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Brief Mindfulness-Based Cognitive Therapy in Women With Myocardial Infarction: Results of a Multicenter Randomized Controlled Trial
No full textBackground: Elevated perceived stress is associated with adverse outcomes following myocardial infarction (MI) and may account for poorer recovery among women vs men. Objectives: This randomized controlled trial tested effects of a mindfulness-based intervention on stress levels among women with MI. Methods: Women with elevated stress (Perceived Stress Scale [PSS-4]≥6) at least 2 months after MI were enrolled from 12 hospitals in the United States and Canada and via community advertising. Participants were randomized to a remotely delivered mindfulness intervention (MBCT-Brief) or heart disease education, both 8 weeks long. Follow-up was 6 months. Changes in stress (PSS-10; primary outcome) and secondary outcomes (depressive symptoms, anxiety, quality of life, disease-specific health status, actigraphy-assessed sleep) were compared between groups. Results: The sample included 130 women with MI (mean age 59.8 ± 12.8 years, 34% racial/ethnic minorities). In intention-to-treat analysis, PSS-10 scores declined in the MBCT-Brief arm (−0.52 [95% CI: −0.77 to −0.28]) but not the heart disease education arm (−0.19 [95% CI: −0.45 to 0.06]; group×time interaction P = 0.070). The effect was stronger in per-protocol analysis of participants who completed ≥4 intervention sessions (P = 0.049). There were no significant differences in secondary outcomes in intention-to-treat or per-protocol analyses. Within the MBCT-Brief arm, more frequent mindfulness practice was associated with greater reductions in stress (P = 0.007), depressive symptoms (P = 0.017), and anxiety (P = 0.036). Conclusions: MBCT-Brief was associated with greater 6-month reductions in stress than an active control among adherent participants. More frequent mindfulness practice was associated with greater improvements in psychological outcomes. Strategies to engage women with MI in mindfulness training and support regular home practice may enhance these effects.Y
Characteristics of Global Light Rain System From GPM/DPR Measurements
No full textUnderstanding the microphysical and macrophysical characteristics of global light rain (0.2-2.5 mm/hr) is important for modeling the hydrological cycle and enhancing the cloud-related parameterization in the numerical weather prediction (NWP) model. To understand the characteristics of light rain systems, this study classified global light rain events using the Global Precipitation Measurement Dual-frequency Precipitation Radar measurements over the 8-years period. As a result, global light rain systems were identified into four types based on microphysical (mass-weighted mean diameter (Dm) and normalized intercept parameter (logNw)) and macrophysical (cloud-echo-top height (CETH)) parameters. The four classified types are (a) Type 1: light rain dominant in tropics and mid-latitude, (b) Type 2: light rain linked to atmospheric deep convection, (c) Type 3: light rain from humid oceanic inflow blocked by topography, and (d) Type 4: light rain associated with subtropical high-pressure systems. Type 2 shows the largest Dm and the smallest logNw, while Type 4 exhibited opposite patterns. Type 3 has the highest CETH and vertically stretching radar reflectivity profiles. Type 1 showed similar distributions of Dm and logNw with Type 3 and radar reflectivity with Type 4 but different distributions of hydrometeor phase with Types 3 and 4. To clarify the characteristics of Type 1, a detailed analysis was conducted, showing larger Dm and logNw, higher radar reflectivity, and stronger seasonality in tropical regions compared to mid-latitudes. This study provides valuable insights into geospatial/statistical characteristics of global light rain, which is expected to enhance the accuracy of cloud parameterization in the NWP model.Y
Utilizing drip metabolites and predictive modeling for non-destructive freshness assessment in pork loin
No full textThis study validated the use of pork drip metabolites for non-destructive freshness prediction. The pork loin was vacuum-packaged and stored for 27 days at 4 °C. The pH, drip loss, total aerobic bacterial counts (TAB), microbial composition and drip metabolites were examined. LASSO and Random Forest (RF) were selected and used for variable selection, while Ridge regression and Support Vector Regression were utilized to develop predictive models. Validation was performed using leave-one-out cross-validation. LASSO and RF selected 13 and 10 metabolites, respectively. The metabolites selected by each method were trained using Ridge regression and SVR. Each of the four trained models achieved R2 values of over 0.9. In the validation step, the model trained by Ridge regression using drip metabolites selected through LASSO showed the lowest RMSE value of 0.283 log CFU/g. Therefore, selected drip metabolites can be used to predict TAB and microbial composition of pork loin through mathematical modeling.Y
Covalent heterostructures of ultrathin amorphous carbon nitride and Si for high-performance vertical photodiodes
No full textDespite its versatility in photocatalysis, the application of carbon nitride (CN) to optoelectronic devices, especially silicon (Si) optoelectronics, has been constrained by a lack of synthetic methods for producing large-scale, highly uniform and processable films. Here we report a large-scale synthesis of ultrathin amorphous carbon nitride (aCN) on Si, achieving high uniformity, ultralow surface roughness and a covalently bonded interface with Si. The ultrathin aCN on Si (aCN/Si) is synthesized via a two-step process involving a dual-heating-zone chemical vapour deposition and subsequent postannealing in a hydrogen atmosphere. During the postannealing process, the initially formed bilayer of polymeric CN and underlying aCN undergoes material transformations, including thinning of the CN film, increasing spatial uniformity and covalent bond formation between nitrogen and silicon atoms, producing a high-quality aCN/Si heterostructure. Based on this aCN/Si, we developed vertical photodiodes that function both as electrical diodes with high rectification ratio (3.8 × 108) and photodetectors with high specific detectivity (1.9 × 1012 Jones), fast photoresponse (6.7 µs) and a broad linear dynamic range (>130 dB). Integrating these aCN/Si vertical photodiodes with amorphous indium-gallium-zinc oxide switching thin-film transistors enables active-matrix-based multispectral imaging across the visible to near-infrared spectrum range. (Figure presented.)N
Do physical activity, psychological health, and food group intake change in early pregnancy before and during COVID-19? A secondary analysis of cohort data from the Korea Nurses Health Study
No full textPurpose: This study aimed to compare the physical activity, psychological health, and food group intake of women in their first trimester of pregnancy before and during the coronavirus disease 2019 (COVID-19) pandemic, and to assess these differences according to annual income levels. Methods: Using pregnancy survey data from the Korea Nurses Health Study, we analyzed 800 cases (381 pre-COVID-19, 419 COVID-19) for physical activity and psychological health, and 592 cases (296 pre-COVID-19, 296 COVID-19) for food group intake. Data were matched using 1:1 propensity score matching. Physical activity, psychological health, and food group intake were compared between periods and income groups. Results: During the pandemic, cycling (t=1.48, p=.003), aerobic exercise (t=0.98, p=.046), and light exercise (t=3.91, p<.001) increased while swimming decreased (t=–1.81, p<.001). Lower-income groups showed decreased running (t=–1.50, p=.004), swimming (t=–1.76, p<.001), and aerobic exercise (t=–1.10, p=.042), while higher-income groups showed increased participation in various physical activities. Depression scores decreased significantly in the lower-income group (t=–1.22, p=.022). Regarding food group intake, consumption of soups, stews (t=–1.63, p=.018), vegetables, kimchi, seaweed, and root (t=–1.60, p=.044) decreased during the pandemic. Lower-income groups showed decreased vegetable consumption (t=–1.43, p=.026) and alcohol intake (t=–1.34, p=.039), while higher-income groups showed increased alcohol consumption (t=1.29, p=.010). Conclusion: The COVID-19 pandemic differently affected health behaviors in early pregnancy based on income levels, highlighting socioeconomic disparities in maintaining healthy behaviors during public health crises. These findings suggest the need for tailored interventions considering income levels when promoting health behaviors among pregnant women during future public health crises.N
Graphene quantum dots as potential broad-spectrum antiviral agents
No full textAs pandemic viruses have become a threat to people, various treatments have been developed, including vaccines, neutralizing antibodies, and inhibitors. However, some mutations in the target envelope protein limit the efficiency of these treatments. Therefore, the development of broad-spectrum antiviral agents targeting mutation-free viral membranes is of considerable importance. Herein, we propose graphene quantum dots (GQDs) as broad-spectrum antiviral agents, wherein the amphiphilic properties of GQDs destroy the viral membranes, regardless of the type of viruses, including SARS-CoV-2 and influenza virus. We observed that GQDs suppress both viral infection and replication and demonstrated their low cytotoxicity in a cell line and a mouse model, revealing the potential of GQDs as a universal first-line treatment for various viral diseases.Y
A phase III randomized study of first-line NUC-1031/cisplatin vs. gemcitabine/cisplatin in advanced biliary tract cancer
No full textBackground & Aims: The previous first-line standard of care for advanced biliary tract cancer (aBTC), gemcitabine/cisplatin, has modest efficacy. NUC-1031 is a phosphoramidate modification of gemcitabine. We report final analyses of the NuTide:121 study, designed to compare the efficacy of NUC-1031/cisplatin to gemcitabine/cisplatin in aBTC. Methods: In this open-label, multicenter study, adult patients with treatment-naïve aBTC were randomized (1:1) to NUC-1031/cisplatin (n = 388) or gemcitabine/cisplatin (n = 385) on Days 1 and 8 of 21-day cycles until disease progression or intolerance. Primary endpoints were overall survival (OS) and objective response rate (blinded independent central review). Three interim analyses (IA) and a final analysis were planned. Results: Baseline characteristics were balanced; median age 65 years, 53% male, primary tumors: intrahepatic cholangiocarcinoma (CCA) (54%), extrahepatic CCA (21%), gallbladder cancer (21%) and ampullary cancer (5%). Enrollment stopped at IA1 as the OS futility boundary was crossed. At final data cut-off, median OS for NUC-1031/cisplatin vs. gemcitabine/cisplatin was 9.2 months (95% CI 8.3–10.4) vs. 12.6 months (95% CI 11.0–15.1) (HR 1.79) and median PFS was 4.9 months (95% CI 4.4–6.0) vs. 6.4 months (95% CI 6.1–7.4) (HR 1.45). Objective response rate was higher for NUC-1031/cisplatin (18.7% vs. 12.4%; OR: 1.59; p = 0.049). The adverse event profile was similar between arms, except for hepatobiliary disorders (25% vs. 11%; higher with NUC-1031/cisplatin) and hematological events (48% vs. 65%; higher with gemcitabine/cisplatin). More patients met criteria for potential drug-induced liver injury (27% vs. 7%) and Hy's law (1.6% vs. 0.5%) with NUC-1031/cisplatin. Treatment exposure was lower for NUC-1031/cisplatin, likely due to early discontinuation for AEs (30% vs. 18%). Conclusions: NuTide:121 was terminated early due to futility. NUC-1031/cisplatin did not set a new standard in first-line aBTC. Impact and implications: Although clinical practice guidelines identified gemcitabine plus cisplatin as standard of care for advanced biliary tract cancer (aBTC) based on clinical studies, the modest efficacy observed with this regimen highlighted the urgent need for more effective therapies. NuTide:121, one of the largest randomized interventional studies conducted in the first-line aBTC population to date, compared the combination of cisplatin with NUC-1031, a phosphoramidate form of gemcitabine, with the standard of care regimen. Despite a higher response rate in the NUC-1031/cisplatin arm, the study was terminated early based on a futility assessment for OS. Early toxicity and in particular liver injury likely contributed to the regimen's failure. This study emphasized some important challenges in study design and further confirmed the difficulties of advancing treatment options in this vulnerable patient population. Trial Registration: ClinicalTrials.gov Identifier: NCT04163900.N
Development of MDM2-Targeting PROTAC for Advancing Bone Regeneration
No full textProteolysis-targeting chimeras (PROTACs) degrade target proteins through the ubiquitin-proteasome system. To date, PROTACs are primarily used to treat various diseases; however, they have not been applied in regenerative therapy. Herein, this work introduces MDM2-targeting PROTACs customized for application in bone regeneration. An MDM2-PROTAC library is constructed by combining Nutlin-3 and CRBN ligands with various linker designs. Through a multistep validation process, this work develops MDM2-PROTACs (CL144 and CL174) that presented potent degradation efficiency and a robust inductive effect on the biomineralization. Next, this work performs whole-transcriptome analysis to dissect the biological effects of the CL144, and reveals the upregulation of osteogenic marker genes. Furthermore, CL144 effectively induced bone regeneration in bone graft and ovariectomy (OVX) models after local and systemic administration, respectively. In the OVX model, the combination treatment with CL144 and alendronate induced a synergistic effect. Overall, this study demonstrates the promising role of MDM2-PROTAC in promoting bone regeneration, marking the first step toward expanding the application of the PROTAC technology.Y
Dietary intake and plasma isoflavones are inversely associated with inflammatory markers in breast cancer survivors: A cross-sectional study
No full textThe role of isoflavones in breast cancer, particularly their relationship with inflammatory markers, remains underexplored. We hypothesized that higher intakes of soy and isoflavones are inversely associated with inflammatory markers in breast cancer survivors. This cross-sectional study included 432 breast cancer survivors (mean age: 52 years). We assessed dietary soy and isoflavone intake and measured plasma concentrations of isoflavones, high-sensitivity C-reactive protein (hsCRP), adiponectin, interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-alpha. Generalized linear and logistic regression models were used to obtain adjusted least squares means (LSmeans) and odds ratios (ORs) for individual or combined (if associated with soy intake) inflammatory markers. Participants with higher soy and isoflavone intakes had lower hsCRP and IL-6 concentrations and higher adiponectin concentrations. The LSmeans (95% confidence intervals, CIs) of the lowest and highest quintiles of soy food intake were 0.71 (0.49, 0.96) and 0.52 (0.33, 0.73) for hsCRP (mg/L), and 0.42 (-0.08, 0.91) and-0.02 (-0.50, 0.46) for the combined scores of hsCRP and adiponectin. The OR (95% CI) comparing extreme quintiles of isoflavone intake was 0.43 (0.20, 0.94) for elevated hsCRP. When plasma isoflavone concentrations were examined in relation to the combined scores of hsCRP and IL-6, the OR (95% CI) comparing the extreme quintiles was 0.32 (0.12, 0.91). Our results suggest that dietary soy and isoflavone intake, as well as plasma isoflavone concentrations, are inversely associated with inflammatory markers in breast cancer survivors. These findings highlight the need for further research to better understand their clinical implications. (c) 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.N
Bystander editing by adenine base editors impairs vision restoration in a mouse model of Leber congenital amaurosis
No full textBase editors (BEs) have emerged as a powerful tool for gene correction with high activity. However, bystander base editing, a byproduct of BEs, presents challenges for precise editing. Here, we investigated the effects of bystander edits on phenotypic restoration in the context of Leber congenital amaurosis (LCA), a hereditary retinal disorder, as a therapeutic model. We observed that in retinal degeneration 12 (rd12) of LCA model mice, the highest editing activity version of an adenine base editors (ABEs), ABE8e, generated substantial bystander editing, resulting in missense mutations despite RPE65 expression, preventing restoration of visual function. Through AlphaFold-based mutational scanning and molecular dynamics simulations, we identified that the ABE8e-driven L43P mutation disrupts RPE65 structure and function. Our findings underscore the need for more stringent requirements in developing precise BEs for future clinical applications.Y