Category: Statistics

Asia Pac J Clin Oncol. 2026 Jul 28. doi: 10.1111/ajco.70147. Online ahead of print.

ABSTRACT

AIM: Tumor heterogeneity, driven by metabolic reprogramming, challenges colorectal cancer (CRC) treatment. Methionine metabolism is crucial for tumor progression, but its role in CRC heterogeneity and the tumor immune microenvironment (TIME) requires systematic investigation.

METHODS: A systematic evaluation of 101 combinations of machine learning and statistical algorithms was conducted within a 10-fold cross-validation framework to develop and validate the optimal model, termed the methionine metabolism-related risk score (MMRS). The Cancer Genome Atlas-Colon Adenocarcinoma (TCGA-COAD) dataset served as the training cohort, while two independent Gene Expression Omnibus (GEO) cohorts (GSE39582 and GSE17536) were employed for external validation. Immune infiltration was assessed using the microenvironment cell populations-counter (MCP-counter) algorithm. Model discrimination was evaluated using time-dependent receiver operating characteristic (ROC) analysis, with the area under the curve (AUC) calculated at 1, 3, and 5 years across all cohorts.

RESULTS: Methionine metabolism-high (MMH) and metabolism-low (MML) subtypes were defined via unsupervised clustering. The MMH subtype exhibited significantly poorer overall survival and an immunosuppressive TIME. From subtype-associated differentially expressed genes (DEGs), 41 prognostic genes were identified. The optimal model (StepCox[both] + plsRcox) formed the MMRS, which effectively stratified patients into high- and low-risk groups with significantly different survival across all cohorts (all p < 0.05). Core signature genes (MID2, KIF7, GSR) were consistently selected. The high-risk group showed depleted antitumor immunity (e.g., fewer CD8+ T and NK cells) and a stroma-rich phenotype with enrichment of cancer-associated fibroblasts, underpinned by oxidative stress and alterations in energy metabolism pathways. Time-dependent ROC analysis confirmed the discriminative capacity of the MMRS, with 5-year AUCs of 0.803 (TCGA-COAD), 0.632 (GSE39582), and 0.608 (GSE17536), respectively, further supporting its prognostic accuracy across independent patient populations.

CONCLUSION: Methionine metabolism heterogeneity is a key determinant of prognosis and immune contexture in CRC. The MMRS is a prognostic signature that effectively stratifies CRC patients by risk, though its clinical utility as a predictive biomarker for treatment selection requires prospective validation.

PMID:42521983 | DOI:10.1111/ajco.70147

Forensic Sci Med Pathol. 2026 Jul 29. doi: 10.1007/s12024-026-01319-1. Online ahead of print.

ABSTRACT

S100B is a calcium-binding protein primarily found in astrocytes and Schwann cells. Accurate estimation of post-mortem interval is vital for reconstructing death timelines and guiding law enforcement. Similarly, precise determination of cause of death serves both legal and medical purposes, aiding judicial outcomes and informing public health strategies. This study aimed to assess serum S100B levels in trauma-related deaths, focusing on head and extracranial injuries, and their variation with postmortem intervals. Serum samples were collected from eighty subjects, including forty trauma cases with head and extracranial injuries and forty non-traumatic controls. Serum S100B concentrations were measured and statistically compared between trauma-related deaths and non-traumatic controls. S100B levels were also measured across different postmortem intervals (0, 6, 12, 24, 48, and 60 h). The current study showed that there was a significant increase in S100B levels in the study group (trauma-related deaths) compared to the control group, with a p-value < 0.001, and no significant differences between head and extracranial causes of death. There was also a significant elevation in S100B concentrations from 0 to 6 h postmortem (p < 0.001). After 6 h post-mortem, several S100B measurements exceeded the assay’s upper reportable limit (4000 ng/L), limiting precise quantification beyond this range. In conclusion, post-mortem serum S100B demonstrates potential as a supplementary tool for early post-mortem interval estimation and differentiating trauma-related deaths, regardless of head injury involvement. However, values beyond 12 h post-mortem exceed assay detection limits, highlighting the need for extended measurement ranges in forensic applications.

PMID:42521978 | DOI:10.1007/s12024-026-01319-1

J Thromb Thrombolysis. 2026 Jul 28. doi: 10.1007/s11239-026-03376-3. Online ahead of print.

ABSTRACT

A growing proportion of patients admitted to the intensive care unit (ICU) receive chronic oral anticoagulation with direct oral anticoagulants (DOACs) or warfarin. The comparative safety of continuing DOACs versus warfarin during critical illness remains uncertain. We evaluated bleeding and clinical outcomes among ICU patients who continued the same oral anticoagulant during the early ICU course. We conducted a retrospective cohort study of adult ICU admissions across Mayo Clinic sites from 2012 to 2023. Eligible patients were taking a DOAC or warfarin at ICU admission and continued the same anticoagulant during the first three ICU calendar days. The primary outcome was major bleeding during the index hospitalization. Secondary outcomes included ICU and hospital mortality, ICU- and hospital-free days, bleeding subtypes, and need for procedural interventions. Among 6,258 eligible ICU admissions, 2,410 patients continued the same oral anticoagulant during the first three ICU calendar days, including 1,074 continuing DOAC therapy and 1,336 continuing warfarin therapy. In the multivariable analysis, there was no statistically significant difference in major bleeding events, (aOR 1.34, 95% CI 0.89-2.02; p = 0.161) between the DOACs and warfarin groups, respectively. Gastrointestinal bleeding (GI) was more frequent among patients continuing warfarin and remained significant after adjustment (adjusted OR 3.90, 95% CI 1.91-7.94; p < 0.001). Hospital mortality was lower with warfarin use than DOACs (5.6% vs 11.6%; p < 0.001; aOR 0.47, 95% CI 0.33-0.68). Among ICU patients selected to continue their baseline oral anticoagulant, continued DOAC therapy was not associated with higher adjusted odds of major bleeding and was associated with lower GI bleeding events than warfarin, but this bleeding advantage did not translate into lower mortality. This discordance suggests that the mortality in this population is driven largely by illness severity, comorbidity, unmeasured confounding and other non-bleeding related pathways.

PMID:42521975 | DOI:10.1007/s11239-026-03376-3

Environ Sci Pollut Res Int. 2026 Jul 28. doi: 10.1007/s11356-026-38083-2. Online ahead of print.

ABSTRACT

Air pollution remains an environmental health risk, with particulate matter (PM_2.5) disproportionately affecting vulnerable communities. Allegheny County, Pennsylvania, a high-PM_2.5 region, requires assessment of exposure variability and risk. This study evaluated spatial and seasonal variation in PM_2.5-equivalent concentrations using community monitoring from 290 homes across Allegheny County (2016-2021). Particle counts (> 0.5 µm) from the ROCIS Low-Cost Monitoring Project were converted to estimated PM_2.5-equivalent mass concentrations, and census tracts were classified by environmental justice (EJ) status and proximity to industrial sources using GIS. Generalized estimating equation (GEE) models assessed spatial and seasonal patterns, and noncancer risks were estimated using hazard quotients (HQs). Overall, 33.8% of the study sites (n = 290) exceeded the WHO 2021 24-h guideline (15 µg/m³) and the 66.6% EPA annual reference (9 µg/m³), based on 3-week site medians-screening-level comparisons rather than regulatory determinations. Compared to the WHO 2021 24-h guideline, median (mean ± SD) PM_2.5 concentrations were highest in Sewickley-median 19.3 µg/m³, range = 6.1-22.8 µg/m³ (16.1 ± 8.8 µg/m³), with GEE estimated at 62% above the Etna baseline, though this rests on only three homes and should be read as exploratory. Winter concentrations were significantly elevated (p < 0.001), with the combined cold season (winter and fall) exceeding the warm season (p < 0.05). Although EJ differences were not statistically significant, 42% of municipalities had HQ ≥ 1, indicating potential noncancer risks. These results highlight fine-scale pollution variability not captured by regulatory monitors and underscore the need for spatially resolved assessments to guide public health interventions.

PMID:42521969 | DOI:10.1007/s11356-026-38083-2

Am J Clin Dermatol. 2026 Jul 28. doi: 10.1007/s40257-026-01060-z. Online ahead of print.

ABSTRACT

BACKGROUND: Alopecia areata is an autoimmune disorder characterised by T-cell-mediated damage of hair follicles, resulting in non-scarring hair loss that can progress to complete scalp (alopecia totalis) or body hair loss (alopecia universalis). While long-term systemic options were historically limited, the emergence of Janus kinase (JAK) inhibitors has revolutionised the treatment of alopecia areata, even in patients with moderate-to-severe disease.

OBJECTIVE: We aimed to evaluate the efficacy and safety of oral JAK inhibitors compared with placebo in adults and adolescents with moderate-to-severe alopecia areata.

METHODS: MEDLINE, Embase and the Cochrane Central Register of Controlled Trials databases were searched from inception to 28 November, 2025. Randomised controlled trials evaluating oral JAK inhibitors in adolescents and adults (aged ≥12 years) with alopecia areata were included. Data extraction and risk of bias assessment were performed independently by multiple reviewers. Primary outcomes were the proportion of patients who achieved Severity of Alopecia Tool (SALT) scores of ≤10 and ≤20, and 50%, 75% and 90% reductions in SALT scores from baseline, as well as treatment-related adverse events (AEs). Data were synthesised using random-effects models to calculate odds ratios (ORs) and mean differences with 95% confidence intervals (CIs).

RESULTS: Twelve randomised controlled trials involving 4141 participants (mean age 35.8 years, mean baseline SALT score 86.0) met the inclusion criteria. All trials enrolled adult participants, with the exception of one randomised controlled trial in which adolescents comprised 15% of the study population. Six trials were rated as having a low risk of bias, while six had “some concerns” primarily because of missing outcome data. Oral JAK inhibitors were significantly more effective than placebo across all primary efficacy endpoints. At week 24, the odds of achieving SALT ≤10 were 5.69 times higher for JAK inhibitors than placebo (95% CI 3.58-9.03); by week 36, this effect increased to an OR of 9.40 (95% CI 4.58-19.29). For SALT ≤20, the OR was 7.99 (95% CI 5.13-12.44) at week 24. Patients treated with oral JAK inhibitors were significantly more likely to achieve SALT50, SALT75 and SALT90 across all timepoints (weeks 12-36). Regarding safety, JAK inhibitors were associated with a higher risk of total AEs (OR 1.60; 95% CI 1.33-1.94), but no statistically significant difference was found for serious AEs (OR 1.04; 95% CI 0.69-1.57) or treatment discontinuation because of AEs (OR 1.22; 95% CI 0.84-1.76).

CONCLUSIONS: Oral JAK inhibitors are effective in promoting scalp, eyebrow and eyelash hair regrowth in adults and adolescents with moderate-to-severe alopecia areata, with a trend of higher response rates at later timepoints across studies. The favourable safety profile of these agents is reassuring. Future research should prioritise head-to-head randomised controlled trials and long-term pharmacovigilance to define comparative efficacy and safety.

PMID:42521957 | DOI:10.1007/s40257-026-01060-z

Geroscience. 2026 Jul 28. doi: 10.1007/s11357-026-02416-3. Online ahead of print.

ABSTRACT

Nonhuman primates are widely used in preclinical biomedical research, with hematobiochemical values serving as key clinical pathology parameters for assessing health status. In this study, we collected and analyzed 2973 blood samples from 566 cynomolgus macaques and 193 rhesus macaques, along with anthropometric measurements such as BMI, body weight, and waist circumference. Corresponding human data were obtained from the NHANES database and incorporated into the study. Regarding white blood cell composition, neutrophil percentages increased while lymphocyte percentages declined with age, with relatively sharp changes observed during both the early stage near sexual maturity and the late stage near aging onset in our macaque and human datasets. The inflammatory indices, calculated based on these compositions, showed similar age-related trends, reflecting age-associated immune modulation in primates. The inflection points approximately correspond to the ages of sexual maturation and aging onset. The statistical analyses predicted a divergence: human aging is primarily defined by metabolic syndrome caused by excess waste accumulation, whereas aging in cynomolgus macaques is fundamentally linked to nutrient deficiency and physical frailty. Despite this contrast, our findings also revealed convergent aging markers across primates. In summary, this study establishes reference indices for hematological and biochemical parameters in macaques, providing valuable insights into age-related changes in primate blood profiles.

PMID:42521934 | DOI:10.1007/s11357-026-02416-3

Environ Monit Assess. 2026 Jul 28;198(8):889. doi: 10.1007/s10661-026-15736-w.

ABSTRACT

Urban expansion modifies land surface characteristics and can influence local climatic conditions, particularly in arid coastal cities where urban processes interact with regional atmospheric forcing. This study investigated long-term relationships among land cover change, population growth, and summer climate variability in Jeddah, Saudi Arabia, using Landsat-derived Normalized Difference Vegetation Index (NDVI), Normalized Difference Built-up Index (NDBI), annual population estimates, and meteorological observations spanning 1992-2022. Temporal trends were evaluated using linear regression, while Pearson correlation and multiple regression analyses were applied to assess associations between urbanization indicators and climatic variables. The results show significant increases in vegetation cover and population together with a significant decline in NDBI over the study period, indicating substantial changes in the urban landscape. In contrast, July air temperature and relative humidity exhibited comparatively weak long-term trends. Built-up intensity showed a significant negative association with July relative humidity, whereas relationships with temperature were weak and statistically nonsignificant. Multiple regression analyses further indicated that land cover characteristics and population explained only a modest proportion of climatic variability. These findings suggest that urban land cover change influences atmospheric moisture more strongly than summer air temperature, while regional atmospheric and coastal processes remain the dominant controls on climate variability in Jeddah. The study provides empirical evidence to support climate-responsive urban planning and sustainable adaptation strategies in rapidly urbanizing arid coastal cities.

PMID:42521932 | DOI:10.1007/s10661-026-15736-w

Biol Trace Elem Res. 2026 Jul 29. doi: 10.1007/s12011-026-05262-8. Online ahead of print.

ABSTRACT

The zinc-to-copper ratio (ZCR) reflects essential metal balance and may be relevant to cardiovascular regulation, yet its association with hypertension in populations exposed to environmental heavy metals remains unclear. We conducted a cross-sectional study of 966 adults (≥ 30 years, recruited in 2008) comprising an exposed group (n = 564) residing within 4 km of the Janghang copper smelter and a non-exposed control group (n = 402) from a rural area approximately 15 km away. Serum zinc, copper, and nickel, along with blood lead, mercury, and urinary cadmium and arsenic were measured. Associations between ZCR and blood pressure were examined using multivariable linear regression, logistic regression, Bayesian kernel machine regression (BKMR), and restricted cubic spline (RCS) analyses, with sensitivity analyses. Higher ZCR was associated with increased systolic and diastolic blood pressure in fully adjusted linear models (SBP: β = 1.75, p = 0.002; DBP: β = 1.47, p < 0.001), with consistent associations in both exposed and control groups. In logistic regression, participants in the highest ZCR tertile had higher odds of hypertension than those in the lowest tertile (adjusted OR = 1.91; 95% CI: 1.25-2.93; p = 0.003). When stratified, the association was more pronounced in the non-exposed group (OR = 2.29; 95% CI: 1.18-4.45; p = 0.014) and somewhat attenuated but still suggestive in the exposed group (OR = 1.71; 95% CI: 0.96-3.06; p = 0.069); the formal interaction test was not statistically significant (p = 0.561). Sensitivity analyses, including exclusion of antihypertensive medication users, yielded consistent findings (OR = 1.83; 95% CI: 1.19-2.80), and the E-value (1.97) indicated limited-to-moderate robustness to unmeasured confounding. Higher ZCR is consistently associated with hypertension across analytical approaches and subgroups, with a suggestive but not statistically significant pattern of effect modification by environmental metal exposure. These findings support ZCR as a potentially informative indicator of essential metal imbalance relevant to blood pressure, warranting further investigation in prospective settings.

PMID:42521928 | DOI:10.1007/s12011-026-05262-8

Biol Trace Elem Res. 2026 Jul 28. doi: 10.1007/s12011-026-05261-9. Online ahead of print.

ABSTRACT

This study aimed to systematically investigate the relationship between mixed heavy metal exposure and serum C-reactive protein (CRP) level using an integrated multi-model statistical strategy. This study included 568 participants from the Manganese-Exposed Workers Healthy Cohort. Serum CRP and 20 blood metal concentrations were measured. Key metals were selected via LASSO regression and overall mixture effects and metal contributions were quantified by Quantile g-computation; and joint effects, nonlinearity, and interactions were evaluated using Bayesian Kernel Machine Regression (BKMR). LASSO regression identified 9 key metals (Calcium, Nickel, Copper, Titanium, Tin, Vanadium, Selenium, Arsenic, Rubidium). GLM revealed inverse linear associations for Ca, Se, Rb, and Ni, and a positive association for Cu with CRP. Quantile g-computation showed the overall mixture was significantly inversely associated with CRP (HR = 0.955, 95% CI: 0.918, 0.996), with calcium contributing the largest negative weight (-0.31). BKMR indicated that the overall mixture effect showed a monotonic decreasing trend across exposure quantiles, with a significant positive association at lower quantiles (0.25-0.5). BKMR also identified a significant positive interaction for tin (posterior mean = 0.051, 95% CI: 0.004, 0.098), with calcium showing the highest posterior inclusion probability (PIP = 0.972). This study suggests that metal mixtures exert exposure-level-dependent effects on CRP with complex interactions. Calcium may act as a central regulator, while tin shows amplified effects at higher co-exposure levels. These findings advance mechanistic understanding of mixture toxicology and inform exposure-level-specific risk assessment.

PMID:42521926 | DOI:10.1007/s12011-026-05261-9

Hematol Transfus Cell Ther. 2026 Jul 28;48(4):106490. doi: 10.1016/j.htct.2026.106490. Online ahead of print.

ABSTRACT

BACKGROUND: Hematopoietic stem cell transplantation is the sole therapeutic approach that can provide a complete cure for thalassemia. However, this procedure is associated with complications that may have life-threatening consequences. To date, long-term survival outcomes after transplantation in thalassemia have not been systematically synthesized. This study aims to specifically evaluate long-term overall survival in patients with thalassemia undergoing hematopoietic stem cell transplantation.

METHODS: A comprehensive search was conducted across multiple databases, including PubMed, CENTRAL, Europe PMC (incorporating medRxiv and bioRxiv), EBSCOHost (Medline), and ProQuest. The search spanned from the inception of each database through July 10, 2024, using a combination of predefined keywords: ‘Hematopoietic Stem Cell Transplantation’, ‘Thalassemia’, ‘Survival Rates’, and synonyms. Risk of bias was assessed using the Quality in Prognosis Studies (QUIPS) tool. Heterogeneity was evaluated via I² statistics, while pooled effect estimates were calculated using the DerSimonian-Laird inverse-variance random-effects model. Statistical significance was defined as p < 0.05. Additionally, a leave-one-out sensitivity analysis was performed to ensure the robustness of the findings.

RESULTS: Out of an initial 690 records identified, four articles involving a total of 616 transplanted thalassemia patients were included in this study. The survival rates were 86.8% (95% CI: 80.1%- 92.3%) in 15 years, 89.2% (95% CI: 82.2%-96.2%) in 20 years, 82.6% (95% CI: 79.9%-85.3%) in 30 years, and 81.4% (95% CI: 74.5%-88.9%) in 39 years. The pooled survival rate was 85% (95% CI: 81%-89%; I² = 40%). The pooled survival rate showed no significant differences in leave-one-out sensitivity analysis.

CONCLUSION: The present meta-analysis shows relatively high long-term overall survival rates in patients with thalassemia after hematopoietic stem cell transplantation. Nonetheless, the relatively small patient population, heterogeneity in anti-thymocyte globulin implementation, and potential confounding risks intrinsic to the study necessitate cautious interpretation of the findings.

PMID:42520329 | DOI:10.1016/j.htct.2026.106490