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Automated Quantification of Extranuclear ERα using Phosphor-integrated Dots for Predicting Endocrine Therapy Resistance in HR+/HER2? Breast Cancer
摘要： In addition to genomic signaling, Estrogen receptor alpha (ERα) is associated with cell proliferation and survival through extranuclear signaling contributing to endocrine therapy (ET) resistance. However, the relationship between extranuclear ERα and ET resistance has not been extensively studied. We sought to measure extranuclear ERα expression by immunohistochemistry using phosphor-integrated dots (IHC-PIDs) and to assess its predictive value for ET resistance. After quantitative detection of ERα by IHC-PIDs in vitro, we developed “the nearest-neighbor method” to calculate the extranuclear ERα. Furthermore, tissue sections from 65 patients with HR+/HER2- BC were examined by IHC-PIDs, and the total ERα, nuclear ERα, extranuclear ERα PIDs score, and ratio of extranuclear-to-nuclear ERα (ENR) were measured using the novel method. We demonstrate that quanti?cation of ERα using IHC-PIDs exhibited strong correlations to real-time qRT-PCR (r2 = 0.94) and ?ow cytometry (r2 = 0.98). High ERα ENR was signi?cantly associated with poor overall survival (p = 0.048) and disease-free survival (DFS) (p = 0.007). Multivariate analysis revealed that the ERα ENR was an independent prognostic factor for DFS [hazard ratio, 3.8; 95% CI, 1.4–11.8; p = 0.006]. Our automated measurement has high accuracy to localize and assess extranuclear ERα. A high ERα ENR in HR+/HER2- BC indicates decreased likelihood of bene?ting from ET.
关键词： estrogen receptor α,endocrine therapy resistance,breast cancer,prognostic,IHC-PIDs
更新于2025-11-21 11:08:12
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Head-to-head comparison of the diagnostic performances of Rubidium-PET and SPECT with CZT camera for the detection of myocardial ischemia in a population of women and overweight individuals
摘要： Background. The aim of this study was to compare the diagnostic performances for the detection of myocardial ischemia of 82-Rb-PET-MPS and 99m-Tc-SPECT-MPS in overweight individuals and women. Methods and Results. Men with BMI ≥ 25 and women referred for MPS were considered for inclusion. All individuals underwent 99m-Tc-SPECT-MPS with CZT cameras and 82-Rb-PET-MPS in 3D-mode. Individuals with at least one positive MPS were referred for coronary angiography (CA) with FFR measurements. A criterion for positivity was a composite endpoint including significant stenosis on CA or, in the absence of CA, the occurrence of acute coronary event during the following year. 313 patients (46% women) with mean BMI of 31.8 ± 6.5 were included. Sensitivity for the detection of myocardial ischemia was higher with 82-Rb-PET-MPS compared with 99m-Tc-SPECT-MPS (85% vs. 57%, P < .05); specificity was equally high with both imaging techniques (93% vs. 94%, P > .05). 82-Rb-PET allowed for a more accurate detection of patients with a high-risk coronary artery disease (HR-CAD) than 99m-Tc-SPECT-MPS (AUC = 0.86 vs. 0.75, respectively; P = .04). Conclusions. In women and overweight individuals, 82-Rb-PET-MPS provides higher sensitivity for the detection of myocardial ischemia than 99m-Tc-SPECT-MPS thanks to a better image quality and an improved detection of HR-CAD.
关键词： CZT camera,MPI,Diagnostic and prognostic application,PET,Myocardial blood flow,SPECT,82-Rubidium,CAD
更新于2025-09-23 15:23:52
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Infrared Spectroscopic Imaging Visualizes a Prognostic Extracellular Matrix-Related Signature in Breast Cancer
摘要： Molecular analysis techniques such as gene expression analysis and proteomics have contributed greatly to our understanding of cancer heterogeneity. In prior studies, gene expression analysis was shown to stratify patient outcome on the basis of tumor-microenvironment associated genes. A specific gene expression profile, referred to as ECM3 (Extracellular Matrix Cluster 3), indicated poorer survival in patients with grade III tumors. In this work, we aimed to visualize the downstream effects of this gene expression profile onto the tissue, thus providing a spatial context to altered gene expression profiles. Using infrared spectroscopic imaging, we identified spectral patterns specific to the ECM3 gene expression profile, achieving a high spectral classification performance of 0.87 as measured by the area under the curve of the receiver operating characteristic curve. On a patient level, we correctly identified 20 out of 22 ECM3 group patients and 19 out of 20 non-ECM3 group patients by using this spectroscopic imaging-based classifier. By comparing pixels that were identified as ECM3 or non-ECM3 with H&E and IHC images, we were also able to observe an association between tissue morphology and the gene expression clusters, showing the ability of our method to capture broad outcome associated features from infrared images.
关键词： extracellular matrix,prognostic signature,gene expression,breast cancer,infrared spectroscopic imaging
更新于2025-09-23 15:21:01
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Combining multimodal imaging and treatment features improves machine learning-based prognostic assessment in patients with glioblastoma multiforme
摘要： Background: For Glioblastoma (GBM), various prognostic nomograms have been proposed. This study aims to evaluate machine learning models to predict patients’ overall survival (OS) and progression‐free survival (PFS) on the basis of clinical, pathological, semantic MRI‐based, and FET‐PET/CT‐derived information. Finally, the value of adding treatment features was evaluated. Methods: One hundred and eighty‐nine patients were retrospectively analyzed. We assessed clinical, pathological, and treatment information. The VASARI set of semantic imaging features was determined on MRIs. Metabolic information was retained from preoperative FET‐PET/CT images. We generated multiple random survival forest prediction models on a patient training set and performed internal validation. Single feature class models were created including "clinical," "pathological," "MRI‐based," and "FET‐PET/CT‐based" models, as well as combinations. Treatment features were combined with all other features. Results: Of all single feature class models, the MRI‐based model had the highest prediction performance on the validation set for OS (C‐index: 0.61 [95% confidence interval: 0.51‐0.72]) and PFS (C‐index: 0.61 [0.50‐0.72]). The combination of all features did increase performance above all single feature class models up to C‐indices of 0.70 (0.59‐0.84) and 0.68 (0.57‐0.78) for OS and PFS, respectively. Adding treatment information further increased prognostic performance up to C‐indices of 0.73 (0.62‐0.84) and 0.71 (0.60‐0.81) on the validation set for OS and PFS, respectively, allowing significant stratification of patient groups for OS. Conclusions: MRI‐based features were the most relevant feature class for prognostic assessment. Combining clinical, pathological, and imaging information increased predictive power for OS and PFS. A further increase was achieved by adding treatment features.
关键词： prognostic model,machine learning,VASARI,glioblastoma,FET‐PET,biomarker,MRI
更新于2025-09-23 15:19:57
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Early tongue carcinomas (clinical stage I and II): echo-guided three-dimensional diode laser mini-invasive surgery with evaluation of histological prognostic parameters. A study of 85 cases with prolonged follow-up
摘要： The management of patients with early stage (cT1–T2) tongue squamous cell carcinoma without clinicoradiologic evidence of neck node metastasis (cN0) has been widely debated over the last 3 decades and still remains controversial. Nevertheless, the identification of patients with low-stage tumours at high-risk for occult cervical metastases is imperative before planning treatments of primary tumours, as well as that of prognostic markers which may possibly select those patients who may benefit of additional workup after surgery in view of the high metastatic potential of the primary tumour. The pre-surgical evaluation of tongue malignant primary tumour (for assessing lateral and deep margins) along with diode laser surgery (with accurate incision, bleeding-free and with reduced/absent post-surgical complications) may lead to a more conservative but equally decisive surgical treatment, also with a greater patient compliance. We studied 85 consecutive cases of cT1–T2 N0 tongue squamous cell carcinoma who had been managed by the following diagnostic/therapeutic protocol: pre-operative high definition ultrasound examination for the evaluation of size and depth, followed by three-dimensional surgical excision by diode laser (wavelength of 800 ± 10 nm, output power of 8 W in continuous wave, flexible optic fibre of 320 μm in contact mode) and detailed histological analyses of well-established prognostic parameters (tumour grade, thickness, depth, front of infiltration and surgical margins) with statistical analysis. No post-surgical photobiomodulation was performed. Overall, 58.82% of patients were stage I, 18% stage II, and the most frequent histotype was squamous cell carcinoma (97.64%). Large nests invasion pattern was observed in 64 cases, expansive pattern in 9, invasion in single cells in 12; front of invasion involved the muscle in 62 cases, vessels in 6, nerves in 15; peritumoural vascular invasion was assessed in 6 patients and perineural invasion in 15. Selective neck lymphadenectomy was performed in 9 cases, and clinically occult node metastases were detected in two cases. At follow-up, 78 patients (98.73%) were alive and free of disease, one patient experienced tumour-related death, while the remaining 6 died for non-disease-related causes. All the histological prognostic parameters were statistically significant (χ2 test; p = 0.05), thus leading to a prognostic weight classification with a three-tiered stratification. On the bases of these results, the authors maintain that the reported diagnostic/therapeutic protocol, including the pre-operative echo-guided three-dimensional evaluation, the following diode laser mini-invasive surgery for tumour excision and the histological examination along with the proposed three-tiered stratification of histological prognostic parameters may allow proper management of clinical stage I and II early tongue carcinomas.
关键词： Ultrasound,Nodal metastasis,Tongue cancer,Diode laser surgery,Neck dissection,Histological prognostic parameters
更新于2025-09-12 10:27:22
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The Evaluation of Prognostic Factors after Vitrectomy for Lamellar Macular Hole Using Optical Coherence Tomography
摘要： Purpose: To evaluate the prognostic factors that predict visual outcome after vitrectomy for lamellar macular hole using optical coherence tomography (OCT). Methods: This study included 26 eyes that underwent pars plana vitrectomy, epiretinal membrane removal, and internal limiting membrane peeling for lamellar macular hole. The maximum parafoveal thickness, maximum height and diameter of lamellar macular hole, maximum height and diameter of intraretinal splitting, thinnest foveal floor thickness, and inner segment/outer segment disruption length on preoperative OCT image were investigated for prognostic factors that predict visual outcome. Results: The mean follow-up period was 32.2 months and the mean best corrected visual acuity improved significantly after vitrectomy from log MAR 0.47 ± 0.32 to log MAR 0.23 ± 0.23. The postoperative visual acuity correlated significantly with preoperative visual acuity, thinnest foveal floor thickness and inner segment/outer segment disruption length, but not with maximum parafoveal thickness, maximum height and diameter of lamellar macular hole and maximum height and diameter of intraretinal splitting. Conclusions: The thinnest foveal floor thickness and inner segment/outer segment disruption length on preoperative OCT image were significant prognostic factors.
关键词： Lamellar macular hole,Optical coherence tomography,Prognostic factors
更新于2025-09-04 15:30:14