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Integrative Multi-Omics Identifies S100A4 as a Translational Hub Linking Environmental Bis(2-Ethylhexyl) Phthalate (DEHP) Exposure to Glioblastoma Risk.3 weeks agoGlioblastoma (GBM) is a highly aggressive central nervous system malignancy with a dismal 5-year survival rate of less than 5%, and poorly understood environmental factors complicate its treatment. One such factor is bis(2-ethylhexyl) phthalate (DEHP, also known as di-2-ethylhexyl phthalate), a common plasticizer with documented neurotoxicity, yet its potential role in GBM pathogenesis remains elusive. In this study, we employed an integrative computational framework that combined network toxicology, single-cell transcriptomics, proteome-wide and metabolome-wide Mendelian randomization (MR), and molecular dynamics (MD) simulations to systematically investigate the interplay between DEHP and GBM risk. Cross-dataset targets were identified by mining toxicogenomic and disease databases, followed by the construction of a protein-protein interaction (PPI) network. This approach identified 76 overlapping targets between DEHP and GBM, which were refined to 24 hub genes through topological analysis. Notably, MR analyses revealed putative causal associations between higher genetically predicted plasma levels of three hub proteins-CD63, CTSS, and S100A4-and an increased risk of GBM, with S100A4 showing the strongest effect (odds ratio [OR] = 2.03, 95% confidence interval [CI] 1.15-3.58, p = 0.0149). This association was consistently validated across 11 independent cohorts, including TCGA, GTEx, and GEO datasets. Molecular docking and dynamics simulations identified S100A4 as the predominant binding target of DEHP, revealing a high-affinity interaction that may stabilize a metastasis-associated conformation. A two-step MR mediation analysis further indicated that S100A4 partially influences GBM risk by altering plasma lipid metabolites, with erucic acid mediating ~17% of the total effect. In conclusion, our analysis provides converging computational and genetic epidemiological evidence for a novel DEHP-S100A4-lipid metabolic axis that may contribute to GBM development. This pathway conceptually bridges environmental toxicology and neuro-oncology and highlights S100A4 and associated lipid disturbances as potential targets for preventive intervention. However, the proposed mechanistic links remain inferential, and definitive confirmation will require future in vitro and in vivo experiments to directly test the impact of DEHP on S100A4 expression, function, and downstream metabolic reprogramming in GBM models.CancerAdvocacy
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The prevalence of obesity and hypertension in paediatric cardiology patients before and after COVID-19 lockdown measures.3 weeks agoThis study is a retrospective clinical audit to evaluate the impact of COVID-19 lockdown measures on the prevalence of obesity and hypertension in paediatric cardiology patients and determine the extent to which these comorbidities were recognised and managed at the East Midlands Congenital Heart Centre (EMCHC), UK. Height, weight and blood pressure (BP) values were extracted from clinic letters before and after COVID-19 lockdown at the EMCHC. BMI and BP percentiles were calculated to categorise BMI and BP stage. Analysis compared pre- and post-lockdown outpatient clinic data of paediatric cardiology patients. 800 patients were included. Mean BMI increased from 17 to 20 kg/m2, with a 3% rise in obesity prevalence. South Asian children were the only ethnic group to show a significant post-lockdown increase in BMI percentile. Patients with severe congenital heart disease (CHD) had lower BMI than those with mild or repaired lesions. Although systolic and diastolic BP percentiles declined significantly post-lockdown (P < 0.001), 29% of patients met thresholds for stage 1 or stage 2 hypertension, likely an overestimate due to single automated readings and white-coat effects. BMI correlated positively with systolic BP in both periods (pre-lockdown r = 0.164; post-lockdown r = 0.297). Only 2% of hypertensive patients and 2% of patients with obesity were appropriately referred for further management.
Obesity and hypertension remain under-recognised and undertreated in paediatric cardiology patients. Strong BMI-BP associations underscore the need for repeated manual BP readings, ambulatory monitoring and routine use of centile-based assessment to optimise long-term cardiovascular outcomes.
• Childhood obesity and hypertension have increased globally, worsened by COVID-19 lockdowns. • Paediatric cardiac patients are especially vulnerable due to limited cardiac reserves and accelerated cardiovascular ageing. • These risks are often under-recognised in clinics.
• Post-lockdown BMI and obesity rose particularly in South Asian children. • Hypertension was common yet seldom documented or acted upon. • Strong BMI-systolic BP correlations, disease-severity differences and missed referrals emphasise the need for percentile use, repeat BP checks and better integrated cardiometabolic pathways in paediatric cardiology.Chronic respiratory diseaseCardiovascular diseasesAccessCare/ManagementAdvocacy -
Global, regional and national prevalence of mental disorders among women at childbearing age from 1992 to 2021.3 weeks agoTo investigate the trends in prevalence of mental disorders - schizophrenia, depressive disorders, bipolar disorder, anxiety disorders, eating disorders, autism spectrum disorders, attention-deficit/hyperactivity disorder, conduct disorder, idiopathic developmental intellectual disability, and other mental disorders - among women of childbearing age at global, regional and national level from1992 to 2021, and further to examine the independent effects of age, period, and birth cohort on mental disorders.
Data were derived from the Global Burden of Disease Study (GBD) 2021. An age-period-cohort analysis was adopted to investigate the annual percentage change in prevalence rate overall (net drifts, % per year) and by age (local drifts, % per year), and age-, period-, and cohort-effect on the prevalence rate among participants between 1992 and 2021.
In 2021, the global prevalence cases of overall mental disorders in women at childbearing age were 343.22 million. Over the past three decades, the largest increase in case number was observed in low socio-demographic index (SDI) region (144.21%), while the most significant increase in age-standardized prevalence rate (ASPR) was identified in high SDI region (18.30%). The global net drift in prevalence rate of mental disorders among participants was estimated as -0.02 (95%CI: -0.04 to -0.00) annually. Moreover, prevalence trends were highly heterogeneous across all the global 204 countries/territories. Anxiety disorders and depression disorders were the top two contributors of overall prevalence of mental disorders, accounting for the largest proportion of total prevalence (66.2% in 1992 and 70.4% in 2021) among all types of mental disorders. For overall global population, an increasing age effect, V-shape pattern of period effect, and stable cohort effect were separately identified upon mental disorder burden. Notably, the V-shape period effect may reflect that positive mental health policy gains (pre-2016) were disrupted by COVID-19 pandemic.
The global burden of mental disorders among women at childbearing age remained high during 1992 and 2021, especially after the COVID-19 pandemic. Notably, anxiety disorders, and depressive disorders were more prevalent in this population. Disparities of mental disorders existed in regions, countries and sub-populations with different age. These findings imply that mental health issue has become a significant public health challenge worldwide. This study has important policy and population health implications, suggesting that country-specific and subpopulation-tailored intervention strategies should be implemented for the purpose to reduce the burden of mental disorders among women at childbearing age worldwide.Chronic respiratory diseaseMental HealthAccessCare/ManagementPolicyAdvocacy -
Nasal high-frequency oscillatory ventilation versus nasal continuous positive airway pressure for respiratory distress syndrome in preterm infants: A systematic review and meta-analysis.3 weeks agoThis systematic review and meta-analysis aimed to evaluate whether nasal high-frequency oscillatory ventilation (NHFOV) reduces the intubation rate compared to nasal continuous positive airway pressure (NCPAP) as a primary respiratory support strategy in preterm infants with respiratory distress syndrome (RDS).
We systematically searched Medline, the Cochrane Library, EMBASE, the Chinese National Knowledge Infrastructure (CNKI), and the Wanfang Database from inception to December 2025 for randomized controlled trials (RCTs). We included RCTs comparing NHFOV with NCPAP as the initial respiratory support for preterm infants with RDS. Data were pooled using a random-effects model. The primary outcome was the rate of endotracheal intubation.
Five RCTs involving 912 preterm infants were included. Compared with NCPAP, NHFOV significantly reduced the intubation rate (relative risk [RR]: 0.51; 95% confidence interval [CI]: 0.37-0.68; P < 0.001). No significant heterogeneity was observed among the studies (P = 0.79; I2 = 0%).
As a primary respiratory support strategy for preterm infants with RDS, NHFOV is superior to NCPAP in reducing the need for endotracheal intubation.Chronic respiratory diseaseAccessCare/ManagementAdvocacy -
Bias mitigation in matched observational studies with continuous treatments: calipered non-bipartite matching and bias-corrected estimation and inference.3 weeks agoIn matched observational studies with continuous treatments, individuals with different treatment doses but the same or similar covariate values are paired for causal inference. While inexact covariate matching (i.e., covariate imbalance after matching) is common in practice, previous matched studies with continuous treatments have often overlooked this issue as long as post-matching covariate balance meets certain criteria. Through re-analyzing a matched observational study on the effect of social distancing on COVID-19 case counts, we show that this routine practice can introduce severe bias for causal inference. Motivated by this finding, we propose a general framework for mitigating bias due to inexact matching in matched observational studies with continuous treatments, covering the matching, estimation, and inference stages. In the matching stage, we propose a carefully designed caliper that incorporates both covariate and treatment dose information to improve matching for downstream treatment effect estimation and inference. For the estimation and inference, we introduce a bias-corrected Neyman estimator paired with a corresponding bias-corrected variance estimator. The effectiveness of our proposed framework is demonstrated through numerical studies and a re-analysis of the aforementioned observational study on the effect of social distancing on COVID-19 case counts. An open-source $\tt {R}$ package for implementing our framework has also been developed.Chronic respiratory diseaseAccessAdvocacy
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Impact of posterior pericardiectomy vs. posterior pericardial Hemovac drainage on POAF and fluid management in CABG patients.3 weeks agoThis study compares posterior pericardiectomy (PP) and posterior pericardial Hemovac drainage (PPHD) in terms of their effects on post-operative atrial fibrillation (POAF) incidence in patients undergoing coronary artery bypass grafting (CABG).
A total of 149 patients (mean age 59.6 ± 7.5 years, 75.8% male) were included in this study. Patients were divided into two groups based on the drainage technique. Demographic characteristics, perioperative parameters, and post-operative POAF incidence were analysed.
POAF incidence was 8.9% in the PP group and 5.1% in the PPHD group, but the difference was not statistically significant (p = 0.385). The first 24-hour drainage volume was significantly higher in the PPHD group (p = 0.034), whereas left thoracic drainage was more pronounced in the PP group (p < 0.001). Residual pleural effusion was more frequent in the PP group compared to the PPHD group (15.6% vs. 3.4%, p = 0.019).
Although the difference in POAF incidence between the two groups was not statistically significant, PPHD demonstrated more effective early drainage and resulted in less residual pleural effusion.Chronic respiratory diseaseCardiovascular diseasesAccessCare/ManagementAdvocacy -
Nurse-Led Family Liaison in Adult Intensive Care: From Pandemic Innovation to an Integrated Model for Patient- and Family-Centred Care.3 weeks agoPatient- and family-centred care (PFCC) is recognised as a marker of quality in intensive care but remains challenging to operationalise in routine practice. During the COVID-19 pandemic, visiting restrictions prompted the rapid introduction of Family Liaison Services (FLSs) to support communication with families. However, evidence on the feasibility, acceptability, and impact of sustained, nurse-led FLS models in adult Intensive Care Units (ICUs) beyond the pandemic remains limited.
To evaluate the feasibility, acceptability, and impact of a nurse-led FLS.
Single-centre mixed-methods service evaluation conducted in an 18-bed quaternary cardiothoracic adult ICU in London, UK, using responses from a validated family satisfaction survey (FS-ICU 24), a purpose-designed staff feedback survey, and routinely collected service activity records.
Data were analysed from routinely collected service activity records (October 2021-September 2025), family satisfaction survey responses collected pre-implementation (2017) and post-implementation (2022 and 2024), and staff feedback surveys (n = 27 responses; 16% response rate). The nurse-led FLS was delivered by experienced ICU nurses rotating into the role and was later integrated with post-ICU follow-up services. Activity data showed increasing demand, with average monthly contacts rising from 19 in 2022 to 34 in 2025. All staff respondents reported the service to be accessible and beneficial to families. Family satisfaction with the ICU experience increased following FLS implementation, particularly in relation to respect and dignity, emotional support, and communication. Free-text family feedback highlighted dissatisfaction related to delayed communication, while staff described improved understanding of family needs and enhanced coordination of family support.
A nurse-led FLS was feasible, acceptable, and associated with improvements in family experience and staff perceptions of family support. Integration with post-ICU follow-up extended continuity of care and facilitated family involvement in service development. Future priorities include sustainable workforce planning, attention to equity in PFCC, and evaluation of longer-term family outcomes.
A nurse-led FLS offers a replicable model for embedding PFCC within adult intensive care.Chronic respiratory diseaseAccessCare/ManagementAdvocacy -
Acute Effect of Inspiratory Muscle Training on Peripheral Tissue Oxygenation Behavior in Individuals With COPD: A Randomized Crossover Study.3 weeks agoChronic Obstructive Pulmonary Disease (COPD) is a pulmonary condition characterized by airflow obstruction, which progresses with systemic alterations such as changes in muscle composition and metabolism, anticipating the activation of the inspiratory metaboreflex. This study aimed to analyze the acute effects of Inspiratory Muscle Training (IMT) on peripheral muscle metabolism in individuals with COPD, using near-infrared spectroscopy (NIRS).
This randomized, blinded, crossover study included 29 individuals with COPD who underwent three distinct sessions: high-load IMT (IMT-Strength, 60% of maximal inspiratory pressure-MIP), low-load IMT (IMT-Endurance, 30% of MIP), and a sham protocol. Tissue oxygenation of the gastrocnemius muscle was assessed using NIRS before and after each protocol.
Differences in mean final tissue oxygen saturation were observed only during the IMT-Endurance protocol. The oxygen desaturation time was shorter during the IMT-Strength protocol compared with the other groups. Although not statistically significant, patients with more severe COPD (GOLD 3-4) exhibited an oxygen desaturation rate higher during the strength IMT compared with the endurance and sham protocols.
Acute high-intensity IMT may accentuate the reduction in peripheral perfusion, especially in patients with advanced COPD, suggesting possible metaboreflex activation. Conversely, endurance IMT may improve peripheral perfusion. These findings reinforce the need for careful and individualized prescription of IMT in the COPD population.
Clinical Trials number: NCT06827379 https://clinicaltrials.gov/study/NCT06827379.Chronic respiratory diseaseAccessCare/ManagementAdvocacy -
Cycle Threshold (Ct) Value Trends in COVID-19: Analyzing Gender, Age, and Severity Factors Across Major Waves in India.3 weeks agoThis study investigates the variations in cycle threshold (Ct) values from RT-PCR tests across different COVID-19 waves, age groups, and genders to assess their correlation with viral load, disease severity, and epidemiological indicators in India.
We analysed a data set of 53,485 confirmed COVID-19 cases, categorizing Ct values across three major COVID-19 waves, age groups, and genders. Non-parametric statistical tests were applied to compare Ct values, and linear regression analysis was conducted to evaluate the association between Ct values and COVID-19 epidemiological indicators.
Ct values varied significantly across COVID-19 waves, with the highest values in the first wave, the lowest in the second, and intermediate values in the third. Children exhibited the highest Ct values, while the elderly had the lowest. Females showed significantly lower Ct values than males. A negative correlation was observed between Ct values and COVID-19 cases and deaths, indicating that lower Ct values reflected higher viral loads and more severe outbreaks.
These findings highlight Ct values as a useful predictive marker for viral load and disease severity. Monitoring Ct values can enhance public health strategies by informing pandemic response efforts and resource allocation.Chronic respiratory diseaseAccessAdvocacy -
Pulmonary rehabilitation for pulmonary hypertension in high-altitude areas: a mixed-methods study of medical staff's perspectives.3 weeks agoIn high-altitude areas, while pulmonary rehabilitation (PR) is recognized as an effective intervention for enhancing exercise tolerance and reducing breathlessness, delivering these programs to patients living at high altitudes presents unique, environment-specific challenges. This study aimed to systematically investigate the current status, barriers, and optimization pathways for PR in patients with pulmonary hypertension (PH) in high-altitude areas, from the perspective of medical staff.
A mixed-methods design was employed, comprising a questionnaire survey of 326 medical staff and semi-structured interviews with 16 staff members from three tertiary hospitals in Xining, Qinghai Province. Quantitative data were analyzed using descriptive statistics, and qualitative data were analyzed using thematic analysis.
Quantitative results revealed that only 62.58% of participants reported the implementation of PR in their departments. While 55.39% indicated that they adjusted the content of PR according to the high-altitude environment. Major barriers identified included insufficient awareness among patients and family members (90.80%), lack of high-altitude PR guidelines (88.04%), and shortage of healthcare human resources (87.42%). Optimization suggestions focused on developing high-altitude PR guidelines (86.50%), increasing in rehabilitation resources (82.82%), and improvement of patients' compliance (78.22%). Qualitative findings identified three core themes: current status of PR and effects, barriers to implementing PR, and optimization suggestions, with 13 subthemes. The quantitative and qualitative findings corroborated each other, indicating insufficient clinical penetration, a lack of standardization, and intertwined multi-level barriers for PR in high-altitude areas. Optimization needs were highly concentrated on guideline development, resource supplementation, technology empowerment, and policy support.
Pulmonary rehabilitation for PH in high-altitude areas exhibits low adoption rates and poor standardization based on medical staff reports, facing a complex barrier system. There is a need to establish an integrated solution centered on high-altitude guidelines, supported by digital technology, and grounded in policy guarantees to facilitate a shift from the current fragmented, experience-based practice toward standardized and systematic services.Chronic respiratory diseaseCardiovascular diseasesAccessCare/ManagementAdvocacy