A Health App Platform Providing a Budget to Purchase Preselected Apps as an Innovative Way to Support Public Health: Qualitative Study With End Users and Other Stakeholders

BACKGROUND: eHealth has the potential to improve health outcomes. However, this potential is largely untapped. Individuals face an overload of apps and have difficulties choosing suitable apps for themselves. In the FitKnip experiment, individuals were given access to a health app platform, where they could purchase reliable preselected health apps with a personal budget of €100 (US $107.35). By conducting a prospective study, we aimed to scientifically evaluate the FitKnip experiment as an innovative way to improve population health. OBJECTIVE: The aim of the experiment was to scientifically evaluate the FitKnip experiment as an innovative way to improve population health. More specifically, we conducted an in-depth qualitative evaluation of the concept and acceptability of FitKnip, its perceived impact on health empowerment, as well as the roles of stakeholders for the future implementation of a health app platform through focus group interviews. METHODS: This study followed a phenomenological research design and included 7 focus group interviews with end users and 1 with stakeholders, held between July and December 2020. End users were recruited through various institutions in the Netherlands, for example, insurance companies and local governments. All focus groups were semistructured using interview guides and were held via videoconferencing due to the COVID-19 pandemic measures. Each participant received access to a health app platform where they were enabled to purchase reliable, preselected health apps with a budget of €100 (US$107.35). The budget was valid for the entire research period. The health app platform offered 38 apps. A third party, a health care coalition, selected the apps to be included in FitKnip. The analyses were conducted according to the principles of the Framework Method. RESULTS: A priori formulated themes were concept, acceptability, health empowerment, and outcomes, and the roles of stakeholders for the future implementation of a health app platform. Both end users (n=31) and stakeholders (n=5) were enthusiastic about the concept of a health app platform. End users indicated missing apps regarding physical health and lifestyle and needing more guidance toward suitable apps. End users saw health empowerment as a precondition to using a health app platform and achieving health outcomes depending on the purchased mobile apps. End users and stakeholders identified potential providers and financing parties of FitKnip. Stakeholders recommended the establishment of a reputable national or international quality guidelines or certification for health and wellbeing apps, that can demonstrate the quality and reliability of mobile health applications. CONCLUSIONS: This study showed the need for a personalized and flexible platform. Next to this, a deeper understanding of the roles of stakeholders in such initiatives is needed especially on financing and reimbursement of health promotion and digital health services. A personalized, flexible health app platform is a promising initiative to support individuals in their health

CD26-negative and CD26-positive tissue-resident fibroblasts contribute to functionally distinct CAF subpopulations in breast cancer

The origin of cancer-associated fibroblasts (CAFs) in cancer remains to be identified. Here, single-cell transcriptomics, in vivo and in vitro studies suggest that CD26+ and CD26- normal fibroblasts transform into distinct CAF subpopulations in mouse models of breast cancer

Publisher Correction: Truncated FGFR2 is a clinically actionable oncogene in multiple cancers.

This paper was originally published under a standard Springer Nature license

Perfect Fit: Identiteitsgebaseerde virtuele coach die ondersteunt bij stoppen met roken en meer bewegen - Ontwikkeling en geleerde lessen

Interactive Intelligenc

Rebalancing of actomyosin contractility enables mammary tumor formation upon loss of E-cadherin

E-cadherin (CDH1) is a master regulator of epithelial cell adherence junctions and a well-established tumor suppressor in Invasive Lobular Carcinoma (ILC). Intriguingly, somatic inactivation of E-cadherin alone in mouse mammary epithelial cells (MMECs) is insufficient to induce tumor formation. Here we show that E-cadherin loss induces extrusion of luminal MMECs to the basal lamina. Remarkably, E-cadherin-deficient MMECs can breach the basal lamina but do not disseminate into the surrounding fat pad. Basal lamina components laminin and collagen IV supported adhesion and survival of E-cadherin-deficient MMECs while collagen I, the principle component of the mammary stromal micro-environment did not. We uncovered that relaxation of actomyosin contractility mediates adhesion and survival of E-cadherin-deficient MMECs on collagen I, thereby allowing ILC development. Together, these findings unmask the direct consequences of E-cadherin inactivation in the mammary gland and identify aberrant actomyosin contractility as a critical barrier to ILC formation

Mammary-specific inactivation of E-cadherin and p53 impairs functional gland development and leads to pleomorphic invasive lobular carcinoma in mice

SUMMARY Breast cancer is the most common malignancy in women of the Western world. Even though a large percentage of breast cancer patients show pathological complete remission after standard treatment regimes, approximately 30–40% are non-responsive and ultimately develop metastatic disease. To generate a good preclinical model of invasive breast cancer, we have taken a tissue-specific approach to somatically inactivate p53 and E-cadherin, the cardinal cell-cell adhesion receptor that is strongly associated with tumor invasiveness. In breast cancer, E-cadherin is found mutated or otherwise functionally silenced in invasive lobular carcinoma (ILC), which accounts for 10–15% of all breast cancers. We show that mammary-specific stochastic inactivation of conditional E-cadherin and p53 results in impaired mammary gland function during pregnancy through the induction of anoikis resistance of mammary epithelium, resulting in loss of epithelial organization and a dysfunctional mammary gland. Moreover, combined inactivation of E-cadherin and p53 induced lactation-independent development of invasive and metastatic mammary carcinomas, which showed strong resemblance to human pleomorphic ILC. Dissemination patterns of mouse ILC mimic the human malignancy, showing metastasis to the gastrointestinal tract, peritoneum, lung, lymph nodes and bone. Our results confirm that loss of E-cadherin contributes to both mammary tumor initiation and metastasis, and establish a preclinical mouse model of human ILC that can be used for the development of novel intervention strategies to treat invasive breast cancer

TRPS1 acts as a context-dependent regulator of mammary epithelial cell growth/differentiation and breast cancer development

The GATA-type zinc finger transcription factor TRPS1 has been implicated in breast cancer. However, its precise role remains unclear, as both amplifications and inactivating mutations in TRPS1 have been reported. Here, we used in vitro and in vivo loss-of-function approaches to dissect the role of TRPS1 in mammary gland development and invasive lobular breast carcinoma, which is hallmarked by functional loss of E-cadherin. We show that TRPS1 is essential in mammary epithelial cells, since TRPS1-mediated suppression of interferon signaling promotes in vitro proliferation and lactogenic differentiation. Similarly, TRPS1 expression is indispensable for proliferation of mammary organoids and in vivo survival of luminal epithelial cells during mammary gland development. However, the consequences of TRPS1 loss are dependent on E-cadherin status, as combined inactivation of E-cadherin and TRPS1 causes persistent proliferation of mammary organoids and accelerated mammary tumor formation in mice. Together, our results demonstrate that TRPS1 can function as a context-dependent tumor suppressor in breast cancer, while being essential for growth and differentiation of normal mammary epithelial cells

PerfectFit

New development version</p

Reusable Virtual Coach for Smoking Cessation and Physical Activity Coaching

Smoking tobacco and physical inactivity are key preventable behavioural risk factors of cardiovascular disease (CVD). Computerised coaching systems can help individuals to modify risky behaviours, thereby preventing CVD. However, most reported eHealth or computerized coaching systems are hard to reuse in slightly different settings. To provide an open-source, reusable computer coaching system, we developed Perfect Fit. The reusability is manifested by building around the open-source text- and voice-based contextual assistant framework Rasa. Rasa provides a simple, standard interface to many popular messaging and voice channels, and custom connectors are easily implemented. A set of algorithms have been developed and connected to Rasa to drive and personalize the conversation flow and the coaching process. Such algorithms make use of data stored in a devoted database. Furthermore, Perfect Fit adheres to best practices and standards in software engineering. The modular design of Perfect Fit will allow researchers to connect the virtual coach to any messaging or voice channel with only modest modification. Perfect Fit is available under open-source license in GitHub and is currently in prototype-phase. Concluding, Perfect Fit will deliver a virtual coach that can easily be adapted and reused in different settings. The coach helps individuals to achieve and maintain abstinence from smoking and sufficient physical activity (PA).Interactive Intelligenc

Lessons learnt in developing a virtual coach for smoking cessation and physical activity promotion

Background: Smoking and physical inactivity are two key preventable risk factors of cardiovascular disease. Yet, as with most health behaviors, they are difficult to change. In the interdisciplinary Perfect Fit project, scientists from different fields join forces to develop an evidence-based virtual coach that supports smokers in quitting smoking and increasing their physical activity. Intervention content, design and implementation as well as lessons learnt are presented in the hopes of guiding other research groups working on similar projects.Methods: Numerous approaches were used and combined to support the development of the Perfect Fit virtual coach. Approaches include literature reviews, empirical studies, collaboration with end-users, content and technical development sprints, interdisciplinary collaboration and iterative proof-of-concept implementation. Findings: The Perfect Fit intervention integrates evidence-based behavioral change techniques as well as new techniques focused on identity change, big data science, sensor technology and personalized real-time coaching. Intervention content of the virtual coaching matches communication preferences and individual needs of end users. Lessons learnt include ways to optimally implement and tailor interactions from the virtual coach (e.g., ‘explain why user is asked for input’, ‘tailor timing and frequency of intervention components’). With regards to the development process, lessons learnt include strategies for effective interdisciplinary collaboration and technical development (e.g., ‘Find a good balance between wishes of end-users and legal possibilities’).Discussion: The Perfect Fit development process was interactive, iterative and challenging at times. We hopethat our experiences and lessons learnt can inspire and benefit others.Interactive Intelligenc