Immunoglobulin (IG) gene repertoire restrictions strongly support antigen selection in the pathogenesis of chronic lymphocytic leukemia (CLL). Given the emerging multifarious interactions between CLL and bystander T cells, we sought to determine whether antigen(s) are also selecting T cells in CLL. We performed a large-scale, next-generation sequencing (NGS) study of the T-cell repertoire, focusing on major stereotyped subsets representing CLL subgroups with undisputed antigenic drive, but also included patients carrying non-subset IG rearrangements to seek for T-cell immunogenetic signatures ubiquitous in CLL. Considering the inherent limitations of NGS, we deployed bioinformatics algorithms for qualitative curation of T-cell receptor rearrangements, and included multiple types of controls. Overall, we document the clonal architecture of the T-cell repertoire in CLL. These T-cell clones persist and further expand overtime, and can be shared by different patients, most especially patients belonging to the same stereotyped subset. Notably, these shared clonotypes appear to be disease-specific, as they are found in neither public databases nor healthy controls. Altogether, these findings indicate that antigen drive likely underlies T-cell expansions in CLL and may be acting in a CLL subset-specific context. Whether these are the same antigens interacting with the malignant clone or tumor-derived antigens remains to be elucidated.

Next Generation Sequencing (NGS) technologies has revolutionized genomics data research by facilitating high-throughput sequencing of genetic material that comes from different sources, such as Whole Exome Sequencing (WES) and RNA Sequencing (RNAseq). The exploitation and integration of this wealth of heterogeneous sequencing data remains a major challenge. There is a clear need for approaches that attempt to process and combine the aforementioned sources in order to create an integrated profile of a patient that will allow us to build the complete picture of a disease. This work introduces such an integrated profile using Chronic Lymphocytic Leukemia (CLL) as the exemplary cancer type. The approach described in this paper links the various NGS sources with the patients’ clinical data. The resulting profile efficiently summarizes the large-scale datasets, links the results with the clinical profile of the patient and correlates indicators arising from different data types. With the use of state-of-the-art machine learning techniques and the association of the clinical information with these indicators, which served as the feature pool for the classification, it has been possible to build efficient predictive models. To ensure reproducibility of the results, open data were exclusively used in the classification assessment. The final goal is to design a complete genomic profile of a cancer patient. The profile includes summarization and visualization of the results of WES and RNAseq analysis (specific variants and significantly expressed genes, respectively) and the clinical profile, integration/comparison of these results and a prediction regarding the disease trajectory. Concluding, this work has managed to produce a comprehensive clinico-genetic profile of a patient by successfully integrating heterogeneous data sources. The proposed profile can contribute to the medical research providing new possibilities in personalized medicine and prognostic views.

Background People with non‐alcoholic fatty liver disease (NAFLD) and non‐alcoholic steatohepatitis (NASH) are stigmatized, partly since ‘non‐alcoholic’ is in the name, but also because of obesity, which is a common condition in this group. Stigma is pervasive in social media and can contribute to poorer health outcomes. We examine how stigma and negative feelings concerning NAFLD/NASH and obesity manifest on Twitter. Methods Using a self‐developed search terms index, we collected NAFLD/NASH tweets from May to October 2019 (Phase I). Because stigmatizing NAFLD/NASH tweets were limited, Phase II focused on obesity (November‐December 2019). Via sentiment analysis, >5000 tweets were annotated as positive, neutral or negative and used to train machine learning–based Natural Language Processing software, applied to 193 747 randomly sampled tweets. All tweets collected were analysed. Results In Phase I, 16 835 tweets for NAFLD and 2376 for NASH were retrieved. Of the annotated NAFLD/NASH tweets, 97/1130 (8.6%) and 63/535 (11.8%), respectively, related to obesity and 13/1130 (1.2%) and 5/535 (0.9%), to stigma; they primarily focused on scientific discourse and unverified information. Of the 193 747 non‐annotated obesity tweets (Phase II), the algorithm classified 40.0% as related to obesity, of which 85.2% were negative, 1.0% positive and 13.7% neutral. Conclusions NAFLD/NASH tweets mostly indicated an unmet information need and showed no clear signs of stigma. However, the negative content of obesity tweets was recurrent. As obesity‐related stigma is associated with reduced care engagement and lifestyle modification, the main NAFLD/NASH treatment, stigma‐reducing interventions in social media should be included in the liver health agenda.

PURPOSE Capitalizing on the promise of patient-reported outcomes (PROs), electronic implementations of PROs (ePROs) are expected to play an important role in the development of novel digital health interventions targeting palliative cancer care. We performed a systematic and mapping review of the scientific literature on the current ePRO-based approaches used for palliative cancer care. METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines, the conducted review answered the research questions: “What are the current ePRO-based approaches for palliative cancer care; what is their contribution/value in the domain of palliative cancer care; and what are the potential gaps, challenges, and opportunities for further research?” After a screening step, the corpus of included articles indexed in PubMed or the Web of Science underwent full text review, which mapped the articles across 15 predefined axes. RESULTS The corpus of 24 mapped studies includes 9 study protocols, 7 technical tools/solutions, 7 pilot/feasibility/acceptability studies, and 1 evaluation study. The review of the corpus revealed (1) an archetype of ePRO-enabled interventions for palliative cancer care, which most commonly use ePROs as study end point assessment instruments rather than integral intervention components; (2) the fact that the literature has not fully embraced the modern definitions that expand the scope of palliative care; (3) the striking shortage of promising ubiquitous computing devices (eg, smart activity trackers); and (4) emerging evidence about the benefits of narrowing down the target cancer population, especially when combined with modern patient-centered intervention design methodologies. CONCLUSION Although research on exploiting ePROs for the development of digital palliative cancer care interventions is considerably active and demonstrates several successful cases, there is considerable room for improvement along the directions of the aforementioned findings.

Background Obesity interventions face the problem of weight regain after treatment as a result of low compliance. Mobile health (mHealth) technologies could potentially increase compliance and aid both health care providers and patients. Objective This study aimed to evaluate the acceptability and usability and define system constraints of an mHealth system used to monitor dietary habits of adolescents in real life, as a first step in the development of a self-monitoring and lifestyle management system against adolescent obesity. Methods We recruited 26 students from a high school in Stockholm, Sweden. After a 30-minute information meeting and 5-minute individual instruction on how to use an mHealth system (smartphone with app and two external sensors), participants used it for 2-3 weeks to objectively collect dietary habits. The app and sensors were used by the participants, without supervision, to record as many main meals and snacks as possible in real life. Feasibility was assessed following the “mHealth evidence reporting and assessment checklist,” and usability was assessed by questionnaires. Compliance was estimated based on system use, where a registration frequency of 3 main meals (breakfast, lunch, and dinner) per day for the period of the experiment, constituted 100% compliance. Results Participants included in the analysis had a mean age of 16.8 years (SD 0.7 years) and BMI of 21.9 kg/m2 (SD 4.1 kg/m2). Due to deviations from study instructions, 2 participants were excluded from the analysis. During the study, 6 participants required additional information on system use. The system received a ‘Good’ grade (77.1 of 100 points) on the System Usability Scale, with most participants reporting that they were comfortable using the smartphone app. Participants expressed a willingness to use the app mostly at home, but also at school; most of their improvement suggestions concerned design choices for the app. Of all main meals, the registration frequency increased from 70% the first week to 76% the second week. Participants reported that 40% of the registered meals were home-prepared, while 34% of the reported drinks contained sugar. On average, breakfasts took place at 8:30 AM (from 5:00 AM to 2:00 PM), lunches took place at 12:15 PM (from 10:15 AM to 6:15 PM), and dinners took place at 7:30 PM (from 3:00 PM to 11:45 PM). When comparing meal occurrence during weekdays vs weekends, breakfasts and lunches were eaten 3 hours later during weekends, while dinner timing was unaffected. Conclusions From an infrastructural and functional perspective, system use was feasible in the current context. The smartphone app appears to have high acceptability and usability in high school students, which are the intended end-users. The system appears promising as a relatively low-effort method to provide real-life dietary habit measurements associated with overweight and obesity risk.