Category: Statistics

MedScience. 2026 May 26. doi: 10.1007/s11684-026-1205-3. Online ahead of print.

ABSTRACT

X-chromosomal genetic variants have been understudied in end-stage renal disease (ESRD), which holds the promise to provide valuable insights into sexually dimorphic traits and diseases. Here we performed an X chromosome-wide association study (XWAS) in a Chinese cohort (N = 2750), comprising 1489 cases with ESRD and 1261 controls, to identify locus associated with ESRD risk. One locus showing a consistent effect direction across sex but primarily supported by the male cohort was identified in COL4A5 (P = 2.43 × 10^-6) in the metaanalysis combining summary statistics from the sex-stratified XWAS. COL4A5 codes for the alpha chain of type IV collagen, which is essential for the integrity of the glomerular basement membrane and normal glomerular function. Two male-specific loci, MIR3202-2 (P = 6.85 × 10^-5) and SYTL4 (P = 1.71 × 10^-5), were identified in the sex-stratified XWAS in males, and expression of SYTL4, TSPAN6, NOX1, CSTF2, and PCDH19 was found to be influenced by the ESRD loci near SYTL4 based on expression quantitative trait loci (eQTL) results from the Genotype-Tissue Expression (GTEx) project. In summary, our findings revealed three X-chromosome loci linked to ESRD risk, which provided foundational knowledge for genetic risk prediction and advanced our understanding of the molecular underpinnings of ESRD.

PMID:42189395 | DOI:10.1007/s11684-026-1205-3

MedScience. 2026 May 26. doi: 10.1007/s11684-026-1250-y. Online ahead of print.

NO ABSTRACT

PMID:42189394 | DOI:10.1007/s11684-026-1250-y

Forensic Sci Med Pathol. 2026 May 26. doi: 10.1007/s12024-026-01270-1. Online ahead of print.

ABSTRACT

This study aimed to assess the reliability of the Demirjian and Olze staging systems for mandibular third molars using panoramic radiographs in a medico-legal context. A retrospective pilot study was conducted on 25 medico-legal cases from a Medico-Legal Institute. Panoramic radiographs were evaluated using the Demirjian (A-H) and Olze (0-3) methods. Chronological age was compared with radiographic findings. Statistical analyses included sensitivity, specificity, predictive values, and Cohen’s kappa coefficient. Demirjian stage H and Olze stages 2-3 were observed only in individuals aged 18 years or older, whereas stages C-G and Olze stage 0 were found exclusively in those under 18. Both staging methods demonstrated high diagnostic performance within this sample, with sensitivity, specificity, and predictive values reaching 100% for identifying legal adulthood. Agreement between methods was complete (κ = 1.00), with high inter- and intra-observer reliability (κ = 0.84; ICC = 0.92). No significant sex-related differences were observed. Panoramic analysis of third molars appears to be a promising, reproducible, and ethically acceptable approach for distinguishing minors from adults in this medico-legal context. However, given the pilot design and limited sample size, these findings should be interpreted with caution. Larger multicenter studies, including the integration of skeletal indicators, are required to establish robust and generalizable reference standards.

PMID:42189383 | DOI:10.1007/s12024-026-01270-1

Updates Surg. 2026 May 26. doi: 10.1007/s13304-026-02685-9. Online ahead of print.

ABSTRACT

Groove pancreatitis (GP) is a rare form of focal chronic pancreatitis involving the pancreaticoduodenal groove and frequently mimics pancreatic ductal adenocarcinoma, posing significant diagnostic and therapeutic challenges. This review comprehensively evaluated the demographics, clinical presentation, diagnostic approaches, and comparative effectiveness of surgical versus non-surgical management strategies in GP. A total of 24 studies comprising 562 patients were included. The patient-weighted mean age was 50.6 years, with a marked male predominance (84.3%). Abdominal pain (92.3%), weight loss (70.5%), and nausea/vomiting (47.1%) were the most common presenting features. Non-surgical management (conservative and endoscopic approaches) achieved complete success in 78.9% (131/166) of patients, while surgical management achieved complete success in 82.4% (197/239). Random-effects meta-analysis revealed pooled complete success proportions of 0.76 (95% CI 0.56-0.88) for non-surgical treatment and 0.775 (95% CI 0.708-0.830) for surgery. Sensitivity analysis restricted to resective surgical procedures demonstrated a pooled complete success rate of 0.823 (95% CI 0.764-0.870) with no observed heterogeneity (I² = 0.0%). Direct comparative analysis showed no statistically significant difference between strategies (risk ratio 0.99; 95% CI 0.73-1.36), indicating equivalent efficacy. Heterogeneity was substantial in the non-surgical group (I² = 64.2%) but low in the surgical group (I² = 5.8%). Given the observational design, treatment heterogeneity, inadequate follow-up, and indirect nature of most comparisons, the available evidence does not establish superiority or equivalence between surgical and non-surgical management. Non-surgical management may be considered as an initial approach in selected patients, whereas surgery remains appropriate for refractory, complicated, or diagnostically uncertain cases.

PMID:42189376 | DOI:10.1007/s13304-026-02685-9

J Autism Dev Disord. 2026 May 26. doi: 10.1007/s10803-026-07365-6. Online ahead of print.

ABSTRACT

BACKGROUND: Vitamin D is discussed in neurodevelopmental and immune pathways relevant to autism spectrum disorder (ASD). This systematic review synthesizes evidence on serum vitamin D status and vitamin D supplementation outcomes in children and adolescents with ASD, with descriptive reporting of one combined vitamin D plus omega-3 arm for context only.

METHODS: PubMed was searched on 16 August 2024 for observational studies reporting serum 25-hydroxyvitamin D [25(OH)D] and for randomized controlled trials (RCTs) of vitamin D supplementation; the primary narrative synthesis of trial evidence was restricted to double-blind, placebo-controlled studies with the maximum Jadad score (5/5).

RESULTS: Eight observational studies met inclusion criteria. Most reported lower 25(OH)D in children with ASD compared with comparator groups, while neonatal findings were mixed across cohorts. Among three placebo-controlled RCTs, one high-dose study reported statistically significant improvements on symptom scales, whereas trials using 2,000 IU/day reported marginal or no effects on ASD-related outcomes. One combined vitamin D plus omega-3 trial arm is summarized descriptively for context.

CONCLUSION: Current evidence does not support vitamin D supplementation as a general ASD-targeted intervention. Larger, well-controlled trials with prespecified baseline status, standardized outcomes, and safety-focused follow-up are needed to clarify potential subgroup effects and clinical relevance.

PMID:42189368 | DOI:10.1007/s10803-026-07365-6

Eat Weight Disord. 2026 May 26. doi: 10.1007/s40519-026-01874-0. Online ahead of print.

ABSTRACT

BACKGROUND: Previous studies have primarily examined the benefits of calorie restriction and fasting for metabolic dysfunction-associated steatotic liver disease (MASLD). However, the impacts of eating timing and frequency on MASLD remain uncertain.

METHODS: This study comprised 2128 participants aged 12 to 19 years, drawn from the National Health and Nutrition Examination Survey (NHANES) data collected during the period 2017 to 2023. Chrononutrition patterns were determined with two 24-h dietary recalls. Logistic regression, accounting for potential confounders, was used to examine the relationship between chrononutrition patterns and MASLD. Subgroup analyses stratified by demographic and clinical variables were used to evaluate their potential impact on the associations observed. Mediation analysis was conducted to assess the indirect effects of metabolic indicators on MASLD risk.

RESULTS: Logistic regression demonstrated that the timing of the first (continuous: OR: 1.07; 95% CI 1.02-1.14) and midpoint (continuous: OR: 1.11; 95% CI 1.00-1.22) food/beverage intake, as well as energy intake at dinner (OR: 1.01; 95% CI 1.00-1.01), were significantly associated with an increased risk of MASLD. Furthermore, the eating window (continuous: OR: 0.95; 95% CI 0.91-0.99) was significantly negatively correlated with the risk of MASLD. Subgroup analyses revealed that the chrononutrition pattern was particularly linked to an elevated risk of MASLD among males and Mexican Americans (P < 0.05). Additionally, HDL-C and NHHR (58.69% and 61.90%, respectively) partially mediated the association between the timing of the first food/beverage intake and MASLD risk.

CONCLUSION: Later timing of the first and midpoint food and beverage intake, as well as greater energy consumption at dinner, are linked to an elevated risk of MASLD. HDL-C and NHHR serve as mediators in these associations, particularly with respect to the timing of the first food or beverage intake.

PMID:42189361 | DOI:10.1007/s40519-026-01874-0

Eur J Psychotraumatol. 2026 Dec;17(1):2652128. doi: 10.1080/20008066.2026.2652128. Epub 2026 May 26.

ABSTRACT

Introduction: Prolonged Grief Disorder (PGD) was newly included in the 11th edition of the International Classification of Diseases (ICD-11) and the text revision of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR). There is a need to increase our understanding of the prevalence, nature, and risk factors of this condition. Research in this area can be advanced by pooling existing datasets.Objective: The MARBLES (Multi-region Archive of Research data on Bereavement and Loss from Empirical Studies) project was initiated to create a consortium of researchers conducting studies on PGD. Its goal is to harmonize and combine data from separate studies into a unified, individual participant data-archive, boosting bereavement research.Methods: To date, data from 16,666 bereaved individuals have been compiled from 32 datasets across nine countries. All datasets include data on PGD symptoms and sociodemographic and loss characteristics; most also include data on emotion regulation and concurrent symptoms. For preliminary analyses presented in this paper, data on sociodemographic and loss-related characteristics and on PGD, posttraumatic stress, and depression symptoms were harmonized.Results: Regarding the preliminary analyses, participants’ mean age was in their mid-40s, about 70% of the participants were female, one in four participants had lost a partner, and one in four participants experienced an unnatural loss. Analyses (with multiple imputation) indicated that 18.3% met criteria for probable PGD (ICD-11).Conclusion: The MARBLES archive demonstrates that it is feasible to build a FAIR archive of PGD symptom data. Although the archive can already be used to study the prevalence, pathogenesis, and predictors of PGD symptoms and associated emotional problems, it is intended as an evolving resource. Its potential will expand as additional datasets are added and use of the archive grows. Future extensions should prioritize the inclusion of underrepresented groups (e.g. migrants) and currently missing social, cognitive, and neurobiological variables.

PMID:42186902 | DOI:10.1080/20008066.2026.2652128

Sci Prog. 2026 Apr-Jun;109(2):368504261456424. doi: 10.1177/00368504261456424. Epub 2026 May 26.

ABSTRACT

ObjectiveAlthough endoscope-assisted evacuation for chronic subdural hematoma (cSDH) may reduce recurrence rates, its adoption has been limited by a procedural learning curve that may affect operative efficiency and clinical outcomes. This study compared conventional burr-hole craniostomy with endoscope-assisted evacuation for symptomatic cSDH and evaluated the challenges of institutional implementation.MethodsWe retrospectively reviewed patients with symptomatic cSDH treated between 2023 and 2025. Patients in the treatment group underwent endoscopic-assisted hematoma evacuation, while those in the control group received conventional burr-hole craniostomy. Continuous variables were compared using Student’s t-test or Mann-Whitney U test, and categorical variables were analyzed using Fisher’s exact or Chi-square tests. Multivariable logistic regression was performed to identify independent predictors of outcomes, with results reported as adjusted odds ratios (aOR) and 95% confidence intervals (CI). Statistical significance was defined as a two-tailed p < 0.05. All analyses were conducted using R software.ResultsA total of 110 patients were included (treatment group, n = 60; control group, n = 50). Patients in the treatment group were older (p = 0.006), whereas baseline characteristics and clinical presentations were otherwise comparable between groups. Operative time was longer in the treatment group (123.8 ± 45.2 vs. 104.3 ± 42.0 minutes, p = 0.02). No significant differences were observed in postoperative Glasgow Coma Scale scores, modified Rankin Scale scores, complication or recurrence rates, length of hospital stay, or functional recovery. Operative time decreased with increasing surgeon experience in unilateral endoscopic cases, indicating the presence of a learning curve.ConclusionEndoscope-assisted evacuation is a safe and effective alternative to conventional burr-hole craniostomy for cSDH, without increased complications or compromised clinical outcomes during institutional adoption.

PMID:42186899 | DOI:10.1177/00368504261456424

Brain. 2026 May 26:awag187. doi: 10.1093/brain/awag187. Online ahead of print.

ABSTRACT

SORL1, the gene encoding the SORLA protein, has arisen as a potential therapeutic target for Alzheimer’s disease (AD). Studies suggest that restoring SORLA function or its trafficking pathways, particularly the SORLA-retromer recycling system, may offer a promising strategy to slow or halt AD progression. While both rare and common SORL1 variants have been associated with increased AD risk, recent evidence suggests a potential involvement of SORL1 in other neurodegenerative conditions. This study assessed the contribution of SORL1 genetic variation to the risk of AD, related dementias (RD), and Parkinson’s disease (PD) using data from six large-scale biobanks, comprising 15,043 AD, 9,943 RD, and 42,763 PD cases, along with 111,969 controls across 11 ancestries. We identified 53 potentially disease-related SORL1 variants (CADD score > 20, MAC ≥ 2, annotated as protein-altering or splicing, and with the mutated allele present only in cases), including 41 novel and 12 previously reported variants. Three were found across multiple ancestries. Overall, 13 variants were found in AD-related cohorts, 5 in RD cohorts, and 35 in PD cohorts. Association analysis identified 10 nominally significant variants associated with AD and 5 with PD. The replication of multiple SORL1 variants across neurodegenerative diseases and ancestrally diverse populations underscores its potential broad genetic contribution to neurodegeneration and reinforces its relevance across distinct clinical phenotypes. Burden analysis identified a nominal association of SORL1 variants in PD in the South Asian population (P = 0.048). A family-based analysis identified a rare predicted-damaging variant in two East Asian families (11:121478242:G:A, p.R176Q) and two variants in two families of European ancestry (11:121514222:A:C, p.N371T; 11:121545392:G:A, p.V672M) that show some evidence of segregation in PD families. Although these variants were slightly more frequent in unrelated PD cases vs. controls, none of them showed statistically significant enrichment in PD, likely due to their very low frequency. Overall, our results extend the understanding of SORL1 beyond AD, suggesting a broader role in neurodegeneration and emphasizing the need for diverse population studies when evaluating genetic risk.

PMID:42186854 | DOI:10.1093/brain/awag187

Stat Med. 2026 Jun;45(13-14):e70612. doi: 10.1002/sim.70612.

ABSTRACT

The majority of response-adaptive randomization (RAR) designs in the literature rely on efficacy data to guide dynamic patient allocation. However, their applicability becomes limited in settings where efficacy outcomes, such as survival, are observed with a random delay. To address this limitation, we introduce SAFER, a novel RAR design that leverages early-emerging safety data to inform treatment allocation decisions, particularly in oncology trials. The design is broadly applicable to contexts where prioritizing the arm with superior safety is desirable. This is especially relevant in noninferiority trials, to demonstrate that an experimental treatment is not inferior to the standard of care, while potentially offering improved tolerability. In such trials, an unavoidable trade-off arises: maintaining statistical efficiency for the efficacy hypothesis while integrating safety-driven adaptations through RAR. The SAFER design addresses this trade-off by dynamically adjusting the allocation proportion based on the observed association between safety and efficacy endpoints. We illustrate the performance of SAFER through a simulation study inspired by the CAPP-IT Phase III oncology trial. Results show that SAFER preserves statistical power, reduces the adverse event rate, and offers flexible adaptation speed depending on the temporal alignment of the endpoints.

PMID:42186850 | DOI:10.1002/sim.70612