective approach for recurrence. However, despite its proven efficacy, this strategy is being progressively used less. Residual apical space may represent a procedure-dependent radiological marker associated with recurrence, particularly in patients undergoing apicectomy and mechanical pleurodesis and may be considered to reduce recurrence rates.

PMID:42321834 | DOI:10.1186/s13019-026-04414-0

J Cardiothorac Surg. 2026 Jun 19. doi: 10.1186/s13019-026-04416-y. Online ahead of print.

ABSTRACT

BACKGROUND: The increasing prevalence of obesity worldwide has led to conflicting research on its cardiovascular effects. Although obesity is an established risk factor for cardiovascular disease (CVD), certain evidence indicates that a higher body mass index (BMI) might unexpectedly reduce the risk of vascular calcification. This study was designed to examine the association between BMI and the presence of abdominal aortic calcification (AAC) within a general population.

METHODS: We analyzed data from 3,116 adults participating in the 2013-2014 National Health and Nutrition Examination Survey (NHANES). Severe AAC was diagnosed using the Kauppila score based on dual-energy X-ray absorptiometry (DXA) scans. The relationships between BMI (treated both continuously and categorically) and severe AAC were evaluated using logistic regression. To investigate potential variations and non-linear patterns, subgroup analyses and restricted cubic spline regression were performed.

RESULTS: After comprehensive adjustment. higher BMI was significantly associated with lower odds of severe AAC (OR = 0.89, 95% CI: 0.81-0.98, p = 0.013). When compared to individuals with normal weight, obese participants had 62% lower odds of severe AAC (OR = 0.38, 95% CI: 0.16-0.94, p = 0.037). This inverse relationship remained significant in subgroups including males, elderly individuals, and those without hypertension or diabetes. Restricted cubic spline analysis indicated a significant non-linear trend (p for nonlinearity = 0.0023).

CONCLUSIONS: An inverse association was observed between BMI and AAC prevalence, implying that overweight and obesity may paradoxically confer a protective effect against vascular calcification. These results contribute evidence supporting the existence of an “obesity paradox” in the context of vascular health.

PMID:42321831 | DOI:10.1186/s13019-026-04416-y

BMC Oral Health. 2026 Jun 19. doi: 10.1186/s12903-026-08949-5. Online ahead of print.

ABSTRACT

BACKGROUND: Alar base widening is a common soft tissue change following Le Fort I osteotomy. Although alar cinch sutures are commonly used to limit this change, their long-term stability remains variable. Nasal sill resection may provide a direct resective option for managing horizontal excess at the alar base; however, its use concomitantly with maxillary orthognathic surgery has not been well described. This retrospective clinical series aimed to describe longitudinal nasal base width changes and patient-reported aesthetic outcomes following nasal sill resection performed concomitantly with maxillary orthognathic surgery.

MATERIALS AND METHODS: Twenty-three patients who underwent nasal sill resection concomitantly with maxillary orthognathic surgery under submental intubation between 2018 and 2020 were included. Alar base width was measured from the right and left alar curvature points to the subnasale/midcolumellar point, and total nasal base width was calculated as the sum of both measurements. Measurements were recorded preoperatively (T0), following osteotomy and fixation (T1), following nasal sill resection (T2), and at 1, 3, 6, and 12 months postoperatively. The Rhinoplasty Outcome Evaluation (ROE) questionnaire was administered preoperatively and at 6 and 12 months postoperatively. Repeated measures analyses with Bonferroni correction were used for longitudinal comparisons, and intra-observer reliability was assessed using the intraclass correlation coefficient.

RESULTS: The mean preoperative total nasal base width was 39.56 ± 3.12 mm. Following osteotomy and fixation, total nasal base width increased to 47.87 ± 3.64 mm, and after nasal sill resection it decreased to 30.78 ± 2.95 mm. Nasal base width gradually increased during follow-up, reaching 36.61 ± 5.96 mm at 12 months. Although the 12-month value was descriptively lower than the preoperative baseline, this difference was not statistically significant after Bonferroni correction (p = 0.693). ROE scores improved from 10.91 ± 2.68 preoperatively to 17.78 ± 2.54 at 6 months and 18.09 ± 2.27 at 12 months (p < 0.001), with no statistically meaningful difference between the 6- and 12-month follow-ups. No major adverse outcomes related to nasal sill resection were documented during the 12-month follow-up period.

CONCLUSION: In this retrospective clinical series, nasal sill resection performed concomitantly with maxillary orthognathic surgery was associated with maintenance of nasal base width close to the preoperative baseline at 12 months, despite an initial postoperative narrowing. Patient-reported nasal aesthetic scores improved during follow-up. However, because of the uncontrolled retrospective design, limited sample size, and absence of objective functional assessment, these findings should be interpreted as descriptive clinical observations and should be further investigated in prospective controlled studies.

PMID:42321823 | DOI:10.1186/s12903-026-08949-5

BMC Med Genomics. 2026 Jun 19. doi: 10.1186/s12920-026-02396-5. Online ahead of print.

ABSTRACT

BACKGROUND: Fluoroquinolone-resistant Escherichia coli is a major global clinical threat, particularly in low- and middle-income countries like Nigeria. However, the full genomic landscape, including the relative contributions of chromosomal mutations, plasmid-mediated resistance, and the role of high-risk clones, remains poorly characterized in this setting. This study aimed to define the genomic mechanisms, clonal distribution, and genotype-phenotype relationships of fluoroquinolone resistance in clinical E. coli isolates from Nigeria.

METHODS: A cross-sectional study of 107 clinical E. coli isolates was conducted. Phenotypic susceptibility to ciprofloxacin and nalidixic acid was determined using VITEK 2 and broth microdilution. Whole-genome sequencing was performed, and analysis included detection of quinolone resistance determining region (QRDR) mutations (gyrA, parC, parE) and plasmid-mediated quinolone resistance (PMQR) genes, multilocus sequence typing (MLST), and phylogenetic analysis. Statistical associations were evaluated using chi-squared tests or Fisher’s exact tests.

RESULTS: Ciprofloxacin non-susceptibility was high at 86.0%. Resistance was primarily driven by a conserved chromosomal mutation profile; the combination of gyrA S83L, gyrA D87N, and parC S80I was present in 85 isolates and was associated with ciprofloxacin non-susceptibility in all affected isolates in this cohort. Isolates with only gyrA mutations were resistant to nalidixic acid but susceptible to ciprofloxacin, consistent with a stepwise resistance pathway. In this cohort, the triple QRDR signature (gyrA S83L + gyrA D87N/Y + parC S80I) was a perfect positive predictor of ciprofloxacin non-susceptibility (85/85; 100%). The ST131 lineage dominated, accounting for 21.5% of isolates and universally carrying the complete triple QRDR profile; notably, no ST131 isolate carried a PMQR determinant. Plasmid-mediated quinolone resistance (PMQR) genes were detected in 15.0% of isolates but were not independently associated with ciprofloxacin non-susceptibility in this cohort in the absence of concomitant QRDR mutations. Efflux pump genes were ubiquitous and non-predictive. Notably, six isolates, all from urine, were non-susceptible (R/I) despite lacking all known QRDR and PMQR determinants, pointing to uncharacterized mechanisms. In a multivariable logistic regression model that included ST131 status, PMQR carriage, and parE mutation status, ST131 was associated with ciprofloxacin non-susceptibility (adjusted OR 5.96, 95% CI 1.21-29.4, p = 0.028), whereas PMQR carriage was not (adjusted OR 0.94, 95% CI 0.18-4.85, p = 0.94). The triple QRDR signature was not included in this model because it perfectly predicted ciprofloxacin non-susceptibility in this cohort. Resistance patterns varied by clinical source, with the highest burden in bloodstream and wound infections. This stepwise hierarchy from first-step gyrA mutations to the classic triple QRDR profile is summarised in the graphical abstract, Fig. 1.

CONCLUSIONS: Fluoroquinolone resistance in Nigerian clinical E. coli is predominantly driven by chromosomal QRDR mutations within successful clones like ST131. PMQR genes and efflux pumps appeared to play a supplementary role rather than being independent drivers of ciprofloxacin resistance in this cohort. These data support prioritising key QRDR mutations in genomic reporting and local stewardship decisions, while the QRDR-negative resistant urine isolates require further investigation.

PMID:42321812 | DOI:10.1186/s12920-026-02396-5