Category: Statistics

J Neurotrauma. 2025 Nov 13. doi: 10.1177/08977151251394741. Online ahead of print.

ABSTRACT

The Blast Exposure Threshold Survey (BETS) is a recently developed measure of lifetime blast exposure. Although promising, it is considered a fundamental tenet to establish that the BETS (and other measures like it) have good psychometric properties before it can be recommended for clinical use. The purpose of this study was to examine the test-retest reliability of the BETS in a military sample. Participants were 83 United States service members and veterans prospectively recruited from three military medical treatment facilities and from the community. Participants were classified into two broad groups as part of a larger study: traumatic brain injury (TBI; n = 41; mild-severe TBI) and controls (n = 42; injured and non-injured controls). Participants completed the BETS, Neurobehavioral Symptom Inventory, and a brief structured interview to gather basic demographic, military, and injury-related information (e.g., age, education, deployments, etc.). In addition, participants completed the BETS on a second occasion (T2) 3 weeks following the first administration (T1). Using Spearman rho correlation analyses, the test-retest reliability of the BETS Generalized Blast Exposure Value (GBEV) was classified as “acceptable” (r = 0.76). However, when comparing individual responses across T1 and T2, 33% of the sample reported significant inconsistencies in the endorsement of the five weapons categories. The most problematic inconsistency (∼10% of the sample) related to the failure of some participants to consistently endorse, or not endorse, exposure to a weapons category at T1 and T2 (e.g., T1 = exposure present; T2 = exposure absent). Less problematic, but also of concern, was the failure of some participants (∼23%) to consistently report the same number of years in which they were exposed to a weapons category from T1 and T2 (e.g., T1 = 10 years; T2 = 5 years). Factors associated with inconsistent reporting from T1 to T2 included higher GBEV scores, older age, higher number of years in the military, higher number of deployments, and higher blast exposure. This is one of the first studies to comprehensively examine the test-retest reliability of the BETS GBEV. Overall, the test-retest reliability of the GBEV was considered statistically acceptable and provides support for the use of the GBEV in both clinical and research settings. Concerningly, however, substantial inconsistencies were found in the basic reporting of weapons exposure in 33% of the sample that need to be addressed. Future researchers should identify ways to improve the BETS to increase response consistency over time.

PMID:41264354 | DOI:10.1177/08977151251394741

JMIR Form Res. 2025 Nov 20;9:e76167. doi: 10.2196/76167.

ABSTRACT

BACKGROUND: Accurate assessment of physical activity (PA) in large population-based cohorts remains a major methodological challenge. Self-reported questionnaires, although commonly used due to low cost and simplicity, are prone to recall and social desirability biases, causing misclassification and weakened associations with health outcomes. Body-worn accelerometers provide more objective and reliable measurements, but their acceptability and feasibility in large-scale epidemiological studies must be carefully evaluated to ensure compliance, data quality, and scalability.

OBJECTIVE: The primary objective was to assess the acceptability of using 3 body-worn accelerometer devices (Fitbit, ActivPAL, and ActiGraph) among healthy middle-aged adults participating in the NutriNet-Santé cohort. The secondary objective was to assess the feasibility of these devices in terms of wear-time compliance under free-living conditions.

METHODS: This is an ancillary study of the European WEALTH (WEarable sensor Assessment of physicaL and eaTing beHaviors) project that was conducted between 2023 and 2024 in a subsample of participants of the NutriNet-Santé surveillance in France. This sample included 126 healthy participants (62 men), with a mean age of 46.3 (SD 11.3) years. Participants wore simultaneously 3 body-worn accelerometer devices (Fitbit [wrist], ActivPAL [thigh], and ActiGraph [waist]) for 7 consecutive days. After the wear period, participants completed a specific 22-item web-based questionnaire, regarding their acceptability of using each device. This questionnaire was based on the Technology Acceptance Model, which identifies perceived usefulness and ease of use as key determinants of technology acceptance. Items were rated on a 5-point Likert scale (1=strongly disagree to 5=strongly agree). Feasibility was assessed based on the accelerometer wear time data reported in a log diary by participants. A valid day was defined as ≥600 minutes per day of wear time, and a valid week as at least 4 of such days. Acceptability scores were compared between devices using ANOVA, and feasibility outcomes were compared using Kruskal-Wallis tests.

RESULTS: The acceptability assessment based on the questionnaire revealed significant differences among the 3 devices (P<.001). The Fitbit achieved the highest acceptability score (mean 80.5/100, SD 8.13) across most criteria such as comfort, ease of use, and social acceptability, while the ActiGraph received the lowest score (mean 71.7, SD 8.68), mainly due to challenges with stability and interference during PA. In terms of feasibility, the 3 accelerometers demonstrated high compliance, with the ActivPAL recording the highest daily wear time, followed by the Fitbit and the ActiGraph (P<.001).

CONCLUSIONS: Results from our study showed that the Fitbit watch appears as the most accepted device for measuring PA in free-living conditions in the NutriNet-Santé study. The large-scale use of such a device must now be evaluated in terms of logistics, cost, and data privacy.

PMID:41264348 | DOI:10.2196/76167

JAMA Oncol. 2025 Nov 20. doi: 10.1001/jamaoncol.2025.4821. Online ahead of print.

ABSTRACT

IMPORTANCE: Incidental meningiomas are common. There is a need for a validated clinical tool to stratify patients into early intervention, serial monitoring, or safe discharge from outpatient care.

OBJECTIVE: To externally validate the Incidental Meningioma: Prognostic Analysis Using Patient Comorbidity and Magnetic Resonance Imaging Tests (IMPACT) tool.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included 33 centers in 15 countries. Adult patients diagnosed with an incidental meningioma from January 2009 to December 2010 were included, up to the point of intervention, death, or last clinical encounter. Patients with radiation-induced meningioma and NF2-related schwannomatosis were excluded. Data collection was completed on December 31, 2023. Statistical analysis was conducted between March 2024 and December 2024.

MAIN OUTCOMES AND MEASURES: The primary outcome of the study was a composite end point comprising growth, symptom development, meningioma-related mortality, and end points related to loss of window of curability. Secondary end points included the occurrence of an intervention and nonmeningioma-related mortality.

RESULTS: Overall, 1248 patients were included. The median (IQR) age was 66 (55-77) years and 999 were female individuals (80%). There were 945 patients (75.7%) who had 1010 treatment-naive meningiomas. During follow-up (median [IQR], 61 [17-108] months), 114 tumors (11.3%) in 113 patients (12%) progressed, 132 tumors (13.1%) in 126 patients (13.3%) underwent an intervention, and 383 patients (40.5%) died without progression or intervention, from a nonmeningioma-related cause. The 5- and 10-year progression-free survival rates were 88.1% (95% CI, 85.8%-90.5%) and 85.7% (95% CI, 83.2%-88.2%), respectively. A low-risk meningioma had a disease progression risk of 3.9%, compared with 24.2% in medium-risk meningioma, and 51.6% in high-risk meningioma (χ2 test, P < .001). Measures of external validity were adequate (Brier score = 0.12; C-statistic = 0.80; 10-year area under the curve, 0.83) and the addition of other variables in a Cox regression analysis did not confound the statistical significance of the IMPACT tool. Patients with an age-adjusted Charlson Comorbidity Index score of 6 or higher (eg, a patient aged 80 years with type 2 diabetes and a previous myocardial infarction) and a performance status of 2 to 4 (unable to carry out any work activities or in a chair/bed for 50% or more of the day) were more likely to die of other causes than to receive intervention following diagnosis.

CONCLUSIONS AND RELEVANCE: This cohort study found that the IMPACT tool accurately predicted the risk of incidental meningioma progression and can be used to stratify patients into early intervention, serial monitoring, or safe discharge from outpatient care.

PMID:41264316 | DOI:10.1001/jamaoncol.2025.4821

Proc Natl Acad Sci U S A. 2025 Nov 25;122(47):e2516805122. doi: 10.1073/pnas.2516805122. Epub 2025 Nov 20.

ABSTRACT

The mechanisms by which light interacts with ice and the impact of photoinduced reactions are central to our understanding of environmental, atmospheric, and astrophysical processes. However, a microscopic description of the photoproducts originating from ultraviolet (UV) absorption and emission processes has remained elusive. Here, we explore the photochemistry of ice using time-dependent hybrid density functional theory on various models of pristine and defective ice Ih. Our investigation of the excited state potential energy surface of the crystal shows that UV absorption can lead to the formation of hydronium ions, hydroxyl radicals, and excess electrons. One of the dominant mechanisms of decay from the excited to the ground-state involves the recombination of the electron with the hydroxyl radical yielding hydronium-hydroxide ion-pairs. We find that the details of this charge recombination process sensitively depend on the presence of defects in the lattice, such as vacancies and preexisting photoproducts. We also observe the formation of Bjerrum defects following UV absorption; we suggest that, together with hydroxide anions, they are likely responsible for prominent features experimentally detected in long UV exposure absorption spectra, remarkably red-shifted relative to short exposure spectra. Our results highlight the key role of defects in determining the onset of absorption and emission processes in ice.

PMID:41264242 | DOI:10.1073/pnas.2516805122

J Cancer Surviv. 2025 Nov 20. doi: 10.1007/s11764-025-01919-w. Online ahead of print.

ABSTRACT

PURPOSE: Routine assessment of cancer survivors’ needs is inconsistently performed in both primary care and oncology. Age influences survivorship needs, with younger survivors facing prolonged symptom burden and late effects, and older survivors experiencing compounded aging-related issues. We describe age-appropriate needs-based care in a university onco-primary care survivorship clinic serving adult survivors of childhood and adult cancers.

METHODS: Between November 1, 2022, and May 31, 2023, the clinic administered age-appropriate assessments during routine visits (ages ≤ 39 years: Adolescent and Young Adult Psycho-Oncology Screening Tool for Survivorship [AYA-SPOST]; ≥ 40 years: NCCN Distress Thermometer and Problem List [NCCN DTPL]). Survivors prioritized their top three concerns, and clinicians addressed them in the visit. Descriptive statistics were used to summarize priority concerns.

RESULTS: Two hundred and twenty-eight patients (100%) completed age-appropriate assessments (AYA-SPOST: 112; NCCN DTPL: 116) and prioritized their concerns at their clinic visit. Leukemia (21%) and lymphoma (18%) were the most common diagnoses. Survivors ≤ 39 years old prioritized anxiety/fear (21%), sleep disturbances (14%), and worry about long-term effects (12%), while those ≥ 40 years old prioritized pain (40%), fatigue (28%), and worry/anxiety (23%). Clinicians discussed survivors’ concerns with them and made 74 referrals to supportive services.

CONCLUSIONS: We implemented age-appropriate needs-based care in an onco-primary care clinic as part of standard care. Patients’ priority concerns helped drive clinical visits to ensure patient-centered care.

IMPLICATIONS FOR CANCER SURVIVORS: Routine use of age-appropriate assessments for different stages of adulthood, with opportunities for survivors to prioritize their concerns, allows clinicians to take immediate action to help address those concerns.

PMID:41264205 | DOI:10.1007/s11764-025-01919-w

J Cancer Res Clin Oncol. 2025 Nov 20;151(12):327. doi: 10.1007/s00432-025-06379-4.

ABSTRACT

AIM: To explore the clinical application value of modified overlap anastomosis for Siewert type II and III adenocarcinoma of esophagogastric junction, and to further evaluate its feasibility and safety.

METHODS: We retrospectively analyzed clinical data from 222 patients with Siewert type II and III adenocarcinoma of the esophagogastric junction admitted to our hospital between January 2017 to October 2023. All patients underwent laparoscopic total gastrectomy with D2 lymph node dissection. 64 patients underwent esophagojejunostomy with modified overlap anastomosis, and 158 patients were operated using the circular stapled anastomosis. Variables that are statistically different were compared between groups using propensity score matching (PSM). The differences in surgical-related indicators and clinical outcomes for the two groups were compared. Finally, we analyzed the risk factors associated with esophagojejunostomy (EJ)-related complications.

RESULTS: There was no statistically significant difference between the two groups of patients in terms of BMI, gender, age, and tumor-related information (P value > 0.05). However, there was then a difference in preoperative hemoglobin between the two groups. To eliminate heterogeneity, we combined patients with PSM. In terms of intraoperative conditions and postoperative recovery after PSM, compared with the circular stapled anastomosis group, the modified overlap group showed the shorter total operation time, shorter the length of the auxiliary incision, shorter time to the soft diet intake, milder postoperative pain. In terms of postoperative complications and overall survival after PSM, the modified overlap group can reduce the probability of abdominal infection and there was no difference in overall survival (OS) and postoperative late complications between the two groups. Multivariate analysis showed that the Siewert type [odds ratio (OR), 0.355; 95% confidence interval (CI) 0.189-0.639, P value = 0.005] was independent risk factors of EJ-related complications.

CONCLUSION: Although the modified overlap group had slightly lower total protein after surgery, it had advantages in operation time, the length of the auxiliary incision, the soft diet intake time, postoperative pain, abdominal infection. General surgeons should exercise heightened vigilance in preventing EJ-related complications for patients classified as Siewert type II. In summary, modified Overlap anastomosis is safe and reliable. It has clinical application value.

PMID:41264122 | DOI:10.1007/s00432-025-06379-4

Environ Geochem Health. 2025 Nov 20;48(1):8. doi: 10.1007/s10653-025-02860-8.

ABSTRACT

The rapid urbanization and industrialization in Pakistan have significantly escalated wastewater generation, much of which remains untreated and is discharged into rivers and canals. This study presents an innovative framework that integrates quantitative analysis of wastewater quality with qualitative insights from community attitudes, focusing on Abbottabad and Lahore City. Comprehensive evaluations of physico-chemical parameters like potential of hydrogen, chemical oxygen demand, total dissolved solids, turbidity, and electrical conductivity alongside microbial indicators such as coliform and E.coli, reveal critical insights into wastewater characteristics and treatment efficiency. Comparisons with World Health Organization standards expose substantial site-to-site variations, with several parameters exceeding permissible limits. Secondary treatment processes effectively mitigate TDS, EC, turbidity, and COD to compliant levels. While initial treatments reduce bacterial loads, regrowth during storage raises concerns about long-term microbial safety. Multivariate statistical analyses, including principal component analysis and Pearson correlation matrices, uncover strong interdependencies among parameters, such as inverse correlations between pH and both TDS and turbidity, and a perfect positive correlation between EC and TDS. Community surveys amplify the study’s scope, revealing widespread dissatisfaction with water and wastewater management, as 74% of respondents associate health issues such as diarrhea, kidney ailments, and vomiting with inadequate treatment systems. This study introduces the novel Enhanced Wastewater Quality Index (EWWQI), integrating both wastewater quality parameters and community perceptions. The Adjusted EWWQI score of 17.0 (poor) highlights the need for improved treatment processes and greater public trust in wastewater management. By integrating scientific evaluation with community perspectives, this study underscores the urgent need for enhanced treatment processes and sustainable management practices. The findings provide actionable insights for policymakers, paving the way for improved wastewater management and addressing critical environmental and public health challenges effectively.

PMID:41264103 | DOI:10.1007/s10653-025-02860-8

Int J Clin Pharm. 2025 Nov 20. doi: 10.1007/s11096-025-02034-7. Online ahead of print.

ABSTRACT

INTRODUCTION: Atrial fibrillation (AF) is a common cardiac arrhythmia with limited options for upstream prevention. While several anti-diabetic drugs have shown cardiovascular benefits, their potential role in modifying AF risk remains unclear.

AIM: This study aimed to evaluate the causal relationship between genetically proxied antidiabetic drug targets and the risk of AF using a drug-target Mendelian randomization (MR) approach.

METHOD: A two-sample MR analysis was conducted to investigate the association between genetic variants related to antidiabetic drug targets and AF. Thirty-eight FDA-approved glucose-lowering agents were identified, and their targets were extracted from the ChEMBL (Chemical Biology Database and Information System) database. Protein quantitative trait loci (pQTL) data from a large plasma proteome GWAS (Genome-Wide Association Study) were used to construct instrumental variables. Positive control testing was conducted to confirm that the selected drug targets were significantly associated with diabetes, using summary statistics from the UK Biobank, FinnGen, and other GWAS datasets. Causal effects on AF were evaluated using multiple independent GWAS cohorts for replication. MR methods included inverse-variance weighted (IVW), MR-Egger, and weighted median approaches with sensitivity analyses for pleiotropy and heterogeneity.

RESULTS: The alpha-glucosidase inhibitor miglitol was causally associated with a reduced risk of AF. Specifically, miglitol was shown to inhibit lactase (LCT), a protein whose elevated levels were associated with increased AF risk (IVW, OR = 1.013; 95%CI, 1.007-1.018; P = 2.37 × 10⁻⁵). This association was confirmed using MR-Egger and weighted median methods and validated across multiple datasets. Sensitivity analyses did not reveal evidence of pleiotropy or confounding factors, supporting the robustness of the findings.

CONCLUSION: This study provides novel genetic evidence suggesting that miglitol may reduce AF risk through lactase inhibition. These findings highlight a potential opportunity for drug repurposing for cardiovascular prevention, particularly for clinical pharmacists managing patients with higher risks in cardiovascular outcomes meanwhile with type 2 diabetes. Further mechanistic and clinical studies are warranted to confirm these observations and explore their translational value in practice.

PMID:41264079 | DOI:10.1007/s11096-025-02034-7

Int J Clin Pharm. 2025 Nov 20. doi: 10.1007/s11096-025-02038-3. Online ahead of print.

ABSTRACT

INTRODUCTION: Cisplatin is a cornerstone chemotherapeutic agent frequently associated with dose-limiting ototoxicity. Increasing evidence suggests that immune-mediated mechanisms may influence interindividual susceptibility to this adverse effect; however, the role of inherited immune traits remains poorly understood.

AIM: This study aimed to evaluate the causal relationship between 33 inherited immune traits and cisplatin-induced ototoxicity using Mendelian randomization (MR), and to identify age-stratified susceptibility markers in pediatric and adult cancer survivors.

METHOD: MR was used to assess the causal effects of genetically predicted immune traits on cisplatin-induced ototoxicity. Single-nucleotide polymorphisms associated with immune traits were selected from large-scale genome-wide association study datasets. The primary analysis used the inverse variance weighted method with MR-Egger, weighted median, weighted mode, and MR-PRESSO as the sensitivity approaches. Bidirectional MR and sensitivity analyses were conducted to assess robustness and rule out reverse causation. Bonferroni correction was employed to minimize potential false-positive findings (P < 0.05/165 ≈ 0.0003).

RESULTS: Transforming Growth Factor-beta principal component analysis (TGF-β PCA) showed an age-stratified effect: it was associated with increased risk of hearing loss in pediatric patients (OR (95% CI): 1.0 × 10¹ (1.6 × 10⁰-6.6 × 10¹), P = 0.014) but conferred strong protection against Speech Recognition Threshold (SRT) impairment (OR (95% CI): 2.8 × 10⁻¹ (1.4 × 10⁻¹-5.3 × 10⁻¹), P = 0.00012) and hearing loss (OR (95% CI): 4.7 × 10⁻¹ (2.7 × 10⁻¹-8.1 × 10⁻¹), P = 0.006) in adults. Additional protective associations have been identified for T Central Memory (TCM) cells and Programmed Cell Death Protein-1 (PD-1) in adults. Reverse MR analysis excluded significant reverse causation. Following Bonferroni correction, the association between TGF-β PCA and SRT remained statistically significant (P < 0.0003) in the adult cohort. However, all other associations in adults and the entire pediatric cohort demonstrated only nominal significance (0.0003 ≤ P < 0.05).

CONCLUSION: Inherited immune traits, particularly TGF-β PCA, PD-1, and TCM cells, exhibit age-stratified causal effects on cisplatin-induced ototoxicity. These findings suggest the use of immunogenetic profiling for risk prediction and personalized strategies in oncology pharmacy practice.

PMID:41264078 | DOI:10.1007/s11096-025-02038-3

Discov Oncol. 2025 Nov 20. doi: 10.1007/s12672-025-04006-9. Online ahead of print.

ABSTRACT

BACKGROUND: Cutaneous malignant melanoma (CMM) is a deadly skin cancer with genetic basis. Although genome-wide association studies (GWAS) have identified various risk loci, their functional consequences remain largely undefined. This study aims to uncover novel CMM-associated genes and investigate their potential biological mechanisms by integrating large-scale genetic and transcriptomic datasets.

METHODS: We combined CMM GWAS summary statistics with gene expression data from GTEx v8 and conducted transcriptome-wide association studies (TWAS) across multiple tissues. Key genes were further examined using MAGMA-based gene-level analysis, Bayesian fine-mapping, Mendelian randomization (MR), and colocalization to infer potential causality. Functional associations were explored via GeneMANIA network analysis.

RESULTS: Two genes, TMEM184B and MAFF, were repeatedly identified across analytical approaches. TMEM184B emerged as a novel gene associated with melanoma risk. Both MR (P < 0.05) and colocalization (PP.H4 > 0.8) provided consistent evidence of causal links between gene expression and CMM susceptibility. Functional network analysis implicated TMEM184B in transmembrane ion transport and MAPK signaling pathways, while MAFF was linked to oxidative stress response pathways.

CONCLUSION: This study identifies TMEM184B as a previously unreported risk gene for CMM and reaffirms the relevance of MAFF in disease predisposition. These findings advance our understanding of melanoma’s genetic architecture and highlight specific, high-priority genes and pathways for future experimental investigation, suggesting they may serve as potential therapeutic targets.

PMID:41264070 | DOI:10.1007/s12672-025-04006-9