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Current clinical tools for breast cancer (BC) diagnosis are insufficient but liquid biopsy of different bodily fluids has recently emerged as a minimally invasive strategy that provides a real-time snapshot of tumour biomarkers for early diagnosis, active surveillance of progression, and post-treatment recurrence. Extracellular vesicles (EVs) are nano-sized membranous structures 50–1000 nm in diameter that are released by cells into biological fluids. EVs contain proteins, nucleic acids, and lipids which play pivotal roles in tumourigenesis and metastasis through cell-to-cell communication. Proteins and miRNAs from small EVs (sEV), which range in size from 50–150 nm, are being investigated as a potential source for novel BC biomarkers using mass spectrometry-based proteomics and next-generation sequencing. This review covers recent developments in sEV isolation and single sEV analysis technologies and summarises the sEV protein and miRNA biomarkers identified for BC diagnosis, prognosis, and chemoresistance. The limitations of current sEV biomarker research are discussed along with future perspective applications.

We evaluated therapeutic peptide candidates for diabetic retinopathy (DR) using a zebrafish model. Three peptides, designed from a type II collagen-derived sequence, were evaluated for toxicity and vascular protective effects. Peptide 1 demonstrated favorable physicochemical stability, low toxicity (> 90% survival), and vascular protective activity. In contrast, Peptides 2 and 3 showed increased toxicity and morphological abnormalities at higher concentrations, limiting their potential utility. In a hyperglycemia-induced zebrafish DR model, Peptide 1 (100–200 µg/ml) reduced retinal vessel thickness with efficacy comparable to aflibercept. Molecular analysis by RT-PCR indicated that Peptide 1 suppressed vascular endothelial growth factor (VEGF) expression and enhanced Tie2 and Angiopoietin-1 (Ang-1) expression, suggesting a role in vascular stabilization. These findings establish zebrafish as a cost-effective and rapid screening platform for early-stage DR drug discovery. These findings support zebrafish as a cost-effective platform for early-stage diabetic retinopathy drug discovery and highlight Peptide 1 as a promising candidate for non-proliferative DR, providing a rationale for further optimization and mechanistic studies toward clinical translation.

High-rate production of multicarbon chemicals via the electrochemical CO 2 reduction can be achieved by efficient CO 2 mass transport. A key challenge for C−C coupling in high-current-density CO 2 reduction is how to promote *CO formation and dimerization. Here, we report molecularly enhanced CO 2 -to-*CO conversion and *CO dimerization for high-rate ethylene production. Nanoconfinement of ascorbic acid by graphene quantum dots enables immobilization and redox reversibility of ascorbic acid in heterogeneous electrocatalysts. Cu nanowire with ascorbic acid nanoconfined by graphene quantum dots (cAA-CuNW) demonstrates high-rate ethylene production with a Faradaic efficiency of 60.7% and a partial current density of 539 mA/cm 2 , a 2.9-fold improvement over that of pristine CuNW. Furthermore, under low CO 2 ratio of 33%, cAA-CuNW still exhibits efficient ethylene production with a Faradaic efficiency of 41.8%. We find that cAA-CuNW increases *CO coverage and optimizes the *CO binding mode ensemble between atop and bridge for efficient C−C coupling. A mechanistic study reveals that ascorbic acid can facilitate *CO formation and dimerization by favorable electron and proton transfer with strong hydrogen bonding. Efficiently producing multicarbon chemicals through electrochemical CO 2 reduction is essential for achieving economically feasible carbon neutrality. Here, the authors present molecularly enhanced CO 2 -to-*CO conversion and *CO dimerization for high-rate ethylene production by nanoconfinement of ascorbic acid.

The present study reports on the first evaluation of a parenting intervention utilizing a smartphone app, BabyMind. The intervention aimed to facilitate mothers' mind-mindedness-attunement to their infants' internal states. Mothers in the intervention group (n = 90) used the BabyMind app from their infants' births and were followed up at age 6 months (n = 66). Mothers in the control group (n = 151) were recruited when their infants were age 6 months and had never used the BabyMind app. Mind-mindedness when interacting with their infants was significantly higher in intervention group mothers than in control group mothers. The intervention was equally effective in facilitating mind-mindedness in young and older mothers. These findings are discussed in terms of the potential for interventions utilizing smartphone apps to improve parenting and children's developmental outcome in vulnerable and hard-to-reach groups.

Poor diet is a leading risk factor for cardiometabolic disease (CMD) in the United States, but its economic costs are unknown. We sought to estimate the cost associated with suboptimal diet in the US. A validated microsimulation model (Cardiovascular Disease Policy Model for Risk, Events, Detection, Interventions, Costs, and Trends [CVD PREDICT]) was used to estimate annual cardiovascular disease (fatal and nonfatal myocardial infarction, angina, and stroke) and type 2 diabetes costs associated with suboptimal intake of 10 food groups (fruits, vegetables, nuts/seeds, whole grains, unprocessed red meats, processed meats, sugar-sweetened beverages, polyunsaturated fats, seafood omega-3 fats, sodium). A representative US population sample of individuals aged 35-85 years was created using weighted sampling from National Health And Nutrition Examination Surveys (NHANES) 2009-2012 cycles. Estimates were stratified by cost type (acute, chronic, drug), sex, age, race, education, BMI, and health insurance. Annual diet-related CMD costs were $301/person (95% CI $287-$316). This translates to $50.4 billion in CMD costs (18.2% of total) for the whole population, of which 84.3% are attributed to acute care ($42.6 billion). The largest annual per capita costs are attributed to low consumption of nuts/seeds ($81; 95% CI $74-$86) and seafood omega-3 fats ($76; 95% CI $70-$83), and the lowest are attributed to high consumption of red meat ($3; 95% CI $2.8-$3.5) and polyunsaturated fats ($20; 95% CI $19-$22). Individual costs are highest for men ($380), those aged ≥65 years ($408), blacks ($320), the less educated ($392), and those with Medicare ($481) or dual-eligible ($536) insurance coverage. A limitation of our study is that dietary intake data were assessed from 24-hour dietary recall, which may not fully capture a diet over a person's life span and is subject to measurement errors. Suboptimal diet of 10 dietary factors accounts for 18.2% of all ischemic heart disease, stroke, and type 2 diabetes costs in the US, highlighting that timely implementation of diet policies could address these health and economic burdens.

Digital cognitive behavioral therapy for insomnia (dCBT-I) has emerged as a treatment for chronic insomnia. Smart rings provide objective, wearable-derived sleep data that may complement subjective sleep diaries, but their role in monitoring treatment response remains unclear. This study evaluated the clinical effectiveness of dCBT-I with smart rings and compared subjective and wearable-derived sleep measures. In this single-arm study, individuals with insomnia completed a dCBT-I program, alongside daily sleep monitoring using a smart ring and sleep diary. Changes in clinical symptoms were analyzed, and sleep parameters were compared across the two tools. Twenty-eight participants completed the study , with significant improvements in insomnia severity (ΔISI = − 6.16, p  = .011) and anxiety symptoms (ΔGAD-7 = − 2.38, p  = .038). Adherence to the smart ring was higher than to sleep diaries (52.5 vs. 44.5 days, p  = .002). Sleep diaries showed significant improvements in sleep parameters, which were not reflected in smart ring data. Systematic differences were observed between data sources. dCBT-I combined with smart rings improved clinical symptoms. However, smart rings did not reflect sleep improvements seen in diaries, limiting their clinical use as a standalone monitoring tool for insomnia management. Clinical trial registration Study of Efficacy of Digital Cognitive BehavioralTherapy with Wearable Device for Insomnia. Registered on 24/03/2024, ClinicalTrials.gov (NCT06339853), https://clinicaltrials.gov/study/NCT06339853 .

The Supplemental Nutrition Assistance Program (SNAP) provides approximately US$70 billion annually to support food purchases by low-income households, supporting approximately 1 in 7 Americans. In the 2018 Farm Bill, potential SNAP revisions to improve diets and health could include financial incentives, disincentives, or restrictions for certain foods. However, the overall and comparative impacts on health outcomes and costs are not established. We aimed to estimate the health impact, program and healthcare costs, and cost-effectiveness of food incentives, disincentives, or restrictions in SNAP. We used a validated microsimulation model (CVD-PREDICT), populated with national data on adult SNAP participants from the National Health and Nutrition Examination Survey (NHANES) 2009-2014, policy effects from SNAP pilots and food pricing meta-analyses, diet-disease effects from meta-analyses, and policy, food, and healthcare costs from published literature to estimate the overall and comparative impacts of 3 dietary policy interventions: (1) a 30% incentive for fruits and vegetables (F&V), (2) a 30% F&V incentive with a restriction of sugar-sweetened beverages (SSBs), and (3) a broader incentive/disincentive program for multiple foods that also preserves choice (SNAP-plus), combining 30% incentives for F&V, nuts, whole grains, fish, and plant-based oils and 30% disincentives for SSBs, junk food, and processed meats. Among approximately 14.5 million adults on SNAP at baseline with mean age 52 years, our simulation estimates that the F&V incentive over 5 years would prevent 38,782 cardiovascular disease (CVD) events, gain 18,928 quality-adjusted life years (QALYs), and save $1.21 billion in healthcare costs. Adding SSB restriction increased gains to 93,933 CVD events prevented, 45,864 QALYs gained, and $4.33 billion saved. For SNAP-plus, corresponding gains were 116,875 CVD events prevented, 56,056 QALYs gained, and $5.28 billion saved. Over a lifetime, the F&V incentive would prevent approximately 303,900 CVD events, gain 649,000 QALYs, and save $6.77 billion in healthcare costs. Adding SSB restriction increased gains to approximately 797,900 CVD events prevented, 2.11 million QALYs gained, and $39.16 billion in healthcare costs saved. For SNAP-plus, corresponding gains were approximately 940,000 CVD events prevented, 2.47 million QALYs gained, and $41.93 billion saved. From a societal perspective (including programmatic costs but excluding food subsidy costs as an intra-societal transfer), all 3 scenarios were cost-saving. From a government affordability perspective (i.e., incorporating food subsidy costs, including for children and young adults for whom no health gains were modeled), the F&V incentive was of low cost-effectiveness at 5 years (incremental cost-effectiveness ratio: $548,053/QALY) but achieved cost-effectiveness ($66,525/QALY) over a lifetime. Adding SSB restriction, the intervention was cost-effective at 10 years ($68,857/QALY) and very cost-effective at 20 years ($26,435/QALY) and over a lifetime ($5,216/QALY). The combined incentive/disincentive program produced the largest health gains and reduced both healthcare and food costs, with net cost-savings of $10.16 billion at 5 years and $63.33 billion over a lifetime. Results were consistent in probabilistic sensitivity analyses: for example, from a societal perspective, 1,000 of 1,000 iterations (100%) were cost-saving for all 3 interventions. Due to the nature of simulation studies, the findings cannot prove the health and cost impacts of national SNAP interventions. Leveraging healthier eating through SNAP could generate substantial health benefits and be cost-effective or cost-saving. A combined food incentive/disincentive program appears most effective and may be most attractive to policy-makers.

Cognitive behavioral therapy for insomnia (CBT-I) has proven to be an effective treatment; however, its accessibility is limited. To address this issue, digital therapeutics for insomnia (DTx-Is), which are software-driven interventions designed to treat insomnia based on CBT-I, have emerged as a potential solution to enhance access. This study aimed to verify the efficacy and safety of WELT-I, a DTx-I. Due to the impact of the global pandemic during the study period, we thought that a decentralized clinical trial (DCT) design that does not require visits to institutions would be appropriate for a clinical study of a digital therapeutic for patients with insomnia. Thus, we also examined the potential of the DCT design as an effective method for validating DTx-Is. A double-blind, sham-controlled randomized DCT was conducted with participants who met the diagnostic criteria for insomnia. Participants were recruited through advertisements posted on an open-access website. WELT-I is a DTx-I based on CBT-I. A sham app was engineered to mirror WELT-I's installation, login, user engagement, and content delivery processes while maintaining double-blind protocols. After randomization, participants were asked to use WELT-I or the sham app for 6 weeks. All treatment processes were fully automated. Sleep parameters were measured through an app-based sleep diary. Self-report questionnaires on sleep, depression, and anxiety were administered via the app at baseline and the end of the study. The primary outcome was sleep efficiency. To investigate the feasibility of the DCT design, compliance, retention rate, participant satisfaction, and time to reach the recruitment goal were evaluated. A total of 89 participants provided consent and underwent screening, and 68 participants were randomly assigned to the WELT-I group (n=33) or control group (n=35). Among them, 14 participants discontinued the trial, leaving 54 participants who completed the study and were included in the final analysis (28 in the WELT-I group and 26 in the control group). WELT-I significantly improved sleep efficiency (least-squares difference=8.28; P=.04) and dysfunctional beliefs about sleep (least-squares difference=-1.03; P=.008) compared with the sham app. The study completed recruitment in 73 days, and the compliance rate was 95% (186/196) in the WELT-I group and 91% (165/182) in the control group. Moreover, the retention rate was 82% (23/28), and the average satisfaction score was 7.2 out of 10. WELT-I showed significant therapeutic efficacy and safety in improving sleep efficiency and sleep-related dysfunctional attitudes in cases of insomnia. In addition, this study demonstrated the feasibility of DCTs, and the findings of rapid recruitment, high compliance and retention rates, and strong participant satisfaction suggest that DCTs have sufficient potential to be expanded to clinical studies verifying the efficacy of other DTx-Is in the future.

Economic incentives through health insurance may promote healthier behaviors. Little is known about health and economic impacts of incentivizing diet, a leading risk factor for diabetes and cardiovascular disease (CVD), through Medicare and Medicaid. A validated microsimulation model (CVD-PREDICT) estimated CVD and diabetes cases prevented, quality-adjusted life years (QALYs), health-related costs (formal healthcare, informal healthcare, and lost-productivity costs), and incremental cost-effectiveness ratios (ICERs) of two policy scenarios for adults within Medicare and Medicaid, compared to a base case of no new intervention: (1) 30% subsidy on fruits and vegetables (\"F&V incentive\") and (2) 30% subsidy on broader healthful foods including F&V, whole grains, nuts/seeds, seafood, and plant oils (\"healthy food incentive\"). Inputs included national demographic and dietary data from the National Health and Nutrition Examination Survey (NHANES) 2009-2014, policy effects and diet-disease effects from meta-analyses, and policy and health-related costs from established sources. Overall, 82 million adults (35-80 years old) were on Medicare and/or Medicaid. The mean (SD) age was 68.1 (11.4) years, 56.2% were female, and 25.5% were non-whites. Health and cost impacts were simulated over the lifetime of current Medicare and Medicaid participants (average simulated years = 18.3 years). The F&V incentive was estimated to prevent 1.93 million CVD events, gain 4.64 million QALYs, and save $39.7 billion in formal healthcare costs. For the healthy food incentive, corresponding gains were 3.28 million CVD and 0.12 million diabetes cases prevented, 8.40 million QALYs gained, and $100.2 billion in formal healthcare costs saved, respectively. From a healthcare perspective, both scenarios were cost-effective at 5 years and beyond, with lifetime ICERs of $18,184/QALY (F&V incentive) and $13,194/QALY (healthy food incentive). From a societal perspective including informal healthcare costs and lost productivity, respective ICERs were $14,576/QALY and $9,497/QALY. Results were robust in probabilistic sensitivity analyses and a range of one-way sensitivity and subgroup analyses, including by different durations of the intervention (5, 10, and 20 years and lifetime), food subsidy levels (20%, 50%), insurance groups (Medicare, Medicaid, and dual-eligible), and beneficiary characteristics within each insurance group (age, race/ethnicity, education, income, and Supplemental Nutrition Assistant Program [SNAP] status). Simulation studies such as this one provide quantitative estimates of benefits and uncertainty but cannot directly prove health and economic impacts. Economic incentives for healthier foods through Medicare and Medicaid could generate substantial health gains and be highly cost-effective.

PurposeFew studies have evaluated the effects of processed red meat (PRM) consumption on chronic disease risk, especially among low average PRM consumption populations. This study examined association between PRM intake and type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) incidences in Korea.MethodsParticipants (n = 10,030; aged 40–69 years) were recruited from the Ansan–Ansung cohort study, a subset of Korean Genome Epidemiology Study. Validated 103-item semi-quantitative food frequency questionnaire was used to assess dietary information, at baseline (2001–2002) and at second follow-up (2005–2006). T2DM and CVD incidences were identified using biennial questionnaire-based interview during a 10-year follow-up period. Cox proportional hazards regression analysis was used to calculate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsOver the 10-year follow-up period, 668 and 493 incident cases of T2DM (62,130 person-years) and CVD (63,150 person-years), respectively, were documented. In crude models, comparing the highest and lowest levels of PRM intake, no significant association occurred with incident T2DM [HR, 95% CI (0.94, 0.76–1.17)], while significant association occurred with incident CVD (0.67, 0.51–0.88). However, in adjusted models, this association was no longer significant, showing HRs (95% CI) of PRM intake for T2DM and CVD of 1.07 (0.85–1.35) and 1.14 (0.85–1.55), respectively.ConclusionsPRM intake did not affect T2DM and CVD incidences among Korean middle-aged adults, although extremely low average consumption of PRM may explain the finding. Therefore, limiting PRM intake may not be a top priority for the prevention of chronic diseases in Korean population.