Pan-vaccine analysis reveals innate immune endotypes predictive of antibody responses to vaccination.

Several studies have shown that the pre-vaccination immune state is associated with the antibody response to vaccination. However, the generalizability and mechanisms that underlie this association remain poorly defined. Here, we sought to identify a common pre-vaccination signature and mechanisms that could predict the immune response across 13 different vaccines. Analysis of blood transcriptional profiles across studies revealed three distinct pre-vaccination endotypes, characterized by the differential expression of genes associated with a pro-inflammatory response, cell proliferation, and metabolism alterations. Importantly, individuals whose pre-vaccination endotype was enriched in pro-inflammatory response genes known to be downstream of nuclear factor-kappa B showed significantly higher serum antibody responses 1 month after vaccination. This pro-inflammatory pre-vaccination endotype showed gene expression characteristic of the innate activation state triggered by Toll-like receptor ligands or adjuvants. These results demonstrate that wide variations in the transcriptional state of the immune system in humans can be a key determinant of responsiveness to vaccination.

Transcriptional atlas of the human immune response to 13 vaccines reveals a common predictor of vaccine-induced antibody responses.

Systems vaccinology has defined molecular signatures and mechanisms of immunity to vaccination. However, comparative analysis of immunity to different vaccines is lacking. We integrated transcriptional data of over 3,000 samples, from 820 adults across 28 studies of 13 vaccines and analyzed vaccination-induced signatures of antibody responses. Most vaccines induced signatures of innate immunity and plasmablasts at days 1 and 7, respectively, after vaccination. However, the yellow fever vaccine induced an early transient signature of T and B cell activation at day 1, followed by delayed antiviral/interferon and plasmablast signatures that peaked at days 7 and 14-21, respectively. Thus, there was no evidence for a 'universal signature' that predicted antibody response to all vaccines. However, accounting for the asynchronous nature of responses, we defined a time-adjusted signature that predicted antibody responses across vaccines. These results provide a transcriptional atlas of immunity to vaccination and define a common, time-adjusted signature of antibody responses.

Digital Technologies in Cardiac Rehabilitation: A Science Advisory From the American Heart Association.

Cardiac rehabilitation has strong evidence of benefit across many cardiovascular conditions but is underused. Even for those patients who participate in cardiac rehabilitation, there is the potential to better support them in improving behaviors known to promote optimal cardiovascular health and in sustaining those behaviors over time. Digital technology has the potential to address many of the challenges of traditional center-based cardiac rehabilitation and to augment care delivery. This American Heart Association science advisory was assembled to guide the development and implementation of digital cardiac rehabilitation interventions that can be translated effectively into clinical care, improve health outcomes, and promote health equity. This advisory thus describes the individual digital components that can be delivered in isolation or as part of a larger cardiac rehabilitation telehealth program and highlights challenges and future directions for digital technology generally and when used in cardiac rehabilitation specifically. It is also intended to provide guidance to researchers reporting digital interventions and clinicians implementing these interventions in practice and to advance a framework for equity-centered digital health in cardiac rehabilitation.

Combined cytotoxic and immune-stimulatory gene therapy for primary adult high-grade glioma: a phase 1, first-in-human trial.

BACKGROUND: High-grade gliomas have a poor prognosis and do not respond well to treatment. Effective cancer immune responses depend on functional immune cells, which are typically absent from the brain. This study aimed to evaluate the safety and activity of two adenoviral vectors expressing HSV1-TK (Ad-hCMV-TK) and Flt3L (Ad-hCMV-Flt3L) in patients with high-grade glioma. METHODS: In this dose-finding, first-in-human trial, treatment-naive adults aged 18-75 years with newly identified high-grade glioma that was evaluated per immunotherapy response assessment in neuro-oncology criteria, and a Karnofsky Performance Status score of 70 or more, underwent maximal safe resection followed by injections of adenoviral vectors expressing HSV1-TK and Flt3L into the tumour bed. The study was conducted at the University of Michigan Medical School, Michigan Medicine (Ann Arbor, MI, USA). The study included six escalating doses of viral particles with starting doses of 1×1010 Ad-hCMV-TK viral particles and 1×109 Ad-hCMV-Flt3L viral particles (cohort A), and then 1×1011 Ad-hCMV-TK viral particles and 1×109 Ad-hCMV-Flt3L viral particles (cohort B), 1×1010 Ad-hCMV-TK viral particles and 1×1010 Ad-hCMV-Flt3L viral particles (cohort C), 1×1011 Ad-hCMV-TK viral particles and 1×1010 Ad-hCMV-Flt3L viral particles (cohort D), 1×1010 Ad-hCMV-TK viral particles and 1×1011 Ad-hCMV-Flt3L viral particles (cohort E), and 1×1011 Ad-hCMV-TK viral particles and 1×1011 Ad-hCMV-Flt3L viral particles (cohort F) following a 3+3 design. Two 1 mL tuberculin syringes were used to deliver freehand a mix of Ad-hCMV-TK and Ad-hCMV-Flt3L vectors into the walls of the resection cavity with a total injection of 2 mL distributed as 0·1 mL per site across 20 locations. Subsequently, patients received two 14-day courses of valacyclovir (2 g orally, three times per day) at 1-3 days and 10-12 weeks after vector administration and standad upfront chemoradiotherapy. The primary endpoint was the maximum tolerated dose of Ad-hCMV-Flt3L and Ad-hCMV-TK. Overall survival was a secondary endpoint. Recruitment is complete and the trial is finished. The trial is registered with ClinicalTrials.gov, NCT01811992. FINDINGS: Between April 8, 2014, and March 13, 2019, 21 patients were assessed for eligibility and 18 patients with high-grade glioma were enrolled and included in the analysis (three patients in each of the six dose cohorts); eight patients were female and ten were male. Neuropathological examination identified 14 (78%) patients with glioblastoma, three (17%) with gliosarcoma, and one (6%) with anaplastic ependymoma. The treatment was well-tolerated, and no dose-limiting toxicity was observed. The maximum tolerated dose was not reached. The most common serious grade 3-4 adverse events across all treatment groups were wound infection (four events in two patients) and thromboembolic events (five events in four patients). One death due to an adverse event (respiratory failure) occurred but was not related to study treatment. No treatment-related deaths occurred during the study. Median overall survival was 21·3 months (95% CI 11·1-26·1). INTERPRETATION: The combination of two adenoviral vectors demonstrated safety and feasibility in patients with high-grade glioma and warrants further investigation in a phase 1b/2 clinical trial. FUNDING: Funded in part by Phase One Foundation, Los Angeles, CA, The Board of Governors at Cedars-Sinai Medical Center, Los Angeles, CA, and The Rogel Cancer Center at The University of Michigan.

Delineating the genotypic and phenotypic spectrum of HECW2-related neurodevelopmental disorders.

BACKGROUND: Variants in HECW2 have recently been reported to cause a neurodevelopmental disorder with hypotonia, seizures and impaired language; however, only six variants have been reported and the clinical characteristics have only broadly been defined. METHODS: Molecular and clinical data were collected from clinical and research cohorts. Massive parallel sequencing was performed and identified individuals with a HECW2-related neurodevelopmental disorder. RESULTS: We identified 13 novel missense variants in HECW2 in 22 unpublished cases, of which 18 were confirmed to have a de novo variant. In addition, we reviewed the genotypes and phenotypes of previously reported and new cases with HECW2 variants (n=35 cases). All variants identified are missense, and the majority of likely pathogenic and pathogenic variants are located in or near the C-terminal HECT domain (88.2%). We identified several clustered variants and four recurrent variants (p.(Arg1191Gln);p.(Asn1199Lys);p.(Phe1327Ser);p.(Arg1330Trp)). Two variants, (p.(Arg1191Gln);p.(Arg1330Trp)), accounted for 22.9% and 20% of cases, respectively. Clinical characterisation suggests complete penetrance for hypotonia with or without spasticity (100%), developmental delay/intellectual disability (100%) and developmental language disorder (100%). Other common features are behavioural problems (88.9%), vision problems (83.9%), motor coordination/movement (75%) and gastrointestinal issues (70%). Seizures were present in 61.3% of individuals. Genotype-phenotype analysis shows that HECT domain variants are more frequently associated with cortical visual impairment and gastrointestinal issues. Seizures were only observed in individuals with variants in or near the HECT domain. CONCLUSION: We provide a comprehensive review and expansion of the genotypic and phenotypic spectrum of HECW2 disorders, aiding future molecular and clinical diagnosis and management.

Resilience and adaptability of social workers in health care settings during COVID-19 in Australia.

In 2020 Coronavirus disease (COVID-19) was identified in Australia. During the pandemic, as essential workers, hospital-based social workers have been on the frontline. This cross-sectional study examines the resilience of social workers during the COVID-19 pandemic, how the pandemic impacted on social work and lessons learnt. Hospital social workers working in three states, namely Victoria, Queensland, and New South Wales were invited to participate in an online web-based survey, providing non-identifiable demographic details and information a) relating to their proximity to COVID-19, b) their degree of resilience (CD-RISC-2), c) professional quality of life, d) perceived social support, e) physical health, f) professional and personal growth during the pandemic, and g) impacts of COVID-19 on their practice. Basic descriptive statistics were computed for variables of interest. Within group, comparisons were made using paired t-tests or one-way ANOVAs for continuous variables as appropriate to investigate possible interstate differences. Regression analyses were conducted to determine which factors contribute to resilience. Social workers, during the pandemic, whether working under the constraints of lockdown or not, demonstrated high levels of resilience. These levels were similar across the three states, unaffected by the degree of infection in the community, indicating that as a group, social workers have high innate levels of resilience. This study provides an in-depth understanding of the impact of COVID-19 on hospital social workers, the long-term impact of the pandemic on social work practice, and potentially useful lessons learnt for the future.

ABC transporters control ATP release through cholesterol-dependent volume-regulated anion channel activity.

Purinergic signaling by extracellular ATP regulates a variety of cellular events and is implicated in both normal physiology and pathophysiology. Several molecules have been associated with the release of ATP and other small molecules, but their precise contributions have been difficult to assess because of their complexity and heterogeneity. Here, we report on the results of a gain-of-function screen for modulators of hypotonicity-induced ATP release using HEK-293 cells and murine cerebellar granule neurons, along with bioluminescence, calcium FLIPR, and short hairpin RNA-based gene-silencing assays. This screen utilized the most extensive genome-wide ORF collection to date, covering 90% of human, nonredundant, protein-encoding genes. We identified two ABCG1 (ABC subfamily G member 1) variants, which regulate cellular cholesterol, as modulators of hypotonicity-induced ATP release. We found that cholesterol levels control volume-regulated anion channel-dependent ATP release. These findings reveal novel mechanisms for the regulation of ATP release and volume-regulated anion channel activity and provide critical links among cellular status, cholesterol, and purinergic signaling.

Pragmatic Considerations in Incorporating Stakeholder Engagement Into a Palliative Care Transitions Study.

BACKGROUND: Stakeholder involvement in health care research has been shown to improve research development, processes, and dissemination. The literature is developing on stakeholder engagement methods and preliminarily validated tools for evaluating stakeholder level of engagement have been proposed for specific stakeholder groups and settings. OBJECTIVES: This paper describes the methodology for engaging a Study Advisory Committee (SAC) in research and reports on the use of a stakeholder engagement survey for measuring level of engagement. METHODS: Stakeholders with previous research connections were recruited to the SAC during the planning process for a multicenter randomized control clinical trial, which is ongoing at the time of this writing. All SAC meetings undergo qualitative analysis, while the Stakeholder Engagement Survey instrument developed by the Patient-Centered Outcomes Research Institute (PCORI) is distributed annually for quantitative evaluation. RESULTS: The trial's SAC is composed of 18 members from 3 stakeholder groups: patients and their caregivers; patient advocacy organizations; and health care payers. After an initial in-person meeting, the SAC meets quarterly by telephone and annually in-person. The SAC monitors research progress and provides feedback on all study processes. The stakeholder engagement survey reveals improved engagement over time as well as continued challenges. CONCLUSIONS: Stakeholder engagement in the research process has meaningfully contributed to the study design, patient recruitment, and preliminary analysis of findings.

Food Insecurity and Mortality in American Adults: Results From the NHANES-Linked Mortality Study.

Food insecurity is a significant public health problem in the United States leading to substantial social, economic, and health care-related burdens. While studies continue to estimate the prevalence of food insecurity, the long-term outcomes are not extensively explored. The purpose of this study was to assess the impact of food insecurity on mortality. We analyzed data on adults (≥ 20 years) from the 1999-2010 National Health and Nutrition Examination Survey, with mortality data obtained through 2015. Among the total study participants (n = 25,247), 17.6% reported food insecurity. Food-insecure individuals were more likely to be younger in age, minorities, poorer, with lesser education, obese, smokers, and with diabetes compared to food-secure counterparts. During a 10.2-year follow-up, among the food insecure, 821 individuals died (11%). The hazard ratio (HR) for mortality among the food insecure compared with the food secure, with adjustment for age and gender only, was 1.58; 95% confidence interval [CI: 1.25, 2.01]. The adjusted HRs for all-cause mortality, HR = 1.46, CI [1.23, 1.72], p < .001, and cardiovascular mortality, HR = 1.75, CI [1.19, 2.57], p < .01, were statistically significantly higher among food-insecure individuals, after adjustment for multiple demographic and health risk factors. Individuals who are food-insecure have a significantly higher probability of death from any cause or cardiovascular disease in long-term follow-up. Comprehensive and interdisciplinary approaches to reducing food insecurity-related disparities and health risks should be implemented. Including food insecurity in health risk assessments and addressing food insecurity as a determinant of long-term outcomes may contribute to lower premature death rates.

Reporting and connecting cell type names and gating definitions through ontologies.

BACKGROUND: Human immunology studies often rely on the isolation and quantification of cell populations from an input sample based on flow cytometry and related techniques. Such techniques classify cells into populations based on the detection of a pattern of markers. The description of the cell populations targeted in such experiments typically have two complementary components: the description of the cell type targeted (e.g. 'T cells'), and the description of the marker pattern utilized (e.g. CD14-, CD3+). RESULTS: We here describe our attempts to use ontologies to cross-compare cell types and marker patterns (also referred to as gating definitions). We used a large set of such gating definitions and corresponding cell types submitted by different investigators into ImmPort, a central database for immunology studies, to examine the ability to parse gating definitions using terms from the Protein Ontology (PRO) and cell type descriptions, using the Cell Ontology (CL). We then used logical axioms from CL to detect discrepancies between the two. CONCLUSIONS: We suggest adoption of our proposed format for describing gating and cell type definitions to make comparisons easier. We also suggest a number of new terms to describe gating definitions in flow cytometry that are not based on molecular markers captured in PRO, but on forward- and side-scatter of light during data acquisition, which is more appropriate to capture in the Ontology for Biomedical Investigations (OBI). Finally, our approach results in suggestions on what logical axioms and new cell types could be considered for addition to the Cell Ontology.

Brief Review and Primer of Key Terminology for Artificial Intelligence and Machine Learning in Hypertension.

Recent breakthroughs in artificial intelligence (AI) have caught the attention of many fields, including health care. The vision for AI is that a computer model can process information and provide output that is indistinguishable from that of a human and, in specific repetitive tasks, outperform a human's capability. The 2 critical underlying technologies in AI are used for supervised and unsupervised machine learning. Machine learning uses neural networks and deep learning modeled after the human brain from structured or unstructured data sets to learn, make decisions, and continuously improve the model. Natural language processing, used for supervised learning, is understanding, interpreting, and generating information using human language in chatbots and generative and conversational AI. These breakthroughs result from increased computing power and access to large data sets, setting the stage for releasing large language models, such as ChatGPT and others, and new imaging models using computer vision. Hypertension management involves using blood pressure and other biometric data from connected devices and generative AI to communicate with patients and health care professionals. AI can potentially improve hypertension diagnosis and treatment through remote patient monitoring and digital therapeutics.

New Estimates of Nitrogen Fixation on Early Earth.

Fixed nitrogen species generated by the early Earth's atmosphere are thought to be critical to the emergence of life and the sustenance of early metabolisms. A previous study estimated nitrogen fixation in the Hadean Earth's N2/CO2-dominated atmosphere; however, that previous study only considered a limited chemical network that produces NOx species (i.e., no HCN formation) via the thermochemical dissociation of N2 and CO2 in lightning flashes, followed by photochemistry. Here, we present an updated model of nitrogen fixation on Hadean Earth. We use the Chemical Equilibrium with Applications (CEA) thermochemical model to estimate lightning-induced NO and HCN formation and an updated version of KINETICS, the 1-D Caltech/JPL photochemical model, to assess the photochemical production of fixed nitrogen species that rain out into the Earth's early ocean. Our updated photochemical model contains hydrocarbon and nitrile chemistry, and we use a Geant4 simulation platform to consider nitrogen fixation stimulated by solar energetic particle deposition throughout the atmosphere. We study the impact of a novel reaction pathway for generating HCN via HCN2, inspired by the experimental results which suggest that reactions with CH radicals (from CH4 photolysis) may facilitate the incorporation of N into the molecular structure of aerosols. When the HCN2 reactions are added, we find that the HCN rainout rate rises by a factor of five in our 1-bar case and is about the same in our 2- and 12-bar cases. Finally, we estimate the equilibrium concentration of fixed nitrogen species under a kinetic steady state in the Hadean ocean, considering loss by hydrothermal vent circulation, photoreduction, and hydrolysis. These results inform our understanding of environments that may have been relevant to the formation of life on Earth, as well as processes that could lead to the emergence of life elsewhere in the universe.

The current state of physical activity assessment and interventions with public policy solutions.

Currently, assessing physical activity (PA) and cardiorespiratory fitness in healthcare settings and supporting patients on their journey toward active living is not a standard of practice in the US, although significant progress is underway. This paper summarizes the foundational as well as supporting public policies necessary to make PA assessment, prescription, and referral a standard of care in the US healthcare system to support active living for all. Measure standardization and healthcare integration will be supported by digital health and public private partnerships, as well as payer strategies and quality and performance incentives. The policy and systems change effort, currently being led by the Physical Activity Alliance's "It's Time to Move" initiative, will improve patient care and the ability to monitor PA levels across the US population, filling in gaps in current national public health surveillance systems. Having patient data available will also allow for additional research that elucidates the relationship between PA and overall health and well-being.

Rationale and Design of the mTECH-Rehab Randomized Controlled Trial: Impact of a Mobile Technology Enabled Corrie Cardiac Rehabilitation Program on Functional Status and Cardiovascular Health.

BACKGROUND: Cardiac rehabilitation (CR) is an evidence-based, guideline-recommended intervention for patients recovering from a cardiac event, surgery or procedure that improves morbidity, mortality, and functional status. CR is traditionally provided in-center, which limits access and engagement, most notably among underrepresented racial and ethnic groups due to barriers including cost, scheduling, and transportation access. This study is designed to evaluate the Corrie Hybrid CR, a technology-based, multicomponent health equity-focused intervention as an alternative to traditional in-center CR among patients recovering from a cardiac event, surgery, or procedure compared with usual care alone. METHODS: The mTECH-Rehab (Impact of a Mobile Technology Enabled Corrie CR Program) trial will randomize 200 patients who either have diagnosis of myocardial infarction or who undergo coronary artery bypass grafting surgery, percutaneous coronary intervention, heart valve repair, or replacement presenting to 4 hospitals in a large academic health system in Maryland, United States, to the Corrie Hybrid CR program combined with usual care CR (intervention group) or usual care CR alone (control group) in a parallel arm, randomized controlled trial. The Corrie Hybrid CR program leverages 5 components: (1) a patient-facing mobile application that encourages behavior change, patient empowerment, and engagement with guideline-directed therapy; (2) Food and Drug Administration-approved smart devices that collect health metrics; (3) 2 upfront in-center CR sessions to facilitate personalization, self-efficacy, and evaluation for the safety of home exercise, followed by a combination of in-center and home-based sessions per participant preference; (4) a clinician dashboard to track health data; and (5) weekly virtual coaching sessions delivered over 12 weeks for education, encouragement, and risk factor modification. The primary outcome is the mean difference between the intervention versus control groups in distance walked on the 6-minute walk test (ie, functional capacity) at 12 weeks post randomization. Key secondary and exploratory outcomes include improvement in a composite cardiovascular health metric, CR engagement, quality of life, health factors (including low-density lipoprotein-cholesterol, hemoglobin A1c, weight, diet, smoking cessation, blood pressure), and psychosocial factors. Approval for the study was granted by the local institutional review board. Results of the trial will be published once data collection and analysis have been completed. CONCLUSIONS: The Corrie Hybrid CR program has the potential to improve functional status, cardiovascular health, and CR engagement and advance equity in access to cardiac rehabilitation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05238103.

What's in This For You? What's in This For Me?: A Win-Win Perspective of Involving Study Advisory Committee Members in Palliative Care Research.

Study advisory committees (SACs) provide critical value to clinical trials by providing unique perspectives that pull from personal and professional experiences related to the trial's healthcare topic. The Emergency Medicine Palliative Care Access (EMPallA) study had the privilege of convening a 16-person SAC from the project's inception to completion. The study team wanted to understand the impact this project had on the SAC members. In this narrative, we use reflective dialogue to share SAC members' lived experiences and the impact the EMPallA study has had on members both personally and professionally. We detail the (1) benefits SAC members, specifically patients, and caregivers, have had through working on this project. (2) The importance of recruiting diverse SAC members with different lived experiences and leveraging their feedback in clinical research. (3) Value of community capacity building to ensure the common vision of the clinical trial is promoted.

Advancing patient-centered research practices in a pragmatic patient-level randomized clinical trial: A thematic analysis of stakeholder engagement in Emergency Medicine Palliative Care Access (EMPallA).

BACKGROUND: Involving patient and community stakeholders in clinical trials adds value by ensuring research prioritizes patient goals both in conduct of the study and application of the research. The use of stakeholder committees and their impact on the conduct of a multicenter clinical trial have been underreported clinically and academically. The aim of this study is to describe how Study Advisory Committee (SAC) recommendations were implemented throughout the Emergency Medicine Palliative Care Access (EMPallA) trial. EMPallA is a multi-center, pragmatic two-arm randomized controlled trial (RCT) comparing the effectiveness of nurse-led telephonic case management and specialty, outpatient palliative care of older adults with advanced illness. METHODS: A SAC consisting of 18 individuals, including patients with palliative care experience, members of healthcare organizations, and payers was convened for the EMPallA trial. The SAC engaged in community-based participatory research and assisted in all aspects from study design to dissemination. The SAC met with the research team quarterly and annually from project inception to dissemination. Using meeting notes and recordings we completed a qualitative thematic analysis using an iterative process to develop themes and subthemes to summarize SAC recommendations throughout the project's duration. RESULTS: The SAC convened 16 times between 2017 and 2020. Over the course of the project, the SAC provided 41 unique recommendations. Twenty-six of the 41 (63%) recommendations were adapted into formal Institutional Review Board (IRB) study modifications. Recommendations were coded into four major themes: Scientific, Pragmatic, Resource and Dissemination. A majority of the recommendations were related to either the Scientific (46%) or Pragmatic (29%) themes. Recommendations were not mutually exclusive across three study phases: Preparatory, execution and translational. A vast majority (94%) of the recommendations made were related to the execution phase. Major IRB study modifications were made based on their recommendations including data collection of novel dependent variables and expanding recruitment to Spanish-speaking patients. CONCLUSIONS: Our study provides an example of successful integration of a SAC in the conduct of a pragmatic, multi-center RCT. Future trials should engage with SACs in all study phases to ensure trials are relevant, inclusive, patient-focused, and attentive to gaps between health care and patient and family needs. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT03325985, 10/30/2017.

Clinical research should involve patient and community stakeholder perspectives to make sure the study addresses questions important to the studied population. One way to do this is by creating a group of stakeholders who can advise on the conduct of a study. We assembled a Study Advisory Committee (SAC) for the Emergency Medicine Palliative Care Access (EMPallA) trial. The purpose of this clinical trial is to compare the effectiveness of nurse-led telephonic case management and specialty, outpatient palliative care of older adults with advanced illness. This paper describes how the SACs involvement translated into direct impacts on the EMPallA trial. The trial research team held regular meetings with the SAC throughout the trial process. Their involvement led to many significant changes in the trial, such as  expanding recruitment inclusion criteria (Spanish-speaking patients), and including survey instruments to measure lonelines and caregiver burden. The SAC also devised strategies to overcome patient and caregiver recruitment and retention challenges, including the creation of patient-friendly materials and training for research coordinators. This study provides a successful example of how actively engaging patient and community stakeholders, through committee engagement, can promote patient priorities in all phases of a trial while facilitating patient recruitment and retention.

Investigating the effect of an mHealth coaching intervention on health beliefs, adherence and blood pressure of patients with hypertension: A longitudinal single group pilot study.

Background: Mobile health technologies have shown promise as delivery platforms for digital health coaching for chronic conditions. However, the impacts of such strategies on users' health beliefs, intentions and ultimately clinical outcomes are understudied. Objective: This study sought (1) to evaluate the effects of a digital health coaching intervention on participants' belief constructs; and (2) to assess relationships between these belief constructs and intentions to utilize the technological intervention, actual adherence metrics and clinical outcomes related to hypertension. Methods: Thirty-four participants with hypertension were recruited from a university community from January to May 2021. They self-measured weight and blood pressure (BP) for 30 days followed by digital coaching delivered via a mobile application for 30 days. Surveys assessed constructs from the Health Belief Model and Technology Acceptance Model, compared to intention, health belief, BP self-monitoring adherence and BP outcomes. A path analysis model was used to assess the relationships between constructs and intention, adherence metrics and clinical outcomes. A Kruskal-Wallis test was used to identify changes in beliefs. Results: Participant health beliefs significantly improved after coaching, including self-efficacy (H(1) = 15.12, p < 0.001), cues to action (H(1) = 5.33, p = 0.02), attitude (H(1) = 10.35, p = 0.002), perceived usefulness (H(1) = 15.02, p < 0.001) and decreased resistance to change (H(1) = 4.05, p = 0.04). Adherence to BP measurements positively correlated with perceived health threat (ß = .033, p = 0.007) and perceived ease of use (ß = .0277, p < 0.001). Self-efficacy (ß = -2.92, p = 0.02) and perceived usefulness (ß = -3.75, p = 0.01) were linked with a decrease in diastolic BP. Conclusions: A mobile health coaching intervention may help participants improve beliefs regarding hypertension self-management.

Generation of 3D ex vivo mouse- and patient-derived glioma explant slice model for integration of confocal time-lapse imaging and spatial analysis.

Development of spatial-integrative pre-clinical models is needed for glioblastoma, which are heterogenous tumors with poor prognosis. Here, we present an optimized protocol to generate three-dimensional ex vivo explant slice glioma model from orthotopic tumors, genetically engineered mouse models, and fresh patient-derived specimens. We describe a step-by-step workflow for tissue acquisition, dissection, and sectioning of 300-µm tumor slices maintaining cell viability. The explant slice model allows the integration of confocal time-lapse imaging with spatial analysis for studying migration, invasion, and tumor microenvironment, making it a valuable platform for testing effective treatment modalities. For complete details on the use and execution of this protocol, please refer to Comba et al. (2022).1.