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Nevin Manimala Statistics

Association of motor skill competence, motivation, and physical activity among Chinese children aged 10-12 years

BMC Psychol. 2026 Jul 17. doi: 10.1186/s40359-026-05195-w. Online ahead of print.

ABSTRACT

Physical activity (PA) in children is affected by physical and psychological factors. Exploring its characteristics and determinants is critical to promoting children’s PA participation. Existing empirical evidence is largely drawn from Western cultural contexts, and cultural divergences create uncertainty regarding whether these established associations generalize to Chinese children. Therefore, this study aimed to investigate the relationships motor skill competence (MSC), motivation, and PA among Chinese children. Participants were 177 fourth to six-grade students (76 boys vs. 101 girls; mean age = 10.94 years old; SD = 0.79) at two elementary school students from the province of Hunan in China. The students’ MSC, motivation and PA were measured using the Test of Gross Motor Development-Third Edition (TGMD-3), the Perceived Locus of Causality scale, and the PA Questionnaire for Older Children respectively. Data were analyzed with descriptive statistics, independent sample t-tests, Pearson’s correlation and linear regression models. Boys scored significantly higher than girls on ball skills and PA. Pearson’s correlation revealed that children’s autonomous motivation and controlled motivation were positively related to PA (r = 0.313, ρ < 0.01; r = 0.259, ρ < 0.05). Children’s MSC were not associated with motivation (ρ > 0.05). The result of linear regression models showed that MSC, autonomous motivation and controlled motivation were significantly associated with PA (F (3, 171) = 10.565, ρ < 0.01). Chinese children’s MSC was not associated with motivaiton. Physical education teachers should target the enhancement of both MSC and motivation as it is an effective strategy for promoting higher levels of PA among children.

PMID:42469925 | DOI:10.1186/s40359-026-05195-w

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Nevin Manimala Statistics

What statistical methods are more appropriate for predicting recruitment at the design stage of a randomised controlled trial?

Trials. 2026 Jul 17. doi: 10.1186/s13063-026-09900-3. Online ahead of print.

ABSTRACT

BACKGROUND: Effective prediction and monitoring of recruitment in randomised controlled trials (RCTs) is critical to ensuring the target sample size is met, with 37% of trials failing to do so. This research aimed to identify various statistical methods for predicting recruitment during the design stage of an RCT and implement them using case-study trials, with a view to determining which method is more appropriate.

METHODS: Various deterministic, Poisson and Bayesian methods were identified and applied to data from six previously conducted RCTs, with varying numbers of participants recruited, sites opened, durations and recruitment outcomes.

RESULTS: Poisson methods were found to be more appropriate for obtaining predictions at the design stage of a trial. They produced confidence intervals to model uncertainty, unlike deterministic methods, and exhibited narrower intervals than Bayesian methods using informative priors. For single-centre trials, a homogeneous Poisson process was recommended, whilst a Non-homogeneous Poisson Process could be more suitable for multicentre trials. However, the non-homogeneous approach yielded more conservative estimates and required site-specific start dates, which may be less readily available at the design stage. Limitations included a lack of usable software for method implementation, difficulties with parameter elicitation, and a lack of additional data required to implement more complex methods, all of which may hinder the application of statistical methods for predicting recruitment which occurs in only 10% of RCTs.

CONCLUSIONS: To enhance transparency and reproducibility, it is recommended that RCTs publish the methods and parameters used in recruitment predictions. This may improve their accuracy, thereby reducing the cost and minimising the research waste associated with insufficient recruitment. Further research across a wider range of trials and methods may also be required due to the complexity of factors which influence recruitment and the variability in the accuracy of statistical methods across trials.

PMID:42469922 | DOI:10.1186/s13063-026-09900-3

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Nevin Manimala Statistics

Why researchers cut corners: motivations, pressures, and personality in questionable research practices

Res Integr Peer Rev. 2026 Jul 17. doi: 10.1186/s41073-026-00229-8. Online ahead of print.

ABSTRACT

BACKGROUND: Some questionable research practices (QRPs) are regarded as core contributors to problems of reproducibility and replication, while others compromise the integrity and credibility of research by obscuring responsibility and incentives. However, evidence on the individual-level drivers of QRP engagement is fragmented. This study examines theory-informed associations between social and psychological factors and self-reported QRP engagement.

METHODS: Using data from a cross-sectional survey of researchers across disciplinary fields (18,376 invited; N = 3,050 respondents), this study examines associations between social and psychological factors and self-reported QRP engagement. The sample reflects a self-selected subset of invited respondents.

RESULTS: I found that commitment to universalism (β = -0.14, 95% CI [-0.18, -0.10]), communalism (β = -0.04, 95% CI [-0.08, 0.0]), and organised scepticism (β = -0.15, 95% CI [-0.2, -0.1]) – as well as higher conscientiousness (β = -0.07, 95% CI [-0.11, -0.03]), agreeableness (β = -0.03, 95% CI [-0.07, 0.00]), emotional stability (opposite to neuroticism) (β = -0.07, 95% CI [-0.11, -0.04]), and openness (β = -0.08, 95% CI [-0.12, -0.04]) – were negatively associated with average self-reported QRP engagement. Publication pressure was associated with greater average self-reported QRP engagement (β = 0.12, 95% CI [0.08, 0.16]), but this association was weaker among respondents with higher scores on a factor interpreted as endorsement of universalism (β = -0.04, 95% CI [-0.08, 0.00]). Funding pressure was not statistically associated with self-reported average QRP engagement. Motivations to falsify theories and findings (β = -0.06, 95% CI [-0.11, -0.01]), and to improve impact and quality of results (β = -0.11, 95% CI [-0.15, -0.06]), were negatively associated with self-reported QRP engagement. Conversely, ego and esteem-related motivation (e.g., fame, achieving social and political goals) was found to have a direct association with mean self-reported QRP engagement (β = 0.11, 95% CI [0.07, 0.15]), whereas career-growth motivations showed no clear direct association (β = -0.03, 95% CI [-0.07, 0.01]). However, both were indirectly associated with QRP engagement through scientific achievement and impact/quality motivations.

CONCLUSIONS: These findings highlight specific social and psychological factors that are associated with self-reported QRP engagement, offering potential leverage points for efforts to promote research integrity and reduce questionable practices. However, because the analytic sample reflects a self-selected subset of invited researchers and is drawn largely from Europe and the United States, the findings may not fully generalise to the broader global research community.

PMID:42469920 | DOI:10.1186/s41073-026-00229-8

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Nevin Manimala Statistics

Clinical and radiological presentations of pulmonary hydatid cysts in Yemen: a retrospective cross-sectional study at a tertiary center

J Cardiothorac Surg. 2026 Jul 17. doi: 10.1186/s13019-026-04584-x. Online ahead of print.

ABSTRACT

BACKGROUND: Pulmonary hydatid cysts caused by Echinococcus granulosus represent a significant health burden in endemic regions such as Yemen. Limited contemporary data are available on the clinical and radiological characteristics of this disease in the Yemeni population. This study aimed to evaluate the clinical presentation, radiological features, surgical management, and early outcomes of pulmonary hydatid cysts at a tertiary center in Sana’a, Yemen.

METHODS: This retrospective cross-sectional study was conducted at Al-Thawra Modern General Hospital between January 2019 and March 2023. The medical records of 114 patients with surgically confirmed pulmonary hydatid cysts were analyzed. Demographic data, clinical presentation, radiological findings, surgical procedures, and early postoperative complications were collected using structured questionnaires. Statistical analyses were performed using SPSS v. 28.0, and 95% confidence intervals were calculated for all the proportions.

RESULTS: Of the 114 patients, 82 (71.9%; 95% CI: 63.1%-79.4%) were male, with a predominant age group of 19-30 years (43.0%; 95% CI: 34.3%-52.2%). Most patients were from urban areas (75.4%; 95% CI: 66.8%-82.4%) and worked as laborers (35.1%) or students (33.3%). Khat chewing was reported by 50.0% (95% CI: 41.0%-59.0%) of the patients. Five patients (4.4%; 95% CI: 1.9%-9.8%) were asymptomatic. The most common symptoms were cough (89.5%; 95% CI: 82.5%-93.9%), dyspnea (76.3%; 95% CI: 67.7%-83.2%), chest pain (64.9%; 95% CI: 55.8%-73.1%), and sputum production (71.1%; 95% CI: 62.2%-78.6%). Radiologically, 97 patients (85.1%; 95% CI: 77.4%-90.5%) had solitary cysts, predominantly in the right lung (67.0%). Most cysts were intact (76.3%; 95% CI: 66.9%-83.6%). Among the 17 patients with multiple cysts, 36 individual cysts were identified (range: 2-4 per patient). Twelve patients (10.5%; 95% CI: 6.0%-17.4%) had concurrent liver hydatid cysts documented on preoperative imaging. Among solitary cysts, peri-cyst changes, including mass effect (39.2%), empyema (5.2%), and pleural effusion (2.1%), were documented. Preoperative albendazole was administered to 8.8% of patients, and 95.6% underwent elective surgery. Capitonnage was performed in 91.2% (95% CI: 84.6%-95.2%) of the cases. Postoperative complications occurred in 7.9% (95% CI: 4.2%-14.3%), with no mortality reported. Hospital stay was less than 1 week for 75.4% (95% CI: 66.8%-82.4%) of patients.

CONCLUSIONS: Pulmonary hydatid cysts in Yemen predominantly affect young urban males and present with respiratory symptoms. Solitary, intact cysts are the most common, and surgical management with capitonnage is safe and effective, with low morbidity rates when performed in specialized centers.

PMID:42469898 | DOI:10.1186/s13019-026-04584-x

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Hybrid coronary revascularization versus off-pump coronary artery bypass grafting in high-risk patients: a single-centre retrospective study of early outcomes

J Cardiothorac Surg. 2026 Jul 17. doi: 10.1186/s13019-026-04636-2. Online ahead of print.

ABSTRACT

BACKGROUND: It is hard to efficiently revascularize high-risk patients with multivessel coronary disease, especially when conventional coronary artery bypass grafting is correlated with high perioperative risk and doing it percutaneously can be bigger issue for high-risk patients. Less invasive and modern alternative to OPCAB is Hybrid coronary revascularization. So we decided to compare this two methods and see which one will have better outcomes for high-risk patients. Our research involves comparing early (30 days) postoperative outcomes between Hybrid Coronary Revascularization (HCR) and Off-Pump Coronary Bypass surgery (OPCAB) in high surgical risk patients with coronary artery disease (EUROSCORE II > 6%, STS > 4% and SYNTAX SCORE > 32).

METHODS: In this single-centre retrospective study, we reviewed high-risk patients treated between Feb 18, 2024 and Dec 14, 2025. After applying predefined eligibility criteria, 87 patients were included, from 28 patients (Mean Age = 66.6 ± 10.7) underwent HCR and 59 (Mean Age = 76.6 ± 4.1) underwent off-pump open aorto-coronary bypass surgery via median sternotomy. We compared early (30 days) postoperative clinical outcomes between two groups. Statistical analysis was performed using IBM SPSS statistics, applying independent-samples t-test and chi-square test as appropriate.

RESULTS: Hybrid Coronary Revascularisation (MIDCAB + PCI) required shorter operative time than Off-Pump Coronary Bypass surgery (OPCAB), but with higher in-hospital costs. HCR was also associated with shorter intubation duration (245.5 ± 51.2 min vs. 576.7 ± 97.3 min, P < 0.001), ICU stay (66.4 ± 15.5 h vs. 102.7 ± 12.7 h, P < 0.001), hospital length of stay (7.3 ± 0.8 days vs. 13.0 ± 3.7 days, P < 0.001), and lower thoracic drainage output (275.4 ± 74.1 ml vs. 615.3 ± 88.5 ml, P < 0.001). Blood transfusion requirements were higher in the HCR group (14.3% vs. 0.0%, P = 0.009). Wound infection occurred only in the OPCAB group (0.0% vs. 27.1%, P = 0.002). The composite 30-day MACCE rate was numerically lower in the HCR group (0.0% vs. 13.6%), but this difference did not reach statistical significance (P = 0.050).

CONCLUSIONS: In high-risk patients with multivessel coronary artery disease, Hybrid Coronary Revascularization (MIDCAB + PCI), compared with traditional Off-Pump Coronary Artery Bypass surgery (OPCAB), was associated with a faster early-recovery profile, including shorter intubation time, ICU stay, and hospitalization, and lower chest-drain output. Multivariable analysis confirmed that these recovery benefits were independent of age, whereas the apparent advantage in overall complications was largely explained by the younger age of the HCR group. Differences in 30-day mortality and MACCE favoured HCR numerically but did not reach statistical significance in this underpowered cohort.Given the retrospective, non-randomized design with unequal group sizes and the absence of time-to-event follow-up, superiority of one strategy over the other cannot be established. Within these limitations, HCR appears to be a safe and feasible option that may be considered in selected elderly and high-risk patients (EUROSCORE II > 6%, STS > 4%, and SYNTAX SCORE > 32) with complex coronary anatomy. Larger, prospective, risk-adjusted studies with longer follow-up are warranted to confirm these findings.

TRIAL REGISTRATION: EC/NVU/PhD/26-001.

PMID:42469895 | DOI:10.1186/s13019-026-04636-2

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A hybrid type 2 cluster randomized trial of an enhanced combined cognitive behavioral therapy and medication management algorithm for treatment of depression among youth living with HIV: study protocol

Implement Sci. 2026 Jul 17. doi: 10.1186/s13012-026-01528-w. Online ahead of print.

ABSTRACT

BACKGROUND: The treatment of depression is essential for improving both psychiatric and medical outcomes for youth with HIV (YWH). Previous studies have shown that the combination of a medication algorithm and CBT tailored for YWH (COMB) is efficacious for decreasing depressive symptoms and improving quality of life, but sustainability of effects remains difficult. Most recently, a cluster-randomized RCT found at Week 24 statistically significant improvement in the site-level mean number of depressive symptoms, the proportion of YWH with a treatment response, and the proportion in remission at COMB sites compared to treatment as usual (TAU) sites (6.7 vs. 10.6, 62% vs. 18%, 48% vs.17%, ps[Formula: see text]0.01, respectively). However, by Week 48, differences were no longer significant between arms for these outcomes. Additionally, viral suppression did not improve in COMB compared to TAU. These findings indicate a “voltage drop” of COMB’s impact. To improve sustainability, we plan to enhance the combination treatment with five additional implementation strategies (COMBEX) suggested in our post-trial interviews from our efficacy study. This protocol paper describes a Hybrid Type 2 Cluster Randomized Trial in which COMBEX will be compared to COMB, with co-primary effectiveness and implementation aims guided by the Consolidated Framework for Sustainability Constructs in Healthcare.

METHODS: Eligibility will include youth with HIV (15-24 years, n = 130) with a diagnosis of ongoing nonpsychotic depression at HIV clinic sites in the US. Using restricted randomization, sites (n = 8) will be assigned to either COMBEX (with its additional implementation strategies) or to COMB. Implementation outcomes of adoption, fidelity, and sustainability will be evaluated, as well as the impact of COMBEX compared to COMB in improving real-world effectiveness of reducing indices of depression (e.g., symptoms, treatment response, remission) and decreasing viral load over 72 weeks. Additionally, an explanatory, sequential, mixed-method approach will be used to evaluate the context of implementation for both COMB and COMBEX, guided by the sustainability framework with data from staff/clinicians (n = 64). Arm comparisons will use t-tests on site-level means.

DISCUSSION: This study will inform the broader implementation of this efficacious approach to treatment of depression for youth with HIV by revealing strategies relevant to its sustainment.

TRIAL REGISTRATION: NCT07211087 (registered October 7, 2025).

PMID:42469890 | DOI:10.1186/s13012-026-01528-w

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Nevin Manimala Statistics

Interparental conflict and children’s sleep quality in the chinese family context: the serial mediating roles of emotional insecurity and subjective well-being

BMC Psychol. 2026 Jul 17. doi: 10.1186/s40359-026-05152-7. Online ahead of print.

ABSTRACT

BACKGROUND: Sleep problems in children are an important risk factor for cognitive, emotional, and behavioral development. Previous studies have shown that interparental conflict is closely associated with poorer sleep quality in children. However, the internal psychological variables involved in this association, particularly how they may be understood within the Chinese family context, remain insufficiently examined. Based on a sample of Chinese children, this study examined the association between interparental conflict and poorer sleep quality in children, and it tested the mediating pathways of emotional insecurity and subjective well-being(SWB).

METHODS: This study employed a quantitatively driven explanatory sequential mixed-methods design combining questionnaire survey data with child interviews. The quantitative component included 900 upper-grade primary school children (M = 10.58, SD = 0.81). Correlation analyses and a serial mediation model were used to examine the associations among interparental conflict, emotional insecurity, SWB, and children’s sleep quality. In the qualitative component, semi-structured interviews were conducted with 23 children, and thematic analysis was used to supplement and contextualize the quantitative findings.

RESULTS: Interparental conflict was significantly associated with poorer sleep quality in children (r = 0.39, p < 0.001), and this association remained significant after emotional insecurity and SWB were included as mediators in the model (β = 0.11, p = 0.006). The statistical indirect effects through emotional insecurity, through SWB, and through emotional insecurity and SWB in sequence, were all significant, with effect values of 0.014, 0.019, and 0.004 respectively. The qualitative findings showed that the interviewed children incorporated interparental conflict into their understanding of family relationships, their own situations, and daily life circumstances. Within the Chinese family context, these responses were more clearly reflected in a contextualized organization of meaning around family harmony, parent-child connection, and relational responsibility.

CONCLUSIONS: Emotional insecurity and SWB are important psychological variables for understanding the association between interparental conflict and poorer sleep quality in children. At the same time, these processes may acquire specific meanings within the Chinese family context.

PMID:42469886 | DOI:10.1186/s40359-026-05152-7

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Efficacy and safety of prothrombin complex concentrate versus fresh frozen plasma in adult patients undergoing cardiac surgery: a systematic review and meta-analysis

J Cardiothorac Surg. 2026 Jul 17. doi: 10.1186/s13019-026-04513-y. Online ahead of print.

ABSTRACT

BACKGROUND: Postoperative bleeding is a common and potentially life-threatening complication following cardiac surgery, often exacerbated by multifactorial coagulopathy from cardiopulmonary bypass, hypothermia, and platelet dysfunction. While fresh frozen plasma (FFP) has traditionally been used for coagulation correction, it has significant limitations, including large volume requirements, slow onset, and increased risk of transfusion-related complications. Prothrombin complex concentrate (PCC) has emerged as a potential alternative, offering rapid coagulation correction with reduced volume load and no ABO compatibility requirements. This systematic review and meta-analysis compared the efficacy and safety of PCC versus FFP in managing coagulopathic bleeding in adult cardiac surgery patients.

METHODS: We conducted a systematic review and meta-analysis following PRISMA guidelines. Electronic databases (MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials) were searched using MeSH terms and keywords related to “Cardiothoracic Surgery”, “Prothrombin Complex Concentrate”, and “Fresh Frozen Plasma”, from inception to Jan 2026. Cohort studies and randomized controlled trials comparing PCC and FFP in patients aged > 18 years undergoing cardiac surgery complicated by bleeding or coagulopathy were included. Primary outcomes were RBC transfusion requirement, chest tube drainage, and thromboembolic events. Secondary outcomes included surgical re-exploration for bleeding, stroke, duration of mechanical ventilation, hospital and ICU stays, and acute kidney injury. Risk of bias was assessed using the Cochrane Risk of Bias Tool 2.0 for RCTs and the Newcastle-Ottawa Scale for observational studies. Statistical analysis was conducted using Review Manager (RevMan) version 5.4, applying risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, both with 95% confidence intervals. The meta-analysis protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under protocol number CRD420251088737.

RESULTS: This meta-analysis included ten studies with 2,643 patients. PCC use moderately reduced RBC transfusion in the first 24 h (RR = 0.84; 95% CI: 0.76-0.93; p = 0.05; I2 = 47%), 12-24-h chest tube drainage (MD = – 188.89 mL; 95% CI: – 248.48 to – 125.30; p < 0.00001; I2 = 50%), and hospital stay (MD = – 1.19 days; 95% CI: – 2.21 to – 0.18; p = 0.004; I2 = 67%). No significant differences were observed for surgical re-exploration (RR = 0.81; 95% CI: 0.66-1.00; p = 0.05; I2 = 0%), mechanical ventilation (MD = – 0.08; 95% CI: – 0.34 to 0.19; p > 0.05; I2 = 73%), ICU stay (MD = – 0.07 days; 95% CI: – 0.59 to 0.45; p = 0.78; I2 = 59%), all-cause mortality (RR = 1.10; 95% CI: 0.82-1.50; p = 0.51; I2 = 0%), thromboembolic events (RR = 1.22; 95% CI: 0.80-1.85; p = 0.35; I2 = 0%), stroke (RR = 1.10; 95% CI: 0.75-1.63; p = 0.63; I2 = 0%), acute kidney injury (RR = 1.08; 95% CI: 0.74-1.56; p = 0.70; I2 = 77%), serious adverse events (RR = 0.78; 95% CI: 0.56-1.09; p = 0.15; I2 = 35%), and any adverse event (RR = 0.95; 95% CI: 0.81-1.11; p = 0.54; I2 = 53%). Moderate to high heterogeneity was noted in several outcomes, for which subgroup analyses were performed.

CONCLUSIONS: This meta-analysis demonstrates that PCC is superior to FFP in reducing RBC transfusion requirements, 12-24-h chest tube drainage, and hospital length of stay in adult cardiac surgery patients, while maintaining a comparable safety profile. Further large-scale, high-quality RCTs are warranted to strengthen the evidence base and inform future guidelines.

PMID:42469870 | DOI:10.1186/s13019-026-04513-y

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Nevin Manimala Statistics

Hantavirus preparedness among undergraduate nursing students in the United Arab Emirates: a cross-sectional study of knowledge, risk perception and preventive practice

BMC Nurs. 2026 Jul 17;25(1):634. doi: 10.1186/s12912-026-05015-x.

ABSTRACT

BACKGROUND: Hantavirus infection is uncommon in many settings but can cause severe pulmonary or renal disease. Nursing students require disease-specific preparedness for exposure-history taking, safe prevention counselling and infection prevention during community and clinical learning. This study examined undergraduate nursing students’ knowledge, risk perception and preventive practice toward hantavirus and identified associated factors.

METHODS: A descriptive analytical cross-sectional survey was conducted among 236 undergraduate nursing students in one nursing program in Ras Al Khaimah, the United Arab Emirates during the 2025-2026 academic year. Data was collected using the researcher-developed Hantavirus Knowledge, Attitudes and Preventive Practices Questionnaire for Nursing Students (HKAPP-NS). Descriptive statistics, Cronbach’s alpha, Pearson correlations and multivariable linear regression with HC3 robust standard errors were used.

RESULTS: Knowledge was low among the 236 complete-case respondents (mean 8.13/20, SD 5.84), with 59.0% classified as having poor knowledge. Attitude was moderate (mean 33.34/50, SD 7.78), and overall practice was higher (mean 42.98/64, SD 15.83). Internal consistency was strong across domains (alpha 0.886-0.967). Attitude correlated with overall practice (r = 0.569, p < 0.001), whereas knowledge did not (r = 0.101, p = 0.120). Previous hantavirus teaching, infection prevention and control training and environmental exposure predicted higher knowledge. Attitude was the strongest independent predictor of overall practice.

CONCLUSIONS: Students reported comparatively frequent precautionary practice but had important disease-specific knowledge gaps, particularly regarding safe rodent-contamination cleanup, routine vaccine availability, specific antiviral treatment and person-to-person transmission. The finding that attitude, rather than knowledge, independently predicted practice suggests that scenario-based One Health education should combine factual teaching with risk appraisal, self-efficacy building, exposure-history taking and prevention counselling to strengthen future nurses’ preparedness for rodent-borne zoonotic infections.

PMID:42469853 | DOI:10.1186/s12912-026-05015-x

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A BRD4/p300/SP1 epigenetic cascade drives microglial P2X4R transcription and promotes neuropathic pain

J Neuroinflammation. 2026 Jul 17. doi: 10.1186/s12974-026-03965-2. Online ahead of print.

ABSTRACT

Persistent upregulation of the purinergic receptor P2X4R is strongly associated with microglial activation in neuropathic pain, yet the epigenetic mechanisms linking chromatin remodeling to its dysregulation remain unclear. Here, we delineate a hierarchical epigenetic cascade that promotes transcriptional activation of P2X4R in spinal microglia following nerve injury. In a mouse spared nerve injury (SNI) model, microglial activation was accompanied by increased expression of P2X4R and the histone acetyltransferase p300, together with enhanced histone acetylation (H3K9ac, H3K27ac, H4K5ac, and H4K8ac) and increased chromatin accessibility at the P2rx4 promoter. Microglia-specific deletion of p300 blunted injury-induced histone acetylation and suppressed P2X4R upregulation. We further demonstrate that the acetylation reader BRD4 is recruited to these regions and cooperates with the transcription factor SP1 to drive P2rx4 transcription, supported by chromatin analyses revealing inducible assembly of a BRD4-p300-SP1 axis. Disruption of this cascade via p300 inhibition (C646) or BRD4 blockade (JQ1) attenuated spinal neuroinflammation and alleviated nociceptive hypersensitivity. Notably, reactivation of P2X4R by BzATP largely reversed the analgesic effects of BRD4 inhibition, establishing P2X4R as a critical downstream effector. Collectively, these findings support a p300-BRD4-SP1 epigenetic cascade linking chromatin remodeling to microglia-mediated neuropathic pain, highlighting this pathway as a potential therapeutic target.

PMID:42469847 | DOI:10.1186/s12974-026-03965-2