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AIM: The relationship between vitamin D status and Kawasaki Disease (KD), as well as coronary artery lesion (CAL), has yet to be established. METHODS: A meta-analysis was conducted to assess the correlation between vitamin D status and KD, as well as the impact of vitamin D status on the progression of KD into CAL. RESULTS: The meta-analysis revealed a consistent and significant association between serum 25(OH)D level and the occurrence KD (studies N = 22; z = -3.51, P < 0.001). Patients with KD had markedly lower levels of vitamin D than healthy controls (SMD: -1.30 ng/mL, 95%CI: -2.05 to -0.55 ng/mL). CONCLUSION: The study provided evidence supporting a significant association between lower serum vitamin D levels and the occurrence of KD, particularly within the Chinese population. However, the findings did not suggest a direct impact of vitamin D on the development of CAL in KD patients.
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Maladie de Kawasaki , Carence en vitamine D , Vitamine D , Maladie de Kawasaki/sang , Maladie de Kawasaki/complications , Humains , Vitamine D/sang , Vitamine D/analogues et dérivés , Carence en vitamine D/complications , Carence en vitamine D/sang , Maladie des artères coronaires/sang , Maladie des artères coronaires/étiologie , Maladie des artères coronaires/épidémiologie , Évolution de la maladieRÉSUMÉ
We experimentally investigated the coalescence-induced droplet-particle jumping phenomenon on a submillimeter scale in symmetric and asymmetric particle arrangements with poly(methyl methacrylate) (PMMA) particles and stainless steel (SS) particles. Coalescence-induced droplet-particle jumping exhibited excellent capability and interesting behavior for both droplet jumping enhancement and particle transport. The particle increased the normalized droplet jumping velocity from 0.250 for no particle case to 0.315 and 0.320 for symmetric and asymmetric particle cases. Compared with similar-sized macrostructures fixed between droplets, better jumping performance with particles may be attributed to avoiding the work of adhesion during droplet-macrostructure separation. Besides, all particles always sunk at the bottom in the symmetric cases, while the stick mode for PMMA particles and sink, wander, and jet modes for SS particles appeared in the asymmetry cases. We revealed that the asymmetric particle arrangement induces an unbalanced surface tension force, which may provide a driving force in the vertical direction. Additionally, a small enough resistive force caused by hydrophobic particles is another necessary condition for the wonder and jet mode. Finally, we realized a significantly superior particle transport in the asymmetric SS particle cases with maximum particle height reaching â¼2.1 mm, â¼12.4 times the particle radius, the most significant vertical self-propelled transport distance currently.
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PURPOSE: At present, dysfunctional CD8+ T-cells in the nasopharyngeal carcinoma (NPC) tumor immune microenvironment (TIME) have caused unsatisfactory immunotherapeutic effects, such as a low response rate of anti-PD-L1 therapy. Therefore, there is an urgent need to identify reliable markers capable of accurately predicting immunotherapy efficacy. METHODS: Utilizing various algorithms for immune-infiltration evaluation, we explored the role of EIF3C in the TIME. We next found the influence of EIF3C expression on NPC based on functional analyses and RNA sequencing. By performing correlation and univariate Cox analyses of CD8+ Tcell markers from scRNA-seq data, we identified four signatures, which were then used in conjunction with the lasso algorithm to determine corresponding coefficients in the resulting EIF3C-related CD8+ T-cell signature (ETS). We subsequently evaluated the prognostic value of ETS using univariate and multivariate Cox regression analyses, Kaplan-Meier curves, and the area under the receiver operating characteristic curve (AUROC). RESULTS: Our results demonstrate a significant relationship between low expression of EIF3C and high levels of CD8+ T-cell infiltration in the TIME, as well as a correlation between EIF3C expression and progression of NPC. Based on the expression levels of four EIF3C-related CD8+ T-cell marker genes, we constructed the ETS predictive model for NPC prognosis, which demonstrated success in validation. Notably, our model can also serve as an accurate indicator for detecting immunotherapy response. CONCLUSION: Our findings suggest that EIF3C plays a significant role in NPC progression and immune modulation, particularly in CD8+ T-cell infiltration. Furthermore, the ETS model holds promise as both a prognostic predictor for NPC patients and a tool for adjusting individualized immunotherapy strategies.
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Lymphocytes T CD8+ , Tumeurs du rhinopharynx , Humains , Cancer du nasopharynx/thérapie , Pronostic , Immunothérapie , Tumeurs du rhinopharynx/thérapie , Microenvironnement tumoralRÉSUMÉ
This study examines a versatile polymer known as polysurfactant, which is synthesized by co-polymerizing flexible acrylamide and sodium acrylate hydrocarbon chain. The polymer serves as a backbone and possesses active functional groups. Notably, the polysurfactant exhibits superior plugging and flooding abilities compared to conventional polymers. The primary objective of this paper is to investigate the properties and oil displacement characteristics of the polysurfactant through indoor physical simulation experiments. The results demonstrate that the multi-branched structure of the polysurfactant enhances its ability to associate, leading to the formation of a unique spatial network structure. The inclusion of multi-branched structures notably amplifies the association effect. The critical concentration for the association is estimated to be around 800 mg/L, at which juncture the polysurfactant exhibits a viscosity retention rate surpassing 90% subsequent to shearing. Furthermore, this spatial network structure exhibits self-recovery capabilities after experiencing shear failure and displaying strong viscosity and shear resistance. In addition, the concentration of the polysurfactant can control the hydrodynamic feature size, which shows its adaptability in regulation and oil-repelling functions at reservoir permeabilities ranging from 500 to 2000 × 10-3 µm2 with resistance coefficients ranging from 108 to 320. During the microscopic oil displacement process, the polysurfactant exerts a significant impact on mobility control, while the elastic pull clearly demonstrates a commendable viscoelastic oil displacement effect. The polysurfactant exhibits a specific degree of emulsification capability towards crude oil, leading to the emulsion exhibiting typical pseudoplastic fluid characteristics. The utilization of emulsification transportation and emulsification blockage contributes to the enhancement of oil recovery. As a result, the polysurfactant exhibits multifaceted capabilities, encompassing profile control, flooding, and plugging, owing to its unique structural characteristics. Through the implementation of a field test focused on flooding in the Daqing Oilfield, a significant enhancement in the recovery rate of 10.85% is observed, accompanied by a favorable input-output ratio of 1:3.86, thereby generating significant economic advantages.
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In this work, we investigate the freezing behavior and ice adhesion properties of sessile drops on micropillared superhydrophobic surfaces (SHSs) with various sizes, which are of practical importance for anti/deicing. First of all, it is demonstrated that the recalescence is related only to the supercooling degree of drops but not to the geometrical parameters of micropillars. The freezing time of sessile drops first increases and then decreases with the area fraction of the SHSs, which demonstrates the nonmonotonic dependence of the icing time on the area fraction. Moreover, the influence of the geometrical parameters of the micropillars on the ice adhesion is discussed. With the decrease of the substrate temperature, the wetting state of the adhesive ice can be transformed from the Cassie ice to the Wenzel ice. For the Cassie ice, the adhesive force is proportional to the area fraction of the SHSs. Interestingly, experimental results show that there exist two interfacial debonding modes of the Wenzel ice: translational debonding and rotational debonding. Furthermore, it is found that the rotational debonding mode contributes to a much lower adhesive force between the ice and the micropillared surface compared to that of the translational debonding mode. By analyzing the critical interfacial energy release rate of the two modes, we deduce the threshold between the two modes, which is quantified as the geometrical parameters of the micropillars. In addition, quantitative relations between the geometrical parameters and the adhesion strengths of the two modes are also obtained. We envision that this work would shed new light on the design optimization of anti/deicing materials.
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MOTIVATION: There has been substantial recent interest in developing methodology for high-dimensional mediation analysis. Yet, the majority of mediation statistical methods lean heavily on mean regression, which limits their ability to fully capture the complex mediating effects across the outcome distribution. To bridge this gap, we propose a novel approach for selecting and testing mediators throughout the full range of the outcome distribution spectrum. RESULTS: The proposed high-dimensional quantile mediation model provides a comprehensive insight into how potential mediators impact outcomes via their mediation pathways. This method's efficacy is demonstrated through extensive simulations. The study presents a real-world data application examining the mediating effects of DNA methylation on the relationship between maternal smoking and offspring birthweight. AVAILABILITY AND IMPLEMENTATION: Our method offers a publicly available and user-friendly function qHIMA(), which can be accessed through the R package HIMA at https://CRAN.R-project.org/package=HIMA.
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Analyse de médiation , Mères , Nouveau-né , Femelle , Humains , Études de cohortes , Méthylation de l'ADN , FumerRÉSUMÉ
Heavy metals pollution in soils is an urgent environmental issue worldwide. Phytoremediation is a green and eco-friendly way of remediating heavy metals. However, a systematic overview of this field is limited, and little is known about future development trends. Therefore, we used CiteSpace software to conduct bibliometric and visual analyses of published literature in the field of phytoremediation of heavy metals in soils from the Web of Science core collection and identified research hotspots and development trends in this field. Researchers are paying increased attention to phytoremediation of heavy metals in soils, especially environmental researchers. A total of 121 countries or regions, 3790 institutions, 4091 funded organisations and 15,482 authors have participated in research in this area. China, India, and Pakistan are the largest contributors. There has been extensive cooperation between countries, institutions, and authors worldwide, but there is a lack of cooperation among top authors. 'Calcareous soil', 'Co-contaminated soil' and 'Metal availability' are the most intensively investigated topics. 'EDTA', 'Plant growth-promoting Rhizobacteria', 'Photosynthesis', 'Biochar' and 'Phytoextraction' are research hotspots in this field. In addition, more and more researchers are beginning to pay attention to research on co-contaminated soil, metal availability, chelating agents, and microbial-assisted phytoremediation. In summary, bibliometric, and visual analyses in the field of phytoremediation of heavy metals in soils identifies probable directions for future research and provides a resource through which to better understand this rapidly advancing subject.
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Métaux lourds , Polluants du sol , Dépollution biologique de l'environnement , Polluants du sol/analyse , Bibliométrie , SolRÉSUMÉ
The negative impacts of soil heavy metals composite pollution on agricultural production and human health are becoming increasingly prevalent. The applications of green chelating agents and microorganisms have emerged as promising alternate methods for enhancing phytoremediation. The regulatory effects of root secretion composition, microbial carbon source utilization, key gene expression, and soil microbial community structure were comprehensively analyzed through a combination of HPLC, Biolog EcoPlates, qPCR, and high-throughput screening techniques. The application of EDDS resulted in a favorable rhizosphere ecological environment for the king grass Piriformospora indica, characterized by a decrease in soil pH by 0.41 units, stimulation of succinic acid and fumaric acid secretion, and an increase in carbon source metabolic activity of amino acids and carbohydrates. Consequently, this improvement enhanced the bioavailability of Cd/Cr and increased the biomass of king grass by 25.7%. The expression of dissimilatory iron-reducing bacteria was significantly upregulated by 99.2%, while there was no significant difference in Clostridium abundance. Furthermore, the richness of the soil rhizosphere fungal community (Ascomycota: 45.8%, Rozellomycota: 16.7%) significantly increased to regulate the proportion of tolerant microbial dominant groups, promoting the improvement of Cd/Cr removal efficiency (Cd: 23.4%, Cr: 18.7%). These findings provide a theoretical basis for the sustainable development of chelating agent-assisted plants-microorganisms combined remediation of heavy metals in soil.
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Basidiomycota , Métaux lourds , Polluants du sol , Humains , Cadmium/métabolisme , Sol/composition chimique , Poaceae/métabolisme , Rhizosphère , Polluants du sol/métabolisme , Métaux lourds/analyse , Microbiologie du sol , Chélateurs , Carbone , Dépollution biologique de l'environnementRÉSUMÉ
So far, alkali/surfactant/polymer flooding is widely used in oilfields to improve recovery. However, the introduction of alkali to the ternary composite leads to substantial damage formation, accelerates the scaling and corrosion loss in all aspects of surface injection and recovery, and consequently increases the cost of oil recovery in the ternary composite drive field. Therefore, environmentally friendly means are in urgent demand. Alternatively, a new non-alkali ternary drive system with salt instead of alkali has been developed based on the basis of ternary composite drive in the Daqing oilfield. In this experiment, a mathematical model of oil repelling by a salt-substituted alkali-free ternary emulsion system is formed, followed by the verification of the wet-lab experiments. The results show that the alkali-free ternary emulsion system can have a synergistic effect of complex salt and petroleum sulfonate surfactant and represents a wide range of ultralow interfacial tensions and good oil-repelling performances. The chromatographic separation occurs in the transmission process due to the adsorption of porous media, and the lower the permeability and the lower the injection rate, the higher the chromatographic separation degree. The use of multistage plug injection can narrow the difference of flow rate between high and low permeability layers and improve the recovery rate to 61.59%. Herein, the results provide theoretical guidance for the application of an alkali-free ternary emulsification system.
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To investigate the biological characteristics of monoclonal antibodies (mAbs) against avian influenza virus (AIV) and the possible mechanism of AIV-related kidney injury. BALB/c mice were immunized with inactivated H5N1 AIV to prepare monoclonal antibody H5-32, and its subtype, titer and cross-reactivity with other influenza viruses were identified. The reactivity of monoclonal antibody with normal human tissue was analyzed by immunohistochemistry. Immunofluorescence and confocal laser scanning technique were used to detect the binding sites between mAb and human renal cortical cells, and Western blotting was used to detect the size of binding fragments. Immunohistochemical analysis confirmed that monoclonal antibody H5-32 cross-reacted with normal human kidney tissue. In human kidney, mAb H5-32 was localized in the cytoplasm of human renal tubular epithelial cells, and its binding fragment size was about 43 kDa. H5N1 AIV appears to bind to human renal tubular epithelial cells, which may be one of the mechanisms of kidney injury caused by AIV infection.
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Sous-type H5N1 du virus de la grippe A , Grippe chez les oiseaux , Humains , Animaux , Souris , Anticorps monoclonaux , Rein , Cortex rénal , Souris de lignée BALB CRÉSUMÉ
In the field of human pose estimation, heatmap-based methods have emerged as the dominant approach, and numerous studies have achieved remarkable performance based on this technique. However, the inherent drawbacks of heatmaps lead to serious performance degradation in methods based on heatmaps for smaller-scale persons. While some researchers have attempted to tackle this issue by improving the performance of small-scale persons, their efforts have been hampered by the continued reliance on heatmap-based methods. To address this issue, this paper proposes the SSA Net, which aims to enhance the detection accuracy of small-scale persons as much as possible while maintaining a balanced perception of persons at other scales. SSA Net utilizes HRNetW48 as a feature extractor and leverages the TDAA module to enhance small-scale perception. Furthermore, it abandons heatmap-based methods and instead adopts coordinate vector regression to represent keypoints. Notably, SSA Net achieved an AP of 77.4% on the COCO Validation dataset, which is superior to other heatmap-based methods. Additionally, it achieved highly competitive results on the Tiny Validation and MPII datasets as well.
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Conscience immédiate , Posture , HumainsRÉSUMÉ
In this article, we present a flexible model for microbiome count data. We consider a quasi-likelihood framework, in which we do not make any assumptions on the distribution of the microbiome count except that its variance is an unknown but smooth function of the mean. By comparing our model to the negative binomial generalized linear model (GLM) and Poisson GLM in simulation studies, we show that our flexible quasi-likelihood method yields valid inferential results. Using a real microbiome study, we demonstrate the utility of our method by examining the relationship between adenomas and microbiota. We also provide an R package "fql" for the application of our method.
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Microbiote , Modèles statistiques , Humains , Fonctions de vraisemblance , Simulation numérique , Loi de PoissonRÉSUMÉ
BACKGROUND AND AIMS: Colonoscopy is an important colorectal cancer (CRC) screening modality; however, not all high-risk groups identified by fecal immunochemical test (FIT) and/or high-risk factor questionnaire (HRFQ) undergo colonoscopy in time. The impact of delays in colonoscopy on CRC detection among high-risk populations remains poorly understood, warranting further clarification. METHODS: A retrospective study was conducted among CRC high-risk population identified by Tianjin CRC screening program. According to the colonoscopy results after HRFQ and FIT, patients were classified into CRC, advanced adenoma, non-advanced adenoma, and normal groups. The time interval between CRC screening and colonoscopy was investigated and its relationship with colonoscopy results. Logistic regression was performed to explore the risk factors of CRC detection. RESULTS: Among the high-risk population without a history of CRC or polyps, 49,810 underwent HRFQ, FIT, and colonoscopy, and a time interval of fewer than 6 months was found for 79.56% of patients (n = 39,630). People with positive FIT were more likely to undergo colonoscopy within 6 months, and detection rates of CRC and/or advanced adenoma were positively related to time intervals. Similar results were found in people with a negative FIT but positive HRFQ. A time interval longer than 6 months was a significant predictor of CRC detection in high-risk populations. CONCLUSION: For high-risk people identified by CRC screening, especially those with a positive FIT, a time interval of 6 months was associated with an increased probability of CRC detection. Our findings emphasize that populations at high risk should undergo colonoscopy at least within 6 months.
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Adénomes , Tumeurs colorectales , Humains , Études rétrospectives , Coloscopie , Tumeurs colorectales/diagnostic , Tumeurs colorectales/épidémiologie , Facteurs de risque , Dépistage précoce du cancer/méthodes , Chine/épidémiologie , Adénomes/diagnostic , Adénomes/épidémiologie , Dépistage de masse/méthodesRÉSUMÉ
The mechanical properties (compressibility or deformability) of cells are closely related to their death, migration, and differentiation. Accurate separation and manipulation of bioparticles based on these mechanical properties are still a challenging in the field of acoustofluidics. In this work, based on surface acoustic waves (SAW) and divergent microchannels, we developed a new method for separating and detecting particles or cells with different compressibility. The difference in acoustic radiation force (Fr) caused by compressibility are gradually amplified and accumulated by decreasing the flow velocity, and they are finally reflected in the particle migration distance. During the transverse migration process, the alternating dominance of the acoustic radiation force and the Stokes resistance force (Fs) drives the particles to create three typical migration patterns: intermittent migration, compound migration, and near-wall migration. In the present tilted SAW device, a 91% separation success rate of â¼10 µm polystyrene (PS) and polydimethylsiloxane (PDMS) particles can be achieved by optimizing the acoustic field input power and the fluid velocity. The application potential of the present divergent microchannel is validated by separating the myelogenous leukemia cell K562 and the natural killer cell NK92 that have similar densities and sizes (â¼15 µm) but different compressibility. The results of this work are expected to provide valuable insights into the acoustofluidics separation and detection of the cells that are with different compressibility.
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Acoustique , Son (physique) , PolystyrènesRÉSUMÉ
Cadmium (Cd) and chromium (Cr) are widespread contaminants with a high risk to the environment and humans. Herein we isolated a novel strain of Serratia marcescens, namely strain S27, from soil co-contaminated with Cd and Cr. This strain showed strong resistance to Cd as well as Cr. S27 cells demonstrated Cd adsorption rate of 45.8% and Cr reduction capacity of 84.4% under optimal growth conditions (i.e., 30 °C, 200 rpm, and pH 7.5). Microscopic characterization of S27 cells revealed the importance of the functional groups C-O-C, C-H-O, C-C, C-H, and -OH, and also indicated that Cr reduction occurred on bacterial cell membrane. Cd(II) and Cr(VI) bioaccumulation on S27 cell surface was mainly in the form of Cd(OH)2 and Cr2O3, respectively. Further, metabolomic analyses revealed that N-arachidonoyl-l-alanine was the key metabolite that promoted Cd and Cr complexation by S27; it primarily promotes γ-linolenic acid (GLA) metabolism, producing siderophores and coordinating with organic acids to enhance metal bioavailability. To summarize, our results suggest that S27 is promising for the bioremediation of environments contaminated with Cd and Cr in tropical regions.
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Cadmium , Chrome , Humains , Chrome/métabolisme , Serratia marcescens/métabolisme , Dépollution biologique de l'environnement , AdsorptionRÉSUMÉ
The present study was to systematically evaluate different licorice flavonoids (LFs) compounds release behaviors from the single payload hydrogel and LFs extracts hydrogels based on the drug solubility in the release medium (DSRM), intermolecular strength of the hydrogel and the "release steric hindrance" (RSH). Two kinds of LFs (LFs 1: LFs 2 = 5:1, W/W) hydrogels were prepared with Carbopol 940 (CBP) as the thickener, and ten LFs single payload hydrogels were prepared according to the actual content in the LFs 1 extracts. The drug release mechanisms were confirmed by in vitro release experiments and molecular dynamic simulation analysis, and evaluated using novel indicators of ERLFs 1/Sin (the enhancement ratio (ER) of drug release percent of LFs 1-CBP hydrogel to the single payload hydrogel), ERLFs 2/ LFs 1 (ER of drug release percent of LFs 2-CBP hydrogel to LFs 1-CBP hydrogel) and ERrelease medium (ER of drug release percent in different release medium). We found that LFs 1-CBP possessed a significantly higher intermolecular strength and RSH than LFs 2-CBP, resulting in a higher viscosity, which had a positive correlation with the payload content and a negative correlation with the drug release percent. Therefore, the ERLFs 2/ LFs 1 values of ten LFs compounds were all higher than 1. For liquiritigenin and retrochalcone with higher DSRM, they displayed similar ERLFs 1/ Sin, ERLFs 2/ LFs 1 and ERrelease medium values (≈1). For formononetin, licoflavone A and licochalcone A with low DSRM, they exhibited ERLFs 1/Sin values >1. The low DSRM was the decisive factor to restrict their release from the single payload hydrogel. The presence of glycyrrhizin acid (GA) in the LFs could facilitate their release from the LFs extracts hydrogel. For isoliquiritin, isoliquiritigenin and glabridin with a lower content in the LFs extracts, they exhibited ERLFs 1/Sin values <1. The RSH predominantly restricted its release. The study provided guidelines for the reasonable design of LFs extracts hydrogel in pharmaceutical topical formulations.
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Glycyrrhiza , Hydrogels , Libération de médicament , Solubilité , Flavonoïdes , Extraits de plantesRÉSUMÉ
BACKGROUND: The optimum timing to wean is crucial to avoid negative outcomes for mechanically ventilated patients. The rapid shallow breathing index (RSBI), a widely used weaning index, has limitations in predicting weaning outcomes. By replacing the tidal volume of the RSBI with diaphragmatic excursion (DE) and diaphragm thickening fraction (DTF) assessed by ultrasonography, we calculated two weaning indices, the diaphragmatic excursion rapid shallow breathing index (DE-RSBI, respiratory rate [RR]/DE) and the diaphragm thickening fraction rapid shallow breathing index (DTF-RSBI, RR/DTF). The aim of this study was to evaluate the predictive values of DTF-RSBI, DE-RSBI and traditional RSBI in weaning failure. METHODS: This prospective observational study included patients undergoing mechanical ventilation (MV) for > 48 h and who were readied for weaning. During a pressure support ventilation (PSV) spontaneous breathing trial (SBT), right hemidiaphragmatic excursion and DTF were measured by bedside ultrasonography as well as RSBI. Weaning failure was defined as: (1) failing the SBT and (2) SBT success but inability to maintain spontaneous breathing for more than 48 h without noninvasive or invasive ventilation. A receiver operator characteristic (ROC) curve was used for analyzing the diagnostic accuracy of RSBI, DE-RSBI, and DTF-RSBI. RESULTS: Of the 110 patients studied, 37 patients (33.6%) failed weaning. The area under the ROC (AUROC) curves for RSBI, DE-RSBI, and DTF-RSBI for predicting failed weaning were 0.639, 0.813, and 0.859, respectively. The AUROC curves for DE-RSBI and DTF-RSBI were significantly higher than for RSBI (P = 0.004 and P < 0.001, respectively). The best cut-off values for predicting failed weaning were RSBI > 51.2 breaths/min/L, DE-RSBI > 1.38 breaths/min/mm, and DTF-RSBI > 78.1 breaths/min/%. CONCLUSIONS: In this study, two weaning indices determined by bedside ultrasonography, the DE-RSBI (RR/DE) and DTF-RSBI (RR/DTF), were shown to be more accurate than the traditional RSBI (RR/VT) in predicting weaning outcome during a PSV SBT.
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Muscle diaphragme , Sevrage de la ventilation mécanique , Muscle diaphragme/imagerie diagnostique , Humains , Respiration , Ventilation artificielle , ÉchographieRÉSUMÉ
Mediation analysis plays a major role in identifying significant mediators in the pathway between environmental exposures and health outcomes. With advanced data collection technology for large-scale studies, there has been growing research interest in developing methodology for high-dimensional mediation analysis. In this paper we present HIMA2, an extension of the HIMA method (Zhang in Bioinformatics 32:3150-3154, 2016). First, the proposed HIMA2 reduces the dimension of mediators to a manageable level based on the sure independence screening (SIS) method (Fan in J R Stat Soc Ser B 70:849-911, 2008). Second, a de-biased Lasso procedure is implemented for estimating regression parameters. Third, we use a multiple-testing procedure to accurately control the false discovery rate (FDR) when testing high-dimensional mediation hypotheses. We demonstrate its practical performance using Monte Carlo simulation studies and apply our method to identify DNA methylation markers which mediate the pathway from smoking to reduced lung function in the Coronary Artery Risk Development in Young Adults (CARDIA) Study.
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Méthylation de l'ADN , Épigénome , Simulation numérique , Marqueurs génétiques , Analyse de médiation , Méthode de Monte CarloRÉSUMÉ
Peptides of importance to both academia and industry are mostly synthesized in the solid-phase mode using a two-dimensional scheme. The so-called Fmoc/tBu strategy, where the groups are removed by piperidine and TFA, respectively, is currently the method of choice for peptide synthesis. However, as the molecular diversity of cyclic and branched peptides becomes a challenging interest, a high level of orthogonal dimensionality is required, such as through triorthogonal protection schemes. Here we present a fourth category of orthogonal protecting groups that are stable under cleavage conditions, including the TFA treatment that removes the tBu-based groups. At the end of the synthetic process and upon some chemical manipulation, the groups in this fourth category were removed with TFA. This new concept of protecting groups could facilitate the synthesis and manipulation of difficult peptides.