Category: Statistics

BMC Microbiol. 2025 Dec 20. doi: 10.1186/s12866-025-04643-8. Online ahead of print.

ABSTRACT

BACKGROUND: Antimicrobial resistance (AMR) in animal-derived food is a significant global health issue, especially in low- and middle-income countries where sanitation, responsible antibiotic use, and surveillance remain weak. In dairy farming, Escherichia coli (E. coli) and Klebsiella species are of particular concern as they frequently exhibit multidrug resistance and produce extended-spectrum β-lactamase (ESBL). Despite their growing public health significance, limited data exist on their distribution in Ethiopia, particularly in the Tigray region. Therefore, this study aimed to determine the prevalence and antimicrobial resistance profiles of E. coli and Klebsiella spp. in dairy farm environments in the Tigray region of northern Ethiopia.

METHODS: A cross-sectional study was conducted between December 2024 and May 2025, analyzing 712 samples from raw bulk tank milk, milk-container swabs, water, and milkers’ stool, each 178. Escherichia coli and Klebsiella spp. were isolated and identified using standard culture and biochemical tests. Antimicrobial susceptibility was determined by the disk diffusion method according to CLSI (2024), and ESBL production was confirmed using the phenotypic double-disk synergy test (DDST). Isolates resistant to one or more antibiotics in three or more antimicrobial classes were classified as Multi-Drug Resistant (MDR). Data were processed and analyzed using SPSS version 26.

RESULTS: Out of 712 samples, 494 (69.4%) were positive for either E. coli or Klebsiella spp., with E. coli (49.6%) predominating over K. pneumoniae (10.3%) and K. oxytoca (9.6%). High resistance levels were observed to tetracycline (62.9%), amoxicillin/clavulanic acid (31.2%), and trimethoprim-sulfamethoxazole (27.7%), while resistance to meropenem remained low (2.4%). Overall, 32.4% of isolates were MDR, with the highest rates in E. coli (32.0%). ESBL production was detected in 53 (10.7%) of isolates, across all sample types and locations.

CONCLUSION: The study revealed a high prevalence of E. coli and Klebsiella spp. in dairy farm environments, with a considerable proportion of MDR and ESBL producers. This poses a serious concern for food safety and public health. These findings highlight the urgent need to enhance hygiene, antimicrobial stewardship, and integrated One Health-based surveillance along the dairy value chain.

PMID:41422193 | DOI:10.1186/s12866-025-04643-8

NPJ Precis Oncol. 2025 Dec 20. doi: 10.1038/s41698-025-01228-6. Online ahead of print.

ABSTRACT

Gene expression profiling in precision oncology is increasing with uncertain validity across platforms. In this study, we examined the application of PurIST, a molecular subtyping algorithm for pancreatic ductal adenocarcinoma (PDAC), across different platforms. We compared PurIST calls between matched samples processed by whole transcriptome and commercial exome capture RNA-seq. In parallel, we compared subtypes between matched samples processed by NanoString and whole transcriptome RNA-seq from the PANCREAS trial (NCT04683315). Between whole transcriptome and exome capture, subtype agreement was 81% with significant increase in basal-like subtype with exome capture. Differences in overall survival in patients with basal-like tumors compared to classical tumors did not reach statistical significance using exome capture (log-rank P = 0.061), whereas with whole transcriptome it was significantly shorter (log-rank P < 0.0001). Subtype agreement between whole transcriptome RNA-seq and NanoString was higher at 95%. PurIST results should be interpreted with caution when using exome capture methods.

PMID:41422185 | DOI:10.1038/s41698-025-01228-6

Psychiatry Res. 2025 Dec 14;356:116907. doi: 10.1016/j.psychres.2025.116907. Online ahead of print.

ABSTRACT

OBJECTIVE: Conflicting evidence exists on the association of obesity, depression and mortality risk. This study evaluates a cohort of subjects with depression from the USA NHANES and all-cause and cardiovascular mortality risks based on baseline BMI and ABSI.

METHODS: A nationally representative cohort study was conducted using NHANES data (2005-2018), including 2854 adults with depression. Weighted Cox regression and restricted cubic spline (RCS) models were applied to assess anthropometric associations with mortality. Weighted receiver operating characteristic (ROC) curves evaluated the diagnostic value of BMI and ABSI.

RESULTS: Each 1-SD BMI increase was predictive of reduced all-cause (HR = 0.81, 95 % CI:0.67-0.98) and cardiovascular mortality (HR = 0.62, 95 % CI:0.43-0.89). Each 1-SD ABSI increase was predictive of elevated all-cause (HR = 1.27, 95 % CI:1.06-1.51) and cardiovascular mortality (HR = 1.60, 95 % CI:1.20-2.15). In these depressed individuals, BMI showed the U-shaped and ABSI the expected curvi-linear relationships with mortality as established from the studies of the NHANES cohorts. In ROC analyses, ABSI showed the best predictive performance for all-cause mortality (AUC = 0.678) and for cardiovascular mortality (AUC = 0.706). BMI Tertile 1 & ABSI Tertile 3 had the highest mortality risks (all-cause HR = 3.09, 95 % CI:1.38-6.93; cardiovascular HR = 5.45, 95 % CI:1.36-21.85). Due to the approximate statistical independence of BMI and ABSI, combining them further improved AUC values (all-cause: 0.691; cardiovascular: 0.722).

CONCLUSION: Among individuals with depression ABSI predicts mortality similar to the general population, while obesity as defined by BMI was “paradoxically” associated with lower mortality. Personalized mortality risk for an individual can be derived by combining the independent risks based on BMI and ABSI.

PMID:41420910 | DOI:10.1016/j.psychres.2025.116907

Neuro Endocrinol Lett. 2025 Dec 16;46(6):356-365. Online ahead of print.

ABSTRACT

PURPOSE: This study assessed the efficacy of 3.0T magnetic resonance angiography (MRA) in individuals with primary hemifacial spasm (pHFS) by investigating the relationship between alterations in the morphology of the vertebrobasilar artery system and pHFS.

METHODS: A comparison was made between pHFS patients and healthy controls with respect to vertebral artery diameter, displacement rate, and other relevant parameters to explore the potential role of morphologic abnormalities in the vertebrobasilar arteries in the pathogenesis of pHFS. Independent t-tests and Wilcoxon rank-sum tests were used with statistical significance set at a p < 0.05.

RESULTS: A total of 100 pHFS patients and 150 healthy participants underwent 3.0T MRA scans for this analysis. The right vertebral artery (VA) diameter in the pHFS group was larger than the healthy control (HC) group (2.71 mm vs. 2.47 mm; p < 0.05) and the left VA deviation distance in the pHFS group was greater than the HC group (7.99 mm vs. 5.27 mm; p < 0.05). The basilar artery deviation distance in the pHFS group was greater than the HC group (7.41 mm vs. 4.78 mm; p < 0.05). The VA deviation rates in the pHFS group were significantly higher than the HC group (89% vs. 72% and 96% vs. 84.67%, respectively; p < 0.05). The VA scores on the symptomatic and non-symptomatic sides were significantly different (p < 0.05). VA migration increased with age (p = 0.034, r = 0.225).

CONCLUSION: The results imply a potential association between morphologic irregularities in the vertebrobasilar arteries and pHFS. Limitations of the study included substantial missing data for displacement measurements (64%-67%), age differences between groups, and selection bias from the surgical population.

PMID:41420884

Neuro Endocrinol Lett. 2025 Dec 16;46(6):315-322. Online ahead of print.

ABSTRACT

BACKGROUND: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition that impairs communication. Increasing research indicates that maternal immune activation (MIA) is one of the most important environmental factors that increase the risk of autism spectrum disorder (ASD) in offspring. Maternal immune activation produces elevated cytokine levels that cross the placental barrier and disrupt fetal neurodevelopment, increasing ASD risk. However, the specific causal pathways and mediating mechanisms remain unclear, limiting our understanding.

METHODS: This mediation Mendelian randomization study examined causal pathways linking immune cell traits (exposures) and inflammatory factors (mediators) to ASD risk.The research merged immune data (731 phenotypes + 48 cytokines) and ASD data from a cohort comprising 18,382 cases and 27,969 controls. Various MR approaches were used to reduce potential biases, along with thorough descriptions of statistical procedures and instrumental variable selection.

RESULTS: The study’s findings propose potential causal relationships among cytokines representing inflammatory factors, immune cells, and ASD through mediation Mendelian randomization. Reverse MR was then employed to investigate the possibility of reverse causality. CD8+ T cell %leukocyte (OR = 1.099, 95% CI: 1.039-1.163, p = 0.001), CCR2+ CD62L+ myeloid dendritic cells (OR = 0.933, p = 0.029), and CD45+ immature myeloid-derived suppressor cells (OR = 1.056, p = 0.001) showed evidence of causal association with ASD risk.Furthermore, reduced Artemin levels and elevated FLT3L and 2B4 levels were significantly linked to ASD risk, indicating that abnormalities in immunomodulatory factors may play a crucial role in the pathogenesis of ASD. Additionally, ASD occurrence may result in alterations in Natural Killer cell receptor 2B4 levels.

CONCLUSION: This mediation Mendelian randomization study provides evidence that immune dysfunction is associated with ASD pathophysiology through inflammatory mediators, requiring functional validation before clinical application.Cytokines act as mediators in the pathogenesis of ASD, providing a theoretical basis for understanding its immunoinflammatory pathogenesis and offering insight into treatment.

PMID:41420879

Cell Rep. 2025 Dec 18;45(1):116724. doi: 10.1016/j.celrep.2025.116724. Online ahead of print.

ABSTRACT

The gut microbiome is integral to human health, yet research data to date have emphasized industrialized populations. Here, we performed large-scale shotgun metagenomic sequencing on 1,893 individuals from rural Honduras, providing the most comprehensive microbiome dataset from Central America. We identify a distinct microbial composition enriched in Prevotella species. Longitudinal analysis in 301 individuals reveals microbiome instability, with shifts in taxonomic diversity and metabolic potential, including changes associated with severe acute respiratory syndrome coronavirus 2 infection. Additionally, we characterize the gut virome and eukaryotic microbiome, identifying uncharacterized viral taxa and a high prevalence of Blastocystis species in individuals with greater microbial diversity. Finally, by integrating host genomic data, we uncover significant host-microbiome associations, highlighting the influence of human genetic variation on microbial composition. These findings expand our understanding of microbiome diversity in non-industrialized populations, underscoring the need for global microbiome research.

PMID:41420859 | DOI:10.1016/j.celrep.2025.116724

Cancer. 2026 Jan 1;132(1):e70236. doi: 10.1002/cncr.70236.

ABSTRACT

BACKGROUND: Clinical studies have shown that outcomes of patients with prostate cancer could vary depending on race. In this study, the authors sought to determine if the treatment effect of apalutamide, an androgen receptor pathway inhibitor (ARPI), on overall survival (OS) varies depending on the race of the patient.

METHODS: This pooled analysis includes individual patient data from two phase 3 trials, TITAN and SPARTAN, which randomized patients to androgen deprivation therapy (ADT) ± apalutamide in metastatic hormone-sensitive and nonmetastatic castration-resistant prostate cancer, respectively. Race was self-identified and categorized as Asian, Black, White, and Others categories. The authors applied a stratified (stratification for the trial) multivariable Cox proportional hazards regression model to determine heterogeneity of treatment effect on OS after adjustment for age, performance status, body mass index, T- and N-stage, Gleason score, comorbidities, and exposure to statins and metformin.

RESULTS: Overall, 2190 patients were included: 16.9% patients were Asian, 3.7% were Black, 67.4% were White, and 12.0% were from the Others category. The authors did not find any significant heterogeneity of treatment effect from apalutamide on OS across racial groups (interaction-p = .46). Among ADT plus apalutamide-treated patients, there was no association of race with OS (hazard ratio for Asian, 0.77 [95% CI, 0.56-1.06]; Black, 0.82 [95% CI, 0.49-1.37]; and Others, 1.00 [95% CI, 0.75-1.34], all compared to White).

CONCLUSIONS: In this study, the authors did not find any evidence of difference in the treatment effect of apalutamide on OS across patients of different races, although interpretation remains limited by poor representation of racial minorities. Among apalutamide-treated patients, there was no association of race with OS.

PMID:41420831 | DOI:10.1002/cncr.70236

Hernia. 2025 Dec 20;30(1):43. doi: 10.1007/s10029-025-03547-w.

ABSTRACT

PURPOSE: The incidence of trocar site hernia (TSH) after bariatric surgery is unclear. This study aims to describe the cumulative incidence of ventral hernia surgery after laparoscopic bariatric surgery in total and by laparoscopic method (LRYGB; Roux-en-Y Gastric Bypass and LSG; Sleeve Gastrectomy).

METHODS: This was a register based observational study on patients subjected to laparoscopic bariatric surgery (LRYGB or LSG) in Sweden 2009-2019. The Scandinavian Obesity Surgery Registry (SOReg) was linked to the Swedish National Patient Register (NPR) to obtain instances of ventral hernia surgery. Nearby codes were used as proxies for TSH surgery, since a specific procedure code for TSH surgery is lacking.

RESULTS: In 64 124 patients, mean follow-up was 67 ± 36 months, LRYGB (n = 52 020) 74 ± 34 months and LSG (n = 12 104) 34 ± 22 months. Mean time between bariatric- and ventral hernia surgery was 36 ± 28 months (range 0-129). The five-year cumulative incidence of surgery for ventral hernia was 2.9% (CI 2.8-3.1). The probability of having hernia surgery was significantly higher for LRYGB compared to LSG (Breslow test, p < 0.001), still significant with differences in follow-up time accounted for (p < 0.001).

CONCLUSION: The incidence of surgery for ventral hernia after laparoscopic bariatric surgery is not negligible in this material covering over a decade of bariatric procedures. Ventral hernia surgery was more common after gastric bypass than after sleeve gastrectomy.

PMID:41420786 | DOI:10.1007/s10029-025-03547-w

Am J Cardiovasc Drugs. 2025 Dec 20. doi: 10.1007/s40256-025-00778-1. Online ahead of print.

ABSTRACT

AIMS: Residual cardiovascular risk remains substantial in patients with atherosclerotic cardiovascular disease (ASCVD) despite high-intensity statin therapy. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), including monoclonal antibodies and small-interfering RNA agents, offer additional risk reduction, yet comparative evidence across individual regimens remains limited.

METHODS AND RESULTS: We conducted a systematic review and network meta-analysis of randomized controlled trials evaluating approved PCSK9i dosages in patients with ASCVD. The primary outcome was major adverse cardiovascular events (MACE); the secondary outcomes included myocardial infarction, stroke, coronary revascularization, cardiovascular mortality, and all-cause death. A total of eight trials involving 49,847 patients were included. Evolocumab (140 mg every 2 weeks or 420 mg monthly) and alirocumab 150 mg every 2 weeks significantly reduced MACE compared with placebo (risk ratios (RR): 0.78, 95% confidence intervals (CI): 0.66-0.93 and RR: 0.47, 95% CI 0.25-0.86, respectively). Evolocumab was also associated with reductions in myocardial infarction, stroke, and revascularization. Alirocumab 150 mg demonstrated the most pronounced effect on revascularization and was superior to both evolocumab and the lower alirocumab dose in this outcome. No regimen significantly reduced cardiovascular or all-cause mortality.

CONCLUSIONS: These findings suggest that PCSK9 inhibitors are effective in ASCVD, with generally similar efficacy across agents; however, regimens achieving lower and sustained low-density lipoprotein cholesterol levels may confer greater benefit, in line with the concept that “the lower, the better.”

TRIAL REGISTRATION: PROSPERO identifier no. CRD420251022108.

PMID:41420785 | DOI:10.1007/s40256-025-00778-1

Graefes Arch Clin Exp Ophthalmol. 2025 Dec 20. doi: 10.1007/s00417-025-07054-7. Online ahead of print.

ABSTRACT

PURPOSE: This post-hoc analysis of two OTX-101 clinical trials assessed the efficacy of 0.09% ciclosporin in treating dry eye disease (DED) patients with moderate-to-severe corneal damage.

METHODS: The criteria for moderate-to-severe corneal damage were defined as a CFS total score (5 zones) of ≥ 6 or single zone ≥ 2 at baseline (modified NEI scale). 516 patients (49% of the intention-to-treat population) met these criteria at baseline. Changes in ocular surface damage (cornea and conjunctiva) and aqueous tear deficiency from baseline were determined through corneal fluorescein staining (CSF), Lissamine green staining (LGS) and Schirmer’s test without anesthesia (ST).

RESULTS: After 12 weeks of treatment with OTX-101 versus (vs.) vehicle, outcomes improved across six parameters: (I) Central CFS mean change from baseline was -0.48 vs. -0.36, p = 0.0144. (II) Total CFS corneal staining change from baseline was -2.30 vs. -1.61 p = 0.0004. (III) Improvement ≥ 50% in total CFS from baseline was 44.8% vs. 33.4% p = 0. 0010. (IV) Conjunctival damage as measured by LGS mean change from baseline was -1.61 vs. -0.99, p = 0.0006. (V) Tear production as measured by ST as percentage of eyes with ≥ 10 mm increase from baseline was 18.2% vs. 8.3% p = 0.0003, and (VI) ST mean change from baseline was +2.94 vs. +0.28 p = 0.0008.

CONCLUSION: Administration of OTX-101 0.09% leads to statistically significant improvement across six parameters in ocular surface staining and tear production in DED patients with moderate to severe corneal damage.

PMID:41420783 | DOI:10.1007/s00417-025-07054-7