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Expression of adenosine A1, A2A, A2B, and A3 receptors in ovarian cancer: their clinical potential in diagnosis and prognosis

Mol Biol Rep. 2026 Jun 3;53(1):878. doi: 10.1007/s11033-026-12052-x.

ABSTRACT

BACKGROUND: Recent studies have emphasized the role of adenosine receptors (ADORs) in the malignant biological behaviors. Therefore, the expression and clinical significance of four subtypes of ADORs (ADORA1, ADORA2A, ADORA2B, and ADORA3) in ovarian tumors were analyzed.

METHODS AND RESULTS: The expression of ADORs in 24 pairs of ovarian tumor tissues and adjacent non-tumor tissues was measured by quantitative real-time PCR. The correlations between the investigated parameters and clinicopathological features were statistically tested. The diagnostic accuracy of ADORs was assessed using receiver operating characteristic curve analysis. Kaplan-Meier method was used to estimate the influence of ADORs expression on the prognosis of patients. Ovarian tumors showed higher expression of ADORA2A (1.5-fold), ADORA2B (2.2-fold), and ADORA3 (2.3-fold), but not ADORA1, compared to normal tissues. High expression of ADORA1 and ADORA2A was associated with younger age (≤ 48.5 years; P = 0.034) and clinical stage III-IV (P = 0.050), respectively. ADORA2B also showed moderate accuracy in ovarian tumors diagnosis (P = 0.001). Survival analyses further demonstrated that high expression of ADORA1 (P = 0.012) and ADORA2B (P = 0.027) was correlated with worse overall survival. Moreover, high ADORA3 expression (P = 0.042) was associated with poor post-progression survival.

CONCLUSIONS: Our results demonstrated that adenosine A2A, A2B, and A3 receptors were differentially expressed between ovarian tumors and paired non-tumor tissues, and that ADORs may be clinically useful biomarkers for diagnosis and outcome prediction in ovarian cancer.

PMID:42234312 | DOI:10.1007/s11033-026-12052-x

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Human papillomavirus (HPV) and p16INK4a expression in early-onset prostate cancer

Int Urol Nephrol. 2026 Jun 3. doi: 10.1007/s11255-026-05218-w. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the potential role of human papillomavirus (HPV) in early onset prostate cancer (PCa) through HPV-DNA detection and genotyping, and immunohistochemical evaluation of p16INK4a expression.

METHODS: This retrospective cross-sectional study included patients diagnosed with PCa at ≤ 55 years of age between 2010 and 2021. Patients with a familial history of PCa, incomplete medical records, immunodeficiency, or insufficient tissue for molecular analysis were excluded. Formalin-fixed, paraffin-embedded (FFPE) prostate biopsy samples were analyzed for HPV-DNA using the HPV 3.5 LCD-Array Kit (Chipron GmbH, Berlin, Germany), a multiplex PCR-based assay targeting 32 HPV genotypes. Immunohistochemical staining for p16INK4a was performed to assess its expression. Clinical data, including PSA levels, Gleason score, ISUP grade, and EAU risk group, were compared between HPV-positive and HPV-negative cases.

RESULTS: HPV-DNA was detected in 12 of 45 cases (26.7%), with genotype 62 being the most frequent. Multiple HPV genotypes were identified in three cases (6.7%). p16INK4a immunopositivity was observed in 91.7% of HPV-positive tumors compared with 69.7% of HPV-negative tumors (p = 0.240). HPV-positive patients showed higher ISUP grades than HPV-negative patients (p = 0.029) and were more likely to be in intermediate or high-risk groups (p = 0.028). No significant differences were observed in PSA levels or Gleason scores.

CONCLUSION: The detection of HPV-DNA in a considerable proportion of early onset PCa specimens, together with the more frequent but not statistically significant p16INK4a positivity in HPV-positive tumors, suggests a possible association with prostate tumor biology. However, the presence of low-risk HPV genotypes and the non-specific nature of p16INK4a expression complicate the interpretation of a direct oncogenic role.

PMID:42234298 | DOI:10.1007/s11255-026-05218-w

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First report of molecular characterization, pathological analysis, and antibacterial susceptibility of Yersinia ruckeri RTACP-14 a isolated from farmed rainbow trout, Oncorhynchus mykiss (Walbaum 1792) in the Indian Himalayan Region

Vet Res Commun. 2026 Jun 3;50(5):362. doi: 10.1007/s11259-026-11301-5.

ABSTRACT

The present study represents the first detailed report of Yersinia ruckeri infection in farmed rainbow trout (Oncorhynchus mykiss) from the Indian Himalayan Region, where intensification of aquaculture has elevated the pathogen load and transmission dynamics, causing occurrence of enteric redmouth disease (ERM). The study examined infections by Y. ruckeri, RTACP-14 A (PX411334), in farmed rainbow trout from the Indian Himalayas. Affected fish displayed clinical signs such as hemorrhagic mouth, deep ulceration at caudal peduncle region, fin degeneration, lesions, black pigmentation, and erratic swimming behaviour. The isolated Y. ruckeri RTACP-14 A strain was identified through biochemical tests and confirmed by 16 S rRNA sequencing showing the closest evolutionary relationship (100) to Y. ruckeri strain BY-1Y. Virulence analysis revealed β-hemolysis, low hydrophobicity, and substantial biofilm formation under glucose-rich conditions. The cumulative mortality increased from 12.5% at day 1 to 83% by day 32 during a controlled experimental infection trial conducted in rainbow trout. Antibiotic susceptibility test showed that Y. ruckeri RTACP-14 A was sensitive to most antibiotics, with imipenem, fosfomycin, and ciprofloxacin exhibiting the largest inhibition zones (> 40 mm), while bacitracin was the only antibiotic to which resistance was observed. The lowest minimum inhibitory concentrations (MICs) were recorded for oxytetracycline (0.125 µg mL– 1), florfenicol (1 µg mL– 1), and tobramycin (1 µg mL– 1). Histopathological analysis revealed gill hyperplasia, intestinal villus necrosis, kidney damage, liver congestion, and muscle degradation, with distinct patterns distinguishing acute from chronic infections. To mitigate outbreaks of enteric red mouth disease caused by Y. ruckeri, trout farmers should adopt best management practices, including maintaining optimal water quality, minimizing handling stress, implementing strict biosecurity measures, and using antimicrobials judiciously within a regulated framework. These measures are essential for safeguarding fish health and welfare, minimizing economic losses, and ensuring the sustainability of trout farming in the region.

PMID:42234297 | DOI:10.1007/s11259-026-11301-5

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pedQTNet: A Deep Learning Approach to Estimate Corrected QT Intervals from Multi-Lead Conventional ECG Waveforms in Pediatric Patients

J Med Syst. 2026 Jun 3;50(1):90. doi: 10.1007/s10916-026-02386-1.

ABSTRACT

Long QT syndrome (LQTS) is a primary risk factor for ventricular arrhythmias and sudden cardiac death in children. Accurate corrected QT intervals (QTc) measurement is imperative but challenging for non-heart-rhythm specialists, especially in children. We developed and evaluated pedQTNet, a deep neural network model for estimating QTc and detecting LQTS in pediatric patients. We analyzed a cohort of 37,992 patients aged 0-18 years with 65,370 ECGs annotated by pediatric electrophysiologists (PEPs) between 2010 and 2020. Using PEP-annotated QTc measurements as ground truth, pedQTNet was trained and calibrated on raw ECG waveforms to optimize QTc estimation and LQTS classification. Performance was compared to GE Healthcare’s Marquette 12SL algorithm, and to PEPs in cross-validation, as well as an additional prospective set of 200 ECGs. In 10-fold cross-validation, pedQTNet estimated QTc’s with a mean absolute error (MAE) of 18.8 ms (95% CI: 18.4-19.2) and predicted LQTS at 470 ms with 85% sensitivity (83%-87%), 87% specificity (87%-88%), positive likelihood ratio (PLR) of 6.7 (6.5-7.0), and negative likelihood ratio (NLR) of 0.17 (0.15-0.19), outperforming Marquette 12SL. In the prospective set, pedQTNet had higher sensitivity than PEPs (100% [69%-100%] vs. 71% [53%-85%], P < 0.05), and a lower but not statistically significant NLR (0.00 [0.00-0.70] vs. 0.30 [0.18-0.50], P = 0.2). PedQTNet demonstrated high QTc estimation accuracy and reliable LQTS detection, outperforming a commercial tool and on par with expert interpretation. Its strong performance supports its clinical use for scalable, automated pediatric ECG screening and LQTS risk assessment, offering a practical tool for enhancing pediatric cardiac care.

PMID:42234295 | DOI:10.1007/s10916-026-02386-1

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Early- versus late-onset mortality trends in breast and female genital cancers in Spain, 1999-2024

Clin Transl Oncol. 2026 Jun 3. doi: 10.1007/s12094-026-04412-7. Online ahead of print.

ABSTRACT

BACKGROUND: Breast and gynaecological cancers represent the leading oncological burden among women worldwide. We aimed to describe long-term mortality trends for these malignancies in Spain over a 26 year period, focusing on differences between early-onset (< 50 years) and late-onset (≥ 50 years) disease.

METHODS: Mortality data (1999-2024) were obtained from the Spanish National Institute of Statistics. Age-standardised mortality rates (ASMRs) were calculated per 100,000 women using the 2013 European Standard Population. Joinpoint regression estimated annual percentage changes (APC) and average annual percentage changes (AAPC) with 95% confidence intervals (CI).

RESULTS: Total annual deaths rose from 9531 to 11,641, despite declining ASMRs for most sites. Breast cancer mortality decreased consistently (AAPC – 1.4%; 95% CI – 1.5, – 1.3), with a more pronounced reduction in the < 50 group (AAPC – 2.5%). Significant ASMR declines were observed for uterus NOS (- 2.3%), ovary (- 0.7%), and cervix uteri (- 0.6%). In the < 50 cohort, ovarian cancer mortality fell sharply (AAPC – 2.1%). Conversely, corpus uteri cancer was the only site showing an increasing trend (AAPC + 0.4%; 95% CI 0.1, 0.8), with a steeper increase observed among women ≥ 50 years. Non-monotonic trends were identified for less common gynaecological cancers.

CONCLUSIONS: Mortality rates for breast and most gynaecological cancers in Spain have declined, although absolute deaths have increased. These trends are potentially consistent with advances in prevention and care alongside population ageing. The rise in corpus uteri cancer represents an emerging public health concern potentially associated with increasing metabolic risk factors, highlighting the need for targeted prevention strategies.

PMID:42234293 | DOI:10.1007/s12094-026-04412-7

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Stand-alone versus supplemented ALIF: a systematic review and meta-analysis of pseudarthrosis and reoperation rates

Neurosurg Rev. 2026 Jun 3;49(1):430. doi: 10.1007/s10143-026-04347-1.

ABSTRACT

Anterior lumbar interbody fusion (ALIF) is widely used for degenerative lumbar disc disease, offering restoration of disc height and sagittal alignment. However, pseudarthrosis remains a relevant complication, and the benefit of supplemental posterior fixation over stand-alone constructs is still debated. To compare the incidence of pseudarthrosis following stand-alone ALIF versus ALIF combined with posterior pedicle screw fixation. A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines and registered in PROSPERO (CRD42024581358). PubMed/MEDLINE, Embase, Cochrane Library, and BVS were searched for studies published between 2013 and September 2024. Clinical studies including patients with degenerative lumbar disease undergoing ALIF with at least 12 months of follow-up were eligible. Study selection and data extraction were performed independently by two reviewers. Risk of bias was assessed using the Joanna Briggs Institute (JBI) tool for observational studies and Risk of Bias 2 (RoB 2) for randomized trials. Random-effects models were used to estimate pooled pseudarthrosis prevalence and clinical outcomes. Fourteen studies comprising 917 patients and over 1,000 operated levels were included. The pooled prevalence of pseudarthrosis was 8.17% (95% CI: 5.04-11.31), with substantial heterogeneity (I²=70.8%). Pseudarthrosis rates were numerically higher in stand-alone ALIF (8.95%; 95% CI: 4.54-13.37) compared with ALIF combined with posterior fixation (6.76%; 95% CI: 3.58-9.94), although the difference was not statistically significant (p = 0.429). Significant clinical improvement was observed, with a mean reduction of 4.16 points in VAS and a 24.46-point improvement in ODI. Meta-regression demonstrated no association between pseudarthrosis rates and clinical outcomes. Notably, stand-alone ALIF was associated with a significantly higher risk of reoperation for symptomatic pseudarthrosis (RR 6.8; 95% CI: 1.9-24.5; p < 0.01). ALIF provides substantial pain relief and functional improvement, with a relatively low overall rate of pseudarthrosis. Although stand-alone constructs showed a trend toward higher pseudarthrosis rates without statistical significance, they were associated with a markedly increased risk of reoperation. These findings suggest that, while fusion rates may appear comparable, supplemental posterior fixation may confer greater mechanical reliability and reduce clinically meaningful failure in selected patients.

PMID:42234274 | DOI:10.1007/s10143-026-04347-1

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Comparative evaluation of PET quantitative methods for myocardial viability assessment in CAD patients and its prognostic value

Int J Cardiovasc Imaging. 2026 Jun 3. doi: 10.1007/s10554-026-03744-3. Online ahead of print.

ABSTRACT

To compare different methods for myocardium quantification and exploratively evaluate the prognostic relationship between PET-measured viable myocardium and clinical outcomes in coronary artery disease (CAD) patients with ischemic cardiomyopathy (ICM). 183 CAD patients who underwent one-day 13NH3 and 18F-FDG PET/CT myocardial viability assessment were retrospectively enrolled. Using Corridor4DM software, different types of myocardium (viable, normal, scar) were quantified via visual analysis, semi-quantitative scoring, and software automatic quantification. As an exploratory secondary analysis, patients were grouped and method-dependent grouping differences were analyzed. The correlation between viable myocardium, treatment decisions, and prognosis was retrospectively evaluated. Software identified the most normal myocardium and the least viable myocardium, while semi-quantitative scoring was the opposite. High inter-method consistency (all ICC>0.75) was observed, in which visual and software analyses showed optimal agreement, contrasting with scoring analysis. No significant differences were found among when viable myocardium<20%, but scoring analysis underestimated viable myocardium as its extent increased (P<0.001). Notably, all three methods exhibited concordant and comparable prognostic predictive value (AUC: 0.595-0.669 for OS and 0.529-0.533 for MACE). And exploratory prognostic analysis (n = 113) revealed no statistically significant interaction between treatment strategy and viability for either OS or MACE. However, a potential trend was observed where revascularization was associated with improved outcomes specifically in patients with a higher extent of viable myocardium (≥ 37%). Three analyses demonstrated high consistency in myocardium quantification, with visual and software analysis showing optimal agreement. Software analysis enhances clinical efficiency, offering improved sensitivity and objectivity. Furthermore, the three methods showed concordant prognostic predictive value; While exploratory analyses suggested potential prognostic trends, no statistically significant interaction was found between treatment strategy and viability. Accurately assessing viable myocardium via software automatic quantification offers an objective tool for assessment, though its role in guiding treatment decisions requires further validation.

PMID:42234272 | DOI:10.1007/s10554-026-03744-3

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Efficacy of diflunisal for hereditary transthyretin amyloidosis: the Swedish real-world experience

Amyloid. 2026 Jun 3:1-7. doi: 10.1080/13506129.2026.2678340. Online ahead of print.

ABSTRACT

BACKGROUND: Diflunisal has been shown to slow the progression of hereditary transthyretin (ATTRv) amyloidosis. We examined the efficacy of diflunisal using data from SveATTR, a longitudinal Swedish registry open for patients with ATTR amyloidosis.

METHODS: Data from diflunisal treated patients registered in SveATTR through Dec 2022 were included. Available data on Kumamoto score, PND score/FAP stage, mBMI, NYHA classification and Karnofsky performance status were analyzed using random coefficients mixed effects modeling, and the results were combined with those of the pivotal diflunisal trial.

RESULTS: In total, 118 registry subjects were included. Estimated mean time of diflunisal therapy was 3.4 (range 0.1 to 10.2) years. Random coefficients mixed effects modeling demonstrated gradual progression of disease over time by upward trend of Kumamoto score, PND score and FAP stage, and downward trend in Karnofsky score and mBMI while NYHA class score remained unchanged. A Bayesian augmentation analysis was undertaken using registry data and pivotal trial data. After 24 months, the probability of superiority for diflunisal over placebo was 99.6% and 97.2% for Kumamoto score and mBMI, respectively.

CONCLUSIONS: SveATTR registry data align with the results of the pivotal trial, providing long-term real-world evidence that confirm the efficacy of diflunisal for ATTRv amyloidosis.

PMID:42233236 | DOI:10.1080/13506129.2026.2678340

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CPSM: An R Package for Cancer Patient Survival Risk Model Using Transcriptomics and Clinical Data

Gigascience. 2026 Jun 2:giag067. doi: 10.1093/gigascience/giag067. Online ahead of print.

ABSTRACT

Traditional Kaplan-Meier curves capture aggregate survival trends within broad patient subgroups but overlook the heterogeneity of individual patients. In contrast, single-patient survival risk models bridge this gap by incorporating each patient’s unique clinical, genomic, and demographic characteristics, generating personalized survival curves. These individualized visualizations enhance patient-clinician communication by translating complex statistics into intuitive, time-based visuals that are easier to interpret. However, the complexity, high dimensionality, and heterogeneity of multi-omics data present significant challenges for analysis, interpretation, and model development. To address these challenges, we introduce the Cancer Patient Survival Model (CPSM), an R package designed to deliver individualized survival and risk predictions through a fully integrated, reproducible computational pipeline. CPSM includes 10 core functions organized into four key steps: (1) Data Preprocessing and Normalization, (2) Feature Selection, (3) Survival Risk-Group Prediction Modeling, and (4) Visualization and Nomogram Construction. We demonstrate the utility of CPSM using publicly available TCGA datasets for four cancer types: glioblastoma multiforme (GBM), acute myeloid leukemia (LAML), pancreatic adenocarcinoma (PAAD) and breast invasive cancer (BRCA). CPSM efficiently handles high-dimensional datasets with over 60,000 RNA transcripts and diverse clinical variables, enabling robust and interpretable individualized survival predictions under varying data conditions. Model performance was evaluated using repeated cross-validation with uncertainty quantification, ensuring robust and reliable estimates in high-dimensional, small-sample settings. In summary, CPSM provides an efficient, user-friendly, end-to-end solution for integrating patient data and generating personalized survival and risk predictions. Its integrated visual tools enhance interpretability and support more informed clinical decision-making. The package is freely available on Bioconductor (https://bioconductor.org/packages/devel/bioc/html/CPSM.html) and GitHub (https://github.com/hks5august/CPSM).

PMID:42233233 | DOI:10.1093/gigascience/giag067

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Clinical Intervention Following Detection of Incident Diabetes Within a Large Psychiatric Service System: A Chart Review Study

Acta Psychiatr Scand. 2026 Jun 3. doi: 10.1111/acps.70114. Online ahead of print.

ABSTRACT

INTRODUCTION: Individuals with mental illness have a markedly reduced life expectancy, partly due to a significantly increased risk of developing type 2 diabetes, driven by lifestyle factors and the adverse metabolic effects of psychotropic medications. This study examined whether abnormal laboratory values indicating incident diabetes, when ordered within psychiatric services, were followed by documented interventions.

METHODS: We used electronic health record data from the Psychiatric Services of the Central Denmark Region and drew a random sample of patients with incident diabetes detected between 2019 and 2024. Incident diabetes was defined by the first laboratory value ordered by the psychiatric services indicating diabetes: glycated haemoglobin ≥ 48 mmol/mol, fasting plasma glucose ≥ 7.0 mmol/L, plasma glucose ≥ 11.1 mmol/L during a 2-h oral glucose tolerance test or random plasma glucose. Patients with pre-existing diabetes, identified through ICD-10 codes or antidiabetic medication history, were excluded. Manual chart review assessed whether incident diabetes was followed, within 3 months, by documented clinical intervention (such as referral, repeat testing, or medication initiation), or was merely acknowledged without further action. Descriptive statistics and adjusted logistic regression analysis were used to characterise the cohort and examine characteristics associated with lack of intervention.

RESULTS: Among 416 patients with incident diabetes (57% male, median age 48 years [IQR: 35-59], 33% with schizophrenia or other psychotic disorders), only 37% received a clinical intervention. The most frequent intervention was referral to a general practitioner (27%), while antidiabetic medication was initiated in only 6% of those who received an intervention. The only characteristic associated with lack of clinical intervention was body mass index < 25 kg/m2 (adjusted odds ratio 3.82, 95% CI: 1.92-8.20).

CONCLUSION: This study suggests that appropriate clinical intervention following detection of incident diabetes is lacking. This may inform future strategies to reduce metabolic and cardiovascular risks among individuals with mental illness.

PMID:42233222 | DOI:10.1111/acps.70114