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Identification of MAPK12 as a Prognostic Biomarker for Esophageal Carcinoma Using Bioinformatics and Machine Learning.1 day agoTo develop a telomere-related prognostic signature for esophageal carcinoma (ESCA), we integrated bioinformatics and machine learning approaches. Hub genes were identified from overlapping differentially expressed genes (DEGs). A prognostic model was constructed using LASSO and multivariate Cox regression, validated in independent GEO datasets, and further verified through cytological experiments. We also elucidated the mechanism by which MAPK12 promotes ESCA migration. The model robustly predicted survival of patients with ESCA, supported by both high-throughput data and experimental evidence. Our findings highlight MAPK12 as a promising biomarker and provide a theoretical basis for understanding ESCA pathogenesis and developing targeted therapies.CancerPolicy
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CCL18: a potential immunosuppressive biomarker for prognosis in ABC diffuse large B-cell lymphoma.1 day agoActivated B-cell (ABC) diffuse large B-cell lymphoma (DLBCL) has worse outcomes than the germinal center B-cell (GCB) subtype, but underlying molecular mechanisms remain poorly understood.
Transcriptomic analysis on 43 DLBCL samples (23 GCB and 20 ABC) was performed using NanoString PanCancer Immune Profiling Panel with 30 cell-of-origin genes. Tumor microenvironment characterization was performed using CIBERSORTx and gene set enrichment analysis (GSEA) deconvolution. Based on our previous findings of MAPK10 downregulation in ABC lymphomas, MAPK10 promoter methylation was studied via pyrosequencing. Prognostic biomarkers were identified using the Cox regression and least absolute shrinkage and selection operator (LASSO) regularization. Therapeutic candidates were identified through connectivity mapping.
ABC lymphomas showed distinct profiles with the overexpression of VTCN1, CDK4, and CXCR5 and the downregulation of MMP9 and MAPK10. GSEA revealed enrichment of inflammatory pathways with immunosuppressive signals in ABC cases. Confirming our prior observations, MAPK10 downregulation in ABC tumors was associated with promoter hypermethylation and inferior overall survival (p < 0.01). Immune deconvolution revealed greater microenvironmental diversity in ABC cases with significant eosinophil enrichment. High CD8+ T-cell abundance was associated with improved survival, particularly in ABC patients (p < 0.01). Multivariate analysis identified CCL18 as an independent adverse prognostic factor (HR: 1.87, 95% CI: 1.25-2.79, p < 0.01). Connectivity mapping identified proteasome inhibitors and CDK4/6 inhibitors as promising therapeutic candidates.
We validated MAPK10 promoter hypermethylation and CCL18 overexpression as prognostic biomarkers in ABC DLBCL. These findings, derived from integrative transcriptomic and immunogenomic profiling, provide clinically relevant insights into disease biology and support biomarker-guided strategies for precision treatment in aggressive B-cell lymphomas.CancerPolicy -
Haem Oxygenase-1, Ferroptosis and Disorders-A Narrative Review.1 day agoFerroptosis is a non-apoptotic form of cell death that is driven by iron and reactive oxygen species (ROS). This process is characterised by lipid peroxidation, which damages cell membranes and distinguishes it from other types of cell death. Excess iron promotes ferroptosis through Fenton chemistry, leading to increased ROS production. While glutathione peroxidase 4 has been identified as a key regulator of this process, other factors, such as the ferroptosis suppressor protein 1 (FSP1), suggest that regulation is more complex. Ferroptosis has been associated with several degenerative diseases, including Alzheimer's disease, Parkinson's disease, acute kidney injury, liver disorders, and cancer. The enzyme haemoxygenase-1 (HO-1) plays dual roles: it can promote ferroptosis by releasing iron or provide protection through its antioxidant effects in various organs and tissues. HO-1 increases iron levels through the catabolism of haem which can heighten sensitivity to ferroptosis by influencing iron trafficking and ferritin expression. Conversely, HO-1 has demonstrated nephroprotective effects in cases of renal injury and other disorders. HO-1's involvement in regulating iron metabolism and its antioxidant capabilities can lead to differing outcomes, highlighting key players in the ferroptosis process. The Nrf2/HO-1 axis is crucial for its antioxidant properties in various disorders. Moreover, dietary sources can enhance HO-1 induction through Nrf2 regulation. Hence, HO-1 acts as both a modulator and a mediator, presenting new therapeutic targets for cancer, neurodegeneration, and kidney and liver diseases.CancerPolicy
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Targeting Ovarian Neoplasms: Subtypes and Therapeutic Options.1 day agoThe ovary, as the primary organ responsible for reproduction and new life, plays a central role in female development, maturation, and health. Neoplasms arising from the ovary and its associated tissues exhibit substantial heterogeneity in their histopathological and molecular profiles, many of which remain poorly understood. This review aims to summarize recent advances in the understanding of genetic alterations underlying ovarian neoplasms and to explore therapeutic strategies informed by molecular biomarkers and tumor microenvironmental factors. A comprehensive literature search was performed, focusing on genomic alterations, biomarker-guided therapies, and tumor microenvironmental modulation in ovarian cancers. Emphasis was placed on studies addressing lipid mediator pathways and their roles in immune regulation and therapeutic response. Based on diagnostic classifications, recurrent alterations in TP53, MYC, PIK3CA, and KRAS are consistently observed across epithelial and germ cell ovarian tumors, whereas non-epithelial subtypes such as sex cord-stromal tumors (SCSTs) and small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT), are predominantly associated with ARID1A and SMARCA4 mutations, respectively. These findings highlight distinct pathogenic mechanisms linked to specific genetic alterations and reveal potential therapeutic vulnerabilities. Moreover, lipid metabolism has been closely implicated in immune surveillance through STING signaling cascades within innate immune cells, suggesting that lipid mediators and their associated genes may represent promising therapeutic targets in ovarian cancers (OCs). Targeting lipid mediators could be particularly effective in relapsed OCs, as modulating innate immune cells within the tumor microenvironment (TME) may enhance immune surveillance and improve antitumor responses. Integrating genetic and microenvironmental insights offers a promising direction for developing more effective and personalized therapeutic strategies in OC.CancerPolicy
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Impact of Real-Time, On-Demand Influenza and Respiratory Syncytial Virus Testing at Point-of-Care on Antibiotic Prescribing and Clinical Outcome in Pediatric Outpatients With Acute Respiratory Illness: A Prospective, Quasi-Randomized, Controlled Study.1 day agoRapid and accurate detection and identification of viral pathogens have an impact on physician decision-making for patients with acute respiratory illness (ARI). We aimed to evaluate the Xpert Xpress Flu/RSV test for the management of antibiotic prescribing in pediatric outpatients with ARI.
We performed a prospective, quasi-randomized, controlled study in Beijing Children's Hospital between December 1, 2021 and April 28, 2022. Outpatients with ARI aged 28 days to 18 years were enrolled and randomly assigned to the Xpert Xpress Flu/RSV test (Xpert) group or the influenza (Flu) antigen test (control) group. Both tests were performed on site.
A total of 771 patients were enrolled and assigned randomly to the Xpert (n = 398) and the control (n = 373) groups. There was no statistically significant difference in antibiotic prescriptions between the two groups, whereas a significant difference was observed for the prescriptions of oseltamivir (p < 0.001). In Flu B-positive patients, a statistically significant decrease in antibiotic use and increase in antiviral use were observed in both Xpert and control groups. Cephalosporin use was significantly decreased in respiratory syncytial virus (RSV)-positive patients in the Xpert group before (n = 8, 17.4%) and after (n = 1, 2.2%)visit (p = 0.035). Among clinical and laboratory parameters, shorter fever length (OR = 0.366) and positive Flu B or RSV (OR = 3.99) were two independent factors for antibiotic withdrawal by logistic regression analysis. There was no significant difference in duration of fever, clinical outcomes, and expenditure between the two groups at the 7-day and 30-day follow-up.
Use of Xpert Xpress Flu/RSV at point-of-care in pediatric outpatients with ARI reduced antibiotic prescription, which has the potential to improve antibiotic stewardship.Chronic respiratory diseaseAccessCare/ManagementAdvocacy -
Impact of the COVID-19 pandemic on routine childhood immunisation coverage and timeliness in Switzerland: a retrospective analysis using data from the Swiss National Vaccination Coverage Survey, 2019-2023.1 day agoThe coronavirus disease 2019 (COVID-19) pandemic has disrupted healthcare systems worldwide, leading to concerns about reduced access to routine childhood immunisations. However, comprehensive data on how the pandemic specifically impacted paediatric vaccination coverage in Switzerland remain limited across the country. The present study provides an analysis of the timeliness and coverage of routine childhood immunisations in Switzerland before and during the COVID-19 pandemic, offering insights into potential fluctuations in coverage.
To assess the impact of the COVID-19 pandemic on routine childhood immunisation in Switzerland by comparing vaccination coverage and timeliness for children under 35 months of age before and during the pandemic. Additionally, the study seeks to identify factors associated with the likelihood of children receiving vaccinations, considering demographic and geographic variables.
We used 2019-2023 data from the Swiss National Vaccination Coverage Survey (SNVCS), a cross-sectional survey that collected immunisation information of children under 35 months of age from a nationally representative sample of households. Children who were eligible for a vaccine from March 2020 to March 2021 were considered as the COVID-affected group and those eligible for a vaccine before this date were included in the pre-COVID-19 cohort. Coverage of the following vaccine doses was considered: diphtheria at one, two and three doses (Di1, Di2, Di3); pneumococcus at one, two and three doses (PCV1, PCV2, PCV3); and measles first and second dose (MCV1, MCV2). Vaccine timeliness was defined as receiving a dose on time with a tolerance period of 30 days. We used logistic regression models to identify and understand the factors that might influence vaccination rates.
For the diphtheria vaccines (Di1, Di2, Di3), while coverage remained high, there was a slight decrease observed in timely vaccination rates for some doses, with reductions of around 1% to 3% compared to pre-COVID-19 levels. The impact on PCV1, PCV2 and PCV3 showed similar trends, with slight reductions in coverage during the pandemic, but these differences were not statistically significant. For measles-containing vaccines (MCV1 and MCV2), coverage during the pandemic was higher compared to pre-COVID-19 rates. Geographic and demographic factors, such as an urban setting, nationality and linguistic region, significantly influence childhood vaccination rates in Switzerland.
While minor declines in vaccine timeliness were observed (diphtheria vaccine, pneumococcal conjugate vaccine), the overall likelihood of vaccination was not significantly affected by the COVID-19 pandemic. However, changes in vaccination recommendations introduced in 2019 may have influenced these trends.Chronic respiratory diseaseAccessCare/ManagementAdvocacy -
Knowledge, attitudes, and practices of asthma patients in Inner Mongolia regarding differentiation between allergic rhinitis accompanied asthma and cough.1 day agoThis study aimed to evaluate the knowledge, attitudes, and practices (KAP) of asthma patients in Inner Mongolia, focusing on their ability to differentiate between allergic rhinitis accompanied by asthma and common coughs.
A cross-sectional survey was conducted from Jan 2024 to April 2024 at the Affiliated Hospital of Inner Mongolia Medical University, involving asthma patients aged 18 years and above. Demographic information and KAP scores were gathered through the distribution of questionnaires.
The study successfully collected 547 valid questionnaires. Among the respondents, 310 (56.67%) were female, and 337 (61.61%) either had a personal smoking history or lived with someone who smoked. Median (Q25, Q75) knowledge, attitude, and practice scores were 17 (15, 18) (possible range: 2-18), 43 (41, 44) (possible range: 11-55), and 33 (31, 35) (possible range: 9-45), respectively. Correlation analysis indicated significant positive correlations between knowledge and practice (r = 0.2095, p < 0.001), as well as attitude and practice (r = 0.1420, p < 0.001). Pathway results showed that smoking history (β = 1.29, p < 0.001) directly affected knowledge. Family history (β = -0.90, p < 0.001) and knowledge (β = 0.15, p < 0.001) directly affected attitude. Knowledge (β = 0.43, p < 0.001) and attitude (β = 0.30, p < 0.001) directly affected practice. Indirect effects analyses also showed that smoking history (β = 0.19, p = 0.002) had an indirect effect on attitude. Smoking history (β = 0.47, p < 0.001), family history (β = -0.57, p < 0.001), and knowledge (β = 0.06, p < 0.001) had indirect effects on practice.
Asthma patients in Inner Mongolia demonstrated moderate knowledge, attitudes, and proactive practices toward distinguishing between allergic rhinitis accompanied by asthma and common coughs. Based on these findings, we recommend strengthening targeted patient education in clinical practice, particularly for individuals with lower knowledge levels, a smoking history, or limited awareness of family health history, to enhance symptom recognition and self-management capacity.Chronic respiratory diseaseAccessCare/ManagementAdvocacy -
Blood bank trends in Kuwait: five-year analysis of donations and investigations.1 day agoReliable national transfusion services require continuous surveillance of donation activity, inventory losses, transfusion-transmissible infection (TTI) screening, and immunohematology workload. Kuwait's centralized service is coordinated by the Kuwait Central Blood Bank (KCBB).
We performed a retrospective analysis of officially requested KCBB annual reports (January 2019-December 2023). Collated variables included donation volumes, donor sex and ABO/RhD distribution, discarded components, and NAT screening outcomes for HBV, HCV, and HIV. Patient-side indicators comprised total immunohematology samples, antibody screening/identification, antenatal testing, and alloantibody profiles. The analysis was descriptive, presenting distributions and temporal trends without inferential testing.
Donations averaged ~82,000 annually, with a decline during the COVID-19 pandemic (2020-2021) and recovery to ~85,000 in 2023. Male donors accounted for >85% of donations. O RhD+ positive (38.7%) and B RhD+ positive (23.7%) were the most common blood groups, while RhD-negative donors comprised 8.6%. Wastage varied yearly, predominantly impacting fresh frozen plasma. NAT-reactive TTI prevalence remained low: HBV 0.06-0.11% (60-110 per 100,000), HCV 0.03-0.08% (30-80 per 100,000), and HIV 0.02-0.05% (20-50 per 100,000) annually. Immunohematology workload (total samples and test activity) fell during 2020-2021 and increased again by 2023. A wide spectrum of clinically significant alloantibodies was identified, most frequently within the Rh, Kell, and Kidd systems, with additional MNS and P1PK specificities. Among antenatal samples, antibody positivity averaged 3.8% (peak 4.7% in 2021); anti-D predominated, followed by anti-K.
KCBB data highlight persistent male predominance among donors, RhD-negative scarcity (8.6%), and variable component wastage, especially FFP. These findings support targeted donor-recruitment strategies, obstetric-transfusion planning for RhD-negative supply, and strengthened inventory management to improve resilience and safety of Kuwait's blood supply.Chronic respiratory diseaseAccessAdvocacy -
Gastroesophageal Reflux, Sleep-Disordered Breathing, and Outcomes in Patients With Idiopathic Pulmonary Fibrosis.1 day agoGastroesophageal reflux disease (GERD) and obstructive sleep apnea (OSA) may negatively impact idiopathic pulmonary fibrosis (IPF), but data on their concurrent contributions are lacking. We aimed to test the contributions of GERD and sleep-disordered breathing (SDB) to IPF outcomes.
We performed a cross-sectional, exploratory study on subjects with IPF. Clinically established GERD diagnosis, questionnaires (Nocturnal GERD Symptom Severity and Impact Questionnaire [N-GSSIQ], the NIH Patient-Reported Outcomes Measurement Information System [PROMIS] sleep impairment and fatigue scales, and Short Form-36 [SF-36]), full pulmonary function tests (PFT), six-minute walk test (6MWT), and nocturnal polysomnography (PSG) were obtained.
Among n = 24 subjects, 17 (71%) had clinically diagnosed GERD. N-GSSIQ scores indicated a nocturnal burden, which was adversely related to sleep impairment (p = 0.010) and daytime fatigue (p = 0.001), tiredness (p = 0.026) and SF-36 social functioning (p = 0.005), energy/fatigue (p = 0.015), pain (p = 0.030), and health change in the prior year (p = 0.035). From PSG, GERD correlated with worse sleep architecture (GERD diagnosis, all p < 0.05) and periodic leg movements index (PLMI) (N-GSSIQ, p = 0.02). GERD was not associated with pulmonary or exercise physiology. Overall, apnea-hypopnea index (AHI) was (median [25% quartile, 75% quartile]) 18.2 (8.1, 27.8)/h, and 19 (79%) subjects had OSA (AHI ≥ 5/h), with most (15/19 [79%]) having moderate or severe disease. SDB measures adversely related to gas exchange and distance walked (all p < 0.05).
A nocturnal burden of GERD was detected and related to sleep disruption, including PLMs, and to daytime complaints. SDB/OSA, of a severity known to have significant health consequences, was common; it was adversely related to pulmonary diffusion and exercise capacity. These findings call for comprehensive, early evaluation of GERD and OSA for improved IPF outcomes.Chronic respiratory diseaseAccessPolicyAdvocacy -
Effects of Individualized Step Targets on Physical Activity in COPD. A Randomized Study.1 day agoImproving physical activity (PA) is important in patients with chronic obstructive pulmonary disease (COPD). Goal setting can be a possible intervention to improve PA, but the increase in PA is not sustainable in the long term. We evaluated the effects of providing an individualized target step count, reflecting the disease condition of each patient, on PA and other factors, such as myokines, after six months in patients with COPD.
We performed a randomized parallel group, open-label study (INTAR-Step study) between the target provision (intervention) group and the usual care (control) group and investigated differences in the proportion of subjects who achieved the target as a primary outcome and differences in changes in PA parameters and myokines as secondary outcomes. This study was registered with UMIN-CTR (UMIN000046390, January 13, 2022).
A total of 73 subjects were analyzed (intervention, n=38; control, n=35). The proportion of participants in the intervention group who achieved their target step count did not show a significant increase relative to the control group (p=0.157). However, the change in step count, and change in duration of activity at ≥3.0 metabolic equivalents were significantly increased in the intervention group. The Changes in the Growth differentiation factor-15 (GDF-15), fatty acid-binding protein-3, and Irisin levels also increased in the intervention group. Furthermore, GDF-15 levels were significantly higher in subjects with increased step counts than in those with decreased step counts.
Providing individualized step targets did not increase the proportion of subjects who achieved their targets, but it increased their step counts after six months. GDF-15 may be involved in the increase in the step count.Chronic respiratory diseaseAccessCare/Management