Citations

Aims Testicular sex cord‐stromal tumours (TSCSTs) are rare neoplasms that arise from (or show differentiation to) elements derived from the sex cords or intertubular stroma. The current classification (World Health Organization, 2022) is based almost entirely on morphology, with many tumour types such as granulosa cell tumours being defined based on their resemblance to ovarian counterparts. Recent studies have uncovered new clinicopathological, molecular and biological nuances within this group of tumours, underscoring differences with ovarian homologues. Methods and results Considering the new data, a group of genitourinary pathology experts (Testicular Sex Cord‐Stromal Tumour [TESST] group) has proposed a revised ‘TESST classification’ that incorporates the best available evidence. This classification is structured and hierarchical, composed of the following tiers: (1) group, (2) category, (3) entity and (4) histological pattern. ‘Group’ refers to the histological compartment a specific tumour belongs to (sex cords, stroma or both), whereas ‘category’ is defined by the phenotype of the tumour, taking non‐neoplastic elements of the ovary and testis as a reference. The third tier, ‘entity’, refers to neoplasms with shared clinicopathological and/or molecular features that justify classifying them as distinct types. Lastly, ‘histological patterns’ are recurrent morphological variations within entities that are not linked to distinct clinicopathological or molecular features. Conclusions We propose a classification that will provide a framework to improve current clinical management and guide future research in the field.

Abstract The minichromosome maintenance 2-7 (MCM2-7) proteins form a hexameric protein complex that is the structural core of replicative helicase, which is essential for accurate DNA replication. While their role in replication is well-established, the biological functions of excess chromatin-bound MCM2-7 proteins remain unclear. Here, we identify a transcriptional regulatory function of MCM2-7 through its interaction with nuclear factor κB (NF-κB) p65. We demonstrate that MCM2-7 proteins and NF-κB p65 reciprocally recruit each other to target gene promoters. Consequently, MCM2-7 proteins facilitate the localization of RNA Pol II to NF-κB target gene promoters and along the gene body, thereby promoting transcription of NF-κB target genes. These findings reveal MCM2-7 proteins promote NF-κB target gene transcription by facilitating p65 and RNA Pol II recruitment, offering a potential avenue for fine-tuning NF-κB target gene transcription.

BACKGROUND: Cardiac computed tomography (CT) acquired during the acute stroke imaging protocol is an emerging modality to detect cardiac thrombi. We determined its yield in patients with acute ischemic stroke. METHODS: We performed a 1-stage individual patient data meta-analysis of 4 prospective observational cohorts (AIS of HEARTS [Acute Ischemic Stroke of Heart-Related Embolic Sources Detected on Acute Cardiac CT Scans]), including patients with acute ischemic stroke who underwent ECG-gated or non–ECG-gated cardiac CT between May 2018 and June 2024. We excluded patients with transient ischemic attack or stroke mimics. The primary outcome was the proportion of patients with a thrombus on cardiac CT. Secondary outcomes were additional scan time, radiation dose, comparison with echocardiography, and 90-day outcomes. We performed logistic regression analyses to compare 90-day outcomes between patients with and without thrombus, adjusting for age, sex, history of atrial fibrillation, ischemic heart disease, chronic heart failure, stroke or transient ischemic attack, anticoagulant use, prestroke modified Rankin Scale score, National Institutes of Health Stroke Scale score, large vessel occlusions, and intravenous thrombolysis, as appropriate for each outcome. RESULTS: We included 3919 patients (median age, 74 [interquartile range (IQR), 63–82], 58% male, median National Institutes of Health Stroke Scale score 6 [IQR, 3–12]). Cardiac CT detected a thrombus in 243 (6.2%) patients. Among 1323 patients that underwent both cardiac CT and transthoracic echocardiography, cardiac CT had a higher yield than transthoracic echocardiography (odds ratio, 7.4 [95% CI, 4.0–15.1]; P <0.001). Median additional scan time was 6 minutes (IQR, 5–7) for ECG-gated and 13 seconds (IQR, 12–61) for non–ECG-gated cardiac CT. Median additional radiation dose was 2.9 mSv (IQR, 1.6–4.1). Patients with thrombi had higher 90-day mortality (33% versus 15%, adjusted odds ratio, 1.6 [95% CI, 1.1–2.3]) and worse modified Rankin Scale scores (median modified Rankin Scale score 3 versus 2, adjusted odds ratio, 1.6 [95% CI, 1.2–2.0]), but similar recurrent stroke rates (5% versus 4%, adjusted odds ratio, 1.4 [95% CI, 0.7–2.5]). CONCLUSIONS: Implementing cardiac CT into the acute stroke imaging protocol is feasible, detects thrombi in ≈6% of patients, and has a higher yield than transthoracic echocardiography. Cardiac thrombi were associated with higher mortality, but not higher stroke recurrence. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT07165093.

Abstract Background and aims Cardiac CT is increasingly used in the acute diagnostic work-up of acute ischemic stroke (AIS), but commonly used scan protocols do not allow assessment of left ventricular ejection fraction (LVEF), a known predictor of functional outcome. We aimed to develop a prediction model for reduced LVEF using clinical and imaging data. Methods This post-hoc analysis of the Mind the Heart study included AIS patients who underwent acute cardiac CT (acquired during diastole) and routine diagnostic work-up, including transthoracic echocardiography (TTE), which served as the reference standard for LVEF. Multivariable logistic regression models incorporating baseline variables, arterial input function (AIF) derived from CT-perfusion, and left atrial and ventricular cardiac CT volumes were developed using the training set (80%) to predict reduced LVEF (&lt;50%). Performance was evaluated on the testing set (20%) using receiver operating characteristic analysis, reporting the area under the curve (AUC), sensitivity, and specificity. Non-linear associations were modeled using restricted cubic splines, and Least Absolute Shrinkage and Selection Operator regression was used for variable selection. We evaluated whether cardiac CT information improved model fit. Results We included 298 AIS patients (61% male, median age 71 [IQR 61-79] years), of whom 87 (29%) had reduced LVEF. The final model showed moderate discrimination (AUC 0.71), sensitivity (0.67) and specificity (0.70). Including cardiac CT volumes in addition to baseline and AIF variables improved model fit (p=0.04). Conclusions Our model may aid risk stratification for reduced LVEF in AIS patients undergoing acute cardiac CT and could support identification of patients in whom additional TTE is warranted. Conflict of interest MMW received the Arthur Fonville Award for Stroke Research in 2025 for this work. SSN received travel grants from the Cultuurfondsbeurs, Remmert Adriaan Laan Fonds, CONTRAST consortium and Dr. Jan Meerwaldt Stichting outside the submitted work, JMC reports grants from Medtronic, Siemens, AstraZeneca and Bayer outside the submitted work (all paid to institution). JMC is shareholder and co-founder of TrianecT. CBM reports grants from Stryker and Boeringher-Ingelheim outside the submitted work (paid to institution) and is shareholder of Nicolab (minority interest). LAR was supported by a personal Dekker Junior Clinical Scientist Grant from the Dutch Heart Foundation.The other authors have no financial conflicts of interest.

Abstract AI-powered pathology foundation models provide general-purpose representations of histopathological images by encoding image tiles into numerical embeddings. However, these embeddings are not directly interpretable in biological or clinical terms and must be translated into biologically meaningful features, such as cell-type composition or gene expression, to enable downstream clinical applications. To bridge this gap, we developed STpath, a framework that integrates histopathology image embeddings derived from existing pathology foundation models with matched, spatially resolved transcriptomics data. STpath consists of cancer-specific XGBoost models trained to infer cell-type compositions and gene expression from histopathology image tiles. We evaluated STpath in colorectal and breast cancer datasets and showed that it provides accurate estimates of the composition of major cell types and the expression of a subset of genes, with further performance gains achieved by combining embeddings from multiple foundation models. Finally, we demonstrated that STpath inferred features that can be used in downstream studies to evaluate their associations with clinical outcomes.

Background: Cardiac CT acquired during the acute stroke imaging protocol is an emerging diagnostic modality to detect cardiac thrombi. We aimed to determine its diagnostic yield in a large, international, multicenter study. Methods: We performed an individual patient data meta-analysis by pooling prospective and retrospective observational data of patients with acute ischemic stroke (AIS) who underwent cardiac CT (ECG-gated or non-ECG-gated) as part of the acute imaging protocol between May 2018 and June 2024. We excluded patients with a TIA or stroke mimic. The primary outcome was the proportion of patients with a cardiac thrombus detected on cardiac CT. Secondary outcomes were additional scan time and radiation dose, comparison of yield with echocardiography, and 90-day mortality and recurrent ischemic stroke rates. Results: We included 3940 patients from 4 hospitals (median age 74 [IQR 63-82], 58.0% male, median NIHSS 6 [IQR 3-12], median time onset to hospital arrival 100 minutes [IQR 62-185]). Atrial fibrillation at baseline was present in 23.1% patients, and 29.6% had a large vessel occlusion. Cardiac CT was non-diagnostic in 17 (0.4%) patients. In total, cardiac CT detected 254 cardiac thrombi in 243/3923 (6.2%) patients. Thrombi were located in the left atrial appendage (n=193), left atrium (n=19), and left ventricle (n=42). Of 95/243 (39.1%) patients with a cardiac thrombus that underwent echocardiography (median interval cardiac CT-echocardiography: 2 days), transthoracic echocardiography detected a thrombus in 18/92 (19.6%) patients and transesophageal echocardiography in 2/5 (40.0%) patients. The diagnostic yield in patients that underwent both modalities was higher for cardiac CT (OR 7.5 [CI 4.0-15.3], p<0.001). Median additional scan time was 6 minutes (IQR 5-7) for ECG-gated and 17 seconds (IQR 15-63) for non-ECG-gated cardiac CT. Median additional radiation dose was 5.4mSv (IQR 3.0-7.6). Patients with a cardiac thrombus on cardiac CT had higher 90-day mortality than those without a thrombus (33.3% vs 14.6%, p<0.001). We found no difference in 90-day recurrent stroke rate (5.4% vs 4.4%, p=0.50). Conclusion: Routine cardiac CT performed during the acute stroke imaging protocol detects a cardiac thrombus in 1 out of 16 patients with AIS, with a 7-times higher yield than routine echocardiography. Mortality rate was doubled in patients with a cardiac thrombus, but 90-day stroke recurrence risk did not differ.

Background: The rate of intracardiac thrombus detection in the hyperacute phase of stroke varies from 5% to 12% between studies. Our aim was to compare the thrombus detection rate between ECG-gated and non-ECG-gated cardiac CT protocols in acute stroke patients, using data from a large, international, multicentre registry. Methods: We conducted an individual patient data meta-analysis by pooling prospective and retrospective observational data from stroke patients assessed at four comprehensive stroke centres who underwent either ECG-gated or non-ECG-gated cardiac CT (extended CT angiography or two-phase non-ECG-gated cardiac CT) as part of the acute stroke imaging protocol between May 2018 and June 2024. The primary outcome was the proportion of patients with a cardiac thrombus in gated vs non gated techniques. Results: Of 3,940 patients, 1,474 (37.4%) underwent ECG-gated and 2,466 (62.6%) non-ECG-gated cardiac CT. Patients in the ECG-gated group were younger (median age 72 [IQR 62–81] vs. 74 [IQR 64–82] years, p = 0.000) and had a lower NIHSS at baseline (median 5 [IQR 2–12] vs. 6 [IQR 3–13], p < 0.00). There was a higher rate of thrombus detection with ECG-gated CT compared to non-gated CT (7.5% vs. 5.5%, p = 0.011. The association remained significant after adjusting for age, sex, baseline NIHSS score, and baseline atrial fibrillation (adjusted OR 1.87, 95% CI 1.42–2.47, p = 0.000). ECG-gated CT was associated with lower radiation dose (3.6 vs. 6.3 mSv, p = 0.000) but longer acquisition time (5.8 vs. 0.28 min, p = 0.000). Conclusion: ECG-gated cardiac CT has a higher detection rate for intracardiac thrombus detection compared to non-ECG-gated CT in patients with acute ischemic stroke.

Abstract Introduction Cardiac CT is increasingly used to screen for cardioembolism in stroke patients. We assessed the frequency and management of non-cardiac incidental findings on prospective ECG-gated cardiac CT in patients with a suspected stroke. Patients and methods This was a post-hoc analysis of the Mind the Heart study, a prospective single-centre cohort study including consecutive adult patients with acute ischaemic stroke (AIS), transient ischaemic attack (TIA), or a stroke mimic who underwent cardiac CT as part of an acute stroke imaging protocol. Endpoints were pre-defined non-cardiac incidental findings that were detected on cardiac CT: pulmonary embolism (PE), potential malignant lesions, pulmonary consolidations or ground-glass densities, bone fractures, lymphadenopathy, focal liver lesions, and ascending aortic or pulmonary artery dilatation. Change of management was defined as additional treatment or follow-up. Results We included 654 patients (57% men, median age 71 [IQR 59–80] years) of whom 451 (69%) had AIS, 48 had TIA (7%), and 155 had a stroke mimic (24%). Overall, 58 non-cardiac incidental findings were found in 55 (8%; 95%CI, 6–11) patients. The most frequent incidental findings were consolidations or ground-glass densities (n = 17, 3%), liver cysts or non-specific hypodensities (n = 14, 2%), pulmonary nodules or masses (n = 9, 1%), and PEs (n = 8, 1%). Incidental findings led to a change of management in 17/55 (31%) patients of whom 13/55 (24%) had additional follow-up and 9/55 (16%) received treatment (anticoagulation n = 8, chemotherapy n = 1). Discussion & Conclusion Non-cardiac incidental findings were observed on cardiac CT in 8% of patients with a suspected stroke. These findings changed management in 31% of these patients.

ABSTRACT Purpose Magnetic resonance elastography (MRE) of the heart has predominantly utilized breath‐held acquisitions with limited anatomic coverage. This work investigates the feasibility of 3D, free‐breathing cardiac MRE. Methods A 3D hybrid radial and EPI acquisition is utilized and combined with retrospective binning of k ‐space via physiologic monitoring, iterative reconstruction, MRE processing and inversions, and post‐processing specialized for cardiac imaging. Results Feasibility of free‐breathing stiffness mapping of the left ventricular myocardium was demonstrated in 11 participants. Myocardial stiffness estimates were obtained throughout the left ventricle for seven temporal states of the cardiac cycle. Stiffness estimates were presented in participant‐specific images, 17‐segment bullseye plots, and stiffness plots throughout the cardiac cycle. Results indicate increased stiffness in systolic states, with localized stiffness heterogeneity observed between participants, illustrating a key benefit of 3D cardiac MRE acquisition. Mean stiffness estimates obtained through 11 subjects were 4.44 ± 0.68 kPa (begin‐systole), 5.74 ± 0.94, 5.42 ± 0.87 (end‐systole), 3.84 ± 0.71 (begin‐diastole), 3.51 ± 0.74, 3.54 ± 0.52, and 3.55 ± 0.59 kPa (end‐diastole). Statistical testing indicated significant differences in stiffness across cardiac states with one‐way, repeated‐measures ANOVA ( p < 0.001) and Friedman's test ( p < 0.001). Experiments in scanning three participants with and without applied motion indicated that stiffness changes were more robustly detected in systole than in diastole, although patterns were subject‐specific. Comparison of free‐breathing stiffness measurements against reference breath‐held measurements yielded similar systolic stiffness estimates. Conclusions This study establishes the feasibility of free‐breathing, 3D cardiac MRE in healthy volunteers. With the current framework, stiffness estimation appears more robust in systole, and the reliability of diastolic estimates is limited and subject‐specific.

ABSTRACT Purpose Abnormal restrictions at myofascial interfaces are a key factor in chronic low back pain (CLBP) with myofascial pain syndrome (MPS), but no established imaging method exists for quantitative assessment. This pilot study evaluated the clinical feasibility of MR elastography (MRE)‐based slip interface imaging (SII) for visualizing myofascial mobility in CLBP‐MPS patients versus age−/sex‐/BMI‐matched healthy participants. A new SII biomarker, maximal normalized displacement discontinuity (), was introduced, and the previously developed normalized octahedral shear strain (NOSS) map was used for comparison. Preliminary assessments of vibration‐frequency effects, repeatability, and group differences in inter‐muscular mobility were conducted. Methods MRE was conducted at 30, 60, and 90 Hz to compare with NOSS for visualizing inter‐muscular slip interfaces at the quadratus lumborum‐erector spinae (QL‐ES) and erector spinae‐multifidus (ES‐M) muscle boundaries at L3‐L4. Repeatability of and NOSS was assessed at 30 Hz (identified as the best‐performing frequency) using within‐subject coefficients of variation and a linear mixed‐effects model from within‐ and between‐day scans. Clinical feasibility was then assessed via Wilcoxon rank‐sum tests in six CLBP‐MPS patients and matched controls. Results at 30 Hz exhibited superior delineation of slip interfaces compared to higher frequencies and NOSS. demonstrated significantly lower variation and better repeatability than NOSS. Healthy participants showed continuous, well‐defined slip interfaces, whereas CLBP‐MPS patients displayed disrupted interfaces with significant mobility reduction at L4 ES‐M. Conclusion SII with lower vibration frequency and map enhances visualization of lower back myofascial mobility and shows potential for assessing differences between healthy individuals and CLBP‐MPS patients.