Endometrial cancer (EC) is driven by complex genetic and epigenetic alterations, but the specific chromatin-dependent mechanisms that sustain malignant proliferation remain incompletely understood. In this study, we found that lysine demethylase 4A (KDM4A) was upregulated in EC and promoted cell proliferation, migration, and invasion, accompanied by increased estrogen-related receptor gamma (ERRγ) expression. Mechanistically, KDM4A promoted ERRγ expression in association with reduced enrichment of the repressive H3K9me3 modification at the ESRRG promoter, suggesting that KDM4A may facilitate ESRRG transcription by attenuating H3K9me3-associated repression. Functionally, ERRγ acted as a downstream mediator associated with increased CDK1 transcription and elevated CDK1 and Cyclin B1 protein expression. These findings suggest that the KDM4A-ERRγ axis contributes to G2/M-phase regulation and EC cell proliferation. Importantly, treatment with the KDM4-family inhibitor QC6352 significantly suppressed EC cell growth in vitro and reduced xenograft tumor growth in vivo. These findings support a model in which KDM4A-associated reduction of H3K9me3 enrichment at the ESRRG promoter contributes to ERRγ upregulation and altered cell-cycle regulation in EC cells. Furthermore, these findings provide preliminary preclinical support for further investigation of KDM4-family inhibition as a potential therapeutic approach in EC.

Excessive daytime sleepiness (EDS) is a common but variable symptom in obstructive sleep apnea (OSA), with unclear associations with disease severity and clinical features. This study aimed to compare demographic and clinical characteristics of OSA patients with and without EDS in an Iranian population.

In this cross-sectional study, 117 patients aged 18-65 years with polysomnography-confirmed OSA were recruited at Rasoul Akram Hospital, Tehran, Iran, from April 2022 to March 2023. EDS was assessed using the Epworth Sleepiness Scale (ESS ≥ 10). Data on demographics, anthropometric measures, clinical variables (e.g., AHI), and medical history were collected. Statistical analyses included Spearman correlations, t-tests, Mann-Whitney U tests, and chi-square tests.

Of 117 patients (63.2% male, mean age 38.18 ± 2.43 years), 42.7% had EDS. No significant correlation was found between AHI and ESS (ρ = 0.121, p = 0.194), nor differences in OSA severity (mild, moderate, severe) between sleepy and non-sleepy groups (p = 0.998). AHI correlated with age, weight, BMI, neck, and waist circumference (p < 0.05); ESS correlated with height, weight, and neck circumference (p < 0.05). Head/neck disease or injury was associated with the absence of EDS (p = 0.014), with a trend linking opioid use to EDS (p = 0.082).

EDS in OSA patients is not strongly tied to AHI but is associated with specific anthropometric features. The novel head/neck disease finding suggests neurological influences on EDS. These results advocate for phenotype-specific OSA management in Middle Eastern populations.

This is a protocol for a Cochrane review (intervention). The objectives are as follows: To evaluate the benefits and harms of oral appliances for obstructive sleep apnoea in adults.

To develop a multidimensional weighted score for progressive fibrotic interstitial lung disease (fILD) on the basis of mortality risk and compare the score with the progressive pulmonary fibrosis (PPF) guideline and Efficacy and Safety of Nintedanib in Patients with Progressive Fibrosing Interstitial Lung Disease (INBUILD) trial criteria.

This was a multicenter retrospective cohort study of fILD patients evaluated from January of 2008 to January of 2020. Disease progression was evaluated by changes in dyspnea, HRCT findings, FVC, DL_CO, and SpO₂. Associations between the disease progression criteria and survival were analyzed by means of Kaplan-Meier curves. By means of univariate Cox regression, a score was determined on the basis of the relative weights for the progression criteria. The score was derived and tested within the same cohort. We compared the score with the PPF guideline and INBUILD trial criteria.

A total of 380 patients were evaluated. Cox regression was used in order to assign points to the progression criteria: a decrease of < 90% in SpO₂ at rest (2 points); disease progression on HRCT (2 points); worsening dyspnea (1 point); a decrease ≥ 3% in SpO₂ at rest (1 point); a decrease of 5-9% in FVC (1 point); and a decrease ≥ 10% in FVC (2 points). The final score was categorized as follows: low risk, 0-2 points (n = 244), median survival = undetermined; intermediate risk, 3-4 points (n = 61), median survival = 81 months (95% CI, 65-96); and high risk, ≥ 5 points (n = 75), median survival = 57 months (95% CI, 38-75; p < 0.001). A total of 136 patients (35.8%) showed disease progression. Kappa concordance was 0.92 (p < 0.001) for the PPF guideline criteria and 0.81 (p < 0.001) for the INBUILD trial criteria.

A multidimensional weighted score allows us to estimate the risk of progressive fILD. When dichotomized, the concordance with the PPF guideline and INBUILD trial criteria is high. External validation is required before routine clinical application.

To describe clinical obstructive sleep apnea (OSA) phenotypes based on emerging groups.

A cross-sectional study was conducted among adult patients referred for home sleep respiratory assessment. Cluster analysis was conducted based on sex, age, Epworth Sleepiness Scale (ESS) score, BMI, neck > 40 cm (women) or > 42 cm (men), hypertension, and time spent with SpO₂ below 90% (T<90%).

The K-means algorithm identified three groups: 1) Severe obesity, borderline sleepiness (n = 1,026) with a mean BMI of 34.7 kg/m², ESS score of 9.3, apnea-hypopnea index (AHI) of 31.3 events/h, and T<90% of 4.9 (%); 2) Moderate disease burden, asymptomatic without hypoxemia (n = 497) with a mean BMI = 28.5 kg/m², ESS score = 6.6, AHI = 25.7 events/h, and T<90% of 1.8%; and 3) Sleepy patients with severe OSA (n = 993) with a mean BMI = 29.5 kg/m², ESS score = 13.6, AHI = 33.9 events/h, and T<90% of 3.6%.

In this large sample of Latin American patients with OSA diagnosed using home respiratory polygraphy, cluster analysis identified three clinically relevant phenotypes. Notably, severe OSA was observed both in patients with severe obesity and borderline daytime symptoms and in overweight patients with excessive daytime sleepiness. These findings highlight the heterogeneity of OSA and emphasize the need for individualized phenotype-based clinical approaches.

Stroke-associated pneumonia (SAP) is a frequent complication after acute ischemic stroke (AIS) and is associated with poor outcomes. This study aimed to develop an interpretable multimodal deep learning model integrating MRI, lesion-related brain regions, and clinical variables for early SAP prediction.

A total of 426 AIS patients were retrospectively enrolled, including 71 patients with SAP. Multimodal MRI data (DWI, T1WI, and T2-FLAIR) were processed using standardized registration and lesion segmentation. A 3D convolutional neural network was used to extract imaging representations, which were fused with clinical variables and AAL3-based brain-region features. Model performance was assessed using stratified five-fold cross-validation and nested cross-validation when applicable, with further evaluation based on receiver operating characteristic (ROC) analysis, calibration analysis, and decision curve analysis. Grad-CAM was applied for model interpretation.

The multimodal fusion model achieved the best performance for SAP prediction, with an AUC of 0.782 (95% CI: 0.712-0.839), compared with the clinical model based on conventional clinical variables (AUC = 0.756), the imaging model based on 3D CNN representations (AUC = 0.693), and the brain-region model based on AAL3-derived lesion location features (AUC = 0.501). The fusion model showed superior clinical utility and favorable calibration. Grad-CAM visualization demonstrated that model predictions were mainly driven by lesion-related cortical and subcortical regions.

A multimodal deep learning framework integrating MRI, brain-region information, and clinical characteristics improved SAP prediction after AIS and provided an interpretable approach for individualized risk stratification.

Raynaud's syndrome (RS) is traditionally considered a benign vasospastic disorder; however, emerging evidence suggests that it may reflect systemic vascular dysfunction and a prothrombotic state. Emerging epidemiological evidence suggests an association between RP and VTE, but further validation across different populations and analytical approaches is needed.

We conducted a retrospective cohort study with the TriNetX global electronic health record database. Adult patients diagnosed with RS between 2015 and 2024 were identified and matched 1:1 with individuals without RS by using propensity score matching, adjusting for demographics, comorbidities, medical utilization, and laboratory parameters. Patients with autoimmune diseases, malignancy, thrombophilia, vascular disease, pregnancy, or anticoagulant and hormonal contraceptive use were excluded to minimize confounding. The primary outcome was incident VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE), assessed with Cox proportional hazards models.

After matching, 93,263 patients were included in each group. During follow-up, VTE occurred in 1,407 patients in the RS group and 1,179 patients in the non-RS group. RS was associated with a significantly increased risk of VTE (hazard ratio [HR] 1.33; 95% confidence interval [CI] 1.24-1.44). Increased risks were observed for both DVT (HR: 1.30; 95% CI: 1.18-1.43) and PE (HR: 1.38; 95% CI: 1.24-1.54). Subgroup analyses showed a more pronounced association in younger individuals and consistent effects across sexes.

RS is associated with an increased risk of venous thromboembolism independent of major confounding conditions.

Insufficient diversity is common among patients and authors in studies supporting guidelines. We hypothesized that the latest severe community-acquired pneumonia (CAP) guidelines suffered from such bias.

We reviewed all original studies supporting the latest severe CAP guidelines. We assessed whether there were language restrictions in the search for studies to be included in each recommendation and recorded the following: the proportion of female patients included in the studies; ethnicity (when available); year of publication; and study location, which was classified by income in accordance with the World Bank classification. We also compiled data on the sex and affiliation of the first and last authors.

The guidelines included 115 references in eight sections; 74 unique references supported the recommendations. There was language restriction in the selection of studies in 3 of 8 questions. The proportion of female patients ranged from 4.7% to 70.5% (mean, 36%). Most of the patients were White (72.2-91.2%), and 80.5% of the studies were conducted in high-income countries. Only 6 (5.2%) of the 115 references included patients from low- or middle-income countries. Most of the first and last authors were male (75.6-88.3%) and were based in high-income countries (96.1%).

The studies supporting the severe CAP guidelines were found to have insufficient diversity and representativeness of patients, sex, and country of origin of the authors. To enhance the generalizability of severe CAP guidelines, strategies must be devised to increase the diversity of patients and authors.

To describe the burden and characteristics of respiratory syncytial virus (RSV) infections among children under five years of age in Brazil during the post-COVID-19 period by using national surveillance data.

This was a retrospective study of reported SARS cases in the Brazilian National Epidemiological Surveillance Information System for the 2022-2023 period. RSV cases were confirmed by antigen or polymerase chain reaction testing and compared with SARS cases of other defined or undefined etiologies. Data were analyzed by age, sex, region of the country, yearly quarter, hospitalization status, and ICU admission. The proportions of RSV-positive cases among total SARS cases and among those with a confirmed etiology were calculated, along with notification rates by age group per 100,000 population.

Of a total of 244,345 SARS cases in children under five years of age, 16.9% were RSV-positive, whereas 60.5% had an undefined etiology. Among SARS cases with a confirmed etiology, RSV accounted for 42.8%, with the highest proportions being observed in infants under six months of age. ICU admission was more common in younger infants (47% in those < 1 month of age). Mortality was low (≈1%), being highest among infants under six months of age. Seasonal peaks occurred mainly between April and May, varying across regions.

RSV remains a major cause of severe respiratory infection and hospitalization among young children in Brazil, particularly infants under six months of age. Strengthening RSV surveillance and expanding preventive strategies-including maternal vaccination and monoclonal antibody use-are key to reducing its impact.

To describe clinical and epidemiological profile of patients with cystic fibrosis (CF) diagnosed outside neonatal screening programs at two referral centers in Rio de Janeiro, Brazil, and to assess the impact of diagnostic delay on disease severity at the time of diagnosis.

This cross-sectional study included 54 patients with a confirmed diagnosis of CF evaluated at two CF referral centers in Rio de Janeiro between 2019 and 2023. Data collected included age at diagnosis, neonatal screening history, clinical manifestations at diagnosis, previous misdiagnoses, microbiological findings, pulmonary function, and nutritional status. Patients were stratified by age at diagnosis (< 5, 5-12, 13-17, and ≥ 18 years) and by pediatric versus adult diagnosis. Chi-square tests were used for categorical comparisons.

Among the 54 patients, 59.3% were male, and 98.1% were not identified by neonatal screening. Median age at diagnosis was 11 years (IQR: 4.5-23.5). Diagnosis during adulthood occurred in 31.5% of patients. Bronchiectasis was present in 88.2% of adults compared with 47.1% of pediatric cases (p = 0.0045). CF-related diabetes was exclusively observed in adults (41.2%; p < 0.001). Prior misdiagnosis occurred in 45 patients (83.3%), most commonly asthma (24.1%), tuberculosis (11.1%), or idiopathic bronchiectasis (7.4%). At diagnosis, the median FEV₁ was 62% of the predicted value among patients with available spirometry. Bacterial airway infection was detected in 81.5% of cases.

Late CF diagnosis in Rio de Janeiro occurred predominantly outside neonatal screening programs, with a median age at diagnosis of 11 years, reflecting substantial missed opportunities for early intervention. Diagnosis during adulthood is associated with higher rates of bronchiectasis and CF-related diabetes, highlighting the irreversible structural and metabolic burden associated with diagnostic delay.