Soy-derived isoflavones as chemo-preventive agents targeting multiple signalling pathways for cancer prevention and therapy.

The chemopreventive and chemotherapeutic properties of soy and soy-derived compounds, especially isoflavones, have been extensively studied in recent years. However, in contrast to their anticancer effects, such as cell growth inhibition, cell cycle arrest and apoptosis induction, isoflavones have also been found to promote the growth of cancer cells. Therefore, the aim of this comprehensive review article is to present the current state of knowledge regarding the molecular mechanisms by which soy-derived isoflavones target multiple cellular signalling pathways in cancer cells. Our findings indicate that soy-derived isoflavones act as, among other things, potent modulators of HOX transcript antisense RNA (HOTAIR)/SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1), vascular endothelial growth factor (VEGF)/C-X-C motif chemokine ligand 12 (CXCL12)/C-X-C motif chemokine receptor type 4 (CXCR4), 17-ß-oestradiol (E2)/oestrogen receptor-α (ERα)/neuroglobin (NGB) and sonic hedgehog signalling pathways, epigenetic modulatory agents (i.a. miR-155, miR-34a and miR-10a-5p) and cancer stem cells and epithelial-to-mesenchymal transition inhibitors. The paper also discusses the latest epidemiological studies and clinical trials and provides an insight into recent extensive research on the chemo-preventive and therapeutic potential of soy-derived isoflavones.

Health care utilization and the associated costs attributable to cardiovascular disease in Ireland: a cross-sectional study.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality and disability globally. We examined healthcare service utilization and costs attributable to CVD in Ireland in the period before the introduction of a major healthcare reform in 2016. METHODS: Secondary analysis of data from 8 113 participants of the first wave of The Irish Longitudinal Study on Ageing. CVD was defined as having a self-reported doctor's diagnosis of myocardial infarction, angina, heart failure, stroke, atrial fibrillation or transient ischaemic attack. Participants self-reported the utilization of healthcare services in the year preceding the interview. Negative binomial regression with average marginal effects (AME) was used to estimate the incremental number of general practitioner (GP) and outpatient department (OPD) visits, accident and emergency department attendances and hospitalisations in population with CVD relative to population without CVD. We calculated the corresponding costs at individual and population levels, by gender and age groups. RESULTS: The prevalence of CVD was 18.2% (95% CI: 17.3, 19.0) Participants with CVD reported higher utilization of all healthcare services. In adjusted models, having CVD was associated with incremental 1.19 (95% CI: 0.99, 1.39) GP and 0.79 (95% CI: 0.65, 0.93) OPD visits. There were twice as many incremental hospitalisations in males with CVD compared to females with CVD (AME (95% CI): 0.20 (0.16, 0.23) vs 0.10 (0.07, 0.14)). The incremental cost of healthcare service use in population with CVD was an estimated €352.2 million (95% CI: €272.8, €431.7), 93% of which was due to use of secondary care services. CONCLUSION: We identified substantially increased use of healthcare services attributable to CVD in Ireland. Continued efforts aimed at CVD primary prevention and management are required.

Psychosocial Outcomes Among Users and Nonusers of Open-Source Automated Insulin Delivery Systems: Multinational Survey of Adults With Type 1 Diabetes.

BACKGROUND: Emerging research suggests that open-source automated insulin delivery (AID) may reduce diabetes burden and improve sleep quality and quality of life (QoL). However, the evidence is mostly qualitative or uses unvalidated, study-specific, single items. Validated person-reported outcome measures (PROMs) have demonstrated the benefits of other diabetes technologies. The relative lack of research investigating open-source AID using PROMs has been considered a missed opportunity. OBJECTIVE: This study aimed to examine the psychosocial outcomes of adults with type 1 diabetes using and not using open-source AID systems using a comprehensive set of validated PROMs in a real-world, multinational, cross-sectional study. METHODS: Adults with type 1 diabetes completed 8 validated measures of general emotional well-being (5-item World Health Organization Well-Being Index), sleep quality (Pittsburgh Sleep Quality Index), diabetes-specific QoL (modified DAWN Impact of Diabetes Profile), diabetes-specific positive well-being (4-item subscale of the 28-item Well-Being Questionnaire), diabetes treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire), diabetes distress (20-item Problem Areas in Diabetes scale), fear of hypoglycemia (short form of the Hypoglycemia Fear Survey II), and a measure of the impact of COVID-19 on QoL. Independent groups 2-tailed t tests and Mann-Whitney U tests compared PROM scores between adults with type 1 diabetes using and not using open-source AID. An analysis of covariance was used to adjust for potentially confounding variables, including all sociodemographic and clinical characteristics that differed by use of open-source AID. RESULTS: In total, 592 participants were eligible (attempting at least 1 questionnaire), including 451 using open-source AID (mean age 43, SD 13 years; n=189, 41.9% women) and 141 nonusers (mean age 40, SD 13 years; n=90, 63.8% women). Adults using open-source AID reported significantly better general emotional well-being and subjective sleep quality, as well as better diabetes-specific QoL, positive well-being, and treatment satisfaction. They also reported significantly less diabetes distress, fear of hypoglycemia, and perceived less impact of the COVID-19 pandemic on their QoL. All were medium-to-large effects (Cohen d=0.5-1.5). The differences between groups remained significant after adjusting for sociodemographic and clinical characteristics. CONCLUSIONS: Adults with type 1 diabetes using open-source AID report significantly better psychosocial outcomes than those not using these systems, after adjusting for sociodemographic and clinical characteristics. Using validated, quantitative measures, this real-world study corroborates the beneficial psychosocial outcomes described previously in qualitative studies or using unvalidated study-specific items.

Physical Activity, Body Composition, Serum Myokines and the Risk of Death in Hemodialysis Patients.

Background and Objectives: The aim of this study was to assess the relationship between habitual physical activity, body composition, serum myokine concentration, and all-cause mortality in chronic hemodialysis patients. Materials and Methods: A prospective cohort study with a 7-year follow-up was conducted in a group of 38 patients (24 men, 14 women, mean age 65.6 ± 13.9 years, dialysis vintage 1.17 ± 1.25 years). Baseline serum concentrations of myokines-follistatin and myostatin-were assessed along with a measurement of physical activity with multidimensional accelerometery, body composition, and the force of forearm muscle contraction. Survival analysis was performed using the Kaplan-Meier method for tertiles of follistatin, serum myostatin, body composition, and physical activity expressed in metabolic equivalents (MET). Results: The mean physical activity among patients was 81 min/24 h (median 38.5 min), and the mean weekly 3MET activity was 493 min (median 218 min). The probability of survival of patients was significantly lower in the subgroup with 3MET/24 h less than 26 min/24 h and 3METt less than 148 min per week compared to the other subgroup (p = 0.006 and p = 0.006, respectively). During the 70-month follow-up, the subgroup with the lowest baseline follistatin concentration showed a significantly lower risk of death (p = 0.02). Baseline myostatin levels were not significant risk factors for mortality, nor were BMI or lean and fat tissue index categories. Conclusions: Physical activity and low plasma follistatin, but not body composition indexes or plasma myostatin, could serve as predictors of all-cause mortality in hemodialysis patients.

Cohort profile update: The Cork and Kerry Diabetes and Heart Disease Study.

Background: The Cork and Kerry Diabetes and Heart Disease Study was established to investigate the prevalence of diabetes and cardiovascular disease among middle-aged adults in Ireland. The Mitchelstown cohort was recruited from a single large primary care centre between 2010-2011. A rescreen of this cohort was conducted in 2015. Methods: Data were collected on cardiovascular health and associated risk factors. In addition, the rescreen incorporated new measures which included information on cognition and frailty, medication adherence, dietary factors and the collection of stool samples with RNA sequencing of the gut microbiome. Results: Of 2047 participants in the original cohort, 237 (11.6%) were deceased, too ill to participate or were lost to follow-up. Of the remaining 1810 baseline study participants, 1378 men and women aged 51-77 years agreed to take part in the rescreen (response rate of 76.1%). The prevalence of hypertension was high, ranging from 50% to 64% depending on the measurement method. An investigation of the association of gut microbiota with metabolic syndrome and obesity indicated greater microbiome diversity in metabolically healthy non-obese individuals relative to their unhealthy counterparts. Analysis of prescribing data over time demonstrated a high prevalence of potentially inappropriate prescribing among older-aged people in primary care which increased as they progressed to more advanced old age. Conclusions: The rescreen has provided new insights into cardiovascular health. In addition, this study is embedded in a single primary care centre, enabling passive follow-up of study participants through electronic health records. All data collected at baseline and rescreen are maintained and stored at the School of Public Health, University College Cork and specific proposals for future collaborations are welcome.

Lunasin and Its Epigenetic Impact in Cancer Chemoprevention.

Cancer diseases are a leading cause of death worldwide. Therefore, it is pivotal to search for bioactive dietary compounds that can avert tumor development. A diet rich in vegetables, including legumes, provides chemopreventive substances, which have the potential to prevent many diseases, including cancer. Lunasin is a soy-derived peptide whose anti-cancer activity has been studied for over 20 years. The results of the previous research have shown that lunasin inhibits histone acetylation, regulates the cell cycle, suppresses proliferation and induces apoptosis of cancer cells. Thus, lunasin seems to be a promising bioactive anti-cancer agent and a potent epigenetic modulator. The present review discusses studies of the underlying molecular mechanisms and new perspectives on lunasin application in epigenetic prevention and anti-cancer therapy.

Availability of psychological care in pediatric diabetes centers - a real need?

The role of a multidisciplinary diabetes team (MDT) in the treatment of a person with diabetes is emphasized by both Polish and international recommendations. The importance of the availability of psychological care for the well-being and mental health of individuals (and their caregivers), as well as for diabetes management and medical outcomes, is a subject of numerous analyzes. Despite the recommendations and research showing the benefits of psychological intervention and support, there is a scarcity of data on the real availability of such care, both in Poland as well as worldwide.

An unusual non­metastatic, mismatch repair­deficient primary gastric squamous cell carcinoma presenting as a large, exophytic, bleeding tumor: A case report.

Primary gastric squamous cell carcinoma (GSCC) is an extremely rare malignancy with a poor prognosis. Despite the improved knowledge regarding its pathogenesis and biology, the treatment options remain limited. The present study reported on the unique case of a mismatch repair-deficient (dMMR) primary GSCC in a 79-year-old woman reporting fatigue and symptoms of upper gastrointestinal tract bleeding. Physical examination revealed abdominal pain at palpation. Gastroscopy revealed a large, exophytic, bleeding tumor. Medical imaging confirmed a mushroom-like polyp in the lumen of the stomach, with no signs of disease spread. Total gastrectomy and D2 lymphadenectomy were performed. Pathological examination of the post-operational material confirmed a well-differentiated SCC invading the mucosa, submucosa and muscle layer. There were no signs of dissemination observed in any of the 32 excised lymph nodes. Notably, according to the last follow-up, the patient remains well, supporting the 5-year GSCC survival rate statistics. To the best of our knowledge, this is the first such GSCC case reported in the Surgical Oncology Outpatient Clinic (Copernicus Memorial Hospital, Lodz, Poland) and these findings add to the limited data on GSCC. Although this is a very rare condition, it should always be considered during the process of diagnosis of gastric tumors.

Cross-sectional survey of compliance behaviour, knowledge and attitudes among cases and close contacts during COVID-19 pandemic.

Objectives: A key public health intervention is self-isolation for cases and restriction of movement for contacts. This study aimed to identify predictors of compliance behaviour and describe knowledge and attitudes among cases and contacts identified by the national Contact Management Programme to inform the global public health response. Study design: Secondary data analysis of anonymised cross-sectional survey data on national sample of cases and close contacts. Methods: A sample of 1000 cases and 1000 contacts was calculated to estimate compliance within a margin of error of 3% with 95% confidence. A telephone survey administered by trained interviewers collected information on socio-demographics, compliance behaviours, knowledge, and attitudes to COVID-19 from cases and close contacts. Data analysis included chi-squared statistics and multivariable logistic regression. Results: Most cases and contacts complied with public health guidance with similar characteristics in those who did and did not comply. Reasons for non-compliance included exercise, medical appointment, shopping, and work. Cases and contacts reported high levels of understanding about symptoms of COVID-19 and satisfaction with available information. Conclusion: Achieving high compliance with public health guidance is feasible and requires political leadership, policy changes and practical solutions.

The Nuclear Transporter Importin 13 Can Regulate Stress-Induced Cell Death through the Clusterin/KU70 Axis.

The cellular response to environmental stresses, such as heat and oxidative stress, is dependent on extensive trafficking of stress-signalling molecules between the cytoplasm and nucleus, which potentiates stress-activated signalling pathways, eventually resulting in cell repair or death. Although Ran-dependent nucleocytoplasmic transport mediated by members of the importin (IPO) super family of nuclear transporters is believed to be responsible for nearly all macromolecular transit between nucleus and cytoplasm, it is paradoxically known to be significantly impaired under conditions of stress. Importin 13 (IPO13) is a unique bidirectional transporter that binds to and releases cargo in a Ran-dependent manner, but in some cases, cargo release from IPO13 is affected by loading of another cargo. To investigate IPO13's role in stress-activated pathways, we performed cell-based screens to identify a multitude of binding partners of IPO13 from human brain, lung, and testes. Analysis of the IPO13 interactome intriguingly indicated more than half of the candidate binding partners to be annotated for roles in stress responses; these included the pro-apoptotic protein nuclear clusterin (nCLU), as well as the nCLU-interacting DNA repair protein KU70. Here, we show, for the first time, that unlike other IPOs which are mislocalised and non-functional, IPO13 continues to translocate between the nucleus and cytoplasm under stress, retaining the capacity to import certain cargoes, such as nCLU, but not export others, such as KU70, as shown by analysis using fluorescence recovery after photobleaching. Importantly, depletion of IPO13 reduces stress-induced import of nCLU and protects against stress-induced cell death, with concomitant protection from DNA damage during stress. Overexpression/FACS experiments demonstrate that nCLU is dependent on IPO13 to trigger stress-induced cell death via apoptosis. Taken together, these results implicate IPO13 as a novel functional nuclear transporter in cellular stress, with a key role thereby in cell fate decision.

Barriers to uptake of Open-Source automated insulin delivery Systems: Analysis of socioeconomic factors and perceived challenges of adults with type 1 diabetes from the OPEN survey.

AIMS: Social and technical trends are empowering people with diabetes to co-create or self-develop medical devices and treatments to address their unmet healthcare needs, for example, open-source automated insulin delivery (AID) systems. This study aims to investigate the perceived barriers towards adoption and maintaining of open-source AID systems. METHODS: This is a multinational study based on a cross-sectional, retrospective web-based survey of non-users of open-source AID. Participants (n = 129) with type 1 diabetes from 31 countries were recruited online to elicit their perceived barriers towards building and maintaining of an open-source AID system. RESULTS: Sourcing the necessary components, lack of confidence in one's own technology knowledge and skills, perceived time and energy required to build a system, and fear of losing healthcare provider support appear to be major barriers towards the uptake of open-source AID. CONCLUSIONS: This study identified a range of structural and individual-level barriers to uptake of open-source AID. Some of these individual-level barriers may be overcome over time through the peer support of the DIY online community as well as greater acceptance of open-source innovation among healthcare professionals. The findings have important implications for understanding the possible wider diffusion of open-source diabetes technology solutions in the future.

Quality of life and psychological well-being among children and adolescents with diabetes and their caregivers using open-source automated insulin delivery systems: Findings from a multinational survey.

BACKGROUND: Open-source automated insulin delivery (AID) systems have shown to be safe and effective in children and adolescents with type 1 diabetes (T1D) in real-world studies. However, there is a lack of evidence on the effect on their caregivers' quality-of-life (QoL) and well-being. The aim of this study was to assess the QoL of caregivers and children and adolescents using open-source AID systems using validated measures. METHODS: In this cross-sectional online survey we examined the caregiver-reported QoL and well-being of users and non-users. Validated questionnaires assessed general well-being (WHO-5), diabetes-specific QoL (PAID, PedsQL) and sleep quality (PSQI). RESULTS: 168 caregivers from 27 countries completed at least one questionnaire, including 119 caregivers of children using open-source AID and 49 not using them. After inclusion of covariates, all measures but the PAID and one subscale of the PedsQL showed significant between-group differences with AID users reporting higher general (WHO-5: p = 0.003), sleep-related (PSQI: p = 0.001) and diabetes-related QoL (PedsQL: p < 0.05). CONCLUSIONS: The results show the potential impact of open-source AID on QoL and psychological well-being of caregivers and children and adolescents with T1D, and can therefore help to inform academia, regulators, and policymakers about the psychosocial health implications of open-source AID.

Nuclear Transporter IPO13 Is Central to Efficient Neuronal Differentiation.

Molecular transport between the nucleus and cytoplasm of the cell is mediated by the importin superfamily of transport receptors, of which the bidirectional transporter Importin 13 (IPO13) is a unique member, with a critical role in early embryonic development through nuclear transport of key regulators, such as transcription factors Pax6, Pax3, and ARX. Here, we examined the role of IPO13 in neuronal differentiation for the first time, using a mouse embryonic stem cell (ESC) model and a monolayer-based differentiation protocol to compare IPO13-/- to wild type ESCs. Although IPO13-/- ESCs differentiated into neural progenitor cells, as indicated by the expression of dorsal forebrain progenitor markers, reduced expression of progenitor markers Pax6 and Nestin compared to IPO13-/- was evident, concomitant with reduced nuclear localisation/transcriptional function of IPO13 import cargo Pax6. Differentiation of IPO13-/- cells into neurons appeared to be strongly impaired, as evidenced by altered morphology, reduced expression of key neuronal markers, and altered response to the neurotransmitter glutamate. Our findings establish that IPO13 has a key role in ESC neuronal differentiation, in part through the nuclear transport of Pax6.

Transcriptomic profile dataset of embryonic stem cells (Wild-type and IPO13-Knock Out) with and without oxidative stress.

The transcriptional response to cellular stress relies upon trafficking of regulators of transcription between the nuclear and cytoplasmic compartments, which occurs through action of members of the importin (IPO) superfamily. As a result of stresses such as oxidative or osmotic stress, one consequence is that importins become mislocalised, leading to inhibition of conventional nuclear transport. Here, we examine IPO13, which has a number of nonconventional characteristics, in the context of cell stress. We used Next Generation RNA Sequencing using the Illumina platform to compare the transcriptomes of Wild-type (WT) and IPO13-Knockout (KO) mouse embryonic stem cells in the absence and presence of oxidative stress. Differences in the mRNA expression profiles were observed between the cell lines in the absence and in the presence of stress. This data will be a key resource to enable characterization of the contribution of nuclear transporter IPO13 to cellular transcription in the absence and presence of oxidative stress, as well as more broadly, in the study of stem cell biology and effect of stress on embryonic stem cell transcription.

Barriers to Uptake of Open-Source Automated Insulin Delivery Systems: Analysis of Socioeconomic Factors and Perceived Challenges of Caregivers of Children and Adolescents With Type 1 Diabetes From the OPEN Survey.

Background: As a treatment option for people living with diabetes, automated insulin delivery (AID) systems are becoming increasingly popular. The #WeAreNotWaiting community plays a crucial role in the provision and distribution of open-source AID technology. However, while a large percentage of children were early adopters of open-source AID, there are regional differences in adoption, which has prompted an investigation into the barriers perceived by caregivers of children with diabetes to creating open-source systems. Methods: This is a retrospective, cross-sectional and multinational study conducted with caregivers of children and adolescents with diabetes, distributed across the online #WeAreNotWaiting online peer-support groups. Participants-specifically caregivers of children not using AID-responded to a web-based questionnaire concerning their perceived barriers to building and maintaining an open-source AID system. Results: 56 caregivers of children with diabetes, who were not using open-source AID at the time of data collection responded to the questionnaire. Respondents indicated that their major perceived barriers to building an open-source AID system were their limited technical skills (50%), a lack of support by medical professionals (39%), and therefore the concern with not being able to maintain an AID system (43%). However, barriers relating to confidence in open-source technologies/unapproved products and fear of digital technology taking control of diabetes were not perceived as significant enough to prevent non-users from initiating the use of an open-source AID system. Conclusions: The results of this study elucidate some of the perceived barriers to uptake of open-source AID experienced by caregivers of children with diabetes. Reducing these barriers may improve the uptake of open-source AID technology for children and adolescents with diabetes. With the continuous development and wider dissemination of educational resources and guidance-for both aspiring users and their healthcare professionals-the adoption of open-source AID systems could be improved.

Costs and underuse of insulin and diabetes supplies: Findings from the 2020 T1International cross-sectional web-based survey.

AIMS: To investigate self-reported out-of-pocket expenses (OoPE) associated with insulin and diabetes supplies for people living with type 1 diabetes (T1D) worldwide. METHODS: A web-based, cross-sectional survey was conducted from August to December 2020. The analysis included comparisons between responses from countries with no, partial, and full healthcare coverage. RESULTS: 1,066 participants from 64 countries took part in the study. ~25% of respondents reported having underused insulin at least once within the last year due to perceived cost. A significant correlation was observed between OoPEs and reported household income for respondents with partial healthcare coverage. 63.2% of participants reported disruption of insulin supplies and 25.3% reported an increase of prices related to the COVID-19 pandemic. CONCLUSIONS: This study confirms previous reports of ~25% of people in the United States with T1D using less insulin and/or fewer supplies at least once in the last year due to cost, a trend associated with the extent of healthcare coverage. Similar trends were observed in some middle/low income countries. Moreover, patients reported an increase in insulin prices and disruption of supplies during the COVID-19 pandemic. This study highlights the importance of self-reported OoPEs and its association with underuse/rationing of insulin.

Lead Levels in Non-Occupationally Exposed Women with Preeclampsia.

There are many controversies regarding the relationship between lead exposure andcomplications in pregnancy. Preeclampsia (PE) is a maternal hypertensive disorder which is one of the main causes of maternal and foetal mortality. The aim of our study was to assess blood lead level (BLL) in Polish women with PE (PE group, n = 66) compared with healthy, non-pregnant women (CNP group, n = 40) and healthy pregnant women (CP group, n = 40). BLL was determined by inductively coupled plasma mass spectrometry (ICP-MS). The systolic blood pressure (SBP), diastolic blood pressure (DBP) and BLL in the CP group were significantly lower than in the PE group (p < 0.001). Logistic regression analyses of BLL showed a significant positive relationship with the presence of PE. Furthermore, both the SBP and DBP values were positively associated with BLL. This study indicates that preeclamptic women tend to present with significantly higher BLL compared to healthy pregnant women. There were no differences in the BLL between the CP and CNP groups.

Why #WeAreNotWaiting-Motivations and Self-Reported Outcomes Among Users of Open-source Automated Insulin Delivery Systems: Multinational Survey.

BACKGROUND: Automated insulin delivery (AID) systems have been shown to be safe and effective in reducing hyperglycemia and hypoglycemia but are not universally available, accessible, or affordable. Therefore, user-driven open-source AID systems are becoming increasingly popular. OBJECTIVE: This study aims to investigate the motivations for which people with diabetes (types 1, 2, and other) or their caregivers decide to build and use a personalized open-source AID. METHODS: A cross-sectional web-based survey was conducted to assess personal motivations and associated self-reported clinical outcomes. RESULTS: Of 897 participants from 35 countries, 80.5% (722) were adults with diabetes and 19.5% (175) were caregivers of children with diabetes. Primary motivations to commence open-source AID included improving glycemic outcomes (476/509 adults, 93.5%, and 95/100 caregivers, 95%), reducing acute (443/508 adults, 87.2%, and 96/100 caregivers, 96%) and long-term (421/505 adults, 83.3%, and 91/100 caregivers, 91%) complication risk, interacting less frequently with diabetes technology (413/509 adults, 81.1%; 86/100 caregivers, 86%), improving their or child's sleep quality (364/508 adults, 71.6%, and 80/100 caregivers, 80%), increasing their or child's life expectancy (381/507 adults, 75.1%, and 84/100 caregivers, 84%), lack of commercially available AID systems (359/507 adults, 70.8%, and 79/99 caregivers, 80%), and unachieved therapy goals with available therapy options (348/509 adults, 68.4%, and 69/100 caregivers, 69%). Improving their own sleep quality was an almost universal motivator for caregivers (94/100, 94%). Significant improvements, independent of age and gender, were observed in self-reported glycated hemoglobin (HbA1c), 7.14% (SD 1.13%; 54.5 mmol/mol, SD 12.4) to 6.24% (SD 0.64%; 44.7 mmol/mol, SD 7.0; P<.001), and time in range (62.96%, SD 16.18%, to 80.34%, SD 9.41%; P<.001). CONCLUSIONS: These results highlight the unmet needs of people with diabetes, provide new insights into the evolving phenomenon of open-source AID technology, and indicate improved clinical outcomes. This study may inform health care professionals and policy makers about the opportunities provided by open-source AID systems. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/15368.