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TMAO promotes metabolic dysfunction-associated fatty liver disease (MAFLD) development through long-non coding RNA- highly upregulated liver cancer (HULC)

J Diabetes Metab Disord. 2025 May 30;24(1):131. doi: 10.1007/s40200-025-01605-9. eCollection 2025 Jun.

ABSTRACT

OBJECTIVES: Trimethylamine N-oxide (TMAO) is related to the pathogenesis of Metabolic dysfunction-associated fatty liver disease (NAFLD). However, the molecular mechanism of how TMAO causes MAFLD development is still unclear. The present study attempted to investigate whether TMAO contributes to MAFLD development through HULC in a cellular model of MAFLD.

METHODS: HepG2 cells were cultured and induced in a fatty liver cell model. HULC knockdown was induced using the CRISPR/Cas13 system. Fatty liver cells were exposed to TMAO concentrations (75µM and 300µM) before and after HULC knockdown. RT-qPCR was used to evaluate the expression of the target genes. Apoptosis was assessed using Annexin V-FITC and PI staining. Statistical analyses included ANOVA and post-hoc tests.

RESULTS: TMAO upregulated the expression of HULC, followed by P38MAPK overexpression (P value < 0.05). Upon HULC knockdown, TMAO could not change P3MAPK expression and its downstream targets, including TNFα, IL-6, and PNPPLA3 in fatty liver cells. Additionally, TMAO significantly induced apoptosis in the fatty acid cellular model (P value < 0.05).

CONCLUSION: In conclusion, the results of this study provide evidence of the TMAO/HULC/P38MAPK axis involvement in the pathogenesis of MAFLD by increasing the expression of genes involved in inflammation and fibrosis. Our data suggests that TMAO reduction could be a therapeutic target in MAFLD through gut microbiome modulation.

PMID:40454183 | PMC:PMC12125414 | DOI:10.1007/s40200-025-01605-9

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Nevin Manimala Statistics

A Bayesian Joint Model of Longitudinal Kidney Disease Progression, Recurrent Cardiovascular Events, and Terminal Event in Patients with Chronic Kidney Disease

Stat Biosci. 2025;17(2):528-554. doi: 10.1007/s12561-024-09429-6. Epub 2024 May 9.

ABSTRACT

Nearly 15% (37 million) of adults in the United States (US) have chronic kidney disease (CKD). The longitudinal decline of kidney function is intricately related to the development of cardiovascular disease (CVD) and eventual “terminal” event (kidney failure and mortality) in patients with CKD. Understanding the mechanism and risk factors underlying the three key outcome processes, (1) CKD progression, (2) CVD, and (3) subsequent terminal event in the CKD patient population remains incomplete. Thus, in this work, we develop a novel trivariate joint model to study the risk factors associated with the interdependent outcomes of kidney function (as measured by longitudinal estimated glomerular filtration rate), recurrent cardiovascular events, and the terminal event. Efficient estimation and inference is proposed within a Bayesian framework using Markov Chain Monte Carlo and Bayesian P-splines for hazard functions. The proposed Bayesian framework is directly generalizable beyond trivariate outcome processes to accommodate other potential modeling of complex multi-disease processes. The method is applied to study the aforementioned trivariate processes using data from the Chronic Renal Insufficiency Cohort Study, an ongoing prospective cohort study, established by the National Institute of Diabetes and Digestive and Kidney Diseases to address the rising epidemic of CKD in the US.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12561-024-09429-6.

PMID:40454178 | PMC:PMC12122633 | DOI:10.1007/s12561-024-09429-6

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The Use of Pictorial Recall Aids Modifies Dietary Assessment Results: Experiences from Quantitative 24-hour Dietary Recalls of Young Children in Nepal and Senegal

Curr Dev Nutr. 2024 Aug 30;9(Suppl 1):104452. doi: 10.1016/j.cdnut.2024.104452. eCollection 2025 Feb.

ABSTRACT

BACKGROUND: Recall bias or memory error is a known limitation of recall-based dietary assessment methods and can lead to substantial misrepresentation of diets. Pictorial recall aids have been used by various studies to mitigate recall bias, but their effect on quantitative, 4-pass 24-h dietary recall (24HR) results has not yet been measured.

OBJECTIVES: This article examines uptake of pictorial recall aids among caregivers of young children in Kathmandu Valley, Nepal, and Guédiawaye Department, Senegal; describes what foods/beverages are subject to recall bias in these contexts; and assesses the effect of these recall aids on estimated dietary outcomes.

METHODS: We used cross-sectional data from 24HR surveys that provided a recall aid to reduce caregiver recall bias. Young children’s dietary outcomes were calculated from the 24HR data. Logistic regressions were used to compare characteristics and estimated dietary outcomes of children by recall aid uptake. McNemar’s test and paired t-tests were used to compare estimated dietary outcomes in initial 24HR data with revised 24HR data that incorporated omitted items identified by the recall aid.

RESULTS: Pictorial recall aids had relatively high uptake by caregivers in both contexts. Beverages, unhealthy snacks, and fruit were most subject to recall bias. Adding omitted items identified by recall aids resulted in statistically significant changes in most dietary outcomes assessed. Children of caregivers who chose to use the recall aid had significantly different estimated dietary outcomes than children of caregivers who did not use the recall aid.

CONCLUSIONS: The use of pictorial recall aids modifies 24HR results in these 2 contexts. Rigorous research is needed to fully understand the impact of recall aids on 24HR methodology and results, with an aim to improve the accuracy of dietary assessment and ultimately inform evidence-based nutrition programming, policy, and recommendations.

PMID:40454165 | PMC:PMC12125692 | DOI:10.1016/j.cdnut.2024.104452

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Perioperative sildenafil citrate administration in hepatectomy: a study protocol of randomized controlled trial

Trials. 2025 Jun 1;26(1):183. doi: 10.1186/s13063-025-08870-2.

ABSTRACT

BACKGROUND: Intraoperative blood loss (IBL) is the major concern in hepatectomy, which was closely relating to the central venous pressure (CVP). The controlled low central venous pressure (CLCVP) technique is moderately required for minimizing hemorrhage during hepatectomy nowadays. Nevertheless, an excessive reduction in CVP might give rise to the jeopardy of inadequate perfusion of vital organs. Sildenafil, being a first-line pharmaceutical for treating pulmonary hypertension, its mechanism of action lies in diminishing pulmonary vascular resistance (PVR) by dilating pulmonary arteries, and thereby alleviating the afterload of the right ventricle. We initially postulate that administration of sildenafil citrate in combination with intermittent Pringle’s maneuver (IPM) can exert a notable impact in efficaciously reducing intraoperative blood loss (IBL), enhancing the surgical field of vision, and augmenting the safety of the operation.

METHODS: This research constitutes a double-blind, randomized, controlled trial. All patients fulfilling the criteria for open or laparoscopic hepatectomy will be randomly allocated to the sildenafil (S) group and the placebo (C) group via the block randomization approach. All surgeons, anesthesiologists, and outcome assessors will remain oblivious to the patient’s group details. The primary outcome is the intraoperative blood loss (IBL). Secondary outcomes include the classification of the surgical field, the cumulative consumption of nitroglycerine, hemodynamic parameters, blood gas analysis, coagulation function (comprising thromboelastogram (TEG), activated partial thromboplastin time (APTT), and prothrombin time (PT)), intraoperative urine output, adverse events in the recovery room (hypotension, hypoxemia and hematuria), biochemical markers (total bilirubin, total albumin, alanine aminotransferase, aspartate aminotransferase, creatinine, urea nitrogen), complete blood count (Hb, Plt, and Hct), cardiac function (brain natriuretic peptide, creatine kinase isoenzyme, troponin), postoperative hospital stay and indwelling time of drainage tube, and postoperative complications. These parameters will be comprehensively compared and analyzed in-depth through appropriate statistical means.

DISCUSSION: This trial evaluated the influence of administration of sildenafil citrate combined with IPM on IBL and surgical results during open or laparoscopic hepatectomy, as well as its safety and feasibility. It is expected to provide an innovative management optimization plan for reducing the bleeding in hepatectomy, and to provide empirical support for the potential value of sildenafil citrate or sildenafil-like drugs in improving the safety and quality of perioperative hepatectomy patients.

TRIAL REGISTRATION: This trial was registered on June 25, 2024, in the US Clinical Trials Registry ( https://register.

CLINICALTRIALS: gov ), with the ClinicalTrial.gov Identifier: NCT06237751. The protocol version is V1.0 (20,231,114).

PMID:40450350 | DOI:10.1186/s13063-025-08870-2

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Impact of a comprehensive two-year research capacity intervention with sexual and reproductive health researchers in Sub-Saharan Africa

Reprod Health. 2025 May 31;22(1):94. doi: 10.1186/s12978-025-02047-5.

ABSTRACT

BACKGROUND: Research training in Sub-Saharan Africa is crucial for strengthening the capacity of healthcare professionals and researchers to address specific sexual and reproductive health (SRH) challenges within their communities. Interventions that enhance research capacity and foster a culture of innovation within existing structures offer a practical and economical strategy capable of addressing national and sub-national SRH needs. This study evaluated an intervention to enhance reproductive health research skills to assess research competence changes among participants.

METHODS: A pre-post intervention design was employed. Pre- and post-program assessments were conducted using the Clinical Research Appraisal Inventory (CRAI)-12 scale to establish baseline and endline levels of research competence. Descriptive statistics, chi-squared and Kruskal Wallis tests were used to analyze data. Our data interpretation is guided by the Social Cognitive Career Theory.

RESULTS: Faculty members and clinicians from Uganda and Rwanda completed the intervention and 84 had complete baseline while 77 had complete endline data. Analyses revealed significant improvements in nearly every item on the CRAI-12 scale after the research training program, including increased Self-Efficacy in Designing and Collecting Data (Factor 1); Reporting, Interpreting and Presenting (Factor 2); Conceptualizing and Collaborating (Factor 3); Setting Expectations for Research Staff (part of Factor 4); Describing the Funding Process (Part of Factor 5); and Protecting Study Participants (Factor 6) (all p = < 0.05). The only items that did not improve significantly were Confidence in Asking Staff to Leave the Project Team when Necessary (part of Factor 4) and Locating the Appropriate Grant Application Forms (part of Factor 5).We proposed a conceptual framework outlining the hypothesized pathways through which training and skill development influence research-related career planning and progression.

CONCLUSIONS: The research training intervention effectively improved participants’ research competence. These findings underscore the importance of structured research training programs in enhancing research skills. Future research should focus on longitudinal assessments to explore sustained changes and the enduring impact of self-efficacy, outcome expectations (anticipations about career-related consequences), and research-related career goals on career planning and skill development.

PMID:40450342 | DOI:10.1186/s12978-025-02047-5

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The dosimetric value and safety evaluation of 3D printed bolus in adjuvant intensity-modulated radiotherapy after radical mastectomy for breast cancer: a prospective cohort study

Radiat Oncol. 2025 May 31;20(1):91. doi: 10.1186/s13014-025-02659-y.

ABSTRACT

PURPOSE: Breast cancer patients may use a bolus to increase the dose to skin in radiotherapy after radical mastectomy. The 3D printed bolus (3DPB) specifically customized based on individual conditions offers better conformity. This study aims to provide clinical insights by evaluating the dosimetric benefits and safety of 3DPB in radiotherapy following radical mastectomy for breast cancer.

MATERIALS AND METHODS: The study included breast cancer patients who received post-mastectomy radiotherapy with 3DPB. Researchers retrospectively collected dose data from patients’ radiotherapy plans, including with and without 3DPB, and prospectively observed the acute and late side effects in the cohort of patients undergoing mixed plan radiotherapy. To compare the dosimetric differences between radiotherapy plans with and without 3DPB, such as the dose distribution data of CTV, PTV, and organs at risk, matched sample T-test was used for data conforming to normal distribution, and non-parametric test was used for data not conforming to normal distribution. P < 0.05 was considered statistically significant.

RESULTS: A total of 35 patients were included with a median follow-up time of 16 months. In terms of radiotherapy side-effects, no level 4 acute side-effects occurred. A total of 82.2% of the patients had no obvious side-effects. No late radiotherapy side-effects of level 2 or higher occurred. In terms of dosage, radiotherapy plans with 3DPB showed better conformance (P < 0.001) and dose homogeneity (P < 0.001) than plans without 3DPB. The results indicated that the V95% dose of CTV1, CTV2, P-CTV, P-CTV1, and P-CTV2 was higher in the plans with 3DPB than in those without 3DPB (all P < 0.001).

CONCLUSIONS: The use of 3DPB in breast cancer radiotherapy is effective, achieving higher and more uniform dose distribution and better target conformity compared to without 3DPB. Additionally, it is associated with a low incidence of acute and late side effects.

PMID:40450338 | DOI:10.1186/s13014-025-02659-y

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Revision rate after surgery for elbow osteochondritis dissecans: a systemic review

J Orthop Surg Res. 2025 May 31;20(1):555. doi: 10.1186/s13018-025-05788-y.

ABSTRACT

BACKGROUND: Humeral capitellum osteochondritis dissecans (OCD) is a common condition among overhead throwing athletes and is typically treated surgically. While stable lesions can be treated nonoperatively, untreated unstable lesions can lead to significant elbow discomfort and impaired quality of life. This study reviews the revision rate and interval in athletes with elbow OCD following primary surgery.

METHODS: Data was extracted from PubMed, Embase, and Medline between 1990 and 2022, and two reviewers independently screened the duplicate reports of complications and revision surgeries. The Methodological Index for Nonrandomized Research score was used for risk of bias assessment. Inclusion criteria were as follows: studies in the English language, those involving humans, those reporting complications, and those performing revision surgeries following capitellar OCD surgery. Logit transformation and random effects were calculated using the Der Simonian Laired estimator, and the Shapiro-Wilk test was first performed to determine whether revision interval data followed a normal distribution. The Wilcoxon rank sum test was used for nonparametric data comparison, while Spearman’s rank correlation assessed whether shorter follow-up periods underestimated the revision rate.

RESULTS: A total of 6,457 studies were identified through the initial literature search (PubMed: 1,924; Embase: 2,532; Medline: 2,001), with 4,147 duplicates removed, leaving 2,310 unique studies for screening. After applying the inclusion criteria, 20 full-text articles were selected, all of which were level IV case series with MINORS scores ranging from 7 to 14 (mean: 10.65), demonstrating moderate heterogeneity (I2 = 41%) and strong inter-reviewer agreement across screening phases (κ = 0.78-0.98). Twenty studies involving 477 elbows (474 athletes) were included, 55 of which underwent revision surgery. The athletes were divided into debridement, microfracture, and osteochondral grafting groups. The overall revision rate was 11.53%, and the revision rate of the three groups were 11.2%, 14.2%, and 9.19%, respectively. Eleven of the 20 studies (24 of 175 athletes underwent revision surgery) with complete data were included in interval analysis of revision surgery. The mean intervals of all participants and three groups were 25, 41.8, 10.4, and 24.2 months, respectively. Spearman’s rank correlation showed no significant association between the follow-up duration and the revision rate (rho = -0.31, p = 0.18) or the revision interval (rho = 0.02, p = 0.95) in the overall cohort. Correlation coefficients across surgical subgroups also varied in direction and were not statistically significant.

CONCLUSION: Approximately 11% of patients required revision surgery following primary treatment for elbow OCD, with an average interval of 25 months. No significant association between follow-up duration and either revision rate or revision interval. Thus, further investigations, rehabilitation programs may be required to decrease this revision rate.

PMID:40450334 | DOI:10.1186/s13018-025-05788-y

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The association of cardiometabolic multimorbidity with depression and length of hospitalization: a population-based cross-sectional study among adults in Turkey

BMC Public Health. 2025 May 31;25(1):2009. doi: 10.1186/s12889-025-23306-x.

ABSTRACT

BACKGROUND: Recent developments suggest a strong association between cardiometabolic multimorbidity, depression, and hospitalization. The aim of this study was to investigate the association of cardiometabolic multimorbidity with depression and the length of hospitalization among individuals aged 40 and older.

METHODS: This study is based on the secondary analysis of data obtained from the 2022 Turkey Health Survey conducted by the Turkish Statistical Institute (TUIK). A weighted sample of 31,425,252 individuals aged 40 and over was analyzed. The dependent variables of the study are depression and hospitalization, while the independent variable is cardiometabolic multimorbidity. Other covariates include gender, age, education level, physical activity, body mass index, tobacco use, and alcohol use. The weights from the database provided by TUIK were used in the data analysis. The relationship between cardiometabolic multimorbidity and depression was investigated using univariate and multivariate logistic regression analysis.

RESULT: Of the included participants, 51.2% were female and 35.5% were between the ages of 40-49. In Model 1, individuals with five cardiometabolic diseases had a 10-fold higher risk of developing depression compared to those with no diseases (OR: 10.0; 95% CI: 9.82-10.23). In Model 2, the risk of depression was 5.1 times higher in individuals with three diseases (OR: 5.1; 95% CI: 5.08-5.14), 5.83 times higher in those with four diseases (OR: 5.3; 95% CI: 5.78-5.88), and 14.6 times higher in individuals with five diseases (OR: 14.6; 95% CI: 14.36-14.99). Furthermore, as the number of cardiometabolic diseases increases, a significant increase in the length of hospitalization was observed (p < 0.001).

CONCLUSIONS: The findings of this study revealed that cardiometabolic multimorbidity may increase the risk of depression and the length of hospitalization in adults. These results may provide guidance for developing disease prevention and control strategies regarding cardiometabolic multimorbidity and associated factors in adults.

PMID:40450317 | DOI:10.1186/s12889-025-23306-x

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Assessing the damage: analyzing the impact of the COVID-19 pandemic on accelerometer-assessed 24-hour movement behaviours in Brazilian adolescents

BMC Public Health. 2025 May 31;25(1):2022. doi: 10.1186/s12889-025-23155-8.

ABSTRACT

BACKGROUND: Although there is consistent evidence of unhealthy changes in the 24-h movement behaviours when comparing pre-COVID-19 periods to the early stages of the pandemic, there is limited research on long-term changes among adolescents. This study aimed to analyze both between- and within-participant differences in accelerometer-assessed 24-h movement behaviours by comparing cross-sectional and prospective data from the pre-COVID-19 period (August to December 2019) to the period following the reopening of schools for in-person classes in southern Brazil (August to December 2022).

METHODS: This is a repeated cross-sectional design with a nested cohort. The 24-h movement behaviours (i.e., light physical activity [LIPA] and moderate-to-vigorous physical activity [MVPA], sedentary behaviour [SB], and sleep time [SPT]) were assessed by processing raw accelerometer data derived from a 24-h/7-day wrist-worn protocol. Compositional multilevel models were applied to compare the 24-h movement behaviour composition between time points for both cross-sectional and prospective data. Self-reported sociodemographic characteristics were examined as potential moderators.

RESULTS: The cross-sectional and prospective samples comprised, respectively, 1276 (53% female, average age of 16.4 ± 1.1) and 249 (53% female, average age of 15.6 ± 0.8) participants. The 24-h movement behaviour composition differed between time-points in the cross-sectional (p < 0.001) and prospective samples (p < 0.001). Differences from 2019 to 2022 were explained by lower MVPA (-3.3 and -5.4 min/day in cross-sectional and prospective analysis, respectively) and a higher SB (4.7 and 34 min/day in cross-sectional and prospective analysis, respectively). No significant differences were observed for LIPA and SPT.

CONCLUSIONS: Differences in the 24-h movement behaviour composition comparing the cross-sectional samples, although statistically significant, were considered trivial and unlikely to have a substantial practical impact. However, considerable differences were observed in the prospective analysis. The results suggest that most of the observed changes over time were expected as a natural consequence of aging during high school, with only a small portion attributable to the residual impact of the pandemic.

PMID:40450307 | DOI:10.1186/s12889-025-23155-8

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Comparison of salivary statherin and beta-defensin-2 levels, oral health behaviors, and demographic factors in children with and without early childhood caries

BMC Oral Health. 2025 May 31;25(1):868. doi: 10.1186/s12903-025-06252-3.

ABSTRACT

BACKGROUND: Early childhood caries (ECC) is a widespread pediatric dental condition that is influenced by a combination of biological, behavioral, and demographic factors. Salivary biomarkers, including beta-defensin-2 (BD-2) and statherin (STATH), offer potential as non-invasive tools for detecting and assessing the risk of ECC. This study aims to compare the levels of salivary statherin and beta-defensin-2, alongside oral health behaviors and demographic factors, in children both with and without early childhood caries.

METHODS: This case-control study involved 75 children diagnosed with ECC and 75 age- and gender-matched caries-free controls. Unstimulated saliva samples were obtained and analyzed via ELISA to quantify the levels of beta-defensin-2 and statherin. Demographic and behavioral data were gathered through structured interviews with parents. Statistical analyses included t-tests, logistic regression, and machine learning models to predict the risk of ECC.

RESULTS: Salivary beta-defensin-2 levels were significantly higher in children with ECC (9.25 ± 2.89 ng/mL) compared to caries-free controls (6.41 ± 2.45 ng/mL, p = 0.003), indicating its potential as a diagnostic biomarker. Statherin levels, although lower in the ECC group, did not differ significantly between groups (p = 0.08). Behavioral factors such as regular dental visits and parental education levels were strongly associated with ECC prevalence. Machine learning models demonstrated high accuracy in predicting ECC, with the Gradient Boosting and CatBoost achieving the highest performance.

CONCLUSIONS: Salivary beta-defensin-2 is a promising ECC risk assessment biomarker, while statherin is less effective as an independent predictor. Behavioral and demographic factors significantly influence ECC prevalence. Machine learning models integrating clinical, demographic, and salivary data provide a robust tool for detection and targeted prevention strategies. Comprehensive approaches combining salivary biomarkers and behavioral interventions are critical to managing ECC, particularly in resource-limited settings.

PMID:40450305 | DOI:10.1186/s12903-025-06252-3