Metadata Correction: Patient Empowerment During the COVID-19 Pandemic by Ensuring Safe and Fast Communication of Test Results: Implementation and Performance of a Tracking System.

[This corrects the article DOI: 10.2196/27348.].

Patient Empowerment During the COVID-19 Pandemic by Ensuring Safe and Fast Communication of Test Results: Implementation and Performance of a Tracking System.

BACKGROUND: Overcoming the COVID-19 crisis requires new ideas and strategies for online communication of personal medical information and patient empowerment. Rapid testing of a large number of subjects is essential for monitoring and delaying the spread of SARS-CoV-2 in order to mitigate the pandemic's consequences. People who do not know that they are infected may not stay in quarantine and, thus, risk infecting others. Unfortunately, the massive number of COVID-19 tests performed is challenging for both laboratories and the units that conduct throat swabs and communicate the results. OBJECTIVE: The goal of this study was to reduce the communication burden for health care professionals. We developed a secure and easy-to-use tracking system to report COVID-19 test results online that is simple to understand for the tested subjects as soon as these results become available. Instead of personal calls, the system updates the status and the results of the tests automatically. This aims to reduce the delay when informing testees about their results and, consequently, to slow down the virus spread. METHODS: The application in this study draws on an existing tracking tool. With this open-source and browser-based online tracking system, we aim to minimize the time required to inform the tested person and the testing units (eg, hospitals or the public health care system). The system can be integrated into the clinical workflow with very modest effort and avoids excessive load to telephone hotlines. RESULTS: The test statuses and results are published on a secured webpage, enabling regular status checks by patients; status checks are performed without the use of smartphones, which has some importance, as smartphone usage diminishes with age. Stress tests and statistics show the performance of our software. CTest is currently running at two university hospitals in Germany-University Hospital Ulm and University Hospital Tübingen-with thousands of tests being performed each week. Results show a mean number of 10 (SD 2.8) views per testee. CONCLUSIONS: CTest runs independently of existing infrastructures, aims at straightforward integration, and aims for the safe transmission of information. The system is easy to use for testees. QR (Quick Response) code links allow for quick access to the test results. The mean number of views per entry indicates a reduced amount of time for both health care professionals and testees. The system is quite generic and can be extended and adapted to other communication tasks.

Analysis, identification and visualization of subgroups in genomics.

MOTIVATION: Cancer is a complex and heterogeneous disease involving multiple somatic mutations that accumulate during its progression. In the past years, the wide availability of genomic data from patients' samples opened new perspectives in the analysis of gene mutations and alterations. Hence, visualizing and further identifying genes mutated in massive sets of patients are nowadays a critical task that sheds light on more personalized intervention approaches. RESULTS: Here, we extensively review existing tools for visualization and analysis of alteration data. We compare different approaches to study mutual exclusivity and sample coverage in large-scale omics data. We complement our review with the standalone software AVAtar ('analysis and visualization of alteration data') that integrates diverse aspects known from different tools into a comprehensive platform. AVAtar supplements customizable alteration plots by a multi-objective evolutionary algorithm for subset identification and provides an innovative and user-friendly interface for the evaluation of concurrent solutions. A use case from personalized medicine demonstrates its unique features showing an application on vaccination target selection. AVAILABILITY: AVAtar is available at: https://github.com/sysbio-bioinf/avatar. CONTACT: hans.kestler@uni-ulm.de, phone: +49 (0) 731 500 24 500, fax: +49 (0) 731 500 24 502.

Peripheral Cytokine Levels Differ by HPV Status and Change Treatment-Dependently in Patients with Head and Neck Squamous Cell Carcinoma.

Cytokines and immune mediators play an important role in the communication between immune cells guiding their response to infectious diseases or cancer. In this study, a comprehensive longitudinal analysis of serum cytokines and immune mediators in head and neck squamous cell carcinoma (HNSCC) patients was performed. In a prospective, non-interventional, longitudinal study, blood samples from 22 HNSCC patients were taken at defined time points (TP) before, during, and every 3 months after completion of (chemo)radio)therapy (CRT/RT) until 12 months after treatment. Serum concentrations of 17 cytokines/immune mediators and High-Mobility-Group-Protein B1 (HMGB1) were measured by fluorescent bead array and ELISA. Concentrations of sFas were significantly elevated during and after CRT/RT, whereas perforin levels were significantly decreased after CRT/RT. Levels of MIP-1ß and Granzyme B differed significantly during CRT/RT by HPV status. Increased HMGB1 levels were observed at recurrence, accompanied by high levels of IL-4 and IL-10. The sFas increase and simultaneous perforin decrease may indicate an impaired immune cell function during adjuvant radiotherapy. Increased levels of pro-inflammatory cytokines in HPV+ compared to HPV- patients seem to reflect the elevated immunogenicity of HPV-positive tumors. High levels of HMGB1 and anti-inflammatory cytokines at recurrence may be interpreted as a sign of immune evasion.

Patterns of antibody responses to nonviral cancer antigens in head and neck squamous cell carcinoma patients differ by human papillomavirus status.

There have been hints that nonviral cancer antigens are differentially expressed in human papillomavirus (HPV)-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC). Antibody responses (AR) to cancer antigens may be used to indirectly determine cancer antigen expression in the tumor using a noninvasive and tissue-saving liquid biopsy. Here, we set out to characterize AR to a panel of nonviral cancer antigens in HPV-positive and HPV-negative HNSCC patients. A fluorescent microbead multiplex serology to 29 cancer antigens (16 cancer-testis antigens, 5 cancer-retina antigens and 8 oncogenes) and 29 HPV-antigens was performed in 382 HNSCC patients from five independent cohorts (153 HPV-positive and 209 HPV-negative). AR to any of the cancer antigens were found in 272/382 patients (72%). The ten most frequent AR were CT47, cTAGE5a, c-myc, LAGE-1, MAGE-A1, -A3, -A4, NY-ESO-1, SpanX-a1 and p53. AR to MAGE-A3, MAGE-A9 and p53 were found at significantly different prevalences by HPV status. An analysis of AR mean fluorescent intensity values uncovered remarkably different AR clusters by HPV status. To identify optimal antigen selections covering a maximum of patients with ≤10 AR, multiobjective optimization revealed distinct antigen selections by HPV status. We identified that AR to nonviral antigens differ by HPV status indicating differential antigen expression. Multiplex serology may be used to characterize antigen expression using serum or plasma as a tissue-sparing liquid biopsy. Cancer antigen panels should address the distinct antigen repertoire of HPV-positive and HPV-negative HNSCC.

Antibody Responses to Cancer Antigens Identify Patients with a Poor Prognosis among HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinoma Patients.

PURPOSE: The identification of high-risk patients within human papillomavirus (HPV)-positive and -negative head and neck squamous cell carcinoma (HNSCC) is needed for improved treatment and surveillance strategies. In this study, we set out to discover antibody responses (AR) with prognostic impact in HNSCC stratified by HPV status. EXPERIMENTAL DESIGN: A fluorescent bead-based multiplex serology assay on 29 cancer antigens (16 cancer-testis antigens, 5 cancer-retina antigens, and 8 oncogenes) and 29 HPV antigens was performed in samples of 362 patients with HNSCC from five independent cohorts (153 HPV positive, 209 HPV negative). A multivariable Cox proportional hazard model with bootstrapping (M = 1000) was used for validation of prognostic antibody responses. RESULTS: Antibody response to any of the cancer antigens was found in 257 of 362 patients (71%). In HPV-negative patients, antibody responses to c-myc, MAGE-A1, -A4, and Rhodopsin E2 (combined as ARhigh risk) were significantly associated with shorter overall survival. In HPV-positive patients, antibody responses to IMP-1 were discovered as a negative prognostic factor. ARhigh risk (HR = 1.76) and antibody responses to IMP-1 (HR = 3.28) were confirmed as independent markers for a poor prognosis in a multivariable Cox proportional hazard model with bootstrapping (M = 1000). CONCLUSIONS: We identified antibody responses to cancer antigens that associate with a dismal prognosis in patients with HNSCC beyond HPV-positive status. ARhigh risk may be used to detect HPV-negative patients with an extraordinarily bad prognosis. Most importantly, antibody response to IMP-1 may serve as a marker for a subgroup of HPV-positive patients who present with a poor prognosis similar to that in HPV-negative patients.

TraqBio - Flexible Progress Tracking for Core Unit Projects.

MOTIVATION: Core service units have become an organisational hallmark in many research institutions world wide. Such service cores provide complex state-of-the-art technologies and expertise to the research community. Typically, a user delivers material or raw data to a core. The core defines work packages for ensuing analysis and returns results back to the user. This core activity can be quite complex and time consuming and usually does not communicate itself to the outside. Naturally, the user is highly interested to follow the progress of a project once handed over to the core unit. This generates a time-intensive direct communication activity back and forth. A more effective, convenient and less disruptive way to track the status of a given project by the researcher, but also by core managers, appears highly desirable. Hence, we developed a lightweight and readily implementable web application that allows efficient progress tracking of core unit projects. RESULTS: The web application TraqBio allows for the convenient tracking of projects. Following project set-up by the core, the user receives an e-mail containing links for tracking the project status. Examples are provided for three common core units, namely genomics, proteomics, and bioinformatics units. TraqBio is a secure lightweight web application that can be either used in a standalone setup or incorporated into an existing web server infrastructure. Being accessible not only from classical desktop computers but also from mobile devices such as smartphones and tablets, TraqBio offers easy integration into every day work.

Sputnik: ad hoc distributed computation.

MOTIVATION: In bioinformatic applications, computationally demanding algorithms are often parallelized to speed up computation. Nevertheless, setting up computational environments for distributed computation is often tedious. Aim of this project were the lightweight ad hoc set up and fault-tolerant computation requiring only a Java runtime, no administrator rights, while utilizing all CPU cores most effectively. RESULTS: The Sputnik framework provides ad hoc distributed computation on the Java Virtual Machine which uses all supplied CPU cores fully. It provides a graphical user interface for deployment setup and a web user interface displaying the current status of current computation jobs. Neither a permanent setup nor administrator privileges are required. We demonstrate the utility of our approach on feature selection of microarray data. AVAILABILITY AND IMPLEMENTATION: The Sputnik framework is available on Github http://github.com/sysbio-bioinf/sputnik under the Eclipse Public License. CONTACT: hkestler@fli-leibniz.de or hans.kestler@uni-ulm.de SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.