Category: Statistics

Clin Rheumatol. 2026 Apr 15. doi: 10.1007/s10067-026-08120-z. Online ahead of print.

ABSTRACT

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by profound metabolic perturbations and dysregulated crosstalk between immune cells and fibroblast-like synoviocytes (FLS). Phenylalanine (PHE), an aromatic amino acid, has been implicated in RA-related metabolic disorders, but its direct immunomodulatory effects on human primary FLS and peripheral blood lymphocytes remain unclear. This study aimed to identify RA-specific metabolic signatures via untargeted metabolomics and validate PHE’s functional role in regulating core pathogenic cells in RA.

METHODS: LC-MS/MS-based untargeted metabolomics was performed on serum from 123 RA patients (2010 ACR/EULAR criteria) and 106 age/sex-matched healthy controls. Differential metabolites and pathways were identified via multivariate statistical analysis (PCA, OPLS-DA) and KEGG enrichment. Primary FLS and peripheral blood lymphocytes were treated with 100 μmol/L PHE (matching RA serum levels). CCK-8, qPCR, multiplex cytokine detection and flow cytometry were used to assess cell viability, pro-inflammatory gene expression, cytokine secretion, and apoptosis.

RESULTS: Metabolomic profiling revealed clear separation between RA and controls, with significant enrichment in phenylalanine metabolism. Eight novel RA-specific biomarkers were identified. Functional validation showed that PHE significantly upregulated mRNA expression of IL-6, IL-8, CXCL12, and MMP3 in FLS (1.8-7.2-fold, all p < 0.01) and enhanced secretion of IL-6 (115 → 180 pg/mL), IL-8 (300 → 550 pg/mL), and CCL2 (3000 → 5500 pg/mL) (all p < 0.01). In lymphocytes, PHE promoted secretion of IL-1β, TNF-α, IL-6, and CXCL8 (all p < 0.001) and increased total apoptosis rate (8.3% → 18.7%, p < 0.01).

CONCLUSION: This study reveals distinct metabolic features in RA patients, confirming PHE as a key pro-inflammatory metabolite that modulates FLS and lymphocyte functions. Key Points • Serum untargeted metabolomics of an RA cohort identifies 8 novel biomarkers and core dysregulated pathways, including phenylalanine metabolism and acylcarnitine-mediated fatty acid β-oxidation. • Phenylalanine directly activates FLS, upregulating pro-inflammatory cytokines, chemokines, and matrix metalloproteinases, enhancing their tissue-destructive potential. • Phenylalanine promotes pro-inflammatory cytokine secretion and induces apoptosis in RA peripheral blood lymphocytes, disrupting immune homeostasis.

PMID:41984350 | DOI:10.1007/s10067-026-08120-z

Appl Health Econ Health Policy. 2026 Apr 15. doi: 10.1007/s40258-026-01043-5. Online ahead of print.

ABSTRACT

OBJECTIVES: Cardiovascular diseases (CVDs) are a leading contributor to morbidity, mortality, and healthcare spending in low- and middle-income countries (LMICs). Despite this burden, economic evidence on system-level interventions to strengthen hypertension and CVD care in sub-Saharan Africa remains limited. This study estimates the costs and budget impact of the Ghana Heart Initiative (GHI), a multi-component health systems strengthening intervention.

METHODS: We conducted a retrospective cost analysis from the health system perspective using an activity-based costing approach. We estimated the financial and economic costs incurred during the design (2018-2019) and initial implementation phase (2020-2022) of the GHI across 42 public health facilities in the Greater Accra Region. Costs were disaggregated by activity cluster and input category. We then projected the budget impact of hypothetical national scale-up under three implementation scenarios that varied in scope and cost-sharing assumptions. All costs were inflation-adjusted and reported in 2024 US dollars (US $).

RESULTS: The total economic cost of designing and implementing the GHI over 4 years was US$1.96 million, of which 91.5% was attributable to implementation activities. Human resources were the primary cost driver. Average annual economic costs were US$11,960 per health facility, US$997 per targeted health provider trained, and US$39.9 per outpatient attendee. Projected annual costs for nationwide scale-up ranged from US$12.1 million to US$30.1 million, depending on implementation scenario, with a streamlined service-delivery-only model representing a lower-bound estimate.

CONCLUSIONS: This study provides granular, activity-level cost estimates for a complex health system strengthening intervention targeting hypertension and CVD care. The findings offer policy-relevant inputs for budget planning and highlight how implementation choices influence the fiscal implications of scaling up system-level CVD interventions in LMICs.

PMID:41984319 | DOI:10.1007/s40258-026-01043-5

J Youth Adolesc. 2026 Apr 15. doi: 10.1007/s10964-026-02357-2. Online ahead of print.

NO ABSTRACT

PMID:41984318 | DOI:10.1007/s10964-026-02357-2

Ecohealth. 2026 Apr 15. doi: 10.1007/s10393-026-01792-8. Online ahead of print.

ABSTRACT

Kashin-Beck disease (KBD) is an endemic disease characterized by its complex etiology and severe impact on human health. It is also regarded as one of the most serious endemic disease in China. This study aimed to investigate the spatial correlation and determinants of this disease. Monitoring data of children and possible influencing factors were collected from 37 KBD regions in Gansu Province. The spatial autocorrelation method was used to describe the spatial aggregation of KBD, and the spatial regression analysis was used to explore the natural environment and socioeconomic factors influencing KBD incidence. The results showed that the X-ray detection rate of KBD demonstrated a significant negative spatial correlation, with Kangle county and its neighboring areas located in southcenter of Gansu Province were hot spots of KBD. The spatial lag model revealed that rainfall, the proportion of afforestation in cultivated land, and population density had negative effects on the X-ray detection rate of KBD. The prevalence of KBD in Gansu Province is determined by a combination of natural environment and socioeconomic factors. Precision prevention and control should be implemented by the specific conditions of each diseased region.

PMID:41984302 | DOI:10.1007/s10393-026-01792-8

Prog Orthod. 2026 Apr 15;27(1):17. doi: 10.1186/s40510-026-00621-6.

ABSTRACT

BACKGROUND: Digital treatment planning software in clear aligner (CA) therapy incorporates virtual simulations to generate planned tooth movements. While baseline tooth positions constitute one of the geometric inputs to digital setups, limited information is available regarding the association between pre-treatment positional asymmetry and the magnitude of planned movements, and how these associations vary by tooth and movement type.

METHODS: A retrospective analysis was conducted on 65 patients (390 anterior teeth) treated with Invisalign^®. Baseline malpositions of anterior teeth were measured using 3D digital models in ClinCheck^®, while planned movements-including rotation, angulation, extrusion, and intrusion-were extracted from the corresponding digital treatment plans. Baseline asymmetry between contralateral teeth was calculated to quantify movement complexity. General Linear Model (GLM) regression analyses were employed to assess the relationship between initial asymmetry and the magnitude of planned movements. Descriptive statistics and normality assessments were also performed.

RESULTS: In the 11-21 tooth pair, baseline asymmetry was significantly associated with planned extrusion (p = .002) and rotation (p < .001), but not intrusion (p = .190) or angulation (p = .270). For the 12-22 pair, significant associations were observed for intrusion (p = .008), angulation (p < .001), and rotation (p < .001), but not extrusion (p = .493). In the 13-23 pair, only extrusion was significantly associated with baseline differences (p < .001); no significant effects were observed for the other movement types.

CONCLUSION: Baseline positional asymmetry was associated with variation in planned extrusion, intrusion, and rotation movements within digital CA setups. These findings should be interpreted as descriptive associations rather than evidence of software-imposed constraints or internal planning strategies, and underscore the relevance of baseline geometry when interpreting digitally planned tooth movements.

PMID:41984292 | DOI:10.1186/s40510-026-00621-6

Physiol Plant. 2026 Mar-Apr;178(2):e70871. doi: 10.1111/ppl.70871.

ABSTRACT

The external traits of Lycium barbarum L. fruits are primary determinants of their commercial value. Ovary locule number is a fundamental developmental structure hypothesized to be a key intrinsic factor influencing these traits. However, systematic investigation into its specific role remains limited. This study systematically investigated the correlation between locule number and key fruit traits, and compared differences between wild and cultivated accessions from the Ningxia region. Multivariate statistical analyses, including correlation analysis and principal component analysis, were employed. The results revealed an unbalanced distribution of locule number, with bilocular ovaries predominating. Furthermore, locule number showed significant positive correlations with size-related traits (single fruit weight, fruit area) but negative correlations with shape indices (fruit shape index, length-to-width ratio). Interestingly, the average locule number in cultivated L. barbarum was significantly higher than in wild accessions. Cultivated accessions exhibited distinct domestication characteristics, including greater single-fruit weight, altered fruit shape index, and color. Single fruit weight and fruit roundness are identified as key indicators for predicting locule number. We conclude that ovary locule number is a key intrinsic factor determining fruit size and shape, with a trade-off: increased locule number promotes enlargement but leads to a rounder shape. Domestication has preferentially selected for genotypes with more locules and larger fruit size. Therefore, locule number can serve as an effective early phenotypic marker for quality breeding programs in L. barbarum.

PMID:41983368 | DOI:10.1111/ppl.70871

Int J Fertil Steril. 2026 Apr 13;20(2):154-158. doi: 10.22074/ijfs.2025.2042418.1769.

ABSTRACT

BACKGROUND: The prognostic value of borderline and pathological sperm morphology (SM) in infertility treatment remains unclear. This study aims to evaluate the potential impact of SM on clinical pregnancy outcomes following intrauterine insemination (IUI).

MATERIALS AND METHODS: This retrospective study reviewed IUI outcomes conducted between July 2012 to January 2017 at an infertility treatment center. Couples who underwent IUI and subsequently achieved a clinical pregnancy were included. Based on semen analysis according to the 6th edition of World Health Organization (WHO) guidelines, the couples were divided into two groups: borderline (4-13% normal forms) and pathological (<4% normal forms) SM. The study assessed the association between SM and pregnancy outcomes, specifically live birth and spontaneous abortion rates.

RESULTS: A total of 111 IUI cycles with confirmed clinical pregnancy were analyzed. Gestational complication rates were 8.3% in the borderline SM group and 17.3% in the pathological SM group, this difference was not statistically significant (P=0.255). However, live birth rates differed significantly between the two groups (borderline: 91.7%, pathological: 69.3%; P=0.009). Overall abortion rates were significantly higher in the Pathological SM group (borderline: 2.8%, pathological: 26.7%; P=0.001). First-trimester abortion rates were 5.6% and 18.7% in the borderline and pathological SM groups, respectively. Logistic regression analysis revealed that for every one-unit increase in the percentage of morphologically normal sperm, the odds of abortion decreased by a factor of 0.6 (P=0.017; OR=0.614; 95% CI: 0.412-0.916).

CONCLUSION: Pathological SM is associated with a significantly higher risk of first-trimester abortion. Therefore, SM is highlighted as a potential predictor of IUI outcomes following clinical pregnancy. Subsequently, SM should be considered a critical factor in fertility assessments, and alternative treatment strategies may be more appropriate for couples with pathological SM undergoing infertility treatment.

PMID:41983363 | DOI:10.22074/ijfs.2025.2042418.1769

Int J Fertil Steril. 2026 Apr 13;20(2):115-123. doi: 10.22074/ijfs.2025.2055868.1841.

ABSTRACT

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder and a leading cause of anovulatory infertility. This study evaluated whether adding vitamin E to a regimen of letrozole, tamoxifen, and estradiol improves ovulation outcomes in infertile women with PCOS.

MATERIALS AND METHODS: In a double-blind, randomized clinical trial conducted in Jahrom, Iran (December 2023-August 2024), 90 infertile women with PCOS were randomly assigned to two groups. Group A (n=45) received letrozole, tamoxifen, estradiol, and vitamin E, while group B (n=45) received the same regimen without vitamin E. The primary outcome was pregnancy rate; secondary outcomes included follicle size, count, and endometrial thickness, measured on cycle days 3, 7, and 12. Data were analyzed using Chi-square, Fisher’s exact, and t tests (Stata 14).

RESULTS: Baseline characteristics including age (mean: 31.21 ± 6.31 Y), BMI (24.96 ± 3.45 kg/m²), and infertility duration (3.48 ± 2.70 Y) were similar between groups (P>0.05). On day 7, the vitamin E group showed significantly larger follicles (14.15 ± 0.36 mm vs. 10.90 ± 0.68 mm), more follicles (5.16 ± 0.36 vs. 3.73 ± 0.83), and thicker endometrium (7.16 ± 0.36 mm vs. 5.16 ± 0.36 mm). These advantages persisted on day 12, including improved follicular maturity and endometrial thickness. Although the pregnancy rate was higher in the vitamin E group (11.1% vs. 6.7%), the difference was not statistically significant (P=0.457). Adverse effects, including ovarian hyperstimulation syndrome (OHSS) and irregular bleeding, did not differ significantly (P=0.553).

CONCLUSION: The results indicate that the addition of vitamin E to the letrozole-tamoxifen-estradiol protocol might be associated with improved ovulatory outcomes in women with PCOS. Nevertheless, no significant effect on pregnancy rates was observed. These findings highlight the potential adjunctive role of vitamin E in ovulation induction among women with PCOS, although further large-scale randomized trials are needed to confirm its clinical relevance (number registration: IRCT20150407021653N20).

PMID:41983358 | DOI:10.22074/ijfs.2025.2055868.1841

BJS Open. 2025 Mar 5;10(2):zrag025. doi: 10.1093/bjsopen/zrag025.

ABSTRACT

BACKGROUND: Patients with sleep apnoea are at increased risk of postoperative cardiac and respiratory complications, but its prevalence in patients undergoing abdominal cancer surgery is poorly defined. The aim of this study was to estimate the prevalence of sleep apnoea in patients undergoing colorectal cancer surgery compared with community-based controls, and to assess the utility of symptoms, signs, and the STOP-Bang questionnaire in identifying sleep apnoea.

METHODS: This prospective observational study included consecutive patients scheduled for colorectal cancer surgery at Umeå University Hospital, Sweden, between 7 January 2015 and 24 May 2020. Overnight polysomnography, including electroencephalogram-based sleep scoring, was undertaken before operation. Prevalence estimates were compared with those of two community-based cohorts from Uppsala, Sweden (female participants from the Sleep and Health in Women cohort; male participants from the Men in Uppsala: A Study of Sleep Apnoea and Cardiometabolic Health cohort). The primary outcome was the prevalence of sleep apnoea.

RESULTS: Of 268 eligible patients, 5 were receiving continuous positive airway pressure therapy and 201 underwent successful polysomnography. Moderate-to-severe sleep apnoea was identified in 98 of 206 patients (48 (95% confidence interval 41 to 54)%) undergoing colorectal cancer surgery, with a similar prevalence in men and women. Among 597 community-based controls, moderate-to-severe sleep apnoea was present in 27 (24 to 31)%. After adjustment for age, sex, and body mass index, the odds ratio for moderate-to-severe sleep apnoea in patients with colorectal cancer was 1.57 (95% confidence interval 1.08 to 2.29; P = 0.019). The STOP-Bang questionnaire demonstrated acceptable sensitivity (85 (95% confidence interval 76 to 91)%) but low specificity (42 (33 to 52)%).

CONCLUSION: Approximately half of patients undergoing colorectal cancer surgery have moderate-to-severe sleep apnoea, exceeding the prevalence in community-based controls. Clinical symptoms, signs, and STOP-Bang screening are insufficient to reliably identify affected patients, indicating that overnight sleep apnoea assessment is required in this population.

PMID:41983353 | DOI:10.1093/bjsopen/zrag025

Eur J Prev Cardiol. 2026 Apr 15:zwag203. doi: 10.1093/eurjpc/zwag203. Online ahead of print.

ABSTRACT

AIM: A high polygenic score for coronary artery disease (PRSCAD) has been demonstrated to be a strong and independent predictor of atherosclerotic cardiovascular disease (ASCVD) in patients with familial hypercholesterolemia (FH). The objective was to investigate if the addition of a PRSCAD to the FH-Risk-Score enhances ASCVD risk prediction compared to the clinical score alone.

METHODS: Data from 3 independent cohorts of patients with FH have been analysed in this longitudinal study (n=1438). The FH-Risk-Score equation was used to calculate the baseline 10-year ASCVD risk. A high PRSCAD was defined as a score > 75th percentile. The performance of the Combined score was assessed using measures of discrimination (C statistics), calibration (predicted risk vs. observed risk), and reclassification (using a 10-year risk cutoff of 20%).

RESULTS: Overall, the event rate was nearly doubled in individuals having a high PRSCAD (15% vs. 9%, HR 1.77, 95% CI 1.20-2.61, P=0.004). This association was stronger in those with a genetic confirmation of FH (17% vs. 8%, HR 2.34, 95% CI 1.50-3.67, P=0.0002). The Combined score was associated with a marginally non-significant higher C-index than the FH-Risk-Score alone (0.746 to 0.750, P=0.60). The difference in C-index was significant in patients with a genetic confirmation of FH in the moderate FH-Risk-Score group (0.617 to 0.717, P=0.05).

CONCLUSION: Overall, the addition of polygenic information using PRSCAD percentiles to the FH-Risk-Score estimate did not significantly enhance ASCVD risk prediction in patients with FH. Replication efforts with larger number of individuals and incident cases are warranted.

PMID:41983333 | DOI:10.1093/eurjpc/zwag203