Appropriate wound management shortens the healing times and reduces the management costs, benefiting the patient in physical terms and potentially reducing the healthcare system’s economic burden. Among the instrumental measurement methods, the image analysis of a wound area is becoming one of the cornerstones of chronic ulcer management. Our study aim is to develop a solid AI method based on a convolutional neural network to segment the wounds efficiently to make the work of the physician more efficient, and subsequently, to lay the foundations for the further development of more in-depth analyses of ulcer characteristics. In this work, we introduce a fully automated model for identifying and segmenting wound areas which can completely automatize the clinical wound severity assessment starting from images acquired from smartphones. This method is based on an active semi-supervised learning training of a convolutional neural network model. In our work, we tested the robustness of our method against a wide range of natural images acquired in different light conditions and image expositions. We collected the images using an ad hoc developed app and saved them in a database which we then used for AI training. We then tested different CNN architectures to develop a balanced model, which we finally validated with a public dataset. We used a dataset of images acquired during clinical practice and built an annotated wound image dataset consisting of 1564 ulcer images from 474 patients. Only a small part of this large amount of data was manually annotated by experts (ground truth). A multi-step, active, semi-supervised training procedure was applied to improve the segmentation performances of the model. The developed training strategy mimics a continuous learning approach and provides a viable alternative for further medical applications. We tested the efficiency of our model against other public datasets, proving its robustness. The efficiency of the transfer learning showed that after less than 50 epochs, the model achieved a stable DSC that was greater than 0.95. The proposed active semi-supervised learning strategy could allow us to obtain an efficient segmentation method, thereby facilitating the work of the clinician by reducing their working times to achieve the measurements. Finally, the robustness of our pipeline confirms its possible usage in clinical practice as a reliable decision support system for clinicians.

PURPOSE: Tumor Protein 53 (p53) expressed from gene TP53 is a seminal tumor suppressor. We aimed to characterize mutational and nonmutational mechanisms of p53 dysfunction in myelodysplastic syndromes (MDS) and to investigate their clinical effect. PATIENTS AND METHODS: We analyzed a cohort of 6,204 patients with MDS and subsets of patients with available information on RNA sequencing of tumor cells (n = 109), high-dimensional phenotype of immune cells (n = 77), and multiomics analysis (RNA sequencing and proteomics) on single cells (n = 15). An independent validation was performed on 914 patients. RESULTS: Biallelic TP53 inactivation was a powerful driver of disease progression and identified high-risk patients, regardless of variant allele frequency. Monoallelic and biallelic inactivation represent disease stages occurring as a multihit process in MDS with TP53 mutations, thus potentially refining the optimal timing of therapeutic interventions in these patients. We identified a subset of MDS (5%) characterized by TP53 wild-type and hyperexpression of abnormal p53 protein in bone marrow progenitors that exhibit dismal outcome. These patients presented upstream p53 signaling aberrations in Pi3K cascade; RAS, WNT, and NF-KB pathways; and MDM2 gene amplification, together with a downstream dysregulation of p53 targets. MDS with p53 dysfunction displayed a distinct immune dysregulation involving myeloid-derived inflammation and impaired antigen presentation, which may be a driver of their poor prognosis and provide the groundwork for innovative immunotherapies. CONCLUSION: The identification of nonmutational p53 dysfunction in MDS may lay the foundation for a mechanistic classification of myeloid neoplasms, moving beyond a purely molecular stratification. The recognition of patients with p53 dysfunction is relevant to provide correct disease-risk assessment and interventions, as well as to refine the design of clinical trials

Campylobacter spp. are a leading and increasing cause of gastrointestinal infections worldwide. Source attribution, which apportions human infection cases to different animal species and food reservoirs, has been instrumental in control- and evidence-based intervention efforts. The rapid increase in whole-genome sequencing data provides an opportunity for higher-resolution source attribution models. Important challenges, including the high dimension and complex structure of WGS data, have inspired concerted research efforts to develop new models. We propose network analysis models as an accurate, high-resolution source attribution approach for the sources of human campylobacteriosis. A weighted network analysis approach was used in this study for source attribution comparing different WGS data inputs. The compared model inputs consisted of cgMLST and wgMLST distance matrices from 717 human and 717 animal isolates from cattle, chickens, dogs, ducks, pigs and turkeys. SNP distance matrices from 720 human and 720 animal isolates were also used. The data were collected from 2015 to 2017 in Denmark, with the animal sources consisting of domestic and imports from 7 European countries. Clusters consisted of network nodes representing respective genomes and links representing distances between genomes. Based on the results, animal sources were the main driving factor for cluster formation, followed by type of species and sampling year. The coherence source clustering (CSC) values based on animal sources were $78\%$, $81\%$ and $78\%$ for cgMLST, wgMLST and SNP, respectively. The CSC values based on Campylobacter species were $78\%$, $79\%$ and $69\%$ for cgMLST, wgMLST and SNP, respectively. Including human isolates in the network resulted in $88\%$, $77\%$ and $88\%$ of the total human isolates being clustered with the different animal sources for cgMLST, wgMLST and SNP, respectively. Between $12\%$ and $23\%$ of human isolates were not attributed to any animal source. Most of the human genomes were attributed to chickens from Denmark, with an average attribution percentage of $52.8\%$, $52.2\%$ and $51.2\%$ for cgMLST, wgMLST and SNP distance matrices respectively, while ducks from Denmark showed the least attribution of $0\%$ for all three distance matrices. The best-performing model was the one using wgMLST distance matrix as input data, which had a CSC value of $81\%$. Results from our study show that the weighted network-based approach for source attribution is reliable and can be used as an alternative method for source attribution considering the high performance of the model. The model is also robust across the different Campylobacter species, animal sources and WGS data types used as input.

Background: Rectal cancer is a malignant neoplasm of the large intestine resulting from the uncontrolled proliferation of the rectal tract. Predicting the pathologic response of neoadjuvant chemoradiotherapy at an MRI primary staging scan in patients affected by locally advanced rectal cancer (LARC) could lead to significant improvement in the survival and quality of life of the patients. In this study, the possibility of automatizing this estimation from a primary staging MRI scan, using a fully automated artificial intelligence-based model for the segmentation and consequent characterization of the tumor areas using radiomic features was evaluated. The TRG score was used to evaluate the clinical outcome. Methods: Forty-three patients under treatment in the IRCCS Sant’Orsola-Malpighi Polyclinic were retrospectively selected for the study; a U-Net model was trained for the automated segmentation of the tumor areas; the radiomic features were collected and used to predict the tumor regression grade (TRG) score. Results: The segmentation of tumor areas outperformed the state-of-the-art results in terms of the Dice score coefficient or was comparable to them but with the advantage of considering mucinous cases. Analysis of the radiomic features extracted from the lesion areas allowed us to predict the TRG score, with the results agreeing with the state-of-the-art results. Conclusions: The results obtained regarding TRG prediction using the proposed fully automated pipeline prove its possible usage as a viable decision support system for radiologists in clinical practice.

Campylobacter spp. are the most common cause of bacterial gastrointestinal infection in humans both in Denmark and worldwide. Studies have found microbial subtyping to be a powerful tool for source attribution, but comparisons of different methodologies are limited. In this study, we compare three source attribution approaches (Machine Learning, Network Analysis, and Bayesian modeling) using three types of whole genome sequences (WGS) data inputs (cgMLST, 5-Mers and 7-Mers). We predicted and compared the sources of human campylobacteriosis cases in Denmark. Using 7mer as an input feature provided the best model performance. The network analysis algorithm had a CSC value of $78.99\%$ and an F1-score value of $67\%$, while the machine-learning algorithm showed the highest accuracy ($98\%$). The models attributed between 965 and all of the 1224 human cases to a source (network applying 5mer and machine learning applying 7mer, respectively). Chicken from Denmark was the primary source of human campylobacteriosis with an average percentage probability of attribution of $45.8\%$ to $65.4\%$, representing Bayesian with 7mer and machine learning with cgMLST, respectively. Our results indicate that the different source attribution methodologies based on WGS have great potential for the surveillance and source tracking of Campylobacter. The results of such models may support decision makers to prioritize and target interventions.

Background: Radiomics is a field of research medicine and data science in which quantitative imaging features are extracted from medical images and successively analyzed to develop models for providing diagnostic, prognostic, and predictive information. The purpose of this work was to develop a machine learning model to predict the survival probability of 85 cervical cancer patients using PET and CT radiomic features as predictors. Methods: Initially, the patients were divided into two mutually exclusive sets: a training set containing 80% of the data and a testing set containing the remaining 20%. The entire analysis was separately conducted for CT and PET features. Genetic algorithms and LASSO regression were used to perform feature selection on the initial PET and CT feature sets. Two different survival models were employed: the Cox proportional hazard model and random survival forest. The Cox model was built using the subset of features obtained with the feature selection process, while all the available features were used for the random survival forest model. The models were trained on the training set; cross-validation was used to fine-tune the models and to obtain a preliminary measurement of the performance. The models were then validated on the test set, using the concordance index as the metric. In addition, alternative versions of the models were developed using tumor recurrence as an adjunct feature to evaluate its impact on predictive performance. Finally, the selected CT and PET features were combined to build a further Cox model. Results: The genetic algorithm was superior to the LASSO regression for feature selection. The best performing model was the Cox model, which was built using the selected CT features; it achieved a concordance index score of 0.707. With the addition of tumor recurrence as a predictive feature, the Cox CT model reached a concordance index score of 0.776. PET features, however, proved to be inadequate for survival prediction. The CT model performed better than the model with combined PET and CT features. Conclusions: The results showed that radiomic features can be used to successfully predict survival probability in cervical cancer patients. In particular, CT radiomic features proved to be better predictors than PET radiomic features in this specific case.