Operational tolerance research in liver transplantation: a bibliometric analysis using a new web resource.

Background: Operational tolerance in liver transplantation (OT-LT), defined as the graft survival with normal function in absence of immunosuppression, has been a field of intense research since the 1980s. Thereafter, tens of clinical trials and hundreds of articles have been published, making it challenging for researchers to assimilate all the information, more so outside of their disciplines. The aim of the present study was to analyze the research in OT-LT through a new web tool (https://tolerance.imib.es). Methods: We have developed a web resource that allowed the identification of the present trends and potential research avenues in OL-LT, an overview biomedical terms that were most often cited, including which journals published the most articles, and an advanced search engine that exploited all the information in these publications. Results: A total of 734 studies were analyzed until November 2023, with a mean of 15 articles published per year, a total sum of 3,751 impact factor points and a total of 26,542 citations. The analysis of citations allowed us to establish a ranking of the most prolific countries, authors, journals and institutions, in addition to the most influential publications in OT-LT. Likewise, keyword and co-occurrence analyses answered which themes involving OT-LT are the most popular, whereas cooperation analysis showed that principal authors in OT-LT form a network, although the lack of international cooperation, especially with regard to clinical trials, appears to be one of the main challenges. Conclusion: Despite its limitations, our web tool will allow both OT-LT expert and novel researchers to be able to draw a comprehensive picture of the past, present and future of OT-LT research.

Efficiency of Machine Learning Algorithms for the Determination of Macrovesicular Steatosis in Frozen Sections Stained with Sudan to Evaluate the Quality of the Graft in Liver Transplantation.

Liver transplantation is the only curative treatment option in patients diagnosed with end-stage liver disease. The low availability of organs demands an accurate selection procedure based on histological analysis, in order to evaluate the allograft. This assessment, traditionally carried out by a pathologist, is not exempt from subjectivity. In this sense, new tools based on machine learning and artificial vision are continuously being developed for the analysis of medical images of different typologies. Accordingly, in this work, we develop a computer vision-based application for the fast and automatic objective quantification of macrovesicular steatosis in histopathological liver section slides stained with Sudan stain. For this purpose, digital microscopy images were used to obtain thousands of feature vectors based on the RGB and CIE L*a*b* pixel values. These vectors, under a supervised process, were labelled as fat vacuole or non-fat vacuole, and a set of classifiers based on different algorithms were trained, accordingly. The results obtained showed an overall high accuracy for all classifiers (>0.99) with a sensitivity between 0.844 and 1, together with a specificity >0.99. In relation to their speed when classifying images, KNN and Naïve Bayes were substantially faster than other classification algorithms. Sudan stain is a convenient technique for evaluating ME in pre-transplant liver biopsies, providing reliable contrast and facilitating fast and accurate quantification through the machine learning algorithms tested.

Genetic Factors Involved in Cardiomyopathies and in Cancer.

Cancer therapy-induced cardiomyopathy (CCM) manifests as left ventricular (LV) dysfunction and heart failure (HF). It is associated withparticular pharmacological agents and it is typically dose dependent, but significant individual variability has been observed. History of prior cardiac disease, abuse of toxics, cardiac overload conditions, age, and genetic predisposing factors modulate the degree of the cardiac reserve and the response to the injury. Genetic/familial cardiomyopathies (CMY) are increasingly recognized in general populations with an estimated prevalence of 1:250. Association between cardiac and oncologic diseases regarding genetics involves not only the toxicity process, but pathogenicity. Genetic variants in germinal cells that cause CMY (LMNA, RAS/MAPK) can increase susceptibility for certain types of cancer. The study of mutations found in cancer cells (somatic) has revealed the implication of genes commonly associated with the development of CMY. In particular, desmosomal mutations have been related to increased undifferentiation and invasiveness of cancer. In this article, the authors review the knowledge on the relevance of environmental and genetic background in CCM and give insights into the shared genetic role in the pathogenicity of the cancer process and development of CMY.

Biology and Therapeutic Targets of Colorectal Serrated Adenocarcinoma; Clues for a Histologically Based Treatment against an Aggressive Tumor.

Serrated adenocarcinoma (SAC) is a tumor recognized by the WHO as a histological subtype accounting for around 9% of colorectal carcinomas. Compared to conventional carcinomas, SACs are characterized by a worse prognosis, weak development of the immune response, an active invasive front and a frequent resistance to targeted therapy due to a high occurrence of KRAS or BRAF mutation. Nonetheless, several high-throughput studies have recently been carried out unveiling the biology of this cancer and identifying potential molecular targets, favoring a future histologically based treatment. This review revises the current evidence, aiming to propose potential molecular targets and specific treatments for this aggressive tumor.

ColPortal, an integrative multiomic platform for analysing epigenetic interactions in colorectal cancer.

Colorectal cancer (CRC) is the third leading cause of cancer mortality worldwide. Different pathological pathways and molecular drivers have been described and some of the associated markers are used to select effective anti-neoplastic therapy. More recent evidence points to a causal role of microbiota and altered microRNA expression in CRC carcinogenesis, but their relationship with pathological drivers or molecular phenotypes is not clearly established. Joint analysis of clinical and omics data can help clarify such relations. We present ColPortal, a platform that integrates transcriptomic, microtranscriptomic, methylomic and microbiota data of patients with colorectal cancer. ColPortal also includes detailed information of histological features and digital histological slides from the study cases, since histology is a morphological manifestation of a complex molecular change. The current cohort consists of Caucasian patients from Europe. For each patient, demographic information, location, histology, tumor staging, tissue prognostic factors, molecular biomarker status and clinical outcomes are integrated with omics data. ColPortal allows one to perform multiomics analyses for groups of patients selected by their clinical data.

Analysis and visualization of disease courses in a semantically-enabled cancer registry.

BACKGROUND: Regional and epidemiological cancer registries are important for cancer research and the quality management of cancer treatment. Many technological solutions are available to collect and analyse data for cancer registries nowadays. However, the lack of a well-defined common semantic model is a problem when user-defined analyses and data linking to external resources are required. The objectives of this study are: (1) design of a semantic model for local cancer registries; (2) development of a semantically-enabled cancer registry based on this model; and (3) semantic exploitation of the cancer registry for analysing and visualising disease courses. RESULTS: Our proposal is based on our previous results and experience working with semantic technologies. Data stored in a cancer registry database were transformed into RDF employing a process driven by OWL ontologies. The semantic representation of the data was then processed to extract semantic patient profiles, which were exploited by means of SPARQL queries to identify groups of similar patients and to analyse the disease timelines of patients. Based on the requirements analysis, we have produced a draft of an ontology that models the semantics of a local cancer registry in a pragmatic extensible way. We have implemented a Semantic Web platform that allows transforming and storing data from cancer registries in RDF. This platform also permits users to formulate incremental user-defined queries through a graphical user interface. The query results can be displayed in several customisable ways. The complex disease timelines of individual patients can be clearly represented. Different events, e.g. different therapies and disease courses, are presented according to their temporal and causal relations. CONCLUSION: The presented platform is an example of the parallel development of ontologies and applications that take advantage of semantic web technologies in the medical field. The semantic structure of the representation renders it easy to analyse key figures of the patients and their evolution at different granularity levels.

Leveraging electronic healthcare record standards and semantic web technologies for the identification of patient cohorts.

BACKGROUND: The secondary use of electronic healthcare records (EHRs) often requires the identification of patient cohorts. In this context, an important problem is the heterogeneity of clinical data sources, which can be overcome with the combined use of standardized information models, virtual health records, and semantic technologies, since each of them contributes to solving aspects related to the semantic interoperability of EHR data. OBJECTIVE: To develop methods allowing for a direct use of EHR data for the identification of patient cohorts leveraging current EHR standards and semantic web technologies. MATERIALS AND METHODS: We propose to take advantage of the best features of working with EHR standards and ontologies. Our proposal is based on our previous results and experience working with both technological infrastructures. Our main principle is to perform each activity at the abstraction level with the most appropriate technology available. This means that part of the processing will be performed using archetypes (ie, data level) and the rest using ontologies (ie, knowledge level). Our approach will start working with EHR data in proprietary format, which will be first normalized and elaborated using EHR standards and then transformed into a semantic representation, which will be exploited by automated reasoning. RESULTS: We have applied our approach to protocols for colorectal cancer screening. The results comprise the archetypes, ontologies, and datasets developed for the standardization and semantic analysis of EHR data. Anonymized real data have been used and the patients have been successfully classified by the risk of developing colorectal cancer. CONCLUSIONS: This work provides new insights in how archetypes and ontologies can be effectively combined for EHR-driven phenotyping. The methodological approach can be applied to other problems provided that suitable archetypes, ontologies, and classification rules can be designed.