Category: Statistics

Discov Oncol. 2025 Nov 7;16(1):2059. doi: 10.1007/s12672-025-03919-9.

ABSTRACT

OBJECTIVE: Elucidating the causal relationship between rheumatoid arthritis (RA) and pancreatic cancer (PC) remains methodologically challenging due to limitations inherent in observational studies. This study applied a bidirectional two-sample Mendelian randomization (MR) design to investigate the potential causal interplay between RA and PC, aiming to uncover shared pathogenic pathways and genetic predispositions through comprehensive instrumental variable analysis.

METHODS: Utilizing genome-wide association study (GWAS) meta-analysis data, we systematically screened and incorporated independent single nucleotide polymorphisms (SNPs) associated with RA and PC as instrumental variables. The primary analytical approach was the inverse-variance weighted fixed-effects model (IVW-FE). To ensure methodological rigor and validate causal inferences, we complemented this with several approaches: simple median, weighted median, and MR-Egger regression. Heterogeneity was assessed using Cochran’s Q test, and pleiotropy was evaluated using MR-Egger intercept analysis. Sensitivity analysis was conducted using the leave-one-out approach. All effect estimates are reported as odds ratios (ORs) with corresponding 95% confidence intervals (CIs).

RESULTS: Seventy-seven SNPs met the predefined inclusion criteria. MR analyses revealed that elevated genetic susceptibility to RA was causally associated with an increased risk of PC (OR = 1.187, 95% CI = 1.355-1.039, P = 0.011). MR-Egger regression analysis indicated no significant pleiotropic effects (intercept p = 0.434). Cochran’s Q statistics indicated no substantial heterogeneity in the causal estimates for RA (P = 0.064). Consistent with these findings, leave-one-out sensitivity analyses confirmed the absence of influential outlier variants in the instrumental variable sets. However, there was no significant causal association between PC and the risk of RA (OR = 0.991, 95% CI = 0.957-1.027, P = 0.620).

CONCLUSIONS: Our results support a unidirectional causal relationship, identifying RA as a potential risk factor for the development of pancreatic cancer, with no evidence for a reverse causal effect.

PMID:41201680 | DOI:10.1007/s12672-025-03919-9

Fish Physiol Biochem. 2025 Nov 7;51(6):189. doi: 10.1007/s10695-025-01590-z.

ABSTRACT

Totoaba (Totoaba macdonaldi) aquaculture offers economic and ecological advantages. However, its culture still relies on fishmeal in diets because alternative protein sources show reduced productive performance. The current study assessed the impact of low concentrations of methionine and taurine together with alternative proteins, on the productive performance of T. macdonaldi over a 60-day experimental period. Four diets were formulated for this purpose, a basal diet (D-BD), the basal diet with methionine (D-MET), the basal diet with taurine (D-TAU), and the basal diet with methionine and taurine (D-MET + TAU). The present experiment used a randomized design. One hundred forty-four juveniles (41.0 ± 0.5 g in weight) were randomly distributed in 12 tanks (500 L) in triplicate groups to assess biological indices, cholesterol content, hepatic gene expression, and the synthesis and transport of taurine. The statistical analysis revealed that the dietary treatments D-MET and D-TAU positively affected the growth rate, whereas their interaction resulted in a significantly higher growth (p < 0.05). The expression of the igf-1 gene in the liver increased and showed a positive interaction. When TAU and MET were limited, there was an observed overexpression of csad in hepatic tissue. Diets supplemented with TAU showed a decrease in total cholesterol level, whereas cholesterol level in the liver increased with MET supplemented alone. Total TAU content in fish tissues was significantly higher when both TAU and MET were supplemented. In conclusion, T. macdonaldi exhibits a limited capacity, for TAU synthesis, and MET limitation appears to restrict growth potential.

PMID:41201678 | DOI:10.1007/s10695-025-01590-z

J Child Adolesc Psychiatr Nurs. 2025 Nov;38(4):e70044. doi: 10.1111/jcap.70044.

ABSTRACT

BACKGROUND: The COVID-19 pandemic has led to an increase in adolescent gaming due to lockdowns and the shift to online learning. Although factors linked to game addiction in adolescents before and during the pandemic have been explored, research on patterns following the easing of restrictions is limited.

PURPOSE: This study examined the relationship between perceived stress, loneliness, resilience, and game addiction among adolescents in Bangkok during the COVID-19 pandemic transition period.

METHODOLOGY: This correlational study included 346 high school students from two schools in Bangkok, Thailand, selected using a proportional stratified random sampling method. Data were collected from November to December 2022 during Thailand’s reclassification of COVID-19 as a communicable disease under a surveillance system. Descriptive statistics and Spearman’s correlation were used for the analysis.

RESULTS: The findings showed that 15.0% of adolescents were at risk of game addiction, with 4.4% being addicted. Most (87.3%) engaged in gaming, and 38.7% played games daily. Perceived stress (r_(s) = 0.14, p = 0.01) and loneliness (r_(s) = 0.25, p < 0.001) were positively correlated with game addiction, while resilience was negatively correlated (r_(s)= -0.26, p < 0.001). All resilience components-“I have” (external support) (r_(s) = -0.21), “I am” (inner strength) (r_(s) = -0.28), and “I can” (interpersonal and problem-solving skills) (r_(s)= -0.24)-were negatively correlated with game addiction (p < 0.001).

CONCLUSIONS: This study identified perceived stress and loneliness as risk factors for game addiction, and resilience as a protective factor. These findings offer valuable insights for professionals, including nurses, to develop targeted prevention programs for adolescents during the pandemic transition period and in the event of future crises.

PMID:41200867 | DOI:10.1111/jcap.70044

Liver Int. 2025 Dec;45(12):e70399. doi: 10.1111/liv.70399.

ABSTRACT

BACKGROUND & AIMS: Hepatorenal syndrome-acute kidney injury (HRS-AKI) is a life-threatening complication of decompensated cirrhosis. The US Food and Drug Administration approved terlipressin use for HRS-AKI based on the CONFIRM study, which demonstrated a significant improvement in HRS reversal with terlipressin versus placebo. The label notes elevated risk of respiratory failure in patients with volume overload or acute-on-chronic liver failure (ACLF) grade 3 and limited benefit when serum creatinine (SCr) exceeds 5 mg/dL.

METHODS: We performed a post hoc analysis of CONFIRM excluding patients with ACLF grade 3 or SCr ≥ 5 mg/dL. This allowed us to assess the efficacy and safety of terlipressin in a population where the benefit-to-risk profile is more favourable. Efficacy outcomes included HRS reversal, renal replacement therapy (RRT), liver transplantation (LT), RRT-free survival, LT-free survival and overall survival. Changes in SCr, Model for End Stage Liver Disease (MELD) and sodium were also assessed.

RESULTS: HRS reversal occurred in 43% (60/141) of patients with terlipressin versus 17% (13/75) with placebo (p < 0.001). Terlipressin was associated with significantly larger reductions (vs. placebo) in SCr (p < 0.001) and increases in serum sodium (p < 0.001). Importantly, LT rates were similar even though MELD scores decreased. 90-day survival was similar between treatment arms. Notably, selecting patients with a favourable benefit-to-risk profile led to a similar incidence of respiratory failure between treatment arms (11% with terlipressin vs. 7% with placebo; p = 0.360).

CONCLUSIONS: In patients with HRS-AKI without baseline ACLF grade 3 or SCr ≥ 5 mg/dL, terlipressin improved clinical outcomes and was not associated with an increased risk of respiratory failure.

TRIAL REGISTRATION: CONFIRM, ClinicalTrials.gov identifier: NCT02770716.

PMID:41200852 | DOI:10.1111/liv.70399

J Sleep Res. 2025 Nov 7:e70235. doi: 10.1111/jsr.70235. Online ahead of print.

ABSTRACT

Studies in mammal models show that reduced sleep is associated with increased food intake. Zebrafish (Danio rerio) is emerging as a promising model for studying sleep and feeding behaviour due to its similarities with mammals. Our goal was to investigate whether sleep restriction increases food intake in zebrafish, its potential effects on central regulation of feeding, and whether effects are similar in both sexes. Individually housed male and female adult zebrafish were exposed to nighttime (ND) or daytime (DD) vibrations and compared to a control group without vibration (n = 30 males and n = 27 females). ND, but not DD, reduced sleep during the disturbance period, with males showing a significant effect and females exhibiting an altered sleep pattern without a statistically significant reduction. ND also significantly increased food intake in males, as measured by daily milligrammes and number of pellets consumed. In contrast, ND females exhibited a decrease in the time spent feeding, suggesting a sex-specific response to sleep disruption. The whole brain expression of neuropeptide Y (npy), proopiomelanocortin (pomc), and its receptor melanocortin-4 (mc4r) were analysed by RT-qPCR. Males from ND exhibited significantly reduced pomc mRNA levels. Grouped-housed (three male and two female) zebrafish exposed to ND also exhibited increased food intake. In conclusion, sleep restriction affected food intake behaviour and the central regulation in zebrafish, with distinct sex-specific effects.

PMID:41200849 | DOI:10.1111/jsr.70235

Circ Genom Precis Med. 2025 Nov 7:e005220. doi: 10.1161/CIRCGEN.124.005220. Online ahead of print.

ABSTRACT

BACKGROUND: Proteins linked to heritable coronary heart disease (CHD) could uncover new pathophysiological mechanisms of atherosclerosis. We report on the protein profile associated with a family history of early-onset CHD and whether the relation between proteins and coronary atherosclerotic burden differs according to family history status, as well as inferences from Mendelian randomization.

METHODS: Data on coronary atherosclerotic burden from computed tomography angiography and Olink proteomics were retrieved for 4521 subjects, free of known CHD, from the SCAPIS (Swedish Cardiopulmonary Bioimage Study). Records of myocardial infarction and coronary revascularization therapies in any parent or sibling of subjects were retrieved from national registers. Linear associations between family history and proteins were adjusted for age, sex, and study site. Statistical interactions between proteins and family history for the association between proteins and the coronary atherosclerotic burden were also studied. Mendelian randomization for causal associations between proteins and CHD was performed with GWAS summary data from UKB-PPP (UK Biobank Pharma Proteomics Project), CARDIoGRAMplusC4D, and FinnGen.

RESULTS: Of 4251 subjects, family history of early-onset CHD was present in 9.5%. Thirty-eight proteins, with biological features of inflammation, lipid metabolism, and vascular function, were associated with family history using a false discovery rate of 0.05. The strongest associations were observed for follistatin and cathepsin D, neither of which was attenuated by adjusting for cardiovascular risk factors. Eighteen proteins were statistical interactors with family history in the association between each protein and the coronary atherosclerotic burden, most notably the LDL (low-density lipoprotein) receptor, transferrin receptor protein 1, and PECAM1 (platelet endothelial cell adhesion molecule 1). In 2-sample Mendelian randomization, a novel association was found for follistatin and myocardial infarction, and previous associations for PCSK9 (proprotein convertase subtilisin/kexin type 9) and PECAM1 were repeated.

CONCLUSIONS: These findings highlight new potential mechanisms for heritable and general atherosclerosis.

PMID:41200820 | DOI:10.1161/CIRCGEN.124.005220

Orthod Craniofac Res. 2025 Nov 7. doi: 10.1111/ocr.70054. Online ahead of print.

ABSTRACT

OBJECTIVE: This prospective study aimed to evaluate the impact on oral health-related quality of life (OHRQoL) in skeletal Class III patients treated with the surgery-first approach using either orthodontic aligners or fixed appliances.

MATERIALS AND METHODS: Patients were treated using the Surgery-First Approach (SFA) combined with either clear aligner (CA) or conventional fixed appliances (FA). A total of 20 patients (male and female) were allocated to the CA group, while 14 were included in the FA group. OHRQoL was assessed using the Orthognathic Quality of Life Questionnaire (OQLQ), the Oral Health Impact Profile-14 (OHIP-14) and the SF-36 at different time periods: (T0) pre-treatment, (T1) 1 week after orthodontic appliance installation, (T2) 4 weeks post-surgery and (T3) 6 months post-surgery. Data analysis was conducted using the Friedman and Mann-Whitney tests, with a significance level of 5%.

RESULTS: No statistically significant differences were found in OHRQoL scores between the CA and FA groups at baseline and after 6 months of treatment. However, significant intra-group improvements were observed over time, particularly between the first and sixth months of treatment.

CONCLUSIONS: Both ortho-surgical approaches, using either clear aligners or fixed appliances, resulted in significant improvements in patient quality of life. These findings highlight the positive impact of orthognathic treatment on dentofacial correction and overall well-being, regardless of the appliance type.

TRAIL REGISTRATION: ClinicalTrials.gov NCT05822271.

PMID:41200809 | DOI:10.1111/ocr.70054

Microbiologyopen. 2025 Dec;14(6):e70148. doi: 10.1002/mbo3.70148.

ABSTRACT

The specific members of the gut microbiota linked to phenylketonuria remain to be identified. This study aimed to assess the association between gut microbiota on phenylalanine (Phe) levels using a two-sample Mendelian randomization (MR) approach. Summary statistics from genome-wide association studies (GWAS) related to individual gut microbiota were obtained from the MiBioGen Global Consortium database. The data set of Phe levels was derived from GWAS summary datasets. Inverse variance weighting (IVW) served as the primary method to infer the causal relationship between gut microbiota and Phe levels. Additional pleiotropy and heterogeneity tests were conducted to evaluate the reliability of the findings. The Family XIII AD3011 group had a protective effect on Phe levels (OR = 0.962, 95% CI: 0.942-0.982, p < 0.001), and these associations remained significant after FDR correction (adjusted p-value = 0.027). There was no evidence of notable heterogeneity and horizontal pleiotropy among the instrumental variables. Our data indicate that Family XIII AD3011 group is associated with reduced Phe levels, highlighting a potential link between gut microbiota and Phe levels. Although MR analysis supports a causal relationship, it may not precisely estimate the effect size, necessitating further studies to validate these findings and quantify the association.

PMID:41200774 | DOI:10.1002/mbo3.70148

J Hum Nutr Diet. 2025 Dec;38(6):e70153. doi: 10.1111/jhn.70153.

ABSTRACT

INTRODUCTION: Weight control is a cornerstone of Type 2 Diabetes (T2D) management. The low-calorie diet program continuous low energy diets (CLED) is currently offered to patients for remission in the United Kingdom, but this may not suit all patients. Intermittent Low Energy Diets (ILED) may be an alternative approach. This survey explored patient characteristics and dietary choice priorities to predict preference for CLED, ILED, and other diets to inform future patient-centered advice.

METHODS: 622 participants (> 18 years) with a diagnosis of T2D recruited via a patient volunteer database, social media and the Prolific research register completed an online survey. Demographics, health characteristics, T2D treatment factors and dietary choice priorities were analyzed to predict preference between CLED and ILED. In addition, we explored qualitative reasons why participants were choosing between these two diets as well as other calorie-restricted diets.

RESULTS: CLED preference was significantly higher among all the < 65 age groups (than those aged > 74), and those who prioritized reduced medicine dependency (1.75 times more likely) and prioritizing speed of weight loss (2.59 times more likely) over improving blood sugar. ILED preference was associated with prioritizing flexibility of food choice (2.73 times more likely) and prioritizing diets which fit in with family meals and social events (2.5 times as likely) over professional support. Content analysis showed that CLED and ILED diets weren’t the most popular dietary choice, with more patients expressing preferences for a daily food based moderate calorie-restricted diet and low carbohydrate diets. Simplicity to follow was a common theme across all diets, demonstrating the importance of ensuring that any prescribed diet has clear and easy instructions.

CONCLUSION: Patients’ dietary preferences are influenced by a range of factors including the outcome and the extent to which the diet will fit into their lifestyles. Understanding patient perspectives about desired dietary outcomes and how they envisage the diet fitting into their lives will enable professionals to provide helpful patient-centered advice which may increase the likelihood of adherence.

PMID:41200771 | DOI:10.1111/jhn.70153

ACS Appl Mater Interfaces. 2025 Nov 7. doi: 10.1021/acsami.5c16152. Online ahead of print.

ABSTRACT

Stable electromechanical responses are the foundation for achieving reliable health monitoring. Long-term stability, in wearable or implantable medical devices, is a key to addressing challenges such as mechanical deformation and body fluid erosion during continuous physiological activities, which seriously restricts the transformation of flexible wearable devices from laboratory prototypes to commercial products. This paper reports on a hierarchical AgNWs-P3HT/PDMS-based flexible strain sensor, having an advantage of performance characterized by constant hysteresis. Employing 80-day experimental assays, it is confirmed that the herein fabricated flexible strain sensor is long-term stable at room temperature in the laboratory environment; there is no statistical difference existing in its sensitivity described by gauge factor (GF) during the testing duration. GF-sensitivity can be improved through reducing the thickness of the composite electrode, such that it can exhibit a very high GF-sensitivity (151.1) with a thinner thickness of 0.2 mm. And it features a wide strain response range (0.1-40%) that covers the physiological deformation levels. Besides, it has good shape-plasticity that can be processed and formed according to the topological structure of the host organ, such as integrating into a contact lens with a circle configuration. Employing human corneal epithelial cells, additionally, it is evidenced that the sensor has excellent biocompatibility through the cytotoxicity assay. Furthermore, it is also confirmed that the sensor can generally realize physiological pressure monitoring and diverse movement action detecting.

PMID:41200740 | DOI:10.1021/acsami.5c16152