Category: Statistics

Biostatistics. 2026 Jan 20;27(1):kxag015. doi: 10.1093/biostatistics/kxag015.

ABSTRACT

Serum prostate-specific antigen (PSA) is widely used for prostate cancer screening. While the genetics of PSA levels have been studied to enhance screening accuracy, the genetic basis of PSA velocity, the rate of PSA change over time, remains unclear. The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a large, randomized study with longitudinal PSA data (15,260 cancer-free males, averaging 5.34 samples per subject) and genome-wide genotype data, provides a unique opportunity to estimate PSA velocity heritability. We developed a mixed model to jointly estimate the heritability of PSA levels at age 54 and PSA velocity. To accommodate the large dataset, we implemented 2 efficient computational approaches: a partitioning and meta-analysis strategy using average information restricted maximum likelihood (AI-REML) and a fast restricted Haseman-Elston (REHE) regression method. Simulations showed that both methods yield unbiased estimates of both heritability metrics, with AI-REML providing smaller variability in the estimation of velocity heritability than REHE. Applying AI-REML to PLCO data, we estimated heritability at 0.32 (s.e. = 0.07) for baseline PSA and 0.45 (s.e. = 0.18) for PSA velocity. These findings reveal a substantial genetic contribution to PSA velocity, supporting future genome-wide studies to identify variants affecting PSA dynamics and improve PSA-based screening.

PMID:42470129 | DOI:10.1093/biostatistics/kxag015

Biostatistics. 2026 Jan 20;27(1):kxag024. doi: 10.1093/biostatistics/kxag024.

ABSTRACT

Understanding the pathways through which diet affects human metabolism is a central task in nutritional epidemiology. This article proposes novel methodology to identify food items associated with blood metabolites in 2 cohorts of healthcare professionals. We analyze 244 metabolites characterized by statistical complexities that include skewness, left-censoring, and structural missingness. Though existing methods can address such factors in low-dimensional settings, they cannot exploit the nutritional or statistical relationships among the 30 considered food intake variables, and they are unsuitable for performing high-dimensional inference. To address these challenges, we develop a novel Bayesian variable selection framework for metabolite response variables based on a skew-normal censored mixture model, while exploiting substantive information on the considered food items via a Markov random field prior. Applying this methodology to the cohort data identifies multiple metabolite-diet associations that are consistent with previous research as well as several potentially novel associations that were not detected using standard methods. The proposed approach is implemented in the R package multimetab, facilitating its use in high-dimensional metabolomic analyses.

PMID:42470128 | DOI:10.1093/biostatistics/kxag024

Prep Biochem Biotechnol. 2026 Jul 17:1-16. doi: 10.1080/10826068.2026.2703129. Online ahead of print.

ABSTRACT

Lactococcus lactis SH6 was engineered for heterologous heparosan production, and its growth medium was optimized using a combination of experimental design and machine learning (ML). One-factor-at-a-time shake flask experiments revealed glucose (10 g/L) and yeast extract (17.5 g/L) as the best substrates, producing 50 mg/L heparosan. Plackett-Burman analysis and steepest ascent optimization revealed significant factors, and a central composite design (CCD) optimized nutrient concentrations, predicting 85 mg/L heparosan (validated at 81 mg/L). ML-Gaussian process regression was applied after CCD optimization to fine-tune and cross-check the optimal medium (glucose 8.94 g/L, yeast extract 22.89 g/L, ascorbate 0.38 g/L, β-glycerophosphate 28.2 g/L), producing 85.28 mg/L heparosan (predicted 88.8 mg/L) at the flask scale. Earlier nisin induction (2 h) at the bioreactor scale increased heparosan titers to 119.7 mg/L, and linear glucose feeding (1.5 g/L.h) extended the production phase to 133 mg/L. Medium optimization resulted in nearly doubling heparosan yield compared to the unoptimized medium, setting a new standard for L. lactis. This work offers a design-of-experiments-ML solution as a viable approach to designing high-yielding, animal-product-free heparosan production methods in a Generally Regarded as Safe (GRAS) microbe.

PMID:42470116 | DOI:10.1080/10826068.2026.2703129

Brain. 2026 Jul 18:awag246. doi: 10.1093/brain/awag246. Online ahead of print.

ABSTRACT

Strong evidence supports the role of low-grade systemic inflammation in neurodegeneration, including cognitive decline. Given the literature documenting chronic persistent inflammation in older Black adults, we investigated the association between circulating inflammatory proteins and cognitive decline in this high-risk population. We used data (n = 642) from the Minority Aging Research Study (MARS) and the Rush Clinical Core, including plasma samples to assess circulating inflammatory proteins (Olink® Target-96 Inflammation) and cognition (global cognition and five cognitive domains) assessed annually following proteomics measurement using previously stored blood samples. Linear mixed-effect and latent class mixed models (age at blood draw for proteomics measurement, sex, and education-adjusted), and elastic-net regression were used. Statistical significance was determined using an FDR threshold of 10%. Participants (62.3 to 99.4 years) were mostly women (80.68%) with 15.1 years of education. In multivariable linear mixed-effect models, we found that higher levels of osteoprotegerin (OPG) and chemokine (C-C motif) ligand 23 (CCL23) were cross-sectionally associated with poorer global cognition (beta=-0.205 and beta=-0.148), and higher CCL23 was associated with poorer semantic memory (beta=-0.206). Furthermore, protein × time interaction analyses indicated that higher OPG, Stem cell factor (SCF), and chemokine (C-X-C motif) ligand 9 (CXCL9) levels were associated with faster decline in global cognition (OPG × time term: beta=-0.042), semantic memory (SCF × time term: beta=-0.059, OPG × time term: beta=-0.043), episodic memory (SCF × time term: beta=-0.064; OPG × time term: beta=-0.044), and visuospatial ability (CXCL9×time term: beta=-0.012). In latent class mixed models, several significant protein × time interactions were observed for episodic memory in the subgroup with initial below-average performance and gradual decline. Using elastic net regression, we identified signatures of global cognitive level (26 proteins), but the prediction of cognitive decline was poor. In older Black adults, circulating inflammatory proteins were linked to cognition, reinforcing the role of systemic inflammation as a potential driver of neurodegeneration in this population.

PMID:42470112 | DOI:10.1093/brain/awag246

Gut Microbes. 2026 Dec 31;18(1):2691347. doi: 10.1080/19490976.2026.2691347. Epub 2026 Jul 17.

ABSTRACT

Although opioids are effective analgesics, they can lead to problematic drug use behaviors that underlie opioid use disorder (OUD). Opioids also cause gut microbiota dysbiosis, which is linked to altered opioid responses. We used a longitudinal paradigm of voluntary oral morphine self-administration to capture multiple facets of drug seeking and preserve both individual behavioral responses and individual gut microbiota variation to investigate the role of the gut microbiota in a mouse model of OUD. Although all the mice consumed morphine, only a subset of the mice that transitioned to a state we defined statistically as compulsive. In compulsive mice, morphine constricted natural variability and fragmented the microbiota community networks, which convergently reorganized to form robust novel connections post-morphine. In contrast, the more variable communities of non-compulsive mice were highly interconnected during morphine disturbance and displayed more continuity post-morphine, suggesting greater flexibility and adaptability. Compulsive mice displayed a greater loss of functional diversity and a shift in favor of potential pathobionts, whereas non-compulsive mice better preserved genera associated with gut health and broader functional diversity. These findings highlight the potential role of persistent and stable opioid-induced microbiota dysbiosis in long-term behavioral changes underlying OUD and contributing to vulnerability to relapse.

PMID:42470107 | DOI:10.1080/19490976.2026.2691347

BMC Psychol. 2026 Jul 17. doi: 10.1186/s40359-026-05195-w. Online ahead of print.

ABSTRACT

Physical activity (PA) in children is affected by physical and psychological factors. Exploring its characteristics and determinants is critical to promoting children’s PA participation. Existing empirical evidence is largely drawn from Western cultural contexts, and cultural divergences create uncertainty regarding whether these established associations generalize to Chinese children. Therefore, this study aimed to investigate the relationships motor skill competence (MSC), motivation, and PA among Chinese children. Participants were 177 fourth to six-grade students (76 boys vs. 101 girls; mean age = 10.94 years old; SD = 0.79) at two elementary school students from the province of Hunan in China. The students’ MSC, motivation and PA were measured using the Test of Gross Motor Development-Third Edition (TGMD-3), the Perceived Locus of Causality scale, and the PA Questionnaire for Older Children respectively. Data were analyzed with descriptive statistics, independent sample t-tests, Pearson’s correlation and linear regression models. Boys scored significantly higher than girls on ball skills and PA. Pearson’s correlation revealed that children’s autonomous motivation and controlled motivation were positively related to PA (r = 0.313, ρ < 0.01; r = 0.259, ρ < 0.05). Children’s MSC were not associated with motivation (ρ > 0.05). The result of linear regression models showed that MSC, autonomous motivation and controlled motivation were significantly associated with PA (F (3, 171) = 10.565, ρ < 0.01). Chinese children’s MSC was not associated with motivaiton. Physical education teachers should target the enhancement of both MSC and motivation as it is an effective strategy for promoting higher levels of PA among children.

PMID:42469925 | DOI:10.1186/s40359-026-05195-w

Trials. 2026 Jul 17. doi: 10.1186/s13063-026-09900-3. Online ahead of print.

ABSTRACT

BACKGROUND: Effective prediction and monitoring of recruitment in randomised controlled trials (RCTs) is critical to ensuring the target sample size is met, with 37% of trials failing to do so. This research aimed to identify various statistical methods for predicting recruitment during the design stage of an RCT and implement them using case-study trials, with a view to determining which method is more appropriate.

METHODS: Various deterministic, Poisson and Bayesian methods were identified and applied to data from six previously conducted RCTs, with varying numbers of participants recruited, sites opened, durations and recruitment outcomes.

RESULTS: Poisson methods were found to be more appropriate for obtaining predictions at the design stage of a trial. They produced confidence intervals to model uncertainty, unlike deterministic methods, and exhibited narrower intervals than Bayesian methods using informative priors. For single-centre trials, a homogeneous Poisson process was recommended, whilst a Non-homogeneous Poisson Process could be more suitable for multicentre trials. However, the non-homogeneous approach yielded more conservative estimates and required site-specific start dates, which may be less readily available at the design stage. Limitations included a lack of usable software for method implementation, difficulties with parameter elicitation, and a lack of additional data required to implement more complex methods, all of which may hinder the application of statistical methods for predicting recruitment which occurs in only 10% of RCTs.

CONCLUSIONS: To enhance transparency and reproducibility, it is recommended that RCTs publish the methods and parameters used in recruitment predictions. This may improve their accuracy, thereby reducing the cost and minimising the research waste associated with insufficient recruitment. Further research across a wider range of trials and methods may also be required due to the complexity of factors which influence recruitment and the variability in the accuracy of statistical methods across trials.

PMID:42469922 | DOI:10.1186/s13063-026-09900-3

Res Integr Peer Rev. 2026 Jul 17. doi: 10.1186/s41073-026-00229-8. Online ahead of print.

ABSTRACT

BACKGROUND: Some questionable research practices (QRPs) are regarded as core contributors to problems of reproducibility and replication, while others compromise the integrity and credibility of research by obscuring responsibility and incentives. However, evidence on the individual-level drivers of QRP engagement is fragmented. This study examines theory-informed associations between social and psychological factors and self-reported QRP engagement.

METHODS: Using data from a cross-sectional survey of researchers across disciplinary fields (18,376 invited; N = 3,050 respondents), this study examines associations between social and psychological factors and self-reported QRP engagement. The sample reflects a self-selected subset of invited respondents.

RESULTS: I found that commitment to universalism (β = -0.14, 95% CI [-0.18, -0.10]), communalism (β = -0.04, 95% CI [-0.08, 0.0]), and organised scepticism (β = -0.15, 95% CI [-0.2, -0.1]) – as well as higher conscientiousness (β = -0.07, 95% CI [-0.11, -0.03]), agreeableness (β = -0.03, 95% CI [-0.07, 0.00]), emotional stability (opposite to neuroticism) (β = -0.07, 95% CI [-0.11, -0.04]), and openness (β = -0.08, 95% CI [-0.12, -0.04]) – were negatively associated with average self-reported QRP engagement. Publication pressure was associated with greater average self-reported QRP engagement (β = 0.12, 95% CI [0.08, 0.16]), but this association was weaker among respondents with higher scores on a factor interpreted as endorsement of universalism (β = -0.04, 95% CI [-0.08, 0.00]). Funding pressure was not statistically associated with self-reported average QRP engagement. Motivations to falsify theories and findings (β = -0.06, 95% CI [-0.11, -0.01]), and to improve impact and quality of results (β = -0.11, 95% CI [-0.15, -0.06]), were negatively associated with self-reported QRP engagement. Conversely, ego and esteem-related motivation (e.g., fame, achieving social and political goals) was found to have a direct association with mean self-reported QRP engagement (β = 0.11, 95% CI [0.07, 0.15]), whereas career-growth motivations showed no clear direct association (β = -0.03, 95% CI [-0.07, 0.01]). However, both were indirectly associated with QRP engagement through scientific achievement and impact/quality motivations.

CONCLUSIONS: These findings highlight specific social and psychological factors that are associated with self-reported QRP engagement, offering potential leverage points for efforts to promote research integrity and reduce questionable practices. However, because the analytic sample reflects a self-selected subset of invited researchers and is drawn largely from Europe and the United States, the findings may not fully generalise to the broader global research community.

PMID:42469920 | DOI:10.1186/s41073-026-00229-8

J Cardiothorac Surg. 2026 Jul 17. doi: 10.1186/s13019-026-04584-x. Online ahead of print.

ABSTRACT

BACKGROUND: Pulmonary hydatid cysts caused by Echinococcus granulosus represent a significant health burden in endemic regions such as Yemen. Limited contemporary data are available on the clinical and radiological characteristics of this disease in the Yemeni population. This study aimed to evaluate the clinical presentation, radiological features, surgical management, and early outcomes of pulmonary hydatid cysts at a tertiary center in Sana’a, Yemen.

METHODS: This retrospective cross-sectional study was conducted at Al-Thawra Modern General Hospital between January 2019 and March 2023. The medical records of 114 patients with surgically confirmed pulmonary hydatid cysts were analyzed. Demographic data, clinical presentation, radiological findings, surgical procedures, and early postoperative complications were collected using structured questionnaires. Statistical analyses were performed using SPSS v. 28.0, and 95% confidence intervals were calculated for all the proportions.

RESULTS: Of the 114 patients, 82 (71.9%; 95% CI: 63.1%-79.4%) were male, with a predominant age group of 19-30 years (43.0%; 95% CI: 34.3%-52.2%). Most patients were from urban areas (75.4%; 95% CI: 66.8%-82.4%) and worked as laborers (35.1%) or students (33.3%). Khat chewing was reported by 50.0% (95% CI: 41.0%-59.0%) of the patients. Five patients (4.4%; 95% CI: 1.9%-9.8%) were asymptomatic. The most common symptoms were cough (89.5%; 95% CI: 82.5%-93.9%), dyspnea (76.3%; 95% CI: 67.7%-83.2%), chest pain (64.9%; 95% CI: 55.8%-73.1%), and sputum production (71.1%; 95% CI: 62.2%-78.6%). Radiologically, 97 patients (85.1%; 95% CI: 77.4%-90.5%) had solitary cysts, predominantly in the right lung (67.0%). Most cysts were intact (76.3%; 95% CI: 66.9%-83.6%). Among the 17 patients with multiple cysts, 36 individual cysts were identified (range: 2-4 per patient). Twelve patients (10.5%; 95% CI: 6.0%-17.4%) had concurrent liver hydatid cysts documented on preoperative imaging. Among solitary cysts, peri-cyst changes, including mass effect (39.2%), empyema (5.2%), and pleural effusion (2.1%), were documented. Preoperative albendazole was administered to 8.8% of patients, and 95.6% underwent elective surgery. Capitonnage was performed in 91.2% (95% CI: 84.6%-95.2%) of the cases. Postoperative complications occurred in 7.9% (95% CI: 4.2%-14.3%), with no mortality reported. Hospital stay was less than 1 week for 75.4% (95% CI: 66.8%-82.4%) of patients.

CONCLUSIONS: Pulmonary hydatid cysts in Yemen predominantly affect young urban males and present with respiratory symptoms. Solitary, intact cysts are the most common, and surgical management with capitonnage is safe and effective, with low morbidity rates when performed in specialized centers.

PMID:42469898 | DOI:10.1186/s13019-026-04584-x

J Cardiothorac Surg. 2026 Jul 17. doi: 10.1186/s13019-026-04636-2. Online ahead of print.

ABSTRACT

BACKGROUND: It is hard to efficiently revascularize high-risk patients with multivessel coronary disease, especially when conventional coronary artery bypass grafting is correlated with high perioperative risk and doing it percutaneously can be bigger issue for high-risk patients. Less invasive and modern alternative to OPCAB is Hybrid coronary revascularization. So we decided to compare this two methods and see which one will have better outcomes for high-risk patients. Our research involves comparing early (30 days) postoperative outcomes between Hybrid Coronary Revascularization (HCR) and Off-Pump Coronary Bypass surgery (OPCAB) in high surgical risk patients with coronary artery disease (EUROSCORE II > 6%, STS > 4% and SYNTAX SCORE > 32).

METHODS: In this single-centre retrospective study, we reviewed high-risk patients treated between Feb 18, 2024 and Dec 14, 2025. After applying predefined eligibility criteria, 87 patients were included, from 28 patients (Mean Age = 66.6 ± 10.7) underwent HCR and 59 (Mean Age = 76.6 ± 4.1) underwent off-pump open aorto-coronary bypass surgery via median sternotomy. We compared early (30 days) postoperative clinical outcomes between two groups. Statistical analysis was performed using IBM SPSS statistics, applying independent-samples t-test and chi-square test as appropriate.

RESULTS: Hybrid Coronary Revascularisation (MIDCAB + PCI) required shorter operative time than Off-Pump Coronary Bypass surgery (OPCAB), but with higher in-hospital costs. HCR was also associated with shorter intubation duration (245.5 ± 51.2 min vs. 576.7 ± 97.3 min, P < 0.001), ICU stay (66.4 ± 15.5 h vs. 102.7 ± 12.7 h, P < 0.001), hospital length of stay (7.3 ± 0.8 days vs. 13.0 ± 3.7 days, P < 0.001), and lower thoracic drainage output (275.4 ± 74.1 ml vs. 615.3 ± 88.5 ml, P < 0.001). Blood transfusion requirements were higher in the HCR group (14.3% vs. 0.0%, P = 0.009). Wound infection occurred only in the OPCAB group (0.0% vs. 27.1%, P = 0.002). The composite 30-day MACCE rate was numerically lower in the HCR group (0.0% vs. 13.6%), but this difference did not reach statistical significance (P = 0.050).

CONCLUSIONS: In high-risk patients with multivessel coronary artery disease, Hybrid Coronary Revascularization (MIDCAB + PCI), compared with traditional Off-Pump Coronary Artery Bypass surgery (OPCAB), was associated with a faster early-recovery profile, including shorter intubation time, ICU stay, and hospitalization, and lower chest-drain output. Multivariable analysis confirmed that these recovery benefits were independent of age, whereas the apparent advantage in overall complications was largely explained by the younger age of the HCR group. Differences in 30-day mortality and MACCE favoured HCR numerically but did not reach statistical significance in this underpowered cohort.Given the retrospective, non-randomized design with unequal group sizes and the absence of time-to-event follow-up, superiority of one strategy over the other cannot be established. Within these limitations, HCR appears to be a safe and feasible option that may be considered in selected elderly and high-risk patients (EUROSCORE II > 6%, STS > 4%, and SYNTAX SCORE > 32) with complex coronary anatomy. Larger, prospective, risk-adjusted studies with longer follow-up are warranted to confirm these findings.

TRIAL REGISTRATION: EC/NVU/PhD/26-001.

PMID:42469895 | DOI:10.1186/s13019-026-04636-2