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Meningiomas are the most common primary intracranial tumors and can be associated with significant morbidity and mortality. Radiologists, neurosurgeons, neuro-oncologists, and radiation oncologists rely on brain MRI for diagnosis, treatment planning, and longitudinal treatment monitoring. However, automated, objective, and quantitative tools for non-invasive assessment of meningiomas on multi-sequence MR images are not available. Here we present the BraTS Pre-operative Meningioma Dataset, as the largest multi-institutional expert annotated multilabel meningioma multi-sequence MR image dataset to date. This dataset includes 1,141 multi-sequence MR images from six sites, each with four structural MRI sequences (T2-, T2/FLAIR-, pre-contrast T1-, and post-contrast T1-weighted) accompanied by expert manually refined segmentations of three distinct meningioma sub-compartments: enhancing tumor, non-enhancing tumor, and surrounding non-enhancing T2/FLAIR hyperintensity. Basic demographic data are provided including age at time of initial imaging, sex, and CNS WHO grade. The goal of releasing this dataset is to facilitate the development of automated computational methods for meningioma segmentation and expedite their incorporation into clinical practice, ultimately targeting improvement in the care of meningioma patients.

Abstract Philips Visual Patient Avatar is an innovative approach to patient monitoring. Computer-based simulation studies have shown that it can improve diagnostic accuracy and confidence while reducing perceived workload. Following its integration into clinical practice, we conducted a single-centre qualitative study at the University Hospital Zurich to explore the views of anaesthesia, post-anaesthesia and intensive care providers on their experience with the technology. We used an online survey to assess its contributions in different clinical situations. We analysed the data thematically to identify key themes. Of the 510 healthcare providers contacted, 131 (25.7%) completed the survey and 154 comments were collected. Key themes included the detection of specific vital sign changes, focusing on temperature and oxygen saturation (41.9%, 34/81 comments in the operating room; 38.6%, 17/44 comments in the intensive care unit; 10.3%, 3/29 comments in the post-anaesthesia care unit). Additionally, the technology was perceived to support daily routines and situational awareness (28.4%, 23/81 comments in the OR; 9.1%, 4/44 comments in the ICU; 10.3%, 3/29 comments in the PACU). The study provides early, but strong evidence that the Philips Visual Patient Avatar assists healthcare providers in specific clinical situations in the perioperative and critical care settings.

Abstract Meningiomas are the most common primary intracranial tumors and can be associated with significant morbidity and mortality. Radiologists, neurosurgeons, neuro-oncologists, and radiation oncologists rely on brain MRI for diagnosis, treatment planning, and longitudinal treatment monitoring. However, automated, objective, and quantitative tools for non-invasive assessment of meningiomas on multi-sequence MR images are not available. Here we present the BraTS Pre-operative Meningioma Dataset, as the largest multi-institutional expert annotated multilabel meningioma multi-sequence MR image dataset to date. This dataset includes 1,141 multi-sequence MR images from six sites, each with four structural MRI sequences (T2-, T2/FLAIR-, pre-contrast T1-, and post-contrast T1-weighted) accompanied by expert manually refined segmentations of three distinct meningioma sub-compartments: enhancing tumor, non-enhancing tumor, and surrounding non-enhancing T2/FLAIR hyperintensity. Basic demographic data are provided including age at time of initial imaging, sex, and CNS WHO grade. The goal of releasing this dataset is to facilitate the development of automated computational methods for meningioma segmentation and expedite their incorporation into clinical practice, ultimately targeting improvement in the care of meningioma patients.

Abstract Spectrum power analysis in the low frequency oscillations (LFO) region of functional near infrared spectroscopy (fNIRS) is a promising method to deliver information about brain activation and therefore might be used for prognostication in patients with disorders of consciousness in the neurocritical care unit alongside with established methods. In this study, we measure the cortical hemodynamic response measured by fNIRS in the LFO region following auditory and somatosensory stimulation in healthy subjects. The significant hemodynamic reaction in the contralateral hemisphere correlation with the physiologic electric response suggests neurovascular coupling. In addition, we investigate power spectrum changes in steady state measurements of cerebral death patients and healthy subjects in the LFO region, the frequency of the heartbeat and respiration. The spectral power within the LFO region was lower in the patients with cerebral death compared to the healthy subjects, whereas there were no differences in spectral power for physiological activities such as heartbeat and respiration rate. This finding indicates the cerebral origin of our low frequency measurements. Therefore, LFO measurements are a potential method to detect brain activation in patients with disorders of consciousness and cerebral death. However, further studies in patients are needed to investigate its potential clinical use.

Abstract Despite significant progress in the medical field, there is still a pressing need for minimal‐invasive tools to assist with decision‐making, especially in cases of polytrauma. Our team explored the potential of serum‐derived large extracellular vesicles, so called microparticles/microvesicles/ectosomes, to serve as a supportive tool in decision‐making in polytrauma situations. We focused on whether monocyte derived large EVs may differentiate between polytrauma patients with internal organ injury (ISS > 15) and those without. Thus, we compared our EV data to soluble biomarkers such as tumour necrosis factor alpha (TNF alpha) and Interleukin‐8 (IL‐8). From the blood of 25 healthy and 26 patients with polytrauma large EVs were isolated, purified, and characterized. TNF alpha and IL‐8 levels were quantified. We found that levels of these monocyte derived large EVs were significantly higher in polytrauma patients with internal organ damage and correlated with the ISS. Interestingly, we also observed a decline in AnnV+CD14+ large EVs during normal recovery after trauma. Thus, inflammatory serological markers as TNF alpha and as IL‐8 demonstrated an inability to discriminate between polytrauma patients with or without internal organ damage, such as spleen, kidney, or liver lacerations/ruptures. However, TNF and IL‐8 levels were elevated in polytrauma cases overall when contrasted with healthy non‐traumatic controls. These findings suggest that delving deeper into the potential of AnnV+ large EVs derived from monocytes could highly beneficial in the managment of polytrauma, potentially surpassing the efficacy of commonly used serum markers.

Abstract The circadian clock is a molecular timekeeper, present from cyanobacteria to mammals, that coordinates internal physiology with the external environment. The clock has a 24-h period however development proceeds with its own timing, raising the question of how these interact. Using the intestine of Drosophila melanogaster as a model for organ development, we track how and when the circadian clock emerges in specific cell types. We find that the circadian clock begins abruptly in the adult intestine and gradually synchronizes to the environment after intestinal development is complete. This delayed start occurs because individual cells at earlier stages lack the complete circadian clock gene network. As the intestine develops, the circadian clock is first consolidated in intestinal stem cells with changes in Ecdysone and Hnf4 signalling influencing the transcriptional activity of Clk/cyc to drive the expression of tim, Pdp1, and vri. In the mature intestine, stem cell lineage commitment transiently disrupts clock activity in differentiating progeny, mirroring early developmental clock-less transitions. Our data show that clock function and differentiation are incompatible and provide a paradigm for studying circadian clocks in development and stem cell lineages.

In March 2020, at the onset of the coronavirus disease 2019 (COVID-19) pandemic in the United States, the Southern California Extracorporeal Membrane Oxygenation (ECMO) Consortium was formed. The consortium included physicians and coordinators from the 4 ECMO centers in San Diego County. Guidelines were created to ensure that ECMO was delivered equitably and in a resource effective manner across the county during the pandemic. A biomedical ethicist reviewed the guidelines to ensure ECMO use would provide maximal community benefit of this limited resource. The San Diego County Health and Human Services Agency further incorporated the guidelines into its plans for the allocation of scarce resources. The consortium held weekly video conferences to review countywide ECMO capacity (including census and staffing), share data, and discuss clinical practices and difficult cases. Equipment exchanges between ECMO centers maximized regional capacity. From March 1 to November 30, 2020, consortium participants placed 97 patients on ECMO. No eligible patients were denied ECMO due to lack of resources or capacity. The Southern California ECMO Consortium may serve as a model for other communities seeking to optimize ECMO resources during the current COVID-19 or future pandemics.

Delayed cerebral ischemia (DCI) occurs in up to one third of patients suffering from aneurysmal subarachnoid hemorrhage (aSAH). Untreated, it leads to secondary cerebral infarctions and is frequently associated with death or severe disability. After aneurysm rupture, erythrocytes in the subarachnoid space lyse and liberate free hemoglobin (Hb), a key driver for the development of DCI. Hemoglobin in the cerebrospinal fluid (CSF-Hb) can be analyzed through a two-step procedure of centrifugation to exclude intact erythrocytes and subsequent spectrophotometric quantification. This analysis can only be done in specialized laboratories but not at the bedside in the intensive care unit. This limits the number of tests done, increases the variability of the results and restricts accuracy. Bedside measurements of CSF-Hb as a biomarker with a point of care diagnostic test system would allow for a continuous monitoring for the risk of DCI in the individual patient. In this study, a microfluidic chip was explored that allows to continuously separate blood particles from CSF or plasma based on acoustophoresis. An in vitro test bench was developed to test in-line measurements with the developed microfluidic chip and a spectrometer. The proof of principle for a continuous particle separation device has been established with diluted blood and CSF samples from animals and aSAH patients, respectively. Processing 1 mL of blood in our microfluidic device was achieved within around 70 min demonstrating only minor deviations from the gold standard centrifugation (7% average error of patient samples), while saving several hours of processing time and additionally the reduction of deviations in the results due to manual labor.

Introduction An increasing number of tracheotomised and/or ventilated patients with high-cost out-of-hospital intensive care needs and, at the same time, a decreasing number of healthcare professionals inevitably lead to challenges in the care of this patient population. In addition, little is known about this population, their health restrictions, needs, patient journeys, care structures and processes. The project ‘Needs, requirements and cross-sectoral care pathways of out-of-hospital ventilated intensive care patients’ (ATME) aims to analyse these aspects and explore current care structures to inform further development of care in line with patients’ needs and requirements.Methods and analysis Qualitative and quantitative methods will be used. In preparation of a semistandardised survey, exploratory interviews will be conducted with tracheotomised and/or ventilated patients with out-of-hospital intensive care needs (TVPOI) (n=15), nursing care providers (n=30), outpatient medical centres, as well as outpatient medical, medical technology and therapeutic care providers (n=35). Three semistandardised survey questionnaires for TVPOI (n=2,000) will be developed and conducted with nursing care facilities (n=250) and outpatient medical centres for mechanical ventilation (n=25). Content analyses will be conducted for qualitative data; survey data will be analysed descriptively. In addition, healthcare claims data will be analysed descriptively to provide information on patient journeys. Three result workshops and one consensus conference will be carried out with representatives of the relevant target groups to analyse the suitability of care structures and to develop recommendations for action to improve TVPOI.Ethics and dissemination The ATME study received a positive vote from the Ethics Committee of the Osnabrück University of Applied Sciences and is registered in ‘Deutsches Register Klinischer Studien (DRKS)’ (registration number: DRKS00030891). The study results will be presented at national conferences and in relevant peer-reviewed journals. Additionally, study results will be published by the funding institution (the Innovation Committee of the Federal Joint Committee) on their website.

Pigs can be an important model for preclinical biological research, including neurological diseases such as Alcohol Use Disorder. Such research often involves longitudinal assessment of changes in motor coordination as the disease or disorder progresses. Current motor coordination tests in pigs are derived from behavioral assessments in rodents and lack critical aspects of face and construct validity. While such tests may permit for the comparison of experimental results to rodents, a lack of validation studies of such tests in the pig itself may preclude the drawing of meaningful conclusions. To address this knowledge gap, an apparatus modeled after a horizontally placed ladder and where the height of the rungs could be adjusted was developed. The protocol that was employed within the apparatus mimicked the walk and turn test of the human standardized field sobriety test. Here, five Sinclair miniature pigs were trained to cross the horizontally placed ladder, starting at a rung height of six inches and decreasing to three inches in one-inch increments. It was demonstrated that pigs can reliably learn to cross the ladder, with few errors, under baseline/unimpaired conditions. These animals were then involved in a voluntary consumption of ethanol study where animals were longitudinally evaluated for motor coordination changes at baseline, 2.5, 5, 7.5, and 10% ethanol concentrations subsequently to consuming ethanol. Consistent with our predictions, relative to baseline performance, motor incoordination increased as voluntary consumption of escalating concentrations of ethanol increased. Together these data highlight that the horizontal ladder test (HLT) test protocol is a novel, optimized and reliable test for evaluating motor coordination as well as changes in motor coordination in pigs.

Background:. The level of type-I interferons (IFNs) in primary sclerosing cholangitis (PSC) was investigated to evaluate its association with disease activity and progression. Methods:. Bioactive type-I IFNs were evaluated in a murine model of PSC and human patients’ sera using a cell-based reporter assay and ELISA techniques. In total, 57 healthy participants, 71 PSC, and 38 patients with primary biliary cholangitis were enrolled in this study. Results:. Bioactive type-I IFNs were elevated in the liver and serum of multidrug resistance protein 2–deficient animals and showed a correlation with the presence of CD45+ immune cells and serum alanine transaminase levels. Concordantly, bioactive type-I IFNs were elevated in the sera of patients with PSC as compared to healthy controls (sensitivity of 84.51%, specificity of 63.16%, and AUROC value of 0.8267). Bioactive IFNs highly correlated with alkaline phosphatase (r=0.4179, p

BackgroundAchieving physical activity (PA) guidelines’ recommendation of 150 minutes of moderate-to-vigorous PA per week has been shown to reduce the risk of many chronic conditions. Despite the overwhelming evidence in this field, PA levels remain low globally. By creating engaging mobile health (mHealth) interventions through strategies such as just-in-time adaptive interventions (JITAIs) that are tailored to an individual’s dynamic state, there is potential to increase PA levels. However, generating personalized content can take a long time due to various versions of content required for the personalization algorithms. ChatGPT presents an incredible opportunity to rapidly produce tailored content; however, there is a lack of studies exploring its feasibility. ObjectiveThis study aimed to (1) explore the feasibility of using ChatGPT to create content for a PA JITAI mobile app and (2) describe lessons learned and future recommendations for using ChatGPT in the development of mHealth JITAI content. MethodsDuring phase 1, we used Pathverse, a no-code app builder, and ChatGPT to develop a JITAI app to help parents support their child’s PA levels. The intervention was developed based on the Multi-Process Action Control (M-PAC) framework, and the necessary behavior change techniques targeting the M-PAC constructs were implemented in the app design to help parents support their child’s PA. The acceptability of using ChatGPT for this purpose was discussed to determine its feasibility. In phase 2, we summarized the lessons we learned during the JITAI content development process using ChatGPT and generated recommendations to inform future similar use cases. ResultsIn phase 1, by using specific prompts, we efficiently generated content for 13 lessons relating to increasing parental support for their child’s PA following the M-PAC framework. It was determined that using ChatGPT for this case study to develop PA content for a JITAI was acceptable. In phase 2, we summarized our recommendations into the following six steps when using ChatGPT to create content for mHealth behavior interventions: (1) determine target behavior, (2) ground the intervention in behavior change theory, (3) design the intervention structure, (4) input intervention structure and behavior change constructs into ChatGPT, (5) revise the ChatGPT response, and (6) customize the response to be used in the intervention. ConclusionsChatGPT offers a remarkable opportunity for rapid content creation in the context of an mHealth JITAI. Although our case study demonstrated that ChatGPT was acceptable, it is essential to approach its use, along with other language models, with caution. Before delivering content to population groups, expert review is crucial to ensure accuracy and relevancy. Future research and application of these guidelines are imperative as we deepen our understanding of ChatGPT and its interactions with human input.

Abstract Extracellular vesicles (EVs) are cell derived membranous nanoparticles. EVs are important mediators of cell–cell communication via the transfer of bioactive content and as such they are being investigated for disease diagnostics as biomarkers and for potential therapeutic cargo delivery to recipient cells. However, existing methods for isolating EVs from biological samples suffer from challenges related to co‐isolation of unwanted materials such as proteins, nucleic acids, and lipoproteins. In the pursuit of improved EV isolation techniques, we introduce multimodal flowthrough chromatography (MFC) as a scalable alternative to size exclusion chromatography (SEC). The use of MFC offers significant advantages for purifying EVs, resulting in enhanced yields and increased purity with respect to protein and nucleic acid co‐isolates from conditioned 3D cell culture media. Compared to SEC, significantly higher EV yields with similar purity and preserved functionality were also obtained with MFC in 2D cell cultures. Additionally, MFC yielded EVs from serum with comparable purity to SEC and similar apolipoprotein B content. Overall, MFC presents an advancement in EV purification yielding EVs with high recovery, purity, and functionality, and offers an accessible improvement to researchers currently employing SEC.

Abstract Explainable artificial intelligence (XAI) has emerged as a promising solution for addressing the implementation challenges of AI/ML in healthcare. However, little is known about how developers and clinicians interpret XAI and what conflicting goals and requirements they may have. This paper presents the findings of a longitudinal multi-method study involving 112 developers and clinicians co-designing an XAI solution for a clinical decision support system. Our study identifies three key differences between developer and clinician mental models of XAI, including opposing goals (model interpretability vs. clinical plausibility), different sources of truth (data vs. patient), and the role of exploring new vs. exploiting old knowledge. Based on our findings, we propose design solutions that can help address the XAI conundrum in healthcare, including the use of causal inference models, personalized explanations, and ambidexterity between exploration and exploitation mindsets. Our study highlights the importance of considering the perspectives of both developers and clinicians in the design of XAI systems and provides practical recommendations for improving the effectiveness and usability of XAI in healthcare.

Abstract Cardiac progenitor cell (CPC)‐derived small extracellular vesicles (sEVs) exhibit great potential to stimulate cardiac repair. However, the multifaceted nature of sEV heterogeneity presents a challenge in understanding the distinct mechanisms underlying their regenerative abilities. Here, a dual‐step multimodal flowthrough and size‐exclusion chromatography method was applied to isolate and separate CPC‐derived sEV subpopulations to study the functional differences related to cardiac repair responses. Three distinct sEV subpopulations were identified with unique protein profiles. Functional cell assays for cardiac repair‐related processes demonstrated that the middle‐sized and smallest‐sized sEV subpopulations exhibited the highest pro‐angiogenic and anti‐fibrotic activities. Proteasome activity was uniquely seen in the smallest‐sized subpopulation. The largest‐sized subpopulation showed no effect in any of the functional assays. This research uncovers the existence of sEV subpopulations, each characterized by a distinct composition and biological function. Enhancing our understanding of sEV heterogeneity will provide valuable insights into sEV mechanisms of action, ultimately accelerating the translation of sEV therapeutics.

Summary: Vibrio cholerae is an aquatic bacterium that causes severe and potentially deadly diarrheal disease. Despite the impact on global health, our understanding of host mucosal responses to Vibrio remains limited, highlighting a knowledge gap critical for the development of effective prevention and treatment strategies. Using a natural infection model, we combine physiological and single-cell transcriptomic studies to characterize conventionally reared adult zebrafish guts and guts challenged with Vibrio. We demonstrate that Vibrio causes a mild mucosal immune response characterized by T cell activation and enhanced antigen capture; Vibrio suppresses host interferon signaling; and ectopic activation of interferon alters the course of infection. We show that the adult zebrafish gut shares similarities with mammalian counterparts, including the presence of Best4+ cells, tuft cells, and a population of basal cycling cells. These findings provide important insights into host-pathogen interactions and emphasize the utility of zebrafish as a natural model of Vibrio infection.

BackgroundDespite major advances in medicine, blood-borne biomarkers are urgently needed to support decision-making, including polytrauma. Here, we assessed serum-derived extracellular vesicles (EVs) as potential markers of decision-making in polytrauma.ObjectiveOur Liquid Biopsy in Organ Damage (LiBOD) study aimed to differentiate polytrauma with organ injury from polytrauma without organ injury. We analysed of blood-borne small EVs at the individual level using a combination of immunocapture and high-resolution imaging.MethodsTo this end, we isolated, purified, and characterized small EVs according to the latest Minimal Information for Studies of Extracellular Vesicles (MISEV) guidelines from human blood collected within 24 h post-trauma and validated our results using a porcine polytrauma model.ResultsWe found that small EVs derived from monocytes CD14+ and CD14+CD61+ were significantly elevated in polytrauma with organ damage. To be precise, our findings revealed that CD9+CD14+ and CD14+CD61+ small EVs exhibited superior performance compared to CD9+CD61+ small EVs in accurately indicating polytrauma with organ damage, reaching a sensitivity and a specificity of 0.81% and 0.97%, respectively. The results in humans were confirmed in an independent porcine model of polytrauma.ConclusionThese findings suggest that these specific types of small EVs may serve as valuable, non-invasive, and objective biomarkers for assessing and monitoring the severity of polytrauma and associated organ damage.

In March 2020, at the onset of the coronavirus disease 2019 (COVID-19) pandemic in the United States, the Southern California Extracorporeal Membrane Oxygenation (ECMO) Consortium was formed. The consortium included physicians and coordinators from the 4 ECMO centers in San Diego County. Guidelines were created to ensure that ECMO was delivered equitably and in a resource effective manner across the county during the pandemic. A biomedical ethicist reviewed the guidelines to ensure ECMO use would provide maximal community benefit of this limited resource. The San Diego County Health and Human Services Agency further incorporated the guidelines into its plans for the allocation of scarce resources. The consortium held weekly video conferences to review countywide ECMO capacity (including census and staffing), share data, and discuss clinical practices and difficult cases. Equipment exchanges between ECMO centers maximized regional capacity. From March 1 to November 30, 2020, consortium participants placed 97 patients on ECMO. No eligible patients were denied ECMO due to lack of resources or capacity. The Southern California ECMO Consortium may serve as a model for other communities seeking to optimize ECMO resources during the current COVID-19 or future pandemics.

Objectives In order to reduce the use of emergency departments, computer-assisted initial assessment was implemented at the medical on-call service 116117. Our study assessed compliance and patient satisfaction.Design Cross-sectional observational postal survey.Setting Medical on-call service 116117 by eight Associations of Statutory Health Insurance Physicians in Germany.Participants The intervention was observed between January 2020 and March 2021. Minors and patients with invalid contact data were excluded. A random sample of eligible patients received standardised questionnaires by mail.Outcome measures We analysed associations of sociodemographic data, health status, previous service use, health literacy, and recommended settings with compliance and patient satisfaction by multivariable, multilevel logistic regression.Interventions Based on symptoms and context factors, the computer software suggested service levels. Staff and patient discussed if higher levels were indicated, services were available and self-transport was possible. They then agreed on recommendations for treatment settings.Results Of 9473 contacted eligible patients, 1756 patients (18.5%) participated. Median age was 66 years (IQR=50–79), and 986 (59.0%) were women. At least one recommended setting was used by 1397 patients (85.4%). General practitioner (GP) practices were used by 143 patients (68.4%). Generally, better compliance was associated with lower depression levels (OR 1.59, 95% CI 1.17 to 2.17, p=0.003), fewer previous hospital stays (OR 2.02, 95% CI 1.27 to 3.23, p=0.003) and recommendations for any setting other than GP practices (OR 0.13, 95% CI 0.06 to 0.29, p

A column model of the Arctic atmosphere is developed including the nonlinear positive feedback responses of surface albedo and water vapour to temperature. The atmosphere is treated as a grey gas and the flux of longwave radiation is governed by the two-stream Schwarzschild equations. Water vapour concentration is determined by the Clausius–Clapeyron equation. Representative concentration pathways (RCPs) are used to model carbon dioxide concentrations into the future. The resulting 9D two-point boundary value problem is solved under various RCPs and the solutions analysed. The model predicts that under the highest carbon pathway, the Arctic climate will undergo an irreversible bifurcation to a warm steady state, which would correspond to annually ice-free conditions. Under the lowest carbon pathway, corresponding to very aggressive carbon emission reductions, the model exhibits only a mild increase in Arctic temperatures. Under the two intermediate carbon pathways, temperatures increase more substantially, and the system enters a region of bistability where external perturbations could possibly cause an irreversible switch to a warm, ice-free state.

BackgroundRegular physical activity (PA) is a key lifestyle component for hypertension prevention. Previous studies have shown that mobile health (mHealth) apps can be an effective tool for improving PA behaviors. However, adherence to and poor engagement with these apps is a challenge. A potential solution to overcome this challenge may be to combine financial incentives with innovative behavior theory, such as the Multiprocess Action Control (M-PAC) framework. Currently, there is a lack of PA financial incentive–driven M-PAC mHealth programs aimed at hypertension prevention. ObjectiveWe aimed to describe the process of developing an 8-week mHealth PA and financial-incentive hypertension education program (Healthy Hearts) and to evaluate usability of the Healthy Hearts program. MethodsThe first 2 stages of the Integrate, Design, Assess, and Share framework were used to guide the development of the Healthy Hearts program. The development process consisted of 2 phases. In phase 1, the research team met to discuss implementing the M-PAC framework to adopt an existing web-based hypertension prevention program to a mobile app. The app was developed using a no-code app development platform, Pathverse (Pathverse Inc), to help decrease overall development time. In phase 2, we created a prototype and conducted usability testing to evaluate lesson 1 of the Healthy Hearts program to further enhance the user experience. We used semistructured interviews and the mHealth App Usability Questionnaire to evaluate program acceptability and usability. ResultsIntervention development among the research team successfully created an 8-week financial-incentive hypertension education program for adults aged 40-65 years who did not currently meet the Canadian Physical Activity Guidelines (