Abstract: Background Reliable predictive imaging markers of response to immune checkpoint inhibitors are needed. Purpose To develop and validate a pretreatment CT-based radiomics signature to predict response to immune checkpoint inhibitors in advanced solid tumors. Materials and Methods In this retrospective study, a radiomics signature was developed in patients with advanced solid tumors (including breast, cervix, gastrointestinal) treated with anti-programmed cell death-1 or programmed cell death ligand-1 monotherapy from August 2012 to May 2018 (cohort 1). This was tested in patients with bladder and lung cancer (cohorts 2 and 3). Radiomics variables were extracted from all metastases delineated at pretreatment CT and selected by using an elastic-net model. A regression model combined radiomics and clinical variables with response as the end point. Biologic validation of the radiomics score with RNA profiling of cytotoxic cells (cohort 4) was assessed with Mann-Whitney analysis. Results The radiomics signature was developed in 85 patients (cohort 1: mean age, 58 years ± 13 [standard deviation]; 43 men) and tested on 46 patients (cohort 2: mean age, 70 years ± 12; 37 men) and 47 patients (cohort 3: mean age, 64 years ± 11; 40 men). Biologic validation was performed in a further cohort of 20 patients (cohort 4: mean age, 60 years ± 13; 14 men). The radiomics signature was associated with clinical response to immune checkpoint inhibitors (area under the curve [AUC], 0.70; 95% CI: 0.64, 0.77; P < .001). In cohorts 2 and 3, the AUC was 0.67 (95% CI: 0.58, 0.76) and 0.67 (95% CI: 0.56, 0.77; P < .001), respectively. A radiomics-clinical signature (including baseline albumin level and lymphocyte count) improved on radiomics-only performance (AUC, 0.74 [95% CI: 0.63, 0.84; P < .001]; Akaike information criterion, 107.00 and 109.90, respectively). Conclusion A pretreatment CT-based radiomics signature is associated with response to immune checkpoint inhibitors, likely reflecting the tumor immunophenotype. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Summers in this issue.

Abstract: In most eukaryotes, pairing of homologous chromosomes is an essential feature of meiosis that ensures homologous recombination and segregation. However, when the pairing process begins, it is still under investigation. Contrasting data exists in Mus musculus, since both leptotene DSB-dependent and preleptotene DSB-independent mechanisms have been described. To unravel this contention, we examined homologous pairing in pre-meiotic and meiotic Mus musculus cells using a threedimensional fuorescence in situ hybridization-based protocol, which enables the analysis of the entire karyotype using DNA painting probes. Our data establishes in an unambiguously manner that 73.83% of homologous chromosomes are already paired at premeiotic stages (spermatogonia-early preleptotene spermatocytes). The percentage of paired homologous chromosomes increases to 84.60% at mid-preleptotene-zygotene stage, reaching 100% at pachytene stage. Importantly, our results demonstrate a high percentage of homologous pairing observed before the onset of meiosis; this pairing does not occur randomly, as the percentage was higher than that observed in somatic cells (19.47%) and between nonhomologous chromosomes (41.1%). Finally, we have also observed that premeiotic homologous pairing is asynchronous and independent of the chromosome size, GC content, or presence of NOR regions.

Abstract: Background: COVID-19 infection, especially in cases with pneumonia, is associated with a high rate of pulmonary embolism (PE). In patients with contraindications for CT pulmonary angiography (CTPA) or non-diagnostic CTPA, perfusion single-photon emission computed tomography/computed tomography (Q-SPECT/CT) is a diagnostic alternative. The goal of this study is to develop a radiomic diagnostic system to detect PE based only on the analysis of Q-SPECT/CT scans.
Methods: This radiomic diagnostic system is based on a local analysis of Q-SPECT/CT volumes that includes both CT and Q-SPECT values for each volume point. We present a combined approach that uses radiomic features extracted from each scan as input into a fully connected classifcation neural network that optimizes a weighted crossentropy loss trained to discriminate between three diferent types of image patterns (pixel sample level): healthy lungs (control group), PE and pneumonia. Four types of models using diferent confguration of parameters were tested.
Results: The proposed radiomic diagnostic system was trained on 20 patients (4,927 sets of samples of three types of image patterns) and validated in a group of 39 patients (4,410 sets of samples of three types of image patterns). In the training group, COVID-19 infection corresponded to 45% of the cases and 51.28% in the test group. In the test group, the best model for determining diferent types of image patterns with PE presented a sensitivity, specifcity, positive predictive value and negative predictive value of 75.1%, 98.2%, 88.9% and 95.4%, respectively. The best model for detecting
pneumonia presented a sensitivity, specifcity, positive predictive value and negative predictive value of 94.1%, 93.6%, 85.2% and 97.6%, respectively. The area under the curve (AUC) was 0.92 for PE and 0.91 for pneumonia. When the results obtained at the pixel sample level are aggregated into regions of interest, the sensitivity of the PE increases to 85%, and all metrics improve for pneumonia.
Conclusion: This radiomic diagnostic system was able to identify the diferent lung imaging patterns and is a frst step toward a comprehensive intelligent radiomic system to optimize the diagnosis of PE by Q-SPECT/CT.