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Mireia Sole, Joan Blanco, Debora Gil, Oliver Valero, Alvaro Pascual, B. Cardenas, et al. (2021). Chromosomal positioning in spermatogenic cells is influenced by chromosomal factors associated with gene activity, bouquet formation, and meiotic sex-chromosome inactivation. Chromosoma, 130, 163–175.
Abstract: Chromosome territoriality is not random along the cell cycle and it is mainly governed by intrinsic chromosome factors and gene expression patterns. Conversely, very few studies have explored the factors that determine chromosome territoriality and its influencing factors during meiosis. In this study, we analysed chromosome positioning in murine spermatogenic cells using three-dimensionally fluorescence in situ hybridization-based methodology, which allows the analysis of the entire karyotype. The main objective of the study was to decipher chromosome positioning in a radial axis (all analysed germ-cell nuclei) and longitudinal axis (only spermatozoa) and to identify the chromosomal factors that regulate such an arrangement. Results demonstrated that the radial positioning of chromosomes during spermatogenesis was cell-type specific and influenced by chromosomal factors associated to gene activity. Chromosomes with specific features that enhance transcription (high GC content, high gene density and high numbers of predicted expressed genes) were preferentially observed in the inner part of the nucleus in virtually all cell types. Moreover, the position of the sex chromosomes was influenced by their transcriptional status, from the periphery of the nucleus when its activity was repressed (pachytene) to a more internal position when it is partially activated (spermatid). At pachytene, chromosome positioning was also influenced by chromosome size due to the bouquet formation. Longitudinal chromosome positioning in the sperm nucleus was not random either, suggesting the importance of ordered longitudinal positioning for the release and activation of the paternal genome after fertilisation.
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Marta Ligero, Alonso Garcia Ruiz, Cristina Viaplana, Guillermo Villacampa, Maria V Raciti, Jaid Landa, et al. (2021). A CT-based radiomics signature is associated with response to immune checkpoint inhibitors in advanced solid tumors. Radiology, 299(1), 109–119.
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.
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Miquel Angel Piera, Jose Luis Muñoz, Debora Gil, Gonzalo Martin, & Jordi Manzano. (2022). A Socio-Technical Simulation Model for the Design of the Future Single Pilot Cockpit: An Opportunity to Improve Pilot Performance. ACCESS - IEEE Access, 10, 22330–22343.
Abstract: The future deployment of single pilot operations must be supported by new cockpit computer services. Such services require an adaptive context-aware integration of technical functionalities with the concurrent tasks that a pilot must deal with. Advanced artificial intelligence supporting services and improved communication capabilities are the key enabling technologies that will render future cockpits more integrated with the present digitalized air traffic management system. However, an issue in the integration of such technologies is the lack of socio-technical analysis in the design of these teaming mechanisms. A key factor in determining how and when a service support should be provided is the dynamic evolution of pilot workload. This paper investigates how the socio-technical model-based systems engineering approach paves the way for the design of a digital assistant framework by formalizing this workload. The model was validated in an Airbus A-320 cockpit simulator, and the results confirmed the degraded pilot behavioral model and the performance impact according to different contextual flight deck information. This study contributes to practical knowledge for designing human-machine task-sharing systems.
Keywords: Human factors ; Performance evaluation ; Simulation; Sociotechnical systems ; System performance
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Guillermo Torres, Sonia Baeza, Carles Sanchez, Ignasi Guasch, Antoni Rosell, & Debora Gil. (2022). An Intelligent Radiomic Approach for Lung Cancer Screening. APPLSCI - Applied Sciences, 12(3), 1568.
Abstract: The efficiency of lung cancer screening for reducing mortality is hindered by the high rate of false positives. Artificial intelligence applied to radiomics could help to early discard benign cases from the analysis of CT scans. The available amount of data and the fact that benign cases are a minority, constitutes a main challenge for the successful use of state of the art methods (like deep learning), which can be biased, over-fitted and lack of clinical reproducibility. We present an hybrid approach combining the potential of radiomic features to characterize nodules in CT scans and the generalization of the feed forward networks. In order to obtain maximal reproducibility with minimal training data, we propose an embedding of nodules based on the statistical significance of radiomic features for malignancy detection. This representation space of lesions is the input to a feed
forward network, which architecture and hyperparameters are optimized using own-defined metrics of the diagnostic power of the whole system. Results of the best model on an independent set of patients achieve 100% of sensitivity and 83% of specificity (AUC = 0.94) for malignancy detection.
Keywords: Lung cancer; Early diagnosis; Screening; Neural networks; Image embedding; Architecture optimization
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Oriol Ramos Terrades, Albert Berenguel, & Debora Gil. (2022). A Flexible Outlier Detector Based on a Topology Given by Graph Communities. BDR - Big Data Research, 29, 100332.
Abstract: Outlier detection is essential for optimal performance of machine learning methods and statistical predictive models. Their detection is especially determinant in small sample size unbalanced problems, since in such settings outliers become highly influential and significantly bias models. This particular experimental settings are usual in medical applications, like diagnosis of rare pathologies, outcome of experimental personalized treatments or pandemic emergencies. In contrast to population-based methods, neighborhood based local approaches compute an outlier score from the neighbors of each sample, are simple flexible methods that have the potential to perform well in small sample size unbalanced problems. A main concern of local approaches is the impact that the computation of each sample neighborhood has on the method performance. Most approaches use a distance in the feature space to define a single neighborhood that requires careful selection of several parameters, like the number of neighbors.
This work presents a local approach based on a local measure of the heterogeneity of sample labels in the feature space considered as a topological manifold. Topology is computed using the communities of a weighted graph codifying mutual nearest neighbors in the feature space. This way, we provide with a set of multiple neighborhoods able to describe the structure of complex spaces without parameter fine tuning. The extensive experiments on real-world and synthetic data sets show that our approach outperforms, both, local and global strategies in multi and single view settings.
Keywords: Classification algorithms; Detection algorithms; Description of feature space local structure; Graph communities; Machine learning algorithms; Outlier detectors
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