iCHECK-DH: Guidelines and Checklist for the Reporting on Digital Health Implementations.

BACKGROUND: Implementation of digital health technologies has grown rapidly, but many remain limited to pilot studies due to challenges, such as a lack of evidence or barriers to implementation. Overcoming these challenges requires learning from previous implementations and systematically documenting implementation processes to better understand the real-world impact of a technology and identify effective strategies for future implementation. OBJECTIVE: A group of global experts, facilitated by the Geneva Digital Health Hub, developed the Guidelines and Checklist for the Reporting on Digital Health Implementations (iCHECK-DH, pronounced "I checked") to improve the completeness of reporting on digital health implementations. METHODS: A guideline development group was convened to define key considerations and criteria for reporting on digital health implementations. To ensure the practicality and effectiveness of the checklist, it was pilot-tested by applying it to several real-world digital health implementations, and adjustments were made based on the feedback received. The guiding principle for the development of iCHECK-DH was to identify the minimum set of information needed to comprehensively define a digital health implementation, to support the identification of key factors for success and failure, and to enable others to replicate it in different settings. RESULTS: The result was a 20-item checklist with detailed explanations and examples in this paper. The authors anticipate that widespread adoption will standardize the quality of reporting and, indirectly, improve implementation standards and best practices. CONCLUSIONS: Guidelines for reporting on digital health implementations are important to ensure the accuracy, completeness, and consistency of reported information. This allows for meaningful comparison and evaluation of results, transparency, and accountability and informs stakeholder decision-making. i-CHECK-DH facilitates standardization of the way information is collected and reported, improving systematic documentation and knowledge transfer that can lead to the development of more effective digital health interventions and better health outcomes.

Correction: iCHECK-DH: Guidelines and Checklist for the Reporting on Digital Health Implementations.

[This corrects the article DOI: 10.2196/46694.].

Substituent Effects in π-Hole Regium Bonding Interactions Between Au(p-X-Py)2 Complexes and Lewis Bases: An ab initio Study.

Long range substituent effects in regium bonding interactions involving Au(I) linear complexes are investigated for the first time. The Au(I) atom is coordinated to two para-substituted pyridine ligands. The interaction energy (RI-MP2/def2-TZVP level of theory) of the π-hole regium bonding assemblies is affected by the pyridine substitution. The Hammett's plot representations for several sets of Lewis bases have been carried out and, in all cases, good regression plots have been obtained (interaction energies vs. Hammett's σ parameter). The Bader's theory of "atoms-in-molecules" has been used to evidence that the electron density computed at the bond critical point that connects the Au-atom to the electron donor can be used as a measure of bond order in regium bonding. Several X-ray structures retrieved from the Cambridge Structural Database (CSD) provide experimental support to the existence of π-hole regium bonding in [Au(Py)2 ]+ derivatives.

COVID-19: an opportunity of systematic integration for Chagas disease. Example of a community-based approach within the Bolivian population in Barcelona.

BACKGROUND: As a Neglected Tropical Disease associated with Latin America, Chagas Disease (CD) is little known in non-endemic territories of the Americas, Europe and Western Pacific, making its control challenging, with limited detection rates, healthcare access and consequent epidemiological silence. This is reinforced by its biomedical characteristics-it is usually asymptomatic-and the fact that it mostly affects people with low social and financial resources. Because CD is mainly a chronic infection, which principally causes a cardiomyopathy and can also cause a prothrombotic status, it increases the risk of contracting severe COVID-19. METHODS: In order to get an accurate picture of CD and COVID-19 overlapping and co-infection, this operational research draws on community-based experience and participative-action-research components. It was conducted during the Bolivian elections in Barcelona on a representative sample of that community. RESULTS: The results show that 55% of the people interviewed had already undergone a previous T. cruzi infection screening-among which 81% were diagnosed in Catalonia and 19% in Bolivia. The prevalence of T. cruzi infection was 18.3% (with 3.3% of discordant results), the SARS-CoV-2 22.3% and the coinfection rate, 6%. The benefits of an integrated approach for COVID-19 and CD were shown, since it only took an average of 25% of additional time per patient and undoubtedly empowered the patients about the co-infection, its detection and care. Finally, the rapid diagnostic test used for COVID-19 showed a sensitivity of 89.5%. CONCLUSIONS: This research addresses CD and its co-infection, through an innovative way, an opportunity of systematic integration, during the COVID-19 pandemic.

Nucleotide excision repair is impaired by binding of transcription factors to DNA.

Somatic mutations are the driving force of cancer genome evolution. The rate of somatic mutations appears to be greatly variable across the genome due to variations in chromatin organization, DNA accessibility and replication timing. However, other variables that may influence the mutation rate locally are unknown, such as a role for DNA-binding proteins, for example. Here we demonstrate that the rate of somatic mutations in melanomas is highly increased at active transcription factor binding sites and nucleosome embedded DNA, compared to their flanking regions. Using recently available excision-repair sequencing (XR-seq) data, we show that the higher mutation rate at these sites is caused by a decrease of the levels of nucleotide excision repair (NER) activity. Our work demonstrates that DNA-bound proteins interfere with the NER machinery, which results in an increased rate of DNA mutations at the protein binding sites. This finding has important implications for our understanding of mutational and DNA repair processes and in the identification of cancer driver mutations.

Sparking the Interest of Girls in Computer Science via Chemical Experimentation and Robotics: The Qui-Bot H2O Case Study.

We report a new learning approach in science and technology through the Qui-Bot H2O project: a multidisciplinary and interdisciplinary project developed with the main objective of inclusively increasing interest in computer science engineering among children and young people, breaking stereotypes and invisible social and gender barriers. The project highlights the social aspect of robotics applied to chemistry, at early ages. We successfully tested the project activities on girls between 3 to 13 years old. After taking part in the project, the users rated their interest in science and technology to be higher than before. Data collected during experiences included background information on students, measurements of the project's impact and students' interest in it, and an evaluation of student satisfaction of this STEM activity. The Qui-Bot H2O project is supported by the actions of territorial public administrations towards gender equality and the contributions of humanistic and technological universities and entities which specialize in education and business.

Enzymatic synthesis of N-acetyllactosamine from lactose enabled by recombinant ß1,4-galactosyltransferases.

Utilising a fast and sensitive screening method based on imidazolium-tagged probes, we report unprecedented reversible activity of bacterial ß1,4-galactosyltransferases to catalyse the transgalactosylation from lactose to N-acetylglucosamine to form N-acetyllactosamine in the presence of UDP. The process is demonstrated by the preparative scale synthesis of pNP-ß-LacNAc from lactose using ß1,4-galactosyltransferase NmLgtB-B as the only biocatalyst.

DisGeNET: a comprehensive platform integrating information on human disease-associated genes and variants.

The information about the genetic basis of human diseases lies at the heart of precision medicine and drug discovery. However, to realize its full potential to support these goals, several problems, such as fragmentation, heterogeneity, availability and different conceptualization of the data must be overcome. To provide the community with a resource free of these hurdles, we have developed DisGeNET (http://www.disgenet.org), one of the largest available collections of genes and variants involved in human diseases. DisGeNET integrates data from expert curated repositories, GWAS catalogues, animal models and the scientific literature. DisGeNET data are homogeneously annotated with controlled vocabularies and community-driven ontologies. Additionally, several original metrics are provided to assist the prioritization of genotype-phenotype relationships. The information is accessible through a web interface, a Cytoscape App, an RDF SPARQL endpoint, scripts in several programming languages and an R package. DisGeNET is a versatile platform that can be used for different research purposes including the investigation of the molecular underpinnings of specific human diseases and their comorbidities, the analysis of the properties of disease genes, the generation of hypothesis on drug therapeutic action and drug adverse effects, the validation of computationally predicted disease genes and the evaluation of text-mining methods performance.

Clinical Outcome of Ischemic Stroke in Old Patients Versus Oldest-Old.

BACKGROUND: It is unclear whether very old patients benefit from stroke unit. The aim of our work was to compare the clinical outcome of patients with ischemic stroke aged either 70 or 80 (G 1) versus oldest-old greater than or equal to 81 years (G 2). METHODS: Of 1187 patients admitted with stroke during 5 years in our stroke unit, we included 252 patients with independent functional status (modified Rankin scale, [mRS] ≤ 2) before the stroke. All patients underwent clinical examination, blood test, electrocardiography, brain imaging, and cerebrovascular ultrasound. Clinical outcome was assessed with the mRS and National Institutes of Health Stroke Scale (NIHSS) at discharge. We considered favorable outcome mRS 0-2 at discharge. RESULTS: Of 252 patients included, 55% were male, 150 (59.5%) patients belonged to G1 and 102 (40.5%) G2. We detected a significant increase of atrial fibrillation, bronchoaspiration, mortality, higher NIHSS at admission, and worse functional status at discharge in G2. No significant differences in other demographic, vascular risk factors, hospital stay, NIHSS at discharge or subtype of stroke were found. NIHSS at discharge was the only independent predictor of good functional status (odds ratio 0.4; 95% confidence interval, 0.3-0.6; P < .001). CONCLUSIONS: Oldest-old patients showed similar NIHSS at discharge than younger patients despite having higher neurological severity at admission. Our results support the hypothesis that oldest-old patients have good recovery potential, and should not be excluded from the stroke unit. The worse functional status detected at discharge in these patients could be attributed to others factors and not to neurological severity.

Plant cell wall imaging by metabolic click-mediated labelling of rhamnogalacturonan II using azido 3-deoxy-D-manno-oct-2-ulosonic acid.

In plants, 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) is a monosaccharide that is only found in the cell wall pectin, rhamnogalacturonan-II (RG-II). Incubation of 4-day-old light-grown Arabidopsis seedlings or tobacco BY-2 cells with 8-azido 8-deoxy Kdo (Kdo-N3 ) followed by coupling to an alkyne-containing fluorescent probe resulted in the specific in muro labelling of RG-II through a copper-catalysed azide-alkyne cycloaddition reaction. CMP-Kdo synthetase inhibition and competition assays showing that Kdo and D-Ara, a precursor of Kdo, but not L-Ara, inhibit incorporation of Kdo-N3 demonstrated that incorporation of Kdo-N3 occurs in RG-II through the endogenous biosynthetic machinery of the cell. Co-localisation of Kdo-N3 labelling with the cellulose-binding dye calcofluor white demonstrated that RG-II exists throughout the primary cell wall. Additionally, after incubating plants with Kdo-N3 and an alkynated derivative of L-fucose that incorporates into rhamnogalacturonan I, co-localised fluorescence was observed in the cell wall in the elongation zone of the root. Finally, pulse labelling experiments demonstrated that metabolic click-mediated labelling with Kdo-N3 provides an efficient method to study the synthesis and redistribution of RG-II during root growth.

IntOGen-mutations identifies cancer drivers across tumor types.

The IntOGen-mutations platform (http://www.intogen.org/mutations/) summarizes somatic mutations, genes and pathways involved in tumorigenesis. It identifies and visualizes cancer drivers, analyzing 4,623 exomes from 13 cancer sites. It provides support to cancer researchers, aids the identification of drivers across tumor cohorts and helps rank mutations for better clinical decision-making.

Remixing music using source separation algorithms to improve the musical experience of cochlear implant users.

Music perception remains rather poor for many Cochlear Implant (CI) users due to the users' deficient pitch perception. However, comprehensible vocals and simple music structures are well perceived by many CI users. In previous studies researchers re-mixed songs to make music more enjoyable for them, favoring the preferred music elements (vocals or beat) attenuating the others. However, mixing music requires the individually recorded tracks (multitracks) which are usually not accessible. To overcome this limitation, Source Separation (SS) techniques are proposed to estimate the multitracks. These estimated multitracks are further re-mixed to create more pleasant music for CI users. However, SS may introduce undesirable audible distortions and artifacts. Experiments conducted with CI users (N = 9) and normal hearing listeners (N = 9) show that CI users can have different mixing preferences than normal hearing listeners. Moreover, it is shown that CI users' mixing preferences are user dependent. It is also shown that SS methods can be successfully used to create preferred re-mixes although distortions and artifacts are present. Finally, CI users' preferences are used to propose a benchmark that defines the maximum acceptable levels of SS distortion and artifacts for two different mixes proposed by CI users.

jHeatmap: an interactive heatmap viewer for the web.

SUMMARY: The generation of large volumes of omics data to conduct exploratory studies has become feasible and is now extensively used to gain new insights in life sciences. The effective exploration of the generated data by experts is a crucial step for the successful extraction of knowledge from these datasets. This requires availability of intuitive and interactive visualization tools that can display complex data. Matrix heatmaps are graphical representations frequently used for the description of complex omics data. Here, we present jHeatmap, a web-based tool that allows interactive matrix heatmap visualization and exploration. It is an adaptable javascript library designed to be embedded by means of basic coding skills into web portals to visualize data matrices as interactive and customizable heatmaps. AVAILABILITY: jHeatmap is freely available at the GitHub code repository at https://github.com/jheatmap/jheatmap. Working examples and the documentation may be found at http://jheatmap.github.io/jheatmap.

Predictors of occult cancer in acute ischemic stroke patients.

BACKGROUND: We investigated the prevalence of occult malignancy (OM) in acute ischemic stroke patients to evaluate if any biological marker could help to detect the presence of OM. METHODS: We retrospectively reviewed all ischemic stroke patients during 48 months. We did not perform any screening for OM. Demographic data, vascular risk factors, routine blood chemistry with fibrinogen and C-reactive protein (CRP), National Institutes of Health Stroke Scale (NIHSS), and etiological subtype of stroke according to Trial of Org 10172 in Acute Stroke Treatment criteria were analyzed. The patients were divided into 2 groups (Non-OM versus OM). RESULTS: We analyzed 631 patients with acute ischemic stroke. The mean age was 69.7 ± 12.7 years, and 59% were men. The distribution of vascular risk factors, etiological subgroups, and NIHSS was comparable between both groups. We detected 13 cases (2.1%) with OM, and this percentage was higher in patients with stroke of undetermined etiology (5.3%). We detected significant higher levels of fibrinogen and CRP in patients with stroke of undetermined cause with OM. Receiver operating characteristic curves showed a sensitivity of 75% and specificity of 96% for levels of CRP more than 20 mg/L, and a sensitivity of 67% and specificity of 91% for fibrinogen levels greater than 600 mg/dL. CONCLUSIONS: OM was present in 2.1 % of overall patients, and 5.3% of patients with stroke of undetermined cause. Baseline levels of fibrinogen more than 600 mg/dL or CRP greater than 20 mg/L in patients with undetermined stroke might be good predictors of OM.

Identification of living Legionella pneumophila using species-specific metabolic lipopolysaccharide labeling.

Legionella pneumophila is a pathogenic bacterium involved in regular outbreaks characterized by a relatively high fatality rate and an important societal impact. Frequent monitoring of the presence of this bacterium in environmental water samples is necessary to prevent these epidemic events, but the traditional culture-based detection and identification method requires up to 10 days. Reported herein is a method allowing identification of Legionella pneumophila by metabolic lipopolysaccharide labeling which targets, for the first time, a precursor to monosaccharides that are specifically present within the O-antigen of the bacterium. This new approach allows easy detection of living Legionella pneumophila, while other Legionella species are not labeled.

Seroprevalence study prior and post vaccination in cancer patients in principality of Andorra (COVONCO study).

BACKGROUND: COVID-19 serologic response in patients with cancer may be lower than in the general population and may be influenced by the type of tumor or anticancer treatment. This study aims to analyze serological response prior and after vaccination of COVID-19 within the oncological population in Andorra. We set out to identify risk factors for a higher or lower serological response. PATIENTS AND METHODS: Observational, unicentric, prospective cohort study of oncologic patients in Andorra. We calculated the seroprevalence of antibodies against SARS-CoV-2 (May 2020-June 2021) and analyzed the main demographic, oncologic features and factors associated with being seropositive. RESULTS: A total of 373 patients were analyzed, mainly with solid tumours (n = 334, 89.5%). At baseline, seroprevalence was 13%, increasing during follow-up to 19%; lower seroprevalence was observed in patients with hematologic malignancies (2.6% vs 14.2%; p = 0.041) and patients receiving biological therapies (0% vs 15%, p = 0.005). In the overall seroprevalence analysis, women (23% vs 11.9%; p = 0.006) and tumour-free patients (p = 0.034) showed higher seroprevalence. The multivariable analysis showed that odds of being seropositive were higher among women (OR: 2.44, 95% CI 1.28-4.64), and patients who underwent surgery (OR: 3.35, 95% CI 1.10-10.20). About 80% of the cohort received at least one dose of COVID-19 vaccination, showing a higher seroprevalence of patients who received ChAdOx1-S than those who received BNT162b2 (24.4% vs 6.4%: p = 0.001). CONCLUSION: The seroprevalence of antibodies against SARS-COV-2 in oncologic patients in Andorra was higher among females and patients who received hormonal therapy and surgery while patients with hematologic malignancies and biologic therapies showed lower seropositivity without finding differences in the type of tumour or anticancer treatment.

EpidemiXs: Harnessing digital technology in the fight against COVID-19 and the associated infodemic.

BACKGROUND: EpidemiXs is an innovative ecosystem of digital tools centralizing official and validated information on COVID-19 for healthcare workers and the general public in a single hub. OBJECTIVE: The vision of EpidemiXs is to foster collaboration between researchers, institutions and individuals to promote "open data" in order to enrich the scientific community and further accelerate science in the fight against COVID-19. METHODS: Through its set of solutions, EpidemiXs Info, EpidemiXs TV and EpidemiXs Studies, this innovative ecosystem contributes to advancing collaborations, data collection and analysis, and helps find funders. RESULTS: EpidemiXs was launched in March 2020 in Spain with 30 healthcare institutions and rapidly reached close to 1 million users and 2 million views. EpidemiXs gained international recognition when it was awarded the Barcelona Health Hub Awards (BHHAwards) 2020 of the category "Best Startup Initiative to help tackle COVID-19". CONCLUSION: EpidemiXs has proven the efficiency of the rapid deployment of digital tools in times of COVID-19.

Design and Evaluation of a Novel Mobile Phone Application to Improve Palliative Home-Care in Resource-Limited Settings.

CONTEXT: Mobile health (mHealth) provides an opportunity to use internet coverage in low- and middle-income countries to improve palliative care access and quality. OBJECTIVES: This study aimed to design a mobile phone application (app) to enable or improve communication between family caregivers, community caregivers, and palliative care teams; to evaluate its acceptability, processes, and mechanisms of action; and to propose refinements. METHODS: A codesign process entailed collaboration between a Project Advisory Group and collaborators in India, Uganda, and Zimbabwe. We then trained community and family caregivers to use an app to communicate patient-reported outcomes to their palliative care providers each week on a data dashboard. App activity was monitored, and qualitative in-depth interviews explored experience with the app and its mechanisms and impact. RESULTS: N = 149 caregivers participated and uploaded n = 837 assessments of patient-reported outcomes. These data were displayed to the palliative care team on an outcomes dashboard on n = 355 occasions. Qualitative data identified: 1) high acceptability and data usage; 2) improved understanding by team members of patient symptoms and concerns; 3) a need for better feedback to caregivers, for better prioritisation of patients according to need, for enhanced training and support to use the app, and for user-led recommendations for ongoing improvement. CONCLUSION: An outcomes-focused app and data dashboard are acceptable to caregivers and health-care professionals. They are beneficial in identifying, monitoring, and communicating patient outcomes and in allocating staff resource to those most in need.

A compendium of mutational cancer driver genes.

A fundamental goal in cancer research is to understand the mechanisms of cell transformation. This is key to developing more efficient cancer detection methods and therapeutic approaches. One milestone towards this objective is the identification of all the genes with mutations capable of driving tumours. Since the 1970s, the list of cancer genes has been growing steadily. Because cancer driver genes are under positive selection in tumorigenesis, their observed patterns of somatic mutations across tumours in a cohort deviate from those expected from neutral mutagenesis. These deviations, which constitute signals of positive selection, may be detected by carefully designed bioinformatics methods, which have become the state of the art in the identification of driver genes. A systematic approach combining several of these signals could lead to a compendium of mutational cancer genes. In this Review, we present the Integrative OncoGenomics (IntOGen) pipeline, an implementation of such an approach to obtain the compendium of mutational cancer drivers. Its application to somatic mutations of more than 28,000 tumours of 66 cancer types reveals 568 cancer genes and points towards their mechanisms of tumorigenesis. The application of this approach to the ever-growing datasets of somatic tumour mutations will support the continuous refinement of our knowledge of the genetic basis of cancer.

A harmonized meta-knowledgebase of clinical interpretations of somatic genomic variants in cancer.

Precision oncology relies on accurate discovery and interpretation of genomic variants, enabling individualized diagnosis, prognosis and therapy selection. We found that six prominent somatic cancer variant knowledgebases were highly disparate in content, structure and supporting primary literature, impeding consensus when evaluating variants and their relevance in a clinical setting. We developed a framework for harmonizing variant interpretations to produce a meta-knowledgebase of 12,856 aggregate interpretations. We demonstrated large gains in overlap between resources across variants, diseases and drugs as a result of this harmonization. We subsequently demonstrated improved matching between a patient cohort and harmonized interpretations of potential clinical significance, observing an increase from an average of 33% per individual knowledgebase to 57% in aggregate. Our analyses illuminate the need for open, interoperable sharing of variant interpretation data. We also provide a freely available web interface (search.cancervariants.org) for exploring the harmonized interpretations from these six knowledgebases.