Nevin Manimala

Rheumatology (Oxford). 2025 Jun 25:keaf311. doi: 10.1093/rheumatology/keaf311. Online ahead of print.

ABSTRACT

OBJECTIVES: Sex-related differences exist in the clinical presentation and treatment outcomes of patients with psoriatic arthritis (PsA). The biological pathways driving these differences remain unknown. We conducted an untargeted proteomic study to identify sex-specific serum proteins and biological pathways in males and females with PsA.

METHODS: We used an aptamer-based panel to measure 6402 serum proteins in 50 male and 50 female patients with active PsA and 50 age- and sex-matched non-psoriatic controls. Differential expression and pathway enrichment analysis identified differentially expressed proteins (DEPs) and enriched pathways between male and female PsA patients. Machine learning classifiers were used to develop sex-specific multi-biomarker models to distinguish PsA patients from controls. Proteins with the highest predictive performances were highlighted from random forest models.

RESULTS: The differential analysis revealed over 20 times more sex-specific DEPs in PsA males vs controls (n = 741) than in PsA females vs controls (n = 31). The enriched pathways among DEPs in PsA males vs PsA females were related to intracellular signalling, vascular function, cytokine signalling, and immune cell functions. All models discriminated PsA from controls for both sexes with an area under the curve of 0.85-0.99. Variable importance analysis identified leukotriene A-4 hydrolase as a significant predictor in PsA females vs controls, whereas interleukin-36 alpha, NEK7, and PIK3CA/PIK3R1 were significant in PsA males vs controls.

CONCLUSION: Significantly more dysregulated proteins and biological pathways were found in males than in females with PsA. The identified proteins and pathways offer potential new targets for sex-based research in PsA.

PMID:40560578 | DOI:10.1093/rheumatology/keaf311

Br J Radiol. 2025 Jun 25:tqaf139. doi: 10.1093/bjr/tqaf139. Online ahead of print.

ABSTRACT

OBJECTIVES: Approximately 10% of breast and 20% of ovarian cancers are hereditary in nature. The most commonly implicated genes are the BRCA genes, and the current gold standard for testing is by direct DNA sequencing. This process is expensive, time-consuming, and has a turnaround time of several weeks. Radiogenomics involves extracting quantitative data from medical imaging and using mathematical models to predict the underlying genetic makeup of tissues.

AIM: To perform a systematic review and meta-analysis evaluating the accuracy of radiogenomics in determining BRCA alteration status.

METHODS: A systematic review was performed in accordance with PRISMA guidelines. Diagnostic test accuracy analyses (ie pooled sensitivity and specificity) were performed. Statistical analyses were performed using RevMan V5.4.

RESULTS: 13 studies compromising 2835 patients were included. Of these, 857 were BRCA alteration carriers. The mean age of patients was 46 years. Radiogenomic methods correctly identified BRCA alteration with a strong diagnostic test accuracy (pooled sensitivity: 0.82, 95% confidence interval (CI): 0.79-0.84, pooled specificity: 0.81, 95% CI: 0.78-0.83).

CONCLUSION: Radiogenomics may be an accurate method to predict BRCA alterations. However, these findings should be validated in larger, prospective studies to determine their utility in clinical practice. Until further refinement of these methods, DNA sequencing should remain the gold standard.

ADVANCES IN KNOWLEDGE: To the best of our knowledge, this is the first systematic review and meta-analysis that has been carried out on this topic. We believe that our results demonstrate the potential clinical utility radiogenomics could have in the BRCA alteration testing process.

PMID:40560570 | DOI:10.1093/bjr/tqaf139

JAMA Surg. 2025 Jun 25. doi: 10.1001/jamasurg.2025.1999. Online ahead of print.

ABSTRACT

IMPORTANCE: Although tumor-infiltrating lymphocytes (TILs) have been implicated as prognostic biomarkers across various malignancies, the clinical application remains challenging. This study evaluated the applicability of artificial intelligence (AI)-powered spatial mapping of TIL density for prognostic assessment in resected pancreatic ductal adenocarcinoma (PDAC).

OBJECTIVE: To evaluate the prognostic significance of AI-powered spatial TIL analysis in resected PDAC and its clinical applicability.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included patients with PDAC who underwent up-front R0 resection at a tertiary referral center between January 2017 and December 2020. Whole-slide images of retrospectively enrolled patients with PDAC and up-front R0 resection were analyzed. An AI-powered whole-slide image analyzer was used for spatial TIL quantification, segmentation of tumor and stroma, and immune phenotype classification as immune-inflamed phenotype, immune-excluded phenotype, or immune-desert phenotype. Study data were analyzed from January 2017 to August 2023.

EXPOSURE: Use of AI-powered spatial analysis of the tumor microenvironment in resected PDACs.

MAIN OUTCOMES AND MEASURES: Tumor microenvironment-related risk factors and their associations with overall survival (OS) and recurrence-free survival (RFS) outcomes were identified.

RESULTS: Among 304 patients, the mean (SD) age was 66.8 (9.4) years with 171 male patients (56.3%), and preoperative clinical stages I and II were represented by 54.3% patients (165 of 304) and 45.7% patients (139 of 304), respectively. The TILs in the tumor microenvironment were predominantly concentrated in the stroma, and the median intratumoral TIL and stromal TIL densities were 100.64/mm2 (IQR, 53.25-121.39/mm2) and 734.88/mm2 (IQR, 443.10-911.16/mm2), respectively. Overall, 9.9% of tumors (30 of 304) were immune inflamed, 85.2% (259 of 304) were immune excluded, and 4.9% (15 of 304) were immune desert. The immune-inflamed phenotype was associated with the most prolonged OS (median not reached; P < .001) and RFS (median not reached; P = .001), followed by immune-excluded phenotype and immune-desert phenotype. High intratumoral TIL density was associated with longer OS (median, 52.47 months; 95% CI, 41.98-62.96; P = .004) and RFS (median, 21.67 months; 95% CI, 14.43-28.91; P = .02). A combined analysis of the pathologic stage with immune phenotype predicted better survival of stage II PDAC stratified as immune-inflamed phenotype than stage I PDAC stratified as non-immune-inflamed phenotype.

CONCLUSIONS AND RELEVANCE: Results of this cohort study suggest that the use of AI has markedly condensed the labor-intensive process of TIL assessment, potentially rendering the process more feasible and practical in clinical application. Importantly, the IP may be one of the most important prognostic biomarkers in resected PDACs.

PMID:40560550 | DOI:10.1001/jamasurg.2025.1999

Int Urol Nephrol. 2025 Jun 25. doi: 10.1007/s11255-025-04624-w. Online ahead of print.

ABSTRACT

OBJECTIVE: To develop a standardized evidence-based practice plan for exercise during dialysis in maintenance hemodialysis patients based on the best evidence.

METHODS: Based on the Johns Hopkins evidence-based nursing practice model as theoretical guidance, the evidence of exercise during dialysis in maintenance hemodialysis patients was systematically retrieved, evaluated and summarized, and an evidence-based practice plan was formed and applied in clinical practice. 35 patients and 19 nurses were reviewed before and after the application of evidence, and the obstacle factors and improvement measures were discussed and analyzed. The effect and significance of the evidence application were analyzed by comparing the patients’ grip strength, 30-s sit-to-stand test, quality of life score, self-efficacy, and dialysis adequacy.

RESULTS: Extracted 28 pieces of evidence from 35 best evidence sources and 8 review indicators were formulated. Following the implementation of evidence-based practices, the adherence rates for the eight indicators showed significant improvement (P < 0.05). The analysis identified 12 barriers and 12 facilitators, leading to the development of 16 change strategies. Before and 1 month, 2 months and 3 months after the application of evidence, the patients’ grip strength, 30-s sit-to-stand test and quality of life score were compared, and the differences were statistically significant (P < 0.05). There was no significant difference in self-efficacy and dialysis adequacy (P > 0.05).

CONCLUSIONS: Evidence-based practice of intradialytic exercise in maintenance hemodialysis patients can standardize intradialytic exercise rehabilitation. It can improve the muscle strength of upper and lower limbs and the quality of life of patients. However, its effect on self-efficacy and dialysis adequacy is limited.

PMID:40560523 | DOI:10.1007/s11255-025-04624-w

Int Urol Nephrol. 2025 Jun 25. doi: 10.1007/s11255-025-04619-7. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Ductal adenocarcinoma (DAC) is the second most common subtype of prostate cancer and is believed to have more aggressive biology compared to acinar adenocarcinoma (AAC). This study aimed to compare pathological and oncological outcomes between DAC and AAC in patients undergoing robotic-assisted radical prostatectomy (RARP).

METHODS: This was a single-center, retrospective cohort study of consecutive patients who underwent RARP between 2008 and 2023. Patients with DAC or AAC on final pathology were included. A 1:1 propensity score matching was performed based on key clinicopathologic variables. Primary outcomes included adverse pathological features, biochemical persistence, and biochemical recurrence (BCR). Statistical analyses included logistic regression and Cox proportional hazards models.

KEY FINDINGS AND LIMITATIONS: Among 844 DAC and 14,357 AAC patients (median follow-up: 4.1 years), DAC was associated with higher extracapsular extension (48.2% vs. 35.4%, difference = 12.8%, 95% CI: 9.4-16.3, p < 0.001), biochemical persistence (8.3% vs. 4.4%, OR = 1.97, 95% CI: 1.52-2.56, p < 0.001), and BCR (20.1% vs. 12.5%, HR = 1.70, 95% CI: 1.44-2.01, p < 0.001). In the matched cohort, DAC had higher biochemical persistence (8.4% vs. 5.5%, OR = 1.58, 95% CI: 1.07-2.33, p = 0.03) but no differences in BCR or overall survival. Limitations include retrospective design and residual confounding.

CONCLUSIONS AND CLINICAL IMPLICATIONS: DAC exhibits more aggressive pathological features and higher biochemical persistence after RARP. These findings may warrant closer surveillance and further prospective studies to guide DAC-specific management strategies. In this report, we compared outcomes after prostate cancer surgery in men with two types of prostate cancer: the common acinar type and the less common, more aggressive ductal type. We found that men with ductal prostate cancer had worse outcomes after surgery, including a higher chance of the cancer not being fully removed. These findings suggest that men with ductal prostate cancer may need closer monitoring and specialized treatment plans.

PMID:40560522 | DOI:10.1007/s11255-025-04619-7

Cardiovasc Drugs Ther. 2025 Jun 25. doi: 10.1007/s10557-025-07741-x. Online ahead of print.

ABSTRACT

INTRODUCTION: Direct oral anticoagulants (DOACs) are the standard treatment for reducing thromboembolic risk in patients with atrial fibrillation (AF); however, bleeding remains a major concern. Factor XIa inhibitors have emerged as a potential alternative, but evidence about their therapeutic potential remains unclear. We performed a systematic review and meta-analysis to evaluate the comparative efficacy and safety of Factor XIa inhibitors versus DOACs for AF.

METHODS: PubMed, Embase, and Cochrane Library were systematically searched until February 15, 2025, to identify RCTs comparing Factor XIa inhibitors with DOACs in AF patients. Risk ratios (RR) with 95% confidence intervals (CI) were pooled using a random-effects model. Statistical analysis was performed in RevMan 5.4 with p-value < 0.05 considered significant, and meta-analyses were conducted using a bivariate random-effects model. Study heterogeneity was measured using I² statistics, and study quality was assessed using the revised Cochrane risk-of-bias (RoB 2) tool.

RESULTS: Three RCTs comprising 16,845 patients (41% females) were included. The mean age of the participants was 74 years. Factor XIa inhibitors were associated with a significantly higher risk of ischemic stroke (RR: 3.32; 95% CI: 2.24-4.90, I²: 0%, p < 0.00001) but a lower risk of major or clinically relevant non-major (CRNM) bleeding (RR: 0.41; 95% CI: 0.33-0.49, I²: 0%, p < 0.00001) and minor bleeding (RR: 0.68; 95% CI: 0.49-0.93, I²: 64%, p = 0.02) compared to DOACs. However, there was no significant difference in the risk of all-cause mortality, cardiovascular mortality, or hemorrhagic stroke between the two groups.

CONCLUSION: Factor XIa inhibitors are associated with a reduced risk of major, minor, and clinically relevant non-major bleeding than DOACs but simultaneously increase the risk of ischemic stroke. No significant differences were found in the risk of hemorrhagic stroke or overall mortality rates compared to DOACs.

PMID:40560486 | DOI:10.1007/s10557-025-07741-x

Environ Monit Assess. 2025 Jun 25;197(7):803. doi: 10.1007/s10661-025-14238-5.

ABSTRACT

Environmental pollution, of which cassava mill effluent is a component, is a global concern that appears particularly devastating to the environment and its habitats. As such, the geospatial assessment of the effects of cassava mill effluent on the environment in Ika North East Local Government Area, Delta State, was conducted. The considered parameters include potential of hydrogen (pH), electrical conductivity (EC), nitrogen (N), chloride (Cl), copper (Cu), iron (Fe), zinc (Zn), lead (Pb), calcium (Ca), magnesium (Mg), and potassium (K). Data were analyzed with a student t-test using a statistical package for the social sciences (SPSS) version 21. The parameters of the sampled soils changed due to cassava mill effluent exceeding WHO standards for land discharge. The affected soil by cassava effluent was acidic (pH = 4.92), while the unaffected soil was neutral (pH = 7.00). The significant difference between the impacted and unaffected soils by cassava mill effluent (P = .036) indicates an alteration of soil quality that can potentially induce toxicological effects on the environment and biodiversity, including humans. The values of pH, EC, N, and Fe, among others, in cassava mill effluent include 5.57, 2210, 0.40, and 50.0411, respectively. The simple linear regression analysis of cassava mill factories showed no pattern, implying the distribution is random (P = .000***). The study offers a spatial understanding of cassava effluent, its environmental impact, and pollution hotspots, enabling targeted interventions and management strategies to prevent soil, water, and air contamination in Ika and other developing regions. By leveraging tools like Geographic Information Systems (GIS) and other geospatial technologies, environmental processes can be monitored, analyzed, and modeled, leading to more informed decisions and effective strategies for sustainable cassava processing and effluent management. The study suggests effluent should be channeled into a designated pond and treated before discharge for effective control and management.

PMID:40560482 | DOI:10.1007/s10661-025-14238-5

Eur J Nutr. 2025 Jun 25;64(5):228. doi: 10.1007/s00394-025-03626-9.

ABSTRACT

PURPOSE: Front-of-package labelling (FOPL) schemes have been developed to provide more useful information to consumers and facilitate more critical and healthier food choices. This single-blinded multi-arm parallel-group randomised controlled trial aimed at assessing the effect of different FOPL schemes on the objective understanding of the nutritional content and intention to purchase products, in El Salvador.

METHODS: Participants (n = 1204) were exposed to two-dimensional images of 15 mock-up products presented at random and balanced orders. Participants were exposed to mock-ups featuring no FOPL scheme (control group, n = 305) or one of the following schemes: black octagonal warning labels (OWL) (n = 302), traffic-light labelling (TFL) (n = 297), or guideline daily amounts (GDA) (n = 300).

RESULTS: The odds for choosing to purchase the least harmful of the options more often was the highest in the OWL group compared to the control group: two times higher in the OWL group (OR 2·21, 95% confidence interval 1·58 – 3·11), and 49% higher in the TFL (1·49, 95%CI 1·06 – 2·11), with no changes in the GDA (1·06, 95%CI 0·75 – 1·50). OWL also resulted in the highest odds for correctly identifying the least harmful option (OR 3·77, 95%CI 2·79 to 5·09), and for correctly identifying a product with higher amounts of sugars, sodium, total fat, and/or saturated fats (3·26, 95%CI 2·40 to 4·43).

CONCLUSION: OWL outperformed GDA and TFL in its ability to improve objective understanding of nutritional information and purchase intention. Results support the adoption of OWL in El Salvador.

TRIAL REGISTRATION NUMBER: ISRCTN 12,389,597.

DATE OF REGISTRATION: 17 July 2023 (retrospectively registered).

PMID:40560477 | DOI:10.1007/s00394-025-03626-9

Eur J Pediatr. 2025 Jun 25;184(7):446. doi: 10.1007/s00431-025-06266-7.

ABSTRACT

Type 1 diabetes (T1D) is a common childhood disease with a complex management that could adversely impact the quality of life of young sufferers. Executive functioning problems and psychopathology are factors that appear to have a detrimental effect on T1D-related quality of life (T1D-QoL). However, research on these factors is limited, and the pathways through which they do so remain unclear. This study aims to replicate the relationship between EF and T1D-QoL and to explore the possible mediating role of the clinical dysregulation profile (CBCL-DP) in this relationship. A total of 68 children and adolescents aged 10-18 living with T1D were recruited for this cross-sectional study. Parents reported on youth executive functioning, T1D-QoL, CBCL-DP, and socio-demographic data. In addition, clinical records of the youth were consulted to collect endocrinological information. Statistical analyses encompassed bivariate correlations, linear regressions, and bootstrap analyses to test the mediation model. Results demonstrate that executive function, CBCL-DP, and T1D-QoL are significantly correlated. The mediation model of the CBCL-DP variable in the relationship between executive function and T1D-QoL is significant. In linear regressions, executive function ceases to be significant on T1D-QoL when CBCL-DP is taken into account. The CBCL-DP significantly accounts for 55% of the variance in T1D-QoL.

CONCLUSION: This study identifies the CBCL-DP as a full mediator between executive function and T1D-QoL, highlighting the importance of emotional and behavioral regulation for quality of life in youth with T1D. The CBCL-DP scale may be useful in identifying regulatory issues and guiding early interventions to improve outcomes in children and adolescents with T1D.

WHAT IS KNOWN: • Previous studies have suggested that EF problems may negatively affect T1D-QoL; however, no studies have investigated the underlying mechanisms by which these variables are associated and the mediating role of CBCL-DP.

WHAT IS NEW: •This study suggests that there is an absence of a direct association between EF problems and T1D-QoL and identifies the CBCL-DP as a complete mediator between these variables. Furthermore, the study indicates that clinical dysregulation acts as a risk factor for diminished T1D-QoL in children and adolescents with T1D.

PMID:40560466 | DOI:10.1007/s00431-025-06266-7

Bull Math Biol. 2025 Jun 25;87(8):102. doi: 10.1007/s11538-025-01482-6.

ABSTRACT

This study investigates the nutrient-driven adaptability of foraging efforts in producer-grazer dynamics. We develop two stoichiometric producer-grazer models: a base model incorporating a fixed energetic cost of feeding and an adaptive model where feeding costs vary over time in response to environmental conditions. By comparing these models, we examine the effects of adaptive foraging strategies on population dynamics. Our adaptive model suggests a potential mechanism for evolutionary rescue, where the population dynamically adjusts to environmental changes, such as fluctuations in food quality, by modifying its feeding strategies. However, when population densities oscillate in predator-prey limit cycles, fast adaptation can lead to very wide amplitude cycles, where populations are in danger of stochastic extinction. Overall, this increases our understanding of the conditions under which nutrient-driven adaptive foraging strategies can yield benefits to grazers.

PMID:40560462 | DOI:10.1007/s11538-025-01482-6