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Four previously undescribed phloroglucinols, including three pairs of enantiomers, (±)-rhodotomentodimer F, (±)-rhodotomentodimer G, and (±)-rhodotomentomonomer E, and one phloroglucinol-sesquiterpene meroterpenoid, rhodotomentodione E, together with one previously reported congener, (±)-rhodomyrtosone A, were obtained from the leaves of Rhodomyrtus tomentosa. The structures including absolute configurations of previously undescribed isolates were elucidated by extensive spectroscopic analysis (HRESIMS and NMR), ECD calculations, and single-crystal X-ray diffraction. (±)-Rhodotomentodimer F is a rare phloroglucinol derivative conjugated by a ß-triketone moiety and an unprecedented resorcinol unit via the formation of a rare bis-furan ring system, whereas (±)-rhodotomentomonomer E shares a rearranged pentacyclic scaffold. Pharmacologically, (±)-rhodotomentomonomer E showed the strongest human acetylcholinesterase (hAChE) inhibitory effect with an IC50 value of 1.04 ± 0.05 µM. Molecular formula studies revealed that hydrogen bonds formed between hAChE residues Glu202, Ser203, Ala204, Gly121, Gly122, Tyr337, and His447 and (±)-rhodotomentomonomer E played crucial roles in its observed activity. These findings indicated that the leaves of Rhodomyrtus tomentosa can supply a rich source of hAChE inhibitors. These inhibitors might potentially be utilized in the therapeutic strategy for Alzheimer's disease, offering promising candidates for further research and development.
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Six pairs of previously undescribed enantiomeric phytocannabinoid-like meroterpenoids, (±)-spinulinoids AâF, and two naturally occurring compounds, (+)-rhododaurichromanic acid A and (E)-4-((3,7-dimethylocta-2,6-dien-1-yl)oxy)benzoic acid, together with one known congener, (-)-rhododaurichromanic acid A, were obtained from the twigs and leaves of Rhododendron spinuliferum. Their structures were established by their extensive spectral data (NMR and HRESIMS), ECD calculations, and single-crystal X-ray diffraction data. Spinulinoids A and B are unprecedented phytocannabinoid-like meroterpenoids constructed by the resorcinol moiety and a ß-bisabolene unit, whereas spinulinoid C represents a rare adduct of quinone and ß-bisabolene with a tricyclic 6/6/6 ring system.
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Agave species are typical crassulacean acid metabolism (CAM) plants commonly cultivated to produce beverages, fibers, and medicines. To date, few studies have examined hemicellulose biosynthesis in Agave H11648, which is the primary cultivar used for fiber production. We conducted PacBio sequencing to obtain full-length transcriptome of five agave tissues: leaves, shoots, roots, flowers, and fruits. A total of 41,807 genes were generated, with a mean length of 2394 bp and an annotation rate of 97.12 % using public databases. We identified 42 glycosyltransferase genes related to hemicellulose biosynthesis, including mixed-linkage glucan (1), glucomannan (5), xyloglucan (16), and xylan (20). Their expression patterns were examined during leaf development and fungal infection, together with hemicellulose content. The results revealed four candidate glycosyltransferase genes involved in xyloglucan and xylan biosynthesis, including glucan synthase (CSLC), xylosyl transferase (XXT), xylan glucuronyltransferase (GUX), and xylan α-1,3-arabinosyltransferase (XAT). These genes can be potential targets for manipulating xyloglucan and xylan traits in agaves, and can also be used as candidate enzymatic tools for enzyme engineering. We have provided the first full-length transcriptome of agave, which will be a useful resource for gene identification and characterization in agave species. We also elucidated the hemicellulose biosynthesis machinery, which will benefit future studies on hemicellulose traits in agave.
Subject(s)
Agave , Gene Expression Regulation, Plant , Glycosyltransferases , Polysaccharides , Transcriptome , Glycosyltransferases/genetics , Glycosyltransferases/metabolism , Agave/genetics , Polysaccharides/biosynthesis , Xylans/metabolism , Xylans/biosynthesis , Gene Expression Profiling , Plant Leaves/genetics , Plant Leaves/metabolism , Plant Proteins/genetics , Plant Proteins/metabolismABSTRACT
Importance: Several clinical practice guidelines advise race- and ethnicity-based screening for youth-onset type 2 diabetes (T2D) due to a higher prevalence among American Indian and Alaska Native, Asian, Black, and Hispanic youths compared with White youths. However, rather than a biological risk, this disparity likely reflects the inequitable distribution of adverse social determinants of health (SDOH), a product of interpersonal and structural racism. Objective: To evaluate prediabetes prevalence by presence or absence of adverse SDOH in adolescents eligible for T2D screening based on weight status. Design, Setting, and Participants: This cross-sectional study and analysis used data from the 2011 to 2018 cycles of the National Health and Nutrition Examination Survey. Data were analyzed from June 1, 2023, to April 5, 2024. Participants included youths aged 12 to 18 years with body mass index (BMI) at or above the 85th percentile without known diabetes. Main Outcomes and Measures: The main outcome consisted of an elevated hemoglobin A1c (HbA1c) level greater than or equal to 5.7% (prediabetes or undiagnosed presumed T2D). Independent variables included race, ethnicity, and adverse SDOH (food insecurity, nonprivate health insurance, and household income <130% of federal poverty level). Survey-weighted logistic regression was used to adjust for confounders of age, sex, and BMI z score and to determine adjusted marginal prediabetes prevalence by race, ethnicity, and adverse SDOH. Results: The sample included 1563 individuals representing 10â¯178â¯400 US youths aged 12 to 18 years (mean age, 15.5 [95% CI, 15.3-15.6] years; 50.5% [95% CI, 47.1%-53.9%] female; Asian, 3.0% [95% CI, 2.2%-3.9%]; Black, 14.9% [95% CI, 11.6%-19.1%]; Mexican American, 18.8% [95% CI, 15.4%-22.9%]; Other Hispanic, 8.1% [95% CI, 6.5%-10.1%]; White, 49.1% [95% CI, 43.2%-55.0%]; and >1 or other race, 6.1% [95% CI, 4.6%-8.0%]). Food insecurity (4.1% [95% CI, 0.7%-7.5%]), public insurance (5.3% [95% CI, 1.6%-9.1%]), and low income (5.7% [95% CI, 3.0%-8.3%]) were each independently associated with higher prediabetes prevalence after adjustment for race, ethnicity, and BMI z score. While Asian, Black, and Hispanic youths had higher prediabetes prevalence overall, increasing number of adverse SDOH was associated with higher prevalence among White youths (8.3% [95% CI, 4.9%-11.8%] for 3 vs 0.6% [95% CI, -0.7% to 2.0%] for 0 adverse SDOH). Conclusions and Relevance: Adverse SDOH were associated with higher prediabetes prevalence, across and within racial and ethnic categories. Consideration of adverse SDOH may offer a more actionable alternative to race- and ethnicity-based screening to evaluate T2D risk in youth.
Subject(s)
Diabetes Mellitus, Type 2 , Prediabetic State , Social Determinants of Health , Humans , Adolescent , Prediabetic State/epidemiology , Prediabetic State/ethnology , Social Determinants of Health/statistics & numerical data , Female , Male , Cross-Sectional Studies , Prevalence , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/ethnology , United States/epidemiology , Child , Nutrition Surveys , Glycated Hemoglobin/analysis , Food Insecurity , Ethnicity/statistics & numerical data , Body Mass IndexABSTRACT
Selenium nanoparticles (SeNPs) has been reported as a beneficial role in alleviating cadmium (Cd) toxicity in plant. However, underlying molecular mechanisms about SeNPs reducing Cd accumulation and alleviating Cd toxicity in wheat are not well understood. A hydroponic culture was performed to evaluate Cd and Se accumulation, cell wall components, oxidative stress and antioxidative system, and transcriptomic response of wheat seedlings after SeNPs addition under Cd stress. Results showed that SeNPs application notably reduced Cd concentration in root and in shoot by 56.9% and 37.3%, respectively. Additionally, SeNPs prompted Cd distribution in root cell wall by 54.7%, and increased lignin, pectin and hemicellulose contents by regulating cell wall biosynthesis and metabolism-related genes. Further, SeNPs alleviated oxidative stress caused by Cd in wheat through signal transduction pathways. We also observed that Cd addition reduced Se accumulation by downregulating the expression level of aquaporin 7. These results indicated that SeNPs alleviated Cd toxicity and reduced Cd accumulation in wheat, which were associated with the synergetic regulation of cell wall biosynthesis pathway, uptake transporters, and antioxidative system via signaling pathways.
Subject(s)
Cadmium , Cell Wall , Selenium , Transcriptome , Triticum , Triticum/drug effects , Triticum/metabolism , Cell Wall/drug effects , Cell Wall/metabolism , Cadmium/toxicity , Selenium/pharmacology , Selenium/chemistry , Transcriptome/drug effects , Oxidative Stress/drug effects , Nanoparticles/toxicity , Nanoparticles/chemistry , Plant Roots/drug effects , Plant Roots/metabolism , Metal Nanoparticles/toxicity , Metal Nanoparticles/chemistry , Gene Expression Regulation, Plant/drug effects , Soil Pollutants/toxicityABSTRACT
Glioblastoma (GBM) is an extremely aggressive primary brain tumor with poor prognosis, short survival time post-diagnosis and high recurrence. Currently, no cure for GBM exists. The identification of an effective therapeutic modality for GBM remains a high priority amongst medical professionals and researches. In recent studies, inhalant cannabidiol (CBD) has demonstrated promise in effectively inhibiting GBM tumor growth. However, exactly how CBD treatment affects the physiology of these tumor cells remains unclear. Stress granules (SG) (a sub-class of biomolecular condensates (BMC)) are dynamic, membrane-less intracellular microstructures which contain proteins and nucleic acids. The formation and signaling of SGs and BMCs plays a significant role in regulating malignancies. This study investigates whether inhaled CBD may play an intervening role towards SGs in GBM tumor cells. Integrated bioinformatics approaches were preformed to gain further insights. This includes use of Immunohistochemistry and flow cytometry to measure SGs, as well as expression and phosphorylation of eukaryotic initiation factor-2α (eIF2α). The findings of this study reveal that CBD receptors (and co-regulated genes) have the potential to play an important biological role in the formation of BMCs within GBM. In this experiment, CBD treatment significantly increased the volume of TIAR-1. This increase directly correlated with elevation in both eIF2α expression and p-eIF2α in CBD treated tissues in comparison to the placebo group (p < 0.05). These results suggest that inhalant CBD significantly up-regulated SGs in GBM, and thus support a theory of targeting BMCs as a potential therapeutic substrate for treating GBM.
Subject(s)
Brain Neoplasms , Cannabidiol , Glioblastoma , Glioblastoma/drug therapy , Glioblastoma/metabolism , Glioblastoma/pathology , Cannabidiol/pharmacology , Humans , Brain Neoplasms/drug therapy , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Stress Granules/metabolism , Stress Granules/drug effects , Cell Line, Tumor , Eukaryotic Initiation Factor-2/metabolismABSTRACT
Eleven alkaloids (1-11) including seven new ones, 1-7, were isolated from the solid fermentation of Aspergillus fumigatus VDL36, an endophytic fungus isolated from the leaves of Vaccinium dunalianum Wight (Ericaceae), a perennial evergreen shrub distributed across the Southwest regions of China, Myanmar, and Vietnam. Their structures were elucidated on the basis of extensive spectroscopic methods. The isolates were evaluated for in vitro antifungal activities against five phytopathogenic fungi (Fusarium oxysporum, Coriolus versicolor, Fusarium solani, Botrytis cinerea, Fusarium graminearum). As a result, the new compounds fumigaclavine I (1), 13-ethoxycyclotryprostatin A (5), 13-dehydroxycyclotryprostatin A (6), and 12ß-hydroxy-13-oxofumitremorgin C (7) exhibited antifungal activities with MIC values of 7.8-62.5 µg/mL which were comparable to the two positive controls ketoconazole (MIC = 7.8-31.25 µg/mL) and carbendazim (MIC = 1.95-7.8 µg/mL). Furthermore, compounds 1 and 5 demonstrated potent protective and curative effects against the tomato gray mold in vivo. Preliminary structure-activity relationships of the tested indole diketopiperazine alkaloids indicate that the introduction of a substituent group at position C-13 enhances their biological activities.
Subject(s)
Alkaloids , Aspergillus fumigatus , Endophytes , Alkaloids/pharmacology , Alkaloids/chemistry , Aspergillus fumigatus/drug effects , Endophytes/chemistry , Molecular Structure , Fusarium/drug effects , Fungicides, Industrial/pharmacology , Fungicides, Industrial/chemistry , Plant Leaves/microbiology , Plant Leaves/chemistry , Microbial Sensitivity Tests , China , Plant Diseases/microbiologyABSTRACT
BACKGROUND: As the major protein (approximately 36%) in rice bran, globulin exhibits excellent foaming and emulsifying properties, endowing its useful application as a foaming and emulsifying agent in the food industry. However, the low water solubility restricts its commercial potential in industrial applications. The present study aimed to improve this protein's processing and functional properties. RESULTS: A novel covalent complex was fabricated by a combination of the Maillard reaction and alkaline oxidation using rice bran globulin (RBG), chitooligosaccharide (C), quercetin (Que) and resveratrol (Res). The Maillard reaction improved the solubility, emulsifying and foaming properties of RBG. The resultant glycosylated protein was covalently bonded with quercetin and resveratrol to form a (RBG-C)-Que-Res complex. (RBG-C)-Que-Res exhibited higher thermal stability and antioxidant ability than the native protein, binary globulin-chitooligosaccharide or ternary globulin-chitooligosaccharide-polyphenol (only containing quercetin or resveratrol) conjugates. (RBG-C)-Que-Res exerted better cytoprotection against the generation of malondialdehyde and reactive oxygen species in HepG2 cells, which was associated with increased activities of antioxidative enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) through upregulated genes SOD1, CAT, GPX1 (i.e. gene for glutathione peroxidase-1), GCLM (i.e. gene for glutamate cysteine ligase modifier subunit), SLC1A11 (i.e. gene for solute carrier family 7, member 11) and SRXN1 (i.e. gene for sulfiredoxin-1). The anti-apoptotic effect of (RBG-C)-Que-Res was confirmed by the downregulation of caspase-3 and p53 and the upregulation of B-cell lymphoma-2 gene expression. CONCLUSION: The present study highlights the potential of (RBG-C)-Que-Res conjugates as functional ingredients in healthy foods. © 2024 Society of Chemical Industry.
Subject(s)
Antioxidants , Chitosan , Oligosaccharides , Oryza , Quercetin , Resveratrol , Humans , Quercetin/chemistry , Quercetin/analogs & derivatives , Oryza/chemistry , Oligosaccharides/chemistry , Resveratrol/chemistry , Resveratrol/pharmacology , Antioxidants/chemistry , Antioxidants/pharmacology , Chitosan/chemistry , Hep G2 Cells , Chitin/chemistry , Chitin/analogs & derivatives , Superoxide Dismutase/metabolism , Superoxide Dismutase/genetics , Plant Proteins/chemistry , Plant Proteins/metabolism , Maillard Reaction , Catalase/metabolism , Catalase/genetics , Glutathione Peroxidase/metabolism , Glutathione Peroxidase/geneticsABSTRACT
X-ray scintillators have gained significant attention in medical diagnostics and industrial applications. Despite their widespread utility, scintillator development faces a significant hurdle when exposed to elevated temperatures, as it usually results in reduced scintillation efficiency and diminished luminescence output. Here we report a molecular design strategy based on a hybrid perovskite (TpyBiCl5) that overcomes thermal quenching through multi-excited state switching. The structure of perovskite provides a platform to modulate the luminescence centers. The rigid framework constructed by this perovskite structure stabilized its triplet states, resulting in TpyBiCl5 exhibiting an approximately 12â times higher (45 % vs. 3.8 %) photoluminescence quantum yield of room temperature phosphorescence than that of its organic ligand (Tpy). Most importantly, the interactions between the components of this perovskite enable the mixing of different excited states, which has been revealed by experimental and theoretical investigations. The TpyBiCl5 scintillator exhibits a detection limit of 38.92â nGy s-1 at 213â K and a detection limit of 196.31â nGy s-1 at 353â K through scintillation mode switching between thermally activated delayed fluorescence and phosphorescence. This work opens up the possibility of solving the thermal quenching in X-ray scintillators by tuning different excited states.
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BACKGROUND: In the era of combination therapy, there has been limited research on body composition. Specific body composition, such as sarcopenia, possesses the potential to serve as a predictive biomarker for toxic effects and clinical response in patients with urothelial carcinoma (UC) undergoing tislelizumab combined with gemcitabine and cisplatin (T + GC). MATERIALS AND METHODS: A total of 112 UC patients who received T + GC were selected at the Affiliated Hospital of Xuzhou Medical University from April 2020 to January 2023. Baseline patient characteristics and detailed hematological parameters were collected using the electronic medical system and laboratory examinations. The computed tomography images of patients were analyzed to calculate psoas muscle mass index (PMI). We evaluated the association between sarcopenia (PMI < 4.5 cm2/m2 in men; PMI < 3.3 cm2/m2 in women) and both hematological toxicity and tumor response. RESULTS: Overall, of the 112 patients (65.2% male, median age 56 years), 43 (38.4%) were defined as sarcopenia. Patients with sarcopenia were notably older (p = 0.037), more likely to have hypertension (p = 0.009), and had poorer ECOG-PS (p = 0.027). Patients with sarcopenia were more likely to develop leukopenia (OR 2.969, 95% CI 1.028-8.575, p = 0.044) after receiving at least two cycles of T + GC. However, these significant differences were not observed in thrombocytopenia and anemia. There were no significant differences in the tumor response and grade 3-4 hematological toxicity between patients with sarcopenia and those without sarcopenia. CONCLUSIONS: Patients with sarcopenia were more likely to develop leukopenia after receiving T + GC. There were no notable alterations observed in relation to anemia or thrombocytopenia. No significant difference was found between the sarcopenia group and non-sarcopenia group in terms of tumor response and grade 3-4 hematological toxicity.
Subject(s)
Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols , Cisplatin , Deoxycytidine , Gemcitabine , Leukopenia , Sarcopenia , Humans , Male , Female , Middle Aged , Sarcopenia/chemically induced , Cisplatin/administration & dosage , Cisplatin/adverse effects , Cisplatin/therapeutic use , Leukopenia/chemically induced , Deoxycytidine/analogs & derivatives , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Aged , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/therapeutic use , Retrospective Studies , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/complications , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/complications , Adult , Urologic Neoplasms/drug therapy , Urologic Neoplasms/complications , Urologic Neoplasms/pathologyABSTRACT
Developing highly sensitive and selective methods that incorporate specific recognition elements is crucial for detecting small molecules because of the limited availability of small molecule antibodies and the challenges in obtaining sensitive signals. In this study, a generalizable photoelectrochemical-colorimetric dual-mode sensing platform was constructed based on the synergistic effects of a molecularly imprinted polymer (MIP)-aptamer sandwich structure and nanoenzymes. The MIP functionalized peroxidase-like Fe3O4 (Fe3O4@MIPs) and alkaline phosphatase mimic Zr-MOF labeled aptamer (Zr-mof@Apt) were used as the recognition elements. By selectively accumulating dibutyl phthalate (DBP), a small molecule target model, on Fe3O4@MIPs, the formation of Zr-MOF@Apt-DBP- Fe3O4@MIPs sandwich structure was triggered. Fe3O4@MIPs oxidized TMB to form blue-colored oxTMB. However, upon selective accumulation of DBP, the catalytic activity of Fe3O4@MIPs was inhibited, resulting in a lighter color that was detectable by the colorimetric method. Additionally, Zr-mof@Apt effectively catalyzed the hydrolysis of L-Ascorbic acid 2-phosphate sesquimagnesium salt hydrate (AAPS), generating ascorbic acid (AA) that could neutralize the photogenerated holes to decrease the photocurrent signals for PEC sensing and reduce oxTMB for colorimetric testing. The dual-mode platform showed strong linearity for different concentrations of DBP from 1.0 pM to 10 µM (PEC) and 0.1 nM to 0.5 µM (colorimetry). The detection limits were 0.263 nM (PEC) and 30.1 nM (colorimetry) (S/N = 3), respectively. The integration of dual-signal measurement mode and sandwich recognition strategy provided a sensitive and accurate platform for the detection of small molecules.
Subject(s)
Biosensing Techniques , Molecularly Imprinted Polymers , Colorimetry/methods , Peroxidase/chemistry , PeroxidasesABSTRACT
OBJECTIVES: To evaluate the histological parameters and bone mechanical properties around implants with low primary stability (PS) in grafted bone substitutes within an oversized osteotomy. MATERIALS AND METHODS: An oversized osteotomy penetrating the double cortical bone layers was made on both femora of 24 New Zealand white rabbits. Bilaterally in the femur of all animals, 48 implants were installed, subdivided into four groups, corresponding to four prepared tissue-engineering bone complexes (TEBCs), which were placed between the implant surface and native bone wall: A: tricalcium phosphate ß (TCP-ß); B: autologous adipose derived-stem cells with TCP-ß (ASCs/TCP-ß); C: ASCs transfected with the enhanced-GFP gene with TCP-ß (EGFP-ASCs/TCP-ß); D: ASCs transfected with the BMP-2 gene with TCP-ß (BMP2-ASCs/TCP-ß). Trichrome fluorescent labeling was conducted. Animals were sacrificed after eight weeks. The trichromatic fluorescent labeling (%TFL), area of new bone (%NB), residual material (%RM), bone-implant contact (%BIC), and the removal torque force (RTF, N/cm) were assessed. RESULTS: ASCs were successfully isolated from adipose tissue, and the primary ASCs were induced into osteogenic, chondrogenic, and adipogenic differentiation. The BMP-2 overexpression of ASCs sustained for ten days and greatly enhanced the expression of osteopontin (OPN). At eight weeks post-implantation, increased %NB and RTF were found in all groups. The most significant value of %TFL, %BIC and lowest %RM was detected in group D. CONCLUSION: The low PS implants osseointegrate with considerable new bone in grafted TEBCs within an oversized osteotomy. Applying BMP-2 overexpressing ASCs-based TEBC promoted earlier osseointegration and more solid bone mechanical properties on low PS implants. Bone graft offers a wedging effect for the implant with low PS at placement and promotes osteogenesis on their surface in the healing period.
Subject(s)
Bone Substitutes , Calcium Phosphates , Dental Implants , Animals , Rabbits , Osseointegration , Osteotomy , Osteogenesis , Coloring AgentsABSTRACT
To reduce the health risks of exposure to Cd and Pb in wheat, a field experiment was conducted to investigate the differences in Cd and Pb bioaccessibility among the grains of 11 wheat cultivars and their relationships with the nutrient compositions of grains. The grain concentrations (Cd: 0.14-0.56 mg kg-1, Pb: 0.08-0.39 mg kg-1) and bioaccessibility (5.28-57.43% and 0.72-7.72% for Cd and Pb in the intestinal phase, respectively) of Cd and Pb differed significantly among the 11 cultivars. A safe wheat cultivar (Shannong16) with a relatively low health risk and the lowest grain Cd and Pb concentrations was selected. Ca, Mg, phytate, and methionine played key roles in affecting Cd and Pb bioaccessibility in wheat, with Ca and phytate significantly negatively correlated with Cd and Pb bioaccessibility. These findings can be used to optimize the selection strategy for safe wheat cultivars for healthy grain production in Cd-polluted farmland.
Subject(s)
Cadmium , Soil Pollutants , Cadmium/analysis , Triticum , Lead , Phytic Acid , Soil Pollutants/analysis , Nutrients , Edible Grain/chemistry , SoilABSTRACT
Research questions regarding how, for whom, and where a treatment achieves its effect on an outcome have become increasingly valued in substantive research. Such questions can be answered by causal moderated mediation analysis, which assesses the heterogeneity of the mediation mechanism underlying the treatment effect across individual and contextual characteristics. Various moderated mediation analysis methods have been developed under the traditional path analysis/structural equation modeling framework. One challenge is that the definitions of moderated mediation effects depend on statistical models of the mediator and the outcome, and no solutions have been provided when either the mediator or the outcome is binary, or when the mediator or outcome model is nonlinear. In addition, it remains unclear to empirical researchers how to make causal arguments of moderated mediation effects due to a lack of clarifications of the underlying assumptions and methods for assessing the sensitivity to violations of the assumptions. This article overcomes the limitations by developing general definition, identification, estimation, and sensitivity analysis for causal moderated mediation effects under the potential outcomes framework. We also developed a user-friendly R package moderate.mediation ( https://cran.r-project.org/web/packages/moderate.mediation/index.html ) that allows applied researchers to easily implement the proposed methods and visualize the initial analysis results and sensitivity analysis results. We illustrated the application of the proposed methods and the package implementation with a re-analysis of the National Evaluation of Welfare-to-Work Strategies (NEWWS) Riverside data.
Subject(s)
Models, Statistical , Software , Humans , CausalityABSTRACT
When designing a study for causal mediation analysis, it is crucial to conduct a power analysis to determine the sample size required to detect the causal mediation effects with sufficient power. However, the development of power analysis methods for causal mediation analysis has lagged far behind. To fill the knowledge gap, I proposed a simulation-based method and an easy-to-use web application ( https://xuqin.shinyapps.io/CausalMediationPowerAnalysis/ ) for power and sample size calculations for regression-based causal mediation analysis. By repeatedly drawing samples of a specific size from a population predefined with hypothesized models and parameter values, the method calculates the power to detect a causal mediation effect based on the proportion of the replications with a significant test result. The Monte Carlo confidence interval method is used for testing so that the sampling distributions of causal effect estimates are allowed to be asymmetric, and the power analysis runs faster than if the bootstrapping method is adopted. This also guarantees that the proposed power analysis tool is compatible with the widely used R package for causal mediation analysis, mediation, which is built upon the same estimation and inference method. In addition, users can determine the sample size required for achieving sufficient power based on power values calculated from a range of sample sizes. The method is applicable to a randomized or nonrandomized treatment, a mediator, and an outcome that can be either binary or continuous. I also provided sample size suggestions under various scenarios and a detailed guideline of app implementation to facilitate study designs.
Subject(s)
Mobile Applications , Humans , Sample Size , Computer Simulation , Causality , NegotiatingABSTRACT
@#Objective To investigate the clinicopathological factors associated with pathological complete response(pCR)of axillary metastatic lymph nodes in breast cancer patients after neoadjuvant chemotherapy(NAC),and to analyze the postoperative survival.Methods A total of 116 patients with breast cancer with axillary lymph node metastasis were collected from Jiaxing Hospital of TCM,Jiaxing Maternity and Child Health Care Hospital and The First Hospital of Jiaxing.Univariate analysis was used to analyze the relationship between clinicopathological factors and the pCR of axillary lymph node metastasis in breast cancer after NAC.Binary Logistic regression was used to analyze the independent predictors of the pCR of axillary lymph node metastasis in breast cancer after NAC.Kaplan-Meier survival curve was used to analyze the disease-free survival rate and overall survival rate of patients with and non-pCR of axillary metastatic lymph nodes.Results Among 116 patients,52 cases of axillary metastatic lymph nodes achieved pCR after NAC,accounting for 44.83%.Univariate analysis showed that age,vascular invasion,pCR of primary breast tumor,the difference of Ki67 before and after NAC,NAC regimen,and the efficacy of NAC were statistically significant between breast cancer patients with pCR and those non-pCR(P<0.05).Binary Logistic regression analysis showed that age,vascular invasion and pCR of primary breast tumor were independent predictors of pCR of axillary metastatic lymph nodes(P<0.05).The 5-year disease-free survival rate(80.40%vs.54.60%)and overall survival rate(90.4%vs.70.10%)of patients with pCR and non-pCR of axillary metastatic lymph nodes were compared.Conclusion Some breast cancer patients with axillary lymph node metastasis can reach pCR in lymph nodes after NAC.Analyzing the correlation between clinical pathological factors and pCR of axillary metastatic lymph nodes after NAC,it was found that pCR of axillary metastatic lymph nodes after NAC is related to age≤50 years old,no vascular infiltration,and primary breast tumor pCR.At the same time,it was found that patients with axillary metastatic lymph node pCR had a better prognosis than those with non-pCR.
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Background@#and Purpose Non-high-density lipoprotein cholesterol (non-HDL-C), which represents the total cholesterol content of all pro-atherogenic lipoproteins, has recently been included as a new target for lipid-lowering therapy in high-risk atherosclerotic patients in multiple guidelines. Herein, we aimed to explore the relationship between non-HDL-C level and the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in preventing stroke recurrence. @*Methods@#This study comprised a post hoc analysis of the CHANCE-2 (Ticagrelor or Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II) trial, from which 5,901 patients with complete data on non-HDL-C were included and categorized by median non-HDL-C levels, using a cutoff of 3.5 mmol/L. The primary efficacy and safety outcomes were recurrent stroke and severe or moderate bleeding within 90 days. @*Results@#Ticagrelor-aspirin significantly reduced the risk of recurrent stroke in patients with low non-HDL-C (71 [4.8%] vs. 119 [7.7%]; adjusted hazard ratio [HR] 0.54; 95% confidence interval [CI], 0.40–0.74), but not in those with high non-HDL-C (107 [7.3%] vs. 108 [7.6%]; adjusted HR, 0.88; 95% CI, 0.67–1.16), compared with clopidogrel-aspirin (P for interaction=0.010). When analyzed as a continuous variable, the benefit of ticagrelor-aspirin for recurrent stroke decreased as non-HDL-C levels increased. No significant differences in the treatment assignments across the non-HDL-C groups were observed in terms of the rate of severe or moderate bleeding (5 [0.3%] vs. 8 [0.5%] in the low non-HDL-C group; 4 [0.3%] vs. 2 [0.1%] in the high non-HDL-C group; P for interaction=0.425). @*Conclusion@#CHANCE-2 participants with low non-HDL-C levels received more clinical benefit from ticagrelor-aspirin versus clopidogrel-aspirin compared to those with high non-HDL-C, following minor ischemic stroke or transient ischemic attack.
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[This corrects the article DOI: 10.1016/j.apsb.2022.06.016.].
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Objective:To investigate the association between the Doppler variables of the ophthalmic artery with the severity of preeclampsia(PE).Methods:Systematic literature was searched between January 1995 and March 2023 in PubMed,Web of Science,Embase,and the Cochrane Library.Studies comparing ophthalmic artery Doppler variables,including peak systolic velocity(PSV),end-diastolic velocity(EDV),resistive index(Rl),pulsa-tility index(PI),and peak ratio(PR,the ratio of the flow velocity of the second peak to that of the initial peak)in patients with PE,severe preeclampsia(sPE),and healthy pregnant women were included.The random-effects model was adopted as the method of pooled analysis,and the I2value was used to assess heterogeneity.The pooled standardized mean difference(SMD)with 95%confidence interval(CI)was used to estimate the associa-tion between ophthalmic artery Doppler variables and PE patient's characteristics.Results:Eight retrospective studies were eventually included in this Meta-analysis.Our pooled results suggested that compared with PE ca-ses,sPE patients had lower PI levels(SMD-0.56,95%CI-0.92~-0.20,P=0.000),higher EDV levels(SMD 0.47,95%CI 0.12~0.83,P=0.028)and higher PR levels(SMD0.96,95%CI 0.13~1.78,P=0.023).Howev-er,there was no significant difference between PE and sPE patients about the PSV and RI(P=0.361,P=0.626).Conclusions:This review demonstrates that ophthalmic artery Doppler variables(PI,EDV and PR)could be useful for predicting PE and PE development(especially in identifying sPE),which in turn may help the practitioner in the management of these complicated cases and in taking early necessary precautions.