Category: Statistics

Saudi Pharm J. 2025 Oct 2;33(5):36. doi: 10.1007/s44446-025-00036-0.

ABSTRACT

In Saudi Arabia, the regulation of community pharmacies currently falls under the Ministry of Health (MOH). There is a need to shift the regulatory framework of community pharmacies to be under the Saudi Food and Drug Authority (SFDA) to align with global standards. However, there is limited knowledge about the perceptions of pharmacists regarding the current regulatory framework in community pharmacies in the Kingdom of Saudi Arabia (KSA).

OBJECTIVES: This study aims to assess pharmacists’ knowledge, perceptions, and preferences regarding the current regulatory framework of community pharmacies and feasibility of transitioning regulatory oversight to SFDA.

METHODOLOGY: A cross-sectional survey design was used to assess the regulation of community pharmacies in Saudi Arabia. The sample consisted of 139 pharmacists from various sectors, selected through random sampling. A structured questionnaire focusing on regulation, awareness, and perceptions was distributed online. The questionnaire’s validity and reliability were ensured through expert review. Descriptive statistics in SPSS were used for data analysis.

RESULTS: The survey findings revealed a diverse representation across the pharmaceutical sector. Hospital pharmacists formed the largest group (37.4%, n = 52), followed by regulatory field workers from the Ministry of Health (21.6%, n = 30) and SFDA (20.1%, n = 28), pharmaceutical industry professionals (11.5%, n = 16), and community pharmacists (9.4%, n = 13). Most participants (51.8%, n = 72) had 1-5 years of experience, while 31.7% (n = 44) had 6-10 years, and 16.5% (n = 23) had more than 10 years of experience. Regarding current regulatory oversight, the majority (82.7%, n = 115) reported being under MOH regulation, with 12.2% (n = 17) under SFDA oversight. The study revealed high awareness of current regulations (77.0%, n = 107), though most participants (62.6%, n = 87) expressed dissatisfaction with the current regulatory framework. Notably, 77.0% (n = 107) preferred SFDA as the future regulator, and 80.6% (n = 112) believed SFDA would perform better in regulating the sector. Most participants demonstrated strong agreement with proposed regulatory changes, with 78.4% (n = 109) agreeing to P1 and 79.1% (n = 110) to P4 statements regarding regulatory reform.

CONCLUSION: The study reveals strong sector-wide preference among pharmaceutical professionals for transitioning community pharmacy regulation to SFDA, driven by dissatisfaction with current MOH oversight. This consensus across all professional categories and experience levels indicates practitioners’ expectations that SFDA regulation would enhance pharmaceutical service quality and regulatory effectiveness in Saudi Arabia.

PMID:41037140 | DOI:10.1007/s44446-025-00036-0

Cancer Causes Control. 2025 Oct 2. doi: 10.1007/s10552-025-02075-3. Online ahead of print.

ABSTRACT

PURPOSE: Childhood and adolescence may represent critical time windows for shaping future breast cancer risk. The association between early-life diet and breast cancer risk has been investigated, but few studies have examined the relation between adolescent diet and benign breast disease (BBD), an established breast cancer risk factor.

METHODS: Among 11,422 female Growing Up Today Study participants followed from 1996 to 2016 who completed food frequency questionnaires, we investigated the associations between adherence to three dietary patterns (Alternative Healthy Eating Index [AHEI], the Empirical Dietary Inflammatory Pattern [EDIP], and the Empirical Dietary Index for Hyperinsulinemia [EDIH]) at ages 10 and 14 years and self-reported BBD diagnosis. Cox proportional hazards models were used to estimates hazard ratios (HRs) and 95% confidence intervals (CIs).

RESULTS: Over 20 years of follow-up, 554 BBD cases were ascertained, with 259 biopsy-confirmed cases. Non-significant inverse associations were observed between greater adherence to the AHEI at age 10 and BBD risk (HR for fourth vs. first quartile = 0.74; 95% CI = 0.50-1.10; p_trend = 0.09), and between AHEI at age 14 and biopsy-confirmed BBD (HR for fourth vs. first quartile = 0.70; 95% CI = 0.48-1.03; p_trend = 0.10). Non-significant positive associations were observed between adherence to the EDIH at age 10 and (HR for fourth vs. first quartile = 1.49; 95% CI = 0.91-2.43; p_trend = 0.09) age 14 (HR for fourth vs. first quartile = 1.33; 95% CI = 0.97-1.82; p_trend = 0.09) and BBD risk. No associations were observed for EDIP. In secondary analyses, the association between EDIH at age 10 and BBD became statistically significant after accounting for change in dietary pattern quartile from age 10 to 14 (HR for fourth vs. first quartile = 2.14; 95% CI = 1.04-4.41). Adjustment for adult diet also strengthened associations between EDIH at age 10 and BBD risk (HR = 1.94; 95% CI = 1.12-3.37; p_trend = 0.007), and showed a significant inverse trend for AHEI (p_trend = 0.04).

CONCLUSION: These findings may suggest that greater early-life adherence to a healthier dietary pattern (AHEI) is associated with lower BBD risk, while consuming a more insulinemic dietary pattern (EDIH) may be associated with increased risk. Associations for EDIH at age 10 were statistically significant in secondary analyses accounting for dietary change and adult diet. Further research is needed to confirm these findings and clarify potential mechanisms.

PMID:41037133 | DOI:10.1007/s10552-025-02075-3

Diabetologia. 2025 Oct 2. doi: 10.1007/s00125-025-06563-8. Online ahead of print.

ABSTRACT

AIMS/HYPOTHESIS: Type 1 diabetes is characterised by the destruction of pancreatic beta cells. Genetic factors account for approximately 50% of the total risk, with variants in the HLA region contributing to half of this genetic risk. Research has historically focused on populations of European ancestry. We developed HLA-focused type 1 diabetes genetic risk scores (T1D GRS_HLA) using SNPs or HLA alleles from four ancestry groups (admixed African [AFR; T1D GRS_HLA-AFR], admixed American [AMR; T1D GRS_HLA-AMR], European [EUR; T1D GRS_HLA-EUR] and Finnish [FIN; T1D GRS_HLA-FIN]). We also developed an across-ancestry GRS (ALL; T1D GRS_HLA-ALL). We assessed the performance of the GRS in each population to determine the transferability of constructed scores.

METHODS: A total of 41,689 samples and 13,695 SNPs in the HLA region were genotyped, with HLA alleles imputed using the HLA-TAPAS multi-ethnic reference panel. Conditionally independent SNPs and HLA alleles associated with type 1 diabetes were identified in each population group to construct T1D GRS_HLA models. Generated T1D GRS_HLA models were used to predict HLA-focused type 1 diabetes genetic risk across four ancestry groups. The performance of each T1D GRS_HLA model was assessed using receiver operating characteristic (ROC) AUCs, and compared statistically.

RESULTS: Each T1D GRS_HLA model included a different number of conditionally independent HLA-region SNPs (AFR, n=5; AMR, n=3; EUR, n=38; FIN, n=6; ALL, n=36) and HLA alleles (AFR, n=6; AMR, n=5; EUR, n=40; FIN, n=8; ALL, n=41). The ROC AUC values for the T1D GRS_HLA from SNPs or HLA alleles were similar, and ranged from 0.73 (T1D GRS_{HLA-allele-AMR} applied to FIN) to 0.88 (T1D GRS_{HLA-allele-EUR} applied to EUR). The ROC AUC using the combined set of conditionally independent SNPs (T1D GRS_HLA-SNP-ALL) or HLA alleles (T1D GRS_{HLA-allele-ALL}) performed uniformly well across all ancestry groups, with values ranging from 0.82 to 0.88 for SNPs and 0.80 to 0.87 for HLA alleles.

CONCLUSIONS/INTERPRETATION: T1D GRS_HLA models derived from SNPs performed equivalently to those derived from HLA alleles across ancestries. In addition, T1D GRS_HLA-SNP-ALL and GRS_{HLA-allele-ALL} models had consistently high ROC AUC values when applied across ancestry groups. Larger studies in more diverse populations are needed to better assess the transferability of T1D GRS_HLA across ancestries.

PMID:41037100 | DOI:10.1007/s00125-025-06563-8

Eur J Appl Physiol. 2025 Oct 2. doi: 10.1007/s00421-025-06008-5. Online ahead of print.

ABSTRACT

AIM: This pilot study aimed to systematically evaluate exercise-induced electrocardiographic (ECG) responses in professional firefighters and to explore the association between premature ventricular complexes (PVCs) and myocardial ischemia in this high-risk occupational group.

METHOD: This pilot cross-sectional study enrolled 21 male firefighters (mean age 43.4 ± 7.18 years) from a single municipal fire department. Participants underwent comprehensive cardiovascular assessment including anthropometric measurements, biochemical analyses (lipid profile, testosterone), submaximal exercise testing (Bruce protocol), and 24-h Holter ECG monitoring. Statistical analyses included Mann-Whitney U tests and effect size calculations.

RESULTS: No exercise-induced ST-segment changes indicative of myocardial ischemia were observed. However, PVCs were detected in 33% of participants (7/21), with exercise testing revealing 18 simple and 2 multiform PVCs, while Holter monitoring recorded 25 simple and 1 multiform PVC. PVC-positive firefighters were significantly older (median 49 vs. 40 years, p = 0.019, r = 0.514). Mean exercise capacity was 12.45 METs, with 81% achieving moderate fitness levels. Post-exercise heart rate recovery (HRR1: 24 ± 11.5 bpm; HRR2: 35.4 ± 11.5 bpm) showed normal patterns.

CONCLUSION: The findings of this pilot study indicate the need for larger-scale investigations, supported by advanced diagnostic modalities, to clarify the clinical relevance of exercise-induced premature ventricular complexes (PVCs) in firefighters. Although no ischemic changes were observed, the presence of subclinical coronary artery disease cannot be definitively excluded. These results provide a meaningful preliminary foundation for developing targeted screening approaches to improve early cardiovascular risk detection in high-physical-demand occupational groups.

PMID:41037097 | DOI:10.1007/s00421-025-06008-5

Odontology. 2025 Oct 2. doi: 10.1007/s10266-025-01222-1. Online ahead of print.

ABSTRACT

The aim of this study was to evaluate changes in tooth color and the bond strength of resin to enamel and dentin after exposure to electronic cigarette (e-cigarette) vapor in an in vitro vaping model, as well as to analyze the chemical composition of the materials present in the vapor. A device with a vacuum pump simulated vaping. Eighty dental slabs (40 dentin and 40 enamel) and were randomly divided into two groups. Half received e-cigarette exposure, and the other remained without vaping (control). Color changes were measured using a spectrophotometer (CIELAB). Composite cylinders were built on substrates using etch-and-rinse or self-etch strategies and subjected to loading tests. Gas chromatography-mass spectrometry (GC-MS) analyzed the organic compound of the e-liquid, while inductively coupled plasma mass spectrometry (ICP-MS) assessed the metal content. Statistical analysis was conducted using MANOVA and ANOVA (α = 0.05), and CIEDE2000 formula. E-cigarette exposure darkened (L*) and yellowed (b*) enamel and dentin. Bond strength in dentin decreased for both adhesion strategies, and in enamel using the etch-and-rinse adhesive. GC-MS identified 72 different volatile compounds, whereas ICP-MS detected 26 distinct metals. Among metals, eight exceeded the WHO (World Health Organization) tolerance limits. E-cigarette exposure altered the color of substrates and reduced resin bond strength in dentin for both adhesives, and in enamel restored with the etch-and-rinse technique. E-liquid had toxic organic compounds and metals. Exposure to e-cigarette can cause tooth discoloration and weaken bonding to dental tissues. Toxic volatile organic and metallic compounds present in vapor can adversely affect oral health.

PMID:41037091 | DOI:10.1007/s10266-025-01222-1

Eur Radiol. 2025 Oct 2. doi: 10.1007/s00330-025-12034-w. Online ahead of print.

ABSTRACT

OBJECTIVES: To construct a combined nomogram using CT enhancement ratio-based habitat imaging and radiological features in predicting the main component of combined hepatocellular carcinoma‑cholangiocarcinoma (cHCC-CCA), and to assess its ability for stratifying the prognosis.

MATERIALS AND METHODS: Patients with pathologically diagnosed cHCC-CCA who underwent contrast-enhanced CT examinations were retrospectively included and randomized into the training and validation cohorts. Tumors were grouped into high hepatocellular carcinoma (HCC) component (high-HCC%) and low-HCC component (low-HCC%) according to pathology. Voxels of tumor from early enhancement ratio and late enhancement ratio maps were clustered into different habitats through the k-means algorithm. The volume fractions of different habitats were quantified. Logistic regression analyses were utilized to identify independent predictors for high-HCC%, construct prediction models, and visualize them as a nomogram. The predictive performance was assessed by receiver operating characteristic analysis. Survival analysis was conducted using the Kaplan-Meier method.

RESULTS: 165 patients were finally included, and 78 (47.27%) patients were grouped as high-HCC%. Four tumor habitats were determined. The fraction of habitat 1 (f₁) was significantly higher, while the fraction of habitat 4 (f₄) was significantly lower in the high-HCC% group than in the low-HCC% group. Tumor capsule, corona enhancement, delayed enhancement, f₁, and f₄ were used to construct the combined nomogram with AUCs of 0.927 and 0.923 in training and validation cohorts, respectively. The combined nomogram predicted-high-HCC% exhibited better prognoses than the predicted-low-HCC% groups in terms of recurrence-free survival and overall survival.

CONCLUSION: Enhancement-based CT habitat imaging exhibited potential for predicting the main component cHCC-CCA, and provided a tool for prognosis stratification.

KEY POINTS: Question The component of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) significantly affected the prognosis, but there is no effective method for predicting the main component of cHCC-CCA. Findings The combined nomogram integrated habitat parameters and radiological features can predict the main component of cHCC-CCA and help stratify the prognosis after hepatectomy. Clinical relevance The habitat-based combined nomogram offers an effective tool for personalized and appropriate treatment in cHCC-CCA patients.

PMID:41037071 | DOI:10.1007/s00330-025-12034-w

Eur Radiol. 2025 Oct 2. doi: 10.1007/s00330-025-12033-x. Online ahead of print.

ABSTRACT

Diffusion-weighted imaging (DWI) offers critical insights into tissue microstructure through the assessment of water molecule random displacements and plays a central role in the assessment of neoplastic and non-neoplastic diseases. To successfully implement and use DWI in clinical practice, guidelines for acquisition, interpretation of image contrast and of artefacts should be followed, taking the disease process and body part into account. We recommend covering a b-value range of 0-1000 s/mm² in the brain (along at least six directions for white matter), and 50-800 s/mm² in the body. Available acquisition acceleration options should be used to reduce repetition time (TR), echo time (TE), and echo-planar imaging (EPI) distortions, while considering the penalty in signal-to-noise ratio (SNR) and image sharpness. DW images and the apparent diffusion coefficient (ADC) map should be read jointly for the clinical interpretation. Areas of slower diffusion are hyperintense on DW images and hypointense on the ADC map, and vice versa. Magnetic susceptibility distortions and signal drop-outs or pile-ups are particularly pronounced at air-tissue or metal-tissue interfaces and may obscure areas of interest or hinder the co-localisation with structural scans. By following these guidelines and recommendations, radiologists and imaging professionals can enhance diagnostic accuracy, reduce variability, and maximise the clinical value of DWI across diverse applications. KEY POINTS: This article provides an overview of DWI principles, clinical applications, potential pitfalls, and emerging advances, alongside expert recommendations for optimal implementation. We provide key considerations tailored to specific applications (neuro and whole-body imaging), including protocol optimisation, adherence to established guidelines, and quality assurance measures to minimise artefacts and ensure reproducibility. By following the guidelines and recommendations summarised in this work, radiologists and imaging professionals can enhance diagnostic accuracy, reduce variability, and maximise the clinical value of DWI across diverse applications.

PMID:41037070 | DOI:10.1007/s00330-025-12033-x

J Anim Breed Genet. 2025 Oct 2. doi: 10.1111/jbg.70018. Online ahead of print.

ABSTRACT

In order to investigate the applicability and efficiency of genomic selection for growth and carcass traits in Nordic beef cattle, single-step genomic BLUP (ssGBLUP) was applied in 4321 Charolais and 4532 Hereford animals with information on approximately 43,000 SNPs each. Statistics including dispersion value (b1), accuracy ratio and the relative accuracy improvement were estimated for genotyped female animals in the validation set. For estimating dispersion, accuracy ratio and relative accuracy improvement, the Legarra-Reverter linear regression (LR) method was used by truncating the phenotypes after 2018, and the validation set comprised females born from 2019 to 2021. Moreover, for ssGBLUP, different alpha values of 0.95 and 0.70 were utilised as weights on the genomic information when the H matrix was blended for the genomic relationship matrix G and the pedigree relationship matrix A. In general, implementing ssGBLUP led to higher accuracy ratios and improved dispersion values (b1 value closer to the optimum value of one), compared to when using pedigree-based BLUP (PBLUP). Using an alpha value of 0.70 gave a dispersion value closer to one compared with when using an alpha value of 0.95. Additionally, the relative accuracy estimation was improved substantially for several traits by using ssGBLUP instead of PBLUP, with the highest (30%) relative improvement for carcass conformation in Swedish Hereford cattle. In conclusion, ssGBLUP would be beneficial to implement in the future Nordic beef cattle breeding programs.

PMID:41036609 | DOI:10.1111/jbg.70018

Cancer Med. 2025 Oct;14(19):e71232. doi: 10.1002/cam4.71232.

ABSTRACT

BACKGROUND: The triglyceride glucose (TyG) index, a simple and reliable surrogate marker of insulin resistance (IR), has garnered increasing attention in metabolic research. Although IR is mechanistically linked to carcinogenesis through multiple pathways, including chronic inflammation, hyperinsulinemia-driven pro-mitogenic signaling, and altered adipokine secretion, the specific utility of the TyG index for cancer risk assessment remains unclear. This systematic review examines whether the TyG index shows consistent associations across cancer types and holds value as an independent risk predictor beyond established metabolic syndrome components.

METHODS: We systematically searched PubMed, Embase, and Web of Science databases from 2008 (the year the TyG index was established as an IR marker) to December 31, 2024, for studies on the TyG index-cancer association. Cohort, cross-sectional, and case-control studies were included. Using meta-analysis, we pooled effect sizes and conducted subgroup analyses by gender, region, population source, and study design. Trial sequential analysis (TSA) evaluated evidence reliability.

RESULTS: This meta-analysis incorporated a total of 20 eligible studies. Our findings demonstrated that elevated TyG index levels were significantly associated with increased risks of various malignancies, including digestive system cancers (OR: 1.22, 95% CI 1.13-1.31), urogenital system cancers (OR: 2.04, 95% CI 1.53-2.71), and breast cancer (OR: 1.64, 95% CI 1.49-1.80) when compared to lower TyG index levels. These associations remained consistent across all pre-specified subgroup analyses stratified by study characteristics. Furthermore, TSA confirmed sufficient statistical power for definitive conclusions.

CONCLUSIONS: The consistent observed association between elevated TyG index and increased cancer risk highlights its potential as a candidate biomarker for further investigation. While these findings support the biological plausibility of insulin resistance in oncogenesis, current evidence-partially derived from observational studies-cannot establish causality or direct clinical utility. Future research should prioritize: (1) prospective validation of TyG index thresholds for cancer risk prediction, (2) mechanistic studies elucidating its role in tumor biology, and (3) assessment of its incremental value to existing risk stratification tools.

PMID:41036596 | DOI:10.1002/cam4.71232

Physiol Rep. 2025 Oct;13(19):e70592. doi: 10.14814/phy2.70592.

ABSTRACT

This study investigated the effects of high-intensity functional training (HIFT) on hormonal and inflammatory biomarker responses during military service. One hundred and twenty-seven male conscripts were assessed over a 19-week training period. The experimental group (EXP: n = 64) followed a structured HIFT program, while the control group (CON: n = 63) adhered to conventional military physical training. Blood samples were collected at baseline (PRE), week 10 (MID), and post-intervention (POST) to measure serum testosterone, cortisol, testosterone/cortisol ratio, insulin-like growth factor 1 (IGF-1), sex hormone-binding globulin (SHBG), high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α). Body composition and physical performance were also measured. Serum testosterone increased in both groups between PRE and POST (EXP: +3.3 ± 3.8 nmol·L^-1, p < 0.001; CON: +3.7 ± 3.4 nmol·L^-1, p < 0.001), while cortisol remained unchanged. Testosterone/cortisol ratio increased in both groups (+0.010 ± 0.010, p < 0.001 for both). IGF-1 increased in CON (+4.4 ± 5.9 nmol·L^-1, p < 0.001) and SHBG increased in EXP (+3.1 ± 9.0 nmol·L^-1, p = 0.005). Inflammatory biomarkers (hs-CRP, IL-6) decreased in both groups. No adverse biomarker responses were observed, suggesting that HIFT was well tolerated during military service.

PMID:41036582 | DOI:10.14814/phy2.70592