Nevin Manimala

Sci Rep. 2025 Aug 21;15(1):30728. doi: 10.1038/s41598-025-16160-9.

ABSTRACT

Prostate cancer (PC) is a significant global health concern, particularly among older men (OM), and smoking is a well-established modifiable risk factor contributing to its incidence and mortality. However, a comprehensive assessment of the global burden of PC attributable to smoking among OM, with specific analyses by age and Socio-demographic Index (SDI) regions, is still lacking. This study utilized data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 to systematically analyze the global burden of PC attributable to smoking among OM (aged 55 years and older) from 1990 to 2021. The analysis included trends in deaths and Disability-Adjusted Life Years (DALYs) across different age groups and SDI regions. The estimated annual percentage change (EAPC) and Joinpoint regression analysis were employed to assess temporal trends. From 1990 to 2021, the global burden of PC attributable to smoking among OM exhibited a significant decline, with the age-standardized death rate decreasing from 3.08 per 100,000 in 1990 to 1.80 per 100,000 in 2021 (EAPC: -2.02, 95% CI: -2.14 to -1.90). Similarly, the age-standardized DALY rate decreased from 65.28 per 100,000 in 1990 to 37.75 per 100,000 in 2021 (EAPC: -2.05, 95% CI: -2.16 to -1.94). However, disparities across SDI regions were evident. The high SDI region experienced the most substantial decline in burden. In contrast, the low-middle SDI region showed an increasing trend, highlighting enduring socioeconomic disparities. Notably, Despite the overall reduction in the global burden, the burden among the older age group, specifically 90-95 years old, remained the most severe in 2021. This study reveals a complex landscape of the global burden of PC attributable to smoking among OM, with an overall decline masking enduring socioeconomic disparities and a severe burden among the older age group. These findings underscore the need for targeted interventions and public health strategies to address these disparities. Future efforts should focus on implementing smoking cessation programs and improving healthcare access in vulnerable populations.

PMID:40841756 | DOI:10.1038/s41598-025-16160-9

Sci Rep. 2025 Aug 21;15(1):30745. doi: 10.1038/s41598-025-15935-4.

ABSTRACT

During the design of hypothesis-driven, comparative laboratory animal experiments, investigators must control for cage effects, ensure full blinding and full randomization while adhering to established experimental designs, notably variations of the Completely Randomized Design and the Randomized Block Designs. Failure to meet these criteria introduces partial or complete confounding by multiple known and unknown variables, resulting in biased outcome measures and rendering valid statistical analysis impossible. Our analysis of a stratified, random sample of comparative laboratory animal experiments conducted in North America and Europe and published in 2022, shows that as few as 0-2.5% utilized valid, unbiased experimental designs. The failure of investigators to adopt valid, unbiased study designs undermines scientific rigour, squanders resources and animal lives, and impedes the reliable translation of preclinical research findings to human and veterinary medicine. We propose practical, achievable solutions focused on enhancing the rigour and validity of study designs. This includes developing a specialized group of scientists with expertise in the design of laboratory animal experiments and data analysis, to ensure future studies are conducted with the highest scientific standards.

PMID:40841741 | DOI:10.1038/s41598-025-15935-4

Sci Rep. 2025 Aug 21;15(1):30741. doi: 10.1038/s41598-025-13294-8.

ABSTRACT

Effective flossing is essential for preventing periodontal disease. However, in a rural Appalachian community, adherence to flossing routines remains low, contributing to significant oral health disparities. The purpose of this study was to conceptualize intention of initiation and sustenance of flossing behaviors using the multi-theory model (MTM) of health behavior change. A cross-sectional survey was administered to individuals recruited from a shopping mall in rural Appalachia. The MTM constructs were measured and data were analyzed using multiple linear regression models. Of the 228 participants, 55% did not floss daily. Behavioral confidence (β = 0.571, p < 0.001) was a significant predictor for the intention of initiation of flossing among non-daily flossers, while emotional transformation (β = 0.377, p = 0.836) significantly explained sustenance among non-daily flossers. For daily flossers, changes in the physical environment (β = 0.432, p = 0.003) significantly predicted the intention of initiation of flossing, whereas emotional transformation (β = 0.344, p = 0.008) and practice for change (β = 0.594, p < 0.001) significantly predicted sustenance of flossing behavior. The MTM appears to be a robust framework for understanding and predicting flossing behaviors in rural Appalachian populations. Interventions designed to enhance behavioral confidence, physical environment changes, emotional transformation, and practice for change could improve flossing adherence. Further research should explore these constructs to develop targeted public health strategies.

PMID:40841729 | DOI:10.1038/s41598-025-13294-8

Sci Rep. 2025 Aug 21;15(1):30782. doi: 10.1038/s41598-025-16307-8.

ABSTRACT

The purpose of this study is to investigate the relationship between physical activity and exercise self-efficacy among college students and to examine the mediating effects of loneliness and body image. Through an analysis of parallel mediating effects, the intrinsic mechanisms underlying these variables are revealed and provide theoretical support for promoting healthy behaviours among college students. The study, conducted in April 2025, employed a cross-sectional design to survey college students across northeast, North, central, East, and South China. A total of 1102 valid questionnaires were collected. The level of physical activity was assessed using the Physical Activity Rating Scale (PARS-3). Exercise self-efficacy was measured using the Exercise Self-Efficacy Scale. Body image was assessed using the Physical Self-Esteem Scale (PSPP), and loneliness was calculated using the UCLA Loneliness Inventory (3rd edition). The data were analysed using SPSS 27 software for descriptive statistics, correlation analyses, and mediation effect analyses. A significant direct positive correlation was found between physical activity and exercise self-efficacy (β = 0.2313, p < 0.001). Furthermore, loneliness and body image played important mediating roles in the relationship between physical activity and exercise self-efficacy. Specifically, physical activity indirectly improved exercise self-efficacy by reducing loneliness (β=-0.124, p < 0.001) and enhancing body image (β = 0.383, p < 0.001). The mediating effect accounted for 32.1% of the total impact, and the mediating effect of body image (28.5%) was significantly more potent than that of loneliness (3.5%). This study reveals the mechanism by which physical activity indirectly increases college students’ sense of exercise self-efficacy by reducing loneliness and improving body image. This finding shows the importance of focusing on individual psychological states when promoting physical activity. Interventions should promote both positive body image and a favourable social environment to improve college students’ exercise self-efficacy and overall psychological well-being.

PMID:40841721 | DOI:10.1038/s41598-025-16307-8

J Patient Rep Outcomes. 2025 Aug 21;9(1):107. doi: 10.1186/s41687-025-00938-6.

ABSTRACT

BACKGROUND: Cervical cancer remains a significant public health issue in underdeveloped regions like Xinjiang, Western China, where health literacy is low and economic disparities are prominent. While previous studies have focused on preventive measures, there is limited research on the willingness to pay (WTP) for cervical cancer treatments. This study aimed to assess patient preferences and WTP from patient perspective for quality of life improvement, unadjusted life-year extension, and targeted and immunotherapy drugs among cervical cancer patients in Xinjiang.

METHODS: A face-to-face survey was conducted using the Contingent Valuation Method (CVM) and Discrete Choice Experiment (DCE) to evaluate WTP for cervical cancer treatments. The CVM assessed patients’ WTP for two scenarios: living in perfect health for 5 or 10 years versus unadjusted life-year extension for the same durations. Health related quality of life (HRQoL) was measured using both the EQ-5D-5 L and EQ-VAS instruments. The DCE evaluated patients’ preferences and WTP for targeted therapy and immunotherapy drugs.

RESULTS: This study included 106 valid questionnaires (response rate 96.4%), primarily comprising stage III cervical cancer patients (EQ-5D-5 L 0.89, EQ-VAS 0.80) with characteristics of low income and educational attainment. Key findings revealed: (1) Patients prioritized quality of life improvement over lifespan extension, with WTP/QALY in the 10-year perfect health scenario exceeding Xinjiang’s 2024 per capita disposable income threshold while other scenarios remained below this value, and WTP/QALY being significantly higher in the 10-year scenario compared to the 5-year scenario; (2) Medication preference analysis demonstrated that quality of life improvement, cost, and incidence of adverse reactions were key decision-making factors, whereas survival extension held relatively lower importance. WTP valuations exhibited significant attribute-specific variations, with the highest WTP corresponding to quality of life improvement attributes and the lowest to survival extension attributes.

CONCLUSIONS: Cervical cancer patients in Xinjiang prioritize quality of life improvement over lifespan extension, with their preferences and WTP being influenced by treatment-related factors, disease characteristics, and socioeconomic background. Therefore, when formulating reimbursement policies and resource allocation strategies, priority should be given to interventions that can significantly improve quality of life, while implementing differentiated support policies for patient populations with varying socioeconomic statuses.

PMID:40841713 | DOI:10.1186/s41687-025-00938-6

Acta Pharmacol Sin. 2025 Aug 21. doi: 10.1038/s41401-025-01636-1. Online ahead of print.

ABSTRACT

Mitochondrial DNA (mtDNA) damage and accumulation activate the cGAS-STING DNA-sensing pathway, which promotes immune clearance of tumor cells. Maintenance of the cytosolic level of mtDNA is key to sustain immune activation. T cell malignancies (T-CMs) are a general name of diseases with abnormal clonal proliferation of T lymphocytes at various stages. Immunotherapy of T-CMs is challenged by the lack of specific antigens to discriminate T-CMs from normal T cells. As intrinsic STING activation can promote the clearance of T-CMs by immune cells, we herein explored whether isoliensinine (IsoL), a natural compound from Nelumbinis Plumula could enhance NK clearance by mtDNA-mediated immune responses in tumor cells. To investigate whether IsoL modulated immune recognition and clearance of T-CMs, we pre-treated three T-CM cell lines (Jurkat, Molt4 and Hut102) with IsoL then co-cultured with NK-92MI cells. We showed that IsoL pre-treatment promoted cytosolic mtDNA accumulation by inducing ROS-dependent mitochondrial damage and inhibiting mitophagy via peroxiredoxin 1 (PRDX1), an antioxidant enzyme. Loss of PRDX1 in T-CMs also induced ROS-dependent mitochondrial DNA damage, and blocked mitophagy by preventing accumulation of mature PINK1, which was required to initiate mitophagy via recruiting Parkin to the damaged mitochondria. Remarkably, IsoL could induce expression of activating ligands in vitro, enhance NK cell infiltrations, and increase apoptosis of T-CMs. Moreover, we demonstrated that IsoL could sensitize T-CMs for NK clearance in vitro and in vivo. These results suggest that IsoL could be a potential therapeutic agent to enhance immune therapy of T-CMs.

PMID:40841706 | DOI:10.1038/s41401-025-01636-1

Infect Dis Poverty. 2025 Aug 21;14(1):88. doi: 10.1186/s40249-025-01356-y.

ABSTRACT

BACKGROUND: Loiasis affects millions in Central Africa and, though historically considered benign, emerging data suggest possible renal involvement. This study investigated the association between Loa microfilaremia and renal function.

METHODS: We conducted a cross-sectional study in the Republic of Congo in May-June 2022. Renal function was assessed via estimated glomerular filtration rate (eGFR) using Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) and European Kidney Function Consortium (EKFC) equations, and proteinuria and/or haematuria (renal abnormalities, RAb). Multinomial logistic regression assessed associations between microfilarial density (MFD) and chronic kidney disease (CKD), using EKFC with Dubois correction. Population attributable fractions were estimated from a logistic model including Loa microfilaremia as a binary variable (present versus absent).

RESULTS: Among 986 participants, CKD prevalence ranged from 13.4% [95% confidence interval (CI) 11.4-15.7%, CKD-EPI] to 17.6% (95% CI 15.3-20.1%, EKFC) for KDIGO stages 1-5, and from 3.0% (95% CI 2.1-4.3%, CKD-EPI) to 7.6% (95% CI 6.1-9.4%, EKFC) for stages 3-5. Loa MFD was associated with higher odds of CKD, particularly in individuals with RAb. Compared to amicrofilaremic participants, those with Loa MFD ≥ 20 000 mf/ml had significantly increased risk: adjusted relative risk ratio (aRRR) for CKD severity categories (≤ 2nd, 2nd-10th, 10th-50th, > 50th eGFR percentile) with RAb were 8.67 (95% CI 2.62-28.64, P = 0.021), 14.26 (95% CI 3.41-59.68, P < 0.001), 5.50 (95% CI 0.55-61.78, P = 0.145), and 26.21 (95% CI 1.64-417.84, P = 0.021). Population attributable fractions of CKD stages 1-5 to Loa microfilaremia was 14.7% (95% CI 4.3-24.0) and 30.1% (95% CI 16.2-42.8) for CKD stages 1-5 with RAb.

CONCLUSIONS: This study provides the first epidemiological evidence linking loiasis to renal impairment, likely via glomerular damage. Given loiasis high endemicity in Central Africa, it may contribute to the burden of unexplained nephropathies. Longitudinal studies and renal biopsies are warranted to clarify underlying mechanisms.

PMID:40841693 | DOI:10.1186/s40249-025-01356-y

Eur J Med Res. 2025 Aug 21;30(1):783. doi: 10.1186/s40001-025-03038-9.

ABSTRACT

OBJECTIVES: Disruption of redox homeostasis and ferroptosis have been increasingly implicated in the pathogenesis of inflammatory lung injury. Glutathione peroxidase 4 (GPX4) and the ratio of reduced to oxidized glutathione (GSH/GSSG) are key regulators in this process. However, the clinical significance of ferroptotic factors in severe community-acquired pneumonia (CAP) is still lacking. This study investigated the prognostic value of serum glutathione peroxidase 4 (GPX4) and the GSH/GSSG ratio in severe CAP.

METHODS: A prospective cohort of 267 ICU-admitted severe CAP patients (2021-2023) was analyzed. Serum GPX4 and GSH/GSSG were measured within 24 h of admission. Patients were grouped by 30-day survival. Statistical analyses included comparative tests, Spearman correlation, ROC curves, Kaplan-Meier survival, and multivariate logistic regression.

RESULTS: Among 267 patients, 79 (29.6%) died within 90 days. Deceased patients had significantly lower GPX4 and GSH/GSSG (both P < 0.001). GPX4 was lower in COVID-19 cases (P = 0.022), while GSH/GSSG showed no such difference. GPX4 and GSH/GSSG were moderately correlated (r = 0.301, P < 0.001). ROC analysis showed good predictive accuracy for 30-day mortality, with an AUC of 0.778 for GPX4, 0.780 for GSH/GSSG, and 0.841 for their combination. Kaplan-Meier analysis indicated lower survival with reduced GPX4 or GSH/GSSG (P < 0.01). Multivariate analysis identified lower GPX4, GSH/GSSG, COVID-19, higher SOFA scores, prolonged ICU stay, and mechanical ventilation as independent mortality risk factors.

CONCLUSIONS: Lower serum GPX4 and GSH/GSSG ratios are associated with increased mortality in severe CAP.

PMID:40841690 | DOI:10.1186/s40001-025-03038-9

Cancer Imaging. 2025 Aug 21;25(1):105. doi: 10.1186/s40644-025-00928-3.

ABSTRACT

BACKGROUND: Accurate preoperative assessment of occult lymph node metastasis (OLNM) plays a crucial role in informing therapeutic decision-making for lung cancer patients. Computed tomography (CT) is the most widely used imaging modality for preoperative work-up. The aim of this study was to develop and validate a CT-based machine learning model integrating intra-and peri-tumoral features to predict OLNM in lung cancer patients.

METHODS: Eligible patients with peripheral lung cancer confirmed by radical surgical excision with systematic lymphadenectomy were retrospectively recruited from January 2019 to December 2021. 1688 radiomics features were obtained from each manually segmented VOI which was composed of gross tumor volume (GTV) covering the boundary of entire tumor and three peritumoral volumes (PTV3, PTV6 and PTV9) that capture the region outside the tumor. A clinical-radiomics model incorporating radiomics signature, independent clinical factors and CT semantic features was established via multivariable logistic regression analysis and presented as a nomogram. Model performance was evaluated by discrimination, calibration, and clinical utility.

RESULTS: Overall, 591 patients were recruited in the training cohort and 253 in the validation cohort. The radiomics signature of PTV9 showed superior diagnostic performance compared to PTV3 and PTV6 models. Integrating GPTV radiomics signature (incorporating Rad-score of GTV and PTV9) with clinical risk factor of serum CEA levels and CT imaging features of lobulation sign and tumor-pleura relationship demonstrated favorable accuracy in predicting OLNM in the training cohort (AUC, 0.819; 95% CI: 0.780-0.857) and validation cohort (AUC, 0.801; 95% CI: 0.741-0.860). The predictive performance of the clinical-radiomics model demonstrated statistically significant superiority over that of the clinical model in both cohorts (all p < 0.05).

CONCLUSIONS: The clinical-radiomics model was able to serve as a noninvasive preoperative prediction tool for personalized risk assessment of OLNM in peripheral lung cancer patients.

PMID:40841689 | DOI:10.1186/s40644-025-00928-3

BMC Pharmacol Toxicol. 2025 Aug 21;26(1):152. doi: 10.1186/s40360-025-00984-2.

ABSTRACT

BACKGROUND: Iron deficiency anemia (IDA) remains a prevalent global health issue. While oral iron therapy is the first-line treatment, the optimal dosing strategy-daily versus alternate-day-remains debated, especially for general population use. Therefore, this review aimed to compare the efficacy and tolerability of daily versus alternate-day oral iron supplementation for IDA in the general population.

METHODS: Searches were conducted across major databases through March 2025. Risk of bias was evaluated utilizing the Cochrane RoB 2 tool, and the certainty of evidence was graded using GRADE. The primary outcome was change in hemoglobin concentration; secondary outcomes included serum iron, ferritin, transferrin saturation, TIBC, MCV, and adverse events. R Studio software, version 4.2.3, and RevMan used for all analyses.

RESULTS: This SRMA (systematic review and meta-analysis) included 11 RCTs involving 1014 participants. The pooled analysis found a small, statistically non-significant increase in hemoglobin with daily dosing over alternate-day (MD: 0.28, 95% CI: -0.01 to 0.56, p = 0.06, z = 1.91). Secondary outcomes revealed no significant differences among groups for serum iron, ferritin, transferrin saturation, TIBC, and MCV. Adverse effects were similar between groups (RR: 1.07, 95% CI: 0.86 to 1.34), though metallic taste was more frequent with daily dosing. Risk of bias was low to moderate across studies. Certainty of evidence was rated very low for most outcomes due to heterogeneity and imprecision.

CONCLUSION: Both daily and alternate-day oral iron supplementation are comparably effective for treating IDA, with alternate-day dosing showing better tolerability. Due to low certainty in evidence, treatment decisions should be individualized pending further high-quality research.

CLINICAL TRIAL NUMBER: Not applicable.

PMID:40841680 | DOI:10.1186/s40360-025-00984-2