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Nevin Manimala Statistics

DNA methylation associated with the serum alanine aminotransferase concentration: evidence from Chinese monozygotic twins

Clin Epigenetics. 2025 Apr 28;17(1):65. doi: 10.1186/s13148-025-01869-1.

ABSTRACT

BACKGROUND: To identify nongenetic factors influences on DNA methylation (DNAm) variations associated with blood Alanine Aminotransferase (ALT) concentration, this study conducted an epigenome-wide association study (EWAS) on Chinese monozygotic twins.

METHODS: A total of 61 pairs of Chinese monozygotic twins involved in this study. Whole blood samples were analyzed for DNAm profiling using the Reduced Representation Bisulfite Sequencing (RRBS) technique. We examined the relationship between DNAm levels at each CpG site and serum ALT using a linear mixed-effects model. Enrichment analysis and causal inference analysis was conducted, and differentially methylated regions (DMRs) were further identified. Candidate CpGs were validated in a community sample. Genome-wide significance were calculated by Bonferroni correction (p < 2.14 × 10-7).

RESULTS: We identified 85 CpGs reaching genome-wide significance (p < 2.14 × 10-7), located in 16 genes including FLT4, ADARB2, MRPS31P2, and RELB. Causal inference suggested that DNAm at 61 out of 85 significant CpGs within 14 genes influenced ALT level. 52 DMRs and 1765 pathways such as low voltage-gated calcium channel activity and focal adhesion were identified having influences on ALT levels. Further validation using community population found four CpGs mapped to FLT4 and three to RELB showing hypomethylation and hypermethylation in cases with abnormal ALT (ALT > 40 U/L), respectively.

CONCLUSION: This study identified several differentially methylated CpG sites associated with serum ALT in the Chinese population, particularly within FLT4 and RELB. These findings provide new insights into the epigenetic modifications underlying liver function.

PMID:40296130 | DOI:10.1186/s13148-025-01869-1

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Analysis of causal effects on metabolic syndrome and inflammatory bowel disease: a Mendelian randomization study

Diabetol Metab Syndr. 2025 Apr 28;17(1):143. doi: 10.1186/s13098-025-01704-w.

ABSTRACT

BACKGROUND: Metabolic syndrome (MetS) is a conglomerate of metabolic abnormalities including hypertension, obesity, hyperglycemia, hypertriglyceridemia, and low levels of high-density lipoprotein cholesterol (HDL-C). The relationship between MetS and Inflammatory Bowel Disease (IBD) has received a lot of attention lately. Epidemiological investigation has yet to determine if the two illnesses are causally related. To investigate the causal link between IBD and MetS levels, we screened publically available genome-wide association study (GWAS) data using Mendelian randomization (MR) analysis. The study aimed to comprehensively analyze the causal association of each component of MetS, including fasting blood glucose(FBG), HDL-C, triglyceride(TG), waist circumference(WC), and hypertension, on the risk of IBD and its subtypes via univariate, two-way, and multivariate MR (MVMR) methods.

METHODS: We selected independent genetic variants of MetS and IBD as instrumental variables (IVs) from published data from the IEU OpenGWAS project and IIBDGC (International Inflammatory Bowel Disease Genetic Consortium), used MR to infer potential causal effects between them, and used a variety of methods (random effect inverse variance weighting (IVW), weighted median, MR-Egger regression, etc.) to ensure the robustness of causal effects.

RESULTS: Univariate two-sample MR (TSMR) revealed that WC was significantly linked to the risk of Crohn’s disease (CD) (OR = 1.659; 95% CI: 1.144-2.405; p = 0.008) and IBD (OR = 1.383; 95% CI: 1.050-1.822; p = 0.021). However, MVMR did not support this finding. In MVMR analysis, hypertension was predicted to be positively associated with the risk of IBD (OR = 2.322516, 95% CI: 1.097713-4.91392, p = 0.0275365), whereas FBG was confirmed to reduce the risk of CD in MVMR studies (OR = 0.4346427, 95% CI: 0.2685399-0.7034868, p = 0.0006948939). Other elements of the MetS did not significantly correlate with IBD.

CONCLUSION: Although confounding factors cannot be completely ruled out, certain metabolic components, such as WC, may impact the risk of IBD. In addition to highlighting the need for more research to understand the underlying mechanisms and potential indirect effects between MetS components and IBD, this research offers insight into therapeutic treatment decisions for patients with IBD and MetS.

PMID:40296126 | DOI:10.1186/s13098-025-01704-w

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Analyzing the nexus between burnout and psychological distress in pediatric oncology nurses: a descriptive correlational investigation

BMC Nurs. 2025 Apr 28;24(1):465. doi: 10.1186/s12912-025-03061-5.

ABSTRACT

BACKGROUND: Burnout and psychological distress are significant concerns among healthcare professionals, particularly pediatric oncology nurses, who face emotional and physical challenges due to their demanding roles. Continuous exposure to life-threatening illnesses, high patient mortality rates, and emotionally taxing interactions contribute to severe occupational stress, potentially affecting both nurse well-being and patient care quality. This study aimed to analyze the relationship between burnout and psychological distress among pediatric oncology nurses at the Children’s Cancer Hospital Foundation (CCHE 57357) in Egypt.

METHODS: A descriptive correlational research design was employed, involving a purposive sample of 188 nurses working in inpatient and intensive care units. Data were collected using three validated tools: (1) a Sociodemographic Data Sheet, (2) the Copenhagen Burnout Inventory (CBI) to assess personal, work-related, and client-related burnout, and (3) the Kessler Psychological Distress Scale (K10) to measure levels of psychological distress. The instruments underwent translation and validation for use in Arabic. Data collection occurred over six months, with statistical analysis conducted using SPSS (version 25). Descriptive statistics, Pearson correlation, and linear regression models examined relationships between burnout and psychological distress.

RESULTS: The findings revealed that 55.8% of nurses had low burnout levels, 31.4% had moderate burnout, and 12.8% exhibited high burnout. In addition, psychological distress levels varied, with 34% experiencing moderate distress, 25% showing very high psychological distress, and 22% reporting high distress. A statistically significant positive correlation (r = 0.59, p = 0.00) was identified between total burnout and psychological distress, indicating that higher burnout levels were associated with increased psychological distress. Regression analysis further confirmed the significant impact of psychological distress on burnout (R² = 0.35, Beta = 0.59, p = 0.00).

CONCLUSION: This study highlights the significant correlation between burnout and psychological distress among pediatric oncology nurses, emphasizing the critical need for specialized interventions to promote mental well-being. The findings stress the importance of implementing stress reduction programs, fostering better work-life balance strategies, and providing comprehensive mental health support to alleviate burnout and distress. Effectively addressing these issues will not only improve nurses’ overall well-being but also contribute to enhancing the quality of care in pediatric oncology settings.

CLINICAL TRIAL REGISTRATION: Not applicable.

PMID:40296125 | DOI:10.1186/s12912-025-03061-5

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Low levels of DNA repair enzyme NEIL2 May exacerbate inflammation and genomic damage in subjects with stable COPD and during severe exacerbations

Respir Res. 2025 Apr 28;26(1):165. doi: 10.1186/s12931-025-03251-4.

ABSTRACT

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease that is an independent risk factor for lung cancer. Reduction in NEIL2 function, a DNA glycosylase involved in DNA repair during transcription, has been associated with an increased incidence of malignancies in humans. NEIL2 knockout mouse models have demonstrated increased inflammation and oxidative DNA damage in the lungs after exposure to an inflammatory insult, but data are lacking regarding NEIL2 function in individuals with COPD. We investigated whether NEIL2 levels and oxidative DNA damage to the transcribed genome are reduced in individuals with stable COPD and during severe acute exacerbations of COPD (AECOPD).

METHODS: The study was conducted at a single center in the US. Eligible subjects underwent a one-time 30 cc venous blood draw. The population consisted of 50 adults: 16 with stable COPD, 11 hospitalized for AECOPD, and 23 individuals without lung disease (controls). We analyzed blood leukocytes for NEIL2 mRNA and DNA damage by RT‒qPCR and LA‒qPCR, respectively, in all groups. Plasma levels of seven biomarkers, CXCL1, CXCL8, CXCL9, CXCL10, CCL2, CCL11 and IL-6, were analyzed in the COPD groups using a magnetic bead panel (Millipore®).

RESULTS: The fold change in NEIL2 mRNA levels were lower in individuals with stable COPD and AECOPD than in controls (0.72 for COPD, p = 0.029; 0.407 for AECOPD, p < 0.001). The difference in NEIL2 mRNA expression between the stable COPD group and AECOPD group was also statistically significant (p < 0.001). The fold change in DNA lesions per 10 kb of DNA was greater in the stable COPD (9.38, p < 0.001) and AECOPD (15.81, p < 0.001) groups than in the control group. The difference in fold change was also greater in the AECOPD group versus stable COPD p < 0.024). Cytokine levels were not significantly different between the COPD groups. NEIL2 levels were correlated with plasma eosinophil levels in the stable COPD group (r = 0.737, p = 0.003).

CONCLUSIONS: NEIL2 mRNA levels are significantly reduced in individuals with COPD and may exacerbate DNA damage and inflammation. These results suggest a possible mechanism that increases inflammation and oxidative genomic damage in COPD.

CLINICAL TRIAL NUMBER: Not applicable.

PMID:40296120 | DOI:10.1186/s12931-025-03251-4

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Time dependent predictors of cardiac inflammatory adverse events in cancer patients receiving immune checkpoint inhibitors

Cardiooncology. 2025 Apr 28;11(1):40. doi: 10.1186/s40959-025-00331-8.

ABSTRACT

BACKGROUND: Cardio-inflammatory immune related adverse events (irAEs) while receiving immune checkpoint inhibitor (ICI) therapy are particularly consequential due to their associations with poorer treatment outcomes. Evaluation of predictive factors of these serious irAEs with a time dependent approach allows better understanding of patients most at risk.

OBJECTIVE: To identify different elements of patient data that are significant predictors of early and late-onset or delayed cardio-inflammatory irAEs through various predictive modeling strategies.

METHODS: A cohort of patients receiving ICI therapy from January 1, 2010 to May 1, 2022 was identified from TriNetX meeting inclusion/exclusion criteria. Patient data collected included occurrence of early and later cardio-inflammatory irAEs, patient survival time, patient demographic information, ICI therapies, comorbidities, and medication histories. Predictive and statistical modeling approaches identified unique risk factors for early and later developing cardio-inflammatory irAEs.

RESULTS: A cohort of 66,068 patients on ICI therapy were identified in the TriNetX platform; 193 (0.30%) experienced early cardio-inflammatory irAEs and 175 (0.26%) experienced later cardio-inflammatory irAEs. Significant predictors for early irAEs included: anti-PD-1 therapy at index, combination ICI therapy at index, and history of peripheral vascular disease. Significant predictors for later irAEs included: a history of myocarditis and/or pericarditis, cerebrovascular disease, and history of non-steroidal anti-inflammatory medication use.

CONCLUSIONS: Cardio-inflammatory irAEs can be divided into clinically meaningful categories of early and late based on time since initiation of ICI therapy. Considering distinct risk factors for early-onset and late-onset events may allow for more effective patient monitoring and risk assessment.

PMID:40296103 | DOI:10.1186/s40959-025-00331-8

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Factors influencing the agreement between teachers and students in the assessment of preclinical endodontics using a rubric

BMC Med Educ. 2025 Apr 28;25(1):626. doi: 10.1186/s12909-025-07193-9.

ABSTRACT

BACKGROUND: Students’ self-assessment and rubrics are pedagogical tools designed to enhance learning and evaluation processes. Achieving convergence between learners and teachers is paramount during the learning of complex treatments such as endodontic procedures, although it can be challenging due to uncontrollable factors that may affect task performance and perception. This study aimed to evaluate the influence of various factors (anatomical difficulty, type of instrumentation system, and training level) on the assessments of root canal treatments (RCT) by teachers and students using a rubric, and to determine the degree of agreement between them.

METHODS: 144 RCT were performed on extracted human molars by 36 dental students using two mechanized systems and subsequently evaluated using a rubric by both the students and four teachers. Rubric yielded a total score for the sum of 4 items analyzed individually: radiographic evaluation, access cavity, instrumentation, and obturation. The influence of the three following factors: anatomical difficulty (categories: minimal, moderate and high), instrumentation system (categories: Protaper Next and Reciproc Blue), and training level (categories: initial and advanced) on teachers’ and students’ RCT total scores and for each item were analyzed by three-way ANOVA. Agreements between teachers and students were measured by intraclass correlation coefficients and quadratic weighted Kappa. Statistical analyses were conducted at a pre-set alpha of 0.05 using Stata 16.

RESULTS: No significant influence of anatomical difficulty, instrumentation system, or training level was observed on RCT total scores given by teachers and students (p > 0.05). However, training level influenced the assessments by teachers in instrumentation as those by students in radiographic evaluation. Agreement was moderate for RCT total scores and substantial for teeth with minimal or high difficulty, after using Protaper Next, and at the initial training level. Agreement was substantial in obturation, and moderate in radiographic evaluation, access cavity, and instrumentation. Some categories in instrumentation and obturation items showed substantial agreement, while fair agreement was observed only in access cavity.

CONCLUSIONS: Educational factors in Endodontics such as anatomical difficulty, mechanized instrumentation system, and level of training did not influence the total scores of preclinical RCT by teachers or students. Agreement for RCT total scores ranged from moderate to substantial. The strongest agreement was observed in obturation, while access cavity yielded the lowest. The rubric as an assessment tool in Endodontics teaching is recommended.

PMID:40296102 | DOI:10.1186/s12909-025-07193-9

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Prevalence and Characteristics of Prostatic Utricles: A Retrospective MRI Study in Middle-Aged to Elderly Men

Prostate. 2025 Apr 28. doi: 10.1002/pros.24907. Online ahead of print.

ABSTRACT

BACKGROUND: Congenital urological malformations encompass a wide range of anomalies affecting the urinary tract and reproductive organs. MRI has emerged as a diagnostic tool in identifying these conditions. Prostatic utricle is an enlarged diverticulum in the posterior urethra, which results from incomplete degradation of the Müllerian ducts or decreased androgenic stimulation of the urogenital sinus. Prostatic utricle is an uncommon congenital anomalies, with 1% incidence in autopsy findings and clinical prevalence of 5% in urologic patients.

METHODS: This retrospective study analyzed 5819 prostate MRI interpretations from 4990 unique patients. The primary objective was to identify congenital abnormalities, focusing on the presence of a utricle and other related anomalies. Prostates suspected to have utricles were reevaluated by genitourinary specialized radiologist and utricles size were measured.

RESULTS: The study identified 127 patients positive for a utricle with an average age of 66 years at examination among the unique cohort. The average prostate size for patients with a utricle was 78.3 cc and the average utricle size was 0.4 cm3. Statistical analysis did not demonstrate any statistical trend between prostate size, age or PSA to utricle size. Additional congenital anomalies detected included one patient with a seminal vesicle cyst, one patient with right seminal vesicle agenesis and bilateral vas deferens agenesis, and two patients with ureterocele.

CONCLUSION: The prevalence of prostate utricle within a cohort of 4990 middle-aged to elderly men is 2.54%.

PMID:40296095 | DOI:10.1002/pros.24907

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Effect of an auxiliary device on scanning accuracy for multiple implants: an in vitro comparative study

Head Face Med. 2025 Apr 28;21(1):32. doi: 10.1186/s13005-025-00511-y.

ABSTRACT

OBJECTIVES: To determine the influence of a consumable auxiliary device, the O-I buckle, on the accuracy of intraoral scanning among complete arches.

METHODS: A standard mandibular model with six implants was used as the master model and was scanned by a precise dental laboratory scanner to establish a reference. Three impression techniques were compared: the conventional splinted open-tray impression (CI group), the digital intraoral scanning technique (IOS group), and IOS with the auxiliary device (OI group). For OI group, six prefabricated O-I buckles were attached for each intraoral scan body (ISB) and the definite models were scanned 10 times. The STL datasets were imported into a 3D inspection software to obtain the trueness and precision values for three scanning ranges (BCDE, BCDEF, and ABCDEF). The trueness was the absolute value of the root mean square (RMS) between the reference and test models, while precision referred to the value of the test group subtracted from each other. The data were statistically analyzed using two-way ANOVA and post hoc multiple comparison tests.

RESULTS: The impression method (p <.001) and scanning range (p <.001) significantly influenced the trueness and precision of implant impressions for complete edentulous arches. The IOS with O-I buckle showed higher trueness compared to the IOS group for all implant configurations with most being significantly different (p =.758, = 0.04, and = < 0.001 for BCDE, BCDEF, and ABCDEF, respectively) and significantly higher precision was seen in group ABCDEF (p <.001). For four and five implants (group BCDE and BCDEF), there was no significant difference comparing IOS with O-I buckle and CI (p >.05). As the range expanded, the trueness and precision of IOS and OI decreased (p <.05), whereas the accuracy of CI remained stable.

CONCLUSIONS: The auxiliary O-I buckle fixed to the ISBs significantly improved the multiple-implant intraoral scanning accuracy for digital impressions in complete arches; With CI as a reference, the accuracy of IOS with OI buckles were comparable for four and five implants.

CLINICAL RELEVANCE: The digitization accuracy of intraoral scanning for complete edentulous arches can be improved through IOS with OI buckles. This may lead to improved passive fit of the restoration, improving patient outcomes in a convenient and cheap way.

PMID:40296092 | DOI:10.1186/s13005-025-00511-y

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Incidence, outcomes and risk factors of postoperative urinary retention in patients undergoing primary total knee arthroplasty: a national inpatient sample database study

BMC Surg. 2025 Apr 28;25(1):186. doi: 10.1186/s12893-025-02930-9.

ABSTRACT

BACKGROUND: Postoperative urinary retention (POUR) was reported as a common complication in patients undergoing primary total knee arthroplasty (pTKA), but descriptions of its prevalence and negative outcomes vary widely and remain inadequately studied.

METHODS: A retrospective cohort study was conducted using the National Inpatient Sample database from 2005 to 2014. The annual incidence, baseline characteristics, and inpatient outcomes of POUR after pTKA were recorded. Logistic regression analysis was performed to estimate potential predictors of POUR. Statistical significance was defined as P < 0.01.

RESULTS: A total of 1,228,621 patients undergoing pTKA were identified. The incidence of POUR after pTKA is increasing annually from 2005 (1.51%, 95%CI 1.44-1.59%) to 2014 (2.29%, 95%CI 2.21-2.37%), and the cumulative incidence of POUR was 1.91% (95%CI 1.89-1.93%). POUR was significantly associated with higher Charlson Comorbidity Index and Elixhauser Comorbidity Index scores, and higher medical costs. In patients experiencing pTKA, the Top 5 most significant risk factors for developing POUR were male gender (odds ratio [OR] = 3.40; 95% confidence interval [CI] 3.30-3.51; P < 0.0001), fluid and electrolyte disorders (OR = 2.02; 95% CI 1.94-2.10; P < 0.0001), age over 60 (OR = 1.97; 95% CI 1.89-2.05; P < 0.0001), paralysis (OR = 1.78; 95% CI 1.46-2.17; P < 0.0001), and psychoses (OR = 1.57; 95% CI 1.43-1.72; P < 0.0001). Although POUR did not result in higher inpatient mortality (0.1% vs. 0.07%, P = 0.1242), it may be associated with the occurrence of other complications such as acute myocardial infarction (0.42% vs. 0.20%, P < 0.0001), pulmonary embolism and infarction (0.80% vs. 0.42%, P < 0.0001), acute renal failure (6.06% vs. 1.49%, P < 0.0001), deep venous thrombosis (0.71% vs. 0.45%, P < 0.0001), acute posthemorrhagic anemia (28.89% vs. 19.45%, P < 0.0001), and infection (0.29% vs. 0.15%, P < 0.0001).

CONCLUSIONS: Although POUR has no effect on inpatient mortality, our large-scale national study provides new insights that it increases postoperative complications and impairs clinical outcomes. Given the increasing incidence of POUR, early identification of high-risk patients, particularly those with identified comorbidities, should be prioritized. Preventive strategies, such as optimized perioperative fluid management, may help mitigate the risk of POUR. Future research should focus on developing preventive strategies to mitigate its impact.

PMID:40296087 | DOI:10.1186/s12893-025-02930-9

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Effectiveness of prior intra-articular corticosteroid injection in elderly patients with knee osteoarthritis undergoing progressive resistance training: a randomized controlled trial

Adv Rheumatol. 2025 Apr 28;65(1):21. doi: 10.1186/s42358-025-00452-9.

ABSTRACT

OBJECTIVE: To evaluate the effectiveness of intra-articular injections (IAIs) with triamcinolone hexacetonide (TH) combined with a progressive resistance exercise program (PREP) in improving pain, function, muscle strength, and quality of life in elderly patients with knee osteoarthritis (OA).

METHODS: Fifty-nine elderly individuals with knee OA were randomized into three groups: IAI with TH (IAI-TH) + PREP, IAI with saline solution (IAI-SS) + PREP, and IAI with placebo + PREP. The IAIs were administered once, one week before starting PREP, which was performed twice weekly for 12 weeks. Outcomes assessed at baseline and at 2, 6, and 12 weeks post-IAI included pain (Numerical Pain Scale – NPS), swelling, function (Western Ontario and McMaster Universities Osteoarthritis Index – WOMAC), quality of life (Short Form-36 – SF-36), performance tests (Six-Minute Walk Test – 6MWT, Timed Up and Go Test – TUGT, Short Physical Performance Battery – SPPB), and muscle strength (one-repetition maximum test – 1RM). Due to the COVID-19 pandemic, only 15 participants per group completed the study protocol.

RESULTS: All groups showed significant intragroup improvements over time in pain, function, muscle strength, and quality of life. However, no statistically significant differences were found between the groups for any of the assessed outcomes. The bodily pain domain of the SF-36 and analgesic consumption were the only measures showing differences over time.

CONCLUSION: The combination of IAI-TH and a 12-week PREP (twice weekly) was not superior to IAI-SS or placebo combined with the same PREP in improving pain, function, or quality of life in elderly patients with knee OA. These findings highlight the role of exercise as a key therapeutic strategy, regardless of prior IAI. Future studies with larger sample sizes and long-term follow-ups are needed to better assess the role of intra-articular corticosteroid injections in OA rehabilitation.

CLINICAL TRIAL NUMBER: ensaiosclinicos.gov.br (RBR-556md5g). Registered 27 October 2022.

PMID:40296068 | DOI:10.1186/s42358-025-00452-9