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GPX8 is transcriptionally regulated by KLF16 and promotes osteosarcoma progression.3 weeks agoStudies have shown that glutathione peroxidase 8 (GPX8) promotes the progression of various cancers. However, the role of GPX8 in osteosarcoma (OS) progression remains unclear. The aim of this study was to investigate the function of GPX8 in OS progression and its underlying mechanisms.
GPX8 expression in OS tissues and cell lines was assessed using immunohistochemistry (IHC), qRT‒PCR and Western blotting. The effects of GPX8 on the proliferative capacity of OS cells were evaluated using CCK-8, EdU, and plate colony formation assays. The role of GPX8 in the migratory and invasive functions of OS cells was examined via scratch wound healing, Transwell, and invasion assays. The effect of GPX8 on the in vivo proliferative ability of OS cells was investigated through a subcutaneous tumour formation experiment in nude mice. Bioinformatics methods were employed to predict the transcription factors that regulate GPX8 expression. Chromatin immunoprecipitation and dual-luciferase reporter assays were performed to investigate the interaction between GPX8 and Kruppel‑like factor 16 (KLF16).
GPX8 is highly expressed in OS tissues and OS cell lines. Knocking down GPX8 expression significantly inhibited OS cell proliferation, migration, and invasion; downregulated CyclinD1 protein expression; and suppressed the EMT process. Conversely, GPX8 overexpression yielded the opposite results. Knocking down GPX8 expression significantly inhibited the tumorigenic ability of OS cells in vivo. KLF16 is highly expressed in OS tissues and cell lines. KLF16 promotes GPX8 expression. Knocking down GPX8 expression inhibited the promoting effects of KLF16 overexpression on OS cell proliferation, invasion, and migration, whereas overexpressing GPX8 reversed the inhibitory effects of KLF16 knockdown on OS cell proliferation, invasion, and migration. The results of the dual-luciferase and ChIP assays demonstrated that KLF16 directly binds to the GPX8 promoter and positively regulates GPX8 expression.
This study demonstrated that GPX8 is a critical oncogene in OS progression and that its expression is regulated by KLF16. Targeting the KLF16/GPX8 axis may offer promising prospects for the development of novel therapeutic strategies against OS.CancerPolicy -
Tinkering with good care: Professional judgment and innovations in Danish nursing homes.3 weeks agoThis article examines the COVID-19 pandemic as a large-scale natural experiment, presenting unique opportunities for reflection and insights into what constitutes 'good care' for front-line managers in Danish nursing homes. Using care and institutional theory, this exploratory study delves into how professional judgment and innovation redefine practices in nursing homes to provide quality care based upon qualitative questions in a national quantitative survey. Our analysis complements prevalent negative lessons on infections, high mortality, and moral distress by highlighting positive lessons about achieving intimacy and tranquillity during an extraordinary period. The article offers insights into the emergence of new care logics in a situation of rupture, as well as insights into the values and tensions inherent in good care work that are worth considering far beyond the pandemic. We offer lessons that relate to the role of professional judgment, the value of 'active life' in relation to a diversity of needs, as well as sufficient time and continuity of care logics.Chronic respiratory diseaseAccess
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Small acts of resistance - community-dwelling oldest old reclaiming autonomy during a pandemic.3 weeks agoThe COVID-19 pandemic impacted societies and social lives worldwide, leading to wide research interest in its consequences across age groups. This paper investigates the ways in which older adults strived to maintain autonomy during the confinement measures and age-based restrictions. The study draws on empirical data collected as part of the Cardiovascular Risk factors, Aging and Dementia (CAIDE85+) study. Data include qualitative interviews with 15 older persons (aged 80 years and older) living in eastern Finland conducted via telephone between August and December 2020. The transcribed data were analyzed using thematic analysis. The findings show that interviewees performed small acts of resistance, manifesting rebelliousness, defiance, and opposition towards restrictive measures imposed by authorities, close family, and friends. Some of the acts were found to be hidden forms of resistance, while others openly challenged official restrictions and recommendations. Also, the refusal to conform to the role of a vulnerable old person indicated indirect resistance towards negative stereotypes. The study contributes to recognizing the different ways in which older adults maintain their sense of autonomy, act as active agents capable of making decisions regarding their own health and well-being, and challenge ageist practices in their everyday lives. The findings highlight the need to challenge age-based categorizations and the perception of all older adults as vulnerable and in need of protection. Greater efforts are needed to include older adults as active participants in decision-making regarding their everyday lives.Chronic respiratory diseaseAccessCare/ManagementAdvocacy
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Adverse events associated with single-use bronchoscopes: analysis from the MAUDE database.3 weeks agoBronchoscopy is an aerosol-generating procedure and associated with a high risk of viral transmission, particularly during the coronavirus disease (COVID-19) pandemic. This circumstance has expedited the adoption of single-use flexible bronchoscopes (SUFBs) due to their potential to mitigate healthcare personnel exposure to SARS-CoV-2 and reduce patient infection risks.
This study aims at analyzing reported adverse events and complications associated with SUFBs, while delineating recommendations for risk mitigation strategies and ensuring patient safety through an examination of data from the Manufacturer and User Facility Device Experience (MAUDE) database.
We conducted an evaluation of adverse events related to SUFBs as documented in the FDA MAUDE database from January 1, 2014, to June 30, 2025. All reports were manually reviewed and categorized based on the primary device problem and any associated patient outcomes.
A total of 280 reports were issued regarding SUFBs. Manual review categorized these into 280 primary device-related problems and 286 patient-related outcomes. The primary category of device-related problems predominately pertained to breakage/fracture (85 cases; 30.4 %), and a loss of image/display (57 cases; 20.4 %). Among patient adverse events, the most frequently encountered were foreign bodies and airway obstruction.
Our study augments the existing clinical literature and body of knowledge by providing a comprehensive understanding of potential problems related to SUFBs. It underscores the imperative for continuous surveillance and vigilance to ensure the safety and effectiveness of SUFBs.Chronic respiratory diseaseAccessCare/Management -
GLP-1 receptor agonist utilization is associated with a low risk of Anesthesia-related complications prior to total joint arthroplasty.3 weeks agoGlucagon-like peptide-1 receptor agonists (GLP-1 RA) have recently garnered increased attention due to their effectiveness in inducing marked weight loss among overweight and obese adults. Recent evidence, however, has raised concerns about a potential link between GLP-1 receptor agonist therapy and perioperative pulmonary aspiration. In this single-institution retrospective series, we aimed to quantify the incidence of intraoperative and early postoperative complications among patients taking GLP-1 RA before elective total joint arthroplasty (TJA).
All patients who underwent primary TJA at our institution between April 2014 and October 2023 were initially screened. Patients were considered eligible for inclusion if they demonstrated consistent preoperative GLP-1 RA utilization. GLP-1 RA medication type, dosage, administration method, and treatment duration were tabulated for each patient. The primary outcomes of interest wereintraoperative anesthesia-related complications, particularly pulmonary aspiration, postoperative medical and surgical complications, and 90-day reoperation.
In total, 83 patients demonstrated consistent GLP-1 RA usage before primary TJA. Of these patients, 63 (75.9%) received semaglutide, 19 (22.9%) liraglutide, and 1 (1.2%) tirzepatide. No cases of acute intraoperative pulmonary aspiration were identified. Intraoperative assessment of gastric contents was not routinely performed; however, one patient was noted to have a full stomach requiring nasogastric decompression. This individual was in the dose-escalation phase of treatment, having self-administered 1 mg of semaglutide five days before surgery. Four patients (4.8%) experienced 90-day medical complications, none of which were attributed to GLP-1 RA use, and one patient (1.2%) required reoperation.
Despite recent studies suggesting an elevated risk of acute intraoperative pulmonary aspiration, our findings underscore the rare nature of intraoperative anesthesia-related adverse events in TJA patients taking GLP-1 RA.Chronic respiratory diseaseAccessAdvocacy -
Integrative Analysis of Endothelial Cell Senescence-Related Genes in Idiopathic Pulmonary Fibrosis.3 weeks agoIdiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease in which endothelial cell senescence (ECS) plays a key role. By integrating two GEO transcriptome datasets (145 IPF patients and 84 controls) and applying LASSO, SVM-RFE, and Boruta algorithms, four key ECS-related genes (ECSRGs), MYCT1, PLEKHA1, PCDH12, and PLXND1, were identified. MYCT1 and PLEKHA1 were downregulated by about 26% and 75%, while PCDH12 and PLXND1 were upregulated by 2.4- and 1.9-fold (p < 0.0001). The four-gene nomogram achieved 93.6% diagnostic accuracy. In TGF-β1-induced HUVECs, silencing MYCT1 or PLEKHA1 increased senescent cells by ~1.4-fold, whereas silencing PCDH12 or PLXND1 reduced α-SMA and COL1A1 levels by ~40%. In bleomycin-induced mice, valproic acid (VPA) lowered collagen deposition by ~60% and normalized gene expression. MYCT1 and PLEKHA1 act as anti-senescence factors, while PCDH12 and PLXND1 act as pro-fibrotic drivers. The four-gene model shows strong diagnostic potential, and VPA may serve as a therapeutic candidate targeting ECS in IPF.Chronic respiratory diseaseAccessCare/Management
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Selective Vulnerability of Executive Control in Obstructive Sleep Apnea: A Mechanistic Pathway to Memory Impairment.3 weeks agoObstructive sleep apnea (OSA) is associated with widespread higher-order cognitive consequences, including deficits in memory and executive function. However, the specific cognitive architecture and underlying mechanisms that link the disease's pathophysiology to these broad cognitive changes remain poorly understood. This study tested the hypothesis that a selective vulnerability of the working memory (WM) executive control system serves as a central hub, mechanistically mediating the relationship between OSA disease burden and memory retention.
Thirty male patients with OSA underwent comprehensive polysomnography and neurocognitive assessment. A data-driven Global Severity Index (GSI) was derived from principal component analysis of the most cognitively-relevant physiological metrics. A multi-task paradigm was used to dissociate performance on tasks of WM maintenance capacity from those requiring executive control. Hierarchical linear regression and mediation analyses were performed, controlling for relevant covariates.
A higher GSI was consistently associated with poorer performance across multiple tasks requiring executive control, but not with measures of WM maintenance capacity or attentional control. Critically, the a priori defined mediation model was supported: the relationship between the GSI and memory retention performance was fully mediated by a latent Executive Control Factor (ECF) derived from the executive tasks.
Our findings delineate a specific mechanistic pathway for the cognitive consequences of OSA. The disease's pathophysiological burden is selectively associated with executive control performance, and this vulnerability appears to serve as a core mechanism that accounts for the disorder's downstream impact on memory function. This work identifies executive control as a critical target for mitigating the broader cognitive impact of OSA.Chronic respiratory diseaseAccessAdvocacy -
Vaccination and vitamin D in relation to disease severity and mortality in patients with COVID-19 disease: a follow-up study.3 weeks agoThe emergence of Coronavirus Disease 2016 (COVID-16), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rapidly escalated into a global pandemic, resulting in millions of confirmed cases and deaths worldwide. The objective of this study was to examine the effects of vitamin D and vaccination on mortality and disease severity in patients with COVID-16. In this cross-sectional study, we observed the suspected and confirmed admitted patients with COVID-19 for the possible outcomes after admission to the hospital. The study included patients with a mean age of 71.01 years (range: 28-66), predominantly aged ≥60 years (85.14%) and male (85.05%). Most patients were unvaccinated (77.03%) upon admission. Admission duration ranged from 1-30 days, with the highest proportion staying 8-14 days (36.16%), followed by 1-3 days and >14 days (each 21.62%). Symptoms appeared 1-46 days pre-admission (median: 8 days). Disease severity was critical (41.86%), severe (28.38%), moderate (25.68%), and mild (4.05%). All patients required oxygen. Mortality was 54.05%, 32.43% were discharged unknown, and 13.51% recovered. Key comorbidities included hypertension (66.22%), diabetes (37.84%), IHD (25.68%), smoking (21.62%), and CKD (12.16%). Universal fever presentation included persistent (44.63%) and moderate (28.66%) types. Common symptoms were shortness of breath (66.67%), cough (75.68%), chest pain (60.81%), fatigue (52.7%), and anorexia (50.0%). Vaccination (22.67%) and vitamin D status showed no significant association with disease severity or outcomes. Most patients were elderly, male, unvaccinated, and had comorbidities; high mortality was observed, with no significant association between outcomes and vaccination or vitamin D status.Chronic respiratory diseaseAccessCare/ManagementAdvocacy
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Performance analysis of artificial intelligence-based classification models for diagnosing asthma in children.3 weeks agoAsthma is a common childhood disease with symptoms such as cough, wheezing, and shortness of breath. This study evaluated the role of artificial intelligence in improving diagnostic accuracy in children.
We included patients aged 6-18 years evaluated at our clinic between January 2024 and January 2025. Those with chronic cough were classified as asthma or non-asthma based on final diagnosis. Demographic, clinical, and pulmonary function data were collected. Eight machine learning models Gradient Boosting, AdaBoost, Random Forest, Logistic Regression, Linear Discriminant Analysis, Decision Tree, k-Nearest Neighbors, and Naive Bayes were applied, and their performance was assessed using accuracy, precision, recall, F1 score, ROC AUC, and MCC.
A total of 900 children were included, with 450 diagnosed with asthma and 450 with non-asthmatic chronic cough. Males comprised 52.9% of the cohort. Feature importance analysis highlighted exercise-induced cough and recurrent bronchiolitis as the most significant predictors for asthma. Gradient Boosting demonstrated the highest diagnostic performance (F1: 0.974, ROC AUC: 0.997), followed closely by Random Forest (F1: 0.972, ROC AUC: 0.997) and AdaBoost (F1: 0.969, ROC AUC: 0.995). Logistic Regression, LDA, Decision Tree, and Naive Bayes showed moderate performance, while KNN had the lowest accuracy (F1: 0.566, ROC AUC: 0.615), indicating variable effectiveness among models.
Machine learning algorithms show promise in improving diagnostic accuracy and efficiency in pediatric asthma, though further research is needed.Chronic respiratory diseaseAccessCare/ManagementAdvocacy -
Hospitalisation and critical care for pneumonia among children aged 5-9 years in Bangladesh: a 10-year retrospective analysis.3 weeks agoMost medical research on pneumonia in children focuses on those <5 years, leaving a gap in understanding pneumonia in children aged 5-9. We aimed to identify the characteristics of children from this age group who had pneumonia and required hospital care, including critical care service.
In this retrospective chart analysis, we examined clinical, demographic, and laboratory characteristics of children aged 5-9 years with clinical and radiologic pneumonia admitted to Dhaka Hospital, International Centre for Diarrhoeal Disease Research, Bangladesh, from 2011 to 2020. We categorised the children into two groups: those who required critical care (admitted to the intensive care unit (ICU)) and those who did not. We compared the two groups to identify factors independently associated with the need for critical care using a log binomial regression model.
Among a total of 154 children who fulfilled the enrolment criteria, 34 were admitted to the ICU requiring critical care, and 120 children were treated in the inpatient ward, as they did not require any critical care. The median age of the children requiring critical care was 69 (interquartile range (IQR) = 60-81) months, compared to 72 (IQR = 62-84) months for those who didn`t require critical care (P = 0.259). Using a log binomial regression model we found hypoxemia (odds ratio (OR) = 10.1; 95% confidence interval (CI) = 1.42-71.92, P = 0.021), convulsion (OR = 281.37; 95% CI = 12.99-6091.72, P < 0.001], sepsis (OR = 27.69; 95% CI = 3.33-230.39, P = 0.002), hypokalaemia (OR = 10.37; 95% CI = 1.40-76.96, P = 0.022) were the independently associated with critical care service among children aged five to nine with pneumonia.
Our results suggest that early recognition and prompt treatment of hypoxemia, convulsions, sepsis, and hypokalaemia may significantly reduce the need for critical care and possibly avert fatal consequences in children with pneumonia, aged 5-9, especially in resource-limited settings.Chronic respiratory diseaseAccessCare/ManagementAdvocacy