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To address the issues of subjectivity and bias that designers face in selecting and constructing narrative cultural themes when introducing narrative design methods into the design of handicraft intangible cultural heritage cultural and creative products, a model incorporating quantitative analysis methods into the narrative theme selection process is proposed. First, based on the theory of cultural levels and semiotic structure, a new narrative text structure is developed to enrich the narrative cultural themes of handicraft intangible cultural heritage. Second, a process model for constructing narrative texts of handicraft intangible cultural heritage is established using kansei engineering, factor analysis, and the TOPSIS method, to minimize the impact of subjective factors in the narrative theme selection process. Finally, using the design of Huangmei Cross Flower cultural and creative products as an example, the feasibility of the model is validated. This method model effectively reduces the transmission bias of cultural features in the narrative design process of handicraft intangible cultural heritage, providing a theoretical foundation for further design practice of handicraft intangible cultural heritage products.
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Metal-coated lattice structures hold significant promise for customizing mechanical properties in diverse industrial applications, including the mechanical arms of unmanned aerial vehicles. However, their intricate geometries pose computational challenges, resulting in time-intensive and costly numerical evaluations. This study introduces a parameterization-based multiscale method to analyze body-centered cubic lattice structures with metal coatings. We establish the validity and precision of our proposed method with a comparative analysis of numerical results at the Representative Volume Element (RVE) scale and experimental findings, specifically addressing both elastic tensile and bending stiffness. Furthermore, we showcase the method's accuracy in interpreting the bending stiffness of coated lattice structures using a homogenized material-based solid model, underscoring its effectiveness in predicting the elastic properties of such structures. In exploring the mechanical characterization of coated lattice structures, we unveil positive correlations between elastic tensile stiffness and both coating thickness and strut diameter. Additionally, the metal coating significantly enhances the structural elastic bending stiffness multiple times over. The diverse failure patterns observed in coated lattices under tensile and bending loads primarily stem from varied loading-induced stress states rather than external factors. This work not only mitigates computational challenges but also successfully bridges the gap between mesoscale RVE mechanical properties and those at the global structural scale.
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Lattice materials are widely used in industries due to their designable capabilities of specific stiffness and energy absorption. However, evaluating the mechanical response of macroscopic lattice structures can be computationally expensive. Homogenization-based multi-scale analysis offers an efficient approach to address this issue. To achieve a simpler, while precise, homogenization, the authors proposed an equidistant segmentation (ES) method for the measurement of the effective shear modulus. In this method, the periodic boundary conditions (PBCs) are approximated by constraining the lateral displacement of nodes between parallel layers of periodic cells. The validations were applied to three typical lattice topologies: body-centered cubic (BCC) lattices, gyroid-, and primitive-triply periodic minimal surface (TPMS) lattices, to predict and compare their anti-vibration capacities. The results demonstrated the rationality and the promising precision of the multi-scale-based equivalent modal analysis through the proposed method and that it eliminated the geometric limitation of lattices with diverse frameworks. Overall, a higher anti-vibration capacity of TPMS was observed. In the study, the authors examined the influence of the relative densities on the balance between the anti-vibration capacity and loading capacity (per unit mass) of the TPMS topologies. Specifically, the unit mass of the TPMS with lower relative densities was able to resist higher frequencies, and the structures were dominated by the anti-vibration capacity. In contrast, a higher relative density is better when emphasizing the loading capacity. These findings may provide notable references to the designers and inform the selection of lattice materials for various industrial applications.
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Computational methods have been proposed to leverage spatially resolved transcriptomic data, pinpointing genes with spatial expression patterns and delineating tissue domains. However, existing approaches fall short in uniformly quantifying spatially variable genes (SVGs). Moreover, from a methodological viewpoint, while SVGs are naturally associated with depicting spatial domains, they are technically dissociated in most methods. Here, we present a framework (PROST) for the quantitative recognition of spatial transcriptomic patterns, consisting of (i) quantitatively characterizing spatial variations in gene expression patterns through the PROST Index; and (ii) unsupervised clustering of spatial domains via a self-attention mechanism. We demonstrate that PROST performs superior SVG identification and domain segmentation with various spatial resolutions, from multicellular to cellular levels. Importantly, PROST Index can be applied to prioritize spatial expression variations, facilitating the exploration of biological insights. Together, our study provides a flexible and robust framework for analyzing diverse spatial transcriptomic data.
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Perfilação da Expressão Gênica , Transferência Intratubária do Zigoto , Transcriptoma/genética , Análise por Conglomerados , Reconhecimento PsicológicoRESUMO
With increasing interest in the rapid development of lattice structures, hybrid additive manufacturing (HAM) technology has become a competent alternative to traditional solutions such as water jet cutting and investment casting. Herein, a HAM technology that combines vat photopolymerization (VPP) and electroless/electroplating processes is developed for the fabrication of multifunctional polymer-metal lattice composites. A VPP 3D printing process is used to deliver complex lattice frameworks, and afterward, electroless plating is employed to deposit a thin layer of nickel-phosphorus (Ni-P) conductive seed layer. With the subsequent electroplating process, the thickness of the copper layer can reach 40 µm within 1 h and the resistivity is around 1.9×10-8 Ωâ m, which is quite close to pure copper (1.7 ×10-8 Ωâ m). The thick metal shell can largely enhance the mechanical performance of lattice structures, including structural strength, ductility, and stiffness, and meanwhile provide current supply capability for electrical applications. With this technology, the frame arms of unmanned aerial vehicles (UAV) are developed to demonstrate the application potential of this HAM technology for fabricating multifunctional polymer-metal lattice composites.
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OBJECTIVES: Drain tube management after liver transplant is controversial. A new peritoneal drainage management protocol was developed to validate clinical characteristics, such as drain characteristics, postoperative complications, duration of postoperative hospital stay, changes in albumin levels, and 30-day readmission rates. MATERIALS AND METHODS: Data from 183 consecutive patients who underwent deceased donor liver transplant at our institution between January 2019 and June 2022 were retrospectively analyzed. A new drain management protocol was implemented on August 1, 2021, which included early removal of the drain tube when the serum albumin level was >3 g/dL and nonchylous fluid drainage was <200 mL/day. RESULTS: When we compared the traditional and new drain management protocol groups (n = 131 vs n = 52), the new management protocol group showed a decrease in the median duration of intraperitoneal drainage. In addition, the median length of postoperative hospital stay decreased from 33 to 27 days and serum albumin levels returned to normal faster at postoperative 3 weeks. No significant differences were found in postoperative hemorrhage, hematoma, hydrops abdominis, infections, biliary complications, orin the rate ofreinterventions and 30-day rehospitalizations. CONCLUSIONS: The new management protocol was associated with fewer postoperative hospital days and faster recovery than traditional management. Our findings may aid in the development of new drain policy recommendations based on preexisting risk factors.
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Transplante de Fígado , Humanos , Transplante de Fígado/efeitos adversos , Estudos Retrospectivos , Fatores de Tempo , Doadores Vivos , Drenagem/efeitos adversos , Drenagem/métodos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/terapia , Tempo de Internação , Albumina Sérica , HospitaisRESUMO
Exploring the evolution of urban elements can improve understanding of the developmental process of city and drive such development into a better direction. However, the non-linearity and complexity of changes in urban elements have brought great challenges to understanding this process. In this paper, we propose a cross-diffusion partial differential equation based on ecological dynamics to simulate the evolutionary process of urban elements from the microscopic viewpoint. The interaction between urban elements is simulated by constructing a non-linear and spatiotemporal change equation, and the main influence between elements is evaluated by the key parameters in the discussed equation. Our model is first experimented to time-series data on population density and housing prices to analyzes the interaction of these two elements in the evolution process. We then extend the model to label data, land cover data, to obtain a quantitative expression of the interaction between different land types in the process of urban land cover change.
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The easy loss of crosslinking ions in alginate can result in structural collapse and loss of its characteristics as a bone scaffold. A novel injectable tissue engineering scaffold containing poly(lactic-co-glycolic acid) (PLGA) microspheres and alginate was fabricated to improve alginate's physiochemical and biological properties. MgCO3and MgO were loaded at a 1:1 ratio into PLGA microspheres to form biodegradable PLGA microspheres containing magnesium (PMg). Subsequently, different concentrations of PMg were mixed into a Ca2+suspension and employed as crosslinking agents for an alginate hydrogel. A pure Ca2+suspension was used as the alginate crosslinking agent in the control group. The influence of PMg on the physiochemical properties of the injectable scaffolds, including the surface morphology, degradation rate, Mg2+precipitation concentration, and the swelling rate, was investigated. MC3T3-E1 cells were seeded onto the hydrogels to evaluate the effect of the resultant alginate on osteoblastic attachment, proliferation, and differentiation. The physicochemical properties of the hydrogels, including morphology, degradation rate, and swelling ratio, were effectively tuned by PMg. Inductively coupled plasma-optical emission spectroscopy results showed that, in contrast to those in pure PMg, the magnesium ions (Mg2+) in alginate hydrogel containing PMg microspheres (Alg-PMg) were released in a dose-dependent and slow-releasing manner. Additionally, Alg-PMg with an appropriate concentration of PMg not only improved cell attachment and proliferation but also upregulated alkaline phosphatase activity, gene expression of osteogenic markers, and related growth factors. These findings indicate that PMg incorporation can regulate the physicochemical properties of alginate hydrogels. The resultant hydrogel promoted cell attachment, matrix mineralization, and bone regeneration. The hydrogel described in this study can be considered a promising injectable scaffold for bone tissue engineering.
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Magnésio , Engenharia Tecidual , Engenharia Tecidual/métodos , Magnésio/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Microesferas , Glicóis , Alginatos/química , Hidrogéis/química , Alicerces Teciduais/química , ÍonsRESUMO
Petroleum industry has started to embrace the advanced petroleum cyber-physical system (CPS) technologies. Offshore petroleum CPS is particularly hard to build, mainly due to the difficulty in detecting and preventing offshore oil leaking. During the oil exploration and transportation process, the remote multi-sensing technology is typically employed for emerging service. It can be utilized for leak detection by enabling the underwater modeling of an offshore petroleum CPS. However, such a technology suffers from insufficient remote sensing resources and expensive computational overhead. In this work, a cross-entropy based leak detection technique is proposed to detect the oil leak, which facilitates the understanding of the oil leak induced marine pollution. Furthermore, a hierarchical parallel approach is proposed on the super computer Tianhe-2 to improve the efficiency of the proposed leak detection technique. Experimental results on Penglai oil spill events demonstrate that the proposed method can effectively identify the sources of oil spilling with accuracy up to [Formula: see text].
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Reliable extreme lightweight is the pursuit in many high-end manufacturing areas. Aided by additive manufacturing (AM), lattice material has become a promising candidate for lightweight optimization. Configuration of lattice units at the material level and the distribution of lattice units at the structure level are the two main research directions recently. This paper proposes a generative strategy for lattice infilling optimization using organic strut-based lattices. A sphere packing algorithm driven by von Mises stress fields determines the lattice distribution density. Two typical configurations, Voronoi polygons and Delaunay triangles, are adopted to constitute the frames, respectively. Based on finite element analysis, a simplified truss model is utilized to evaluate the lattice distribution in terms of mechanical properties. Optimization parameters, including node number, mapping gradient, and the range of varying circle size, are investigated through the genetic algorithm (GA). Multiple feasible solutions are obtained for further solidification modelling. To avoid the stress concentration, the organic strut-based lattice units are created by the iso-surface modelling method. The effectiveness of the proposed generative approach is illustrated through a classical 3-point bending beam. The stiffness of the optimized structure, verified through experimental testing, has increased 80% over the one using the traditional uniform body center cubic (BCC) lattice distribution.
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Natural polymer hydrogels are widely used in various aspects of biomedical engineering, such as wound repair, owing to their abundance and biosafety. However, the low strength and the lack of function restricted their development and application scope. Herein, we fabricated novel multifunctional chitin/PEGDE-tannic acid (CPT) hydrogels through chemical- and physical-crosslinking strategies, using chitin as the base material, polyethylene glycol diglycidyl ether (PEGDE) and tannic acid (TA) as crosslinking agents, and 90 % ethanol as the regenerative bath. CPT hydrogels maintained a stable three-dimensional porous structure with suitable water contents and excellent biocompatibility. The mechanical properties of hydrogels were greatly improved (tensile stress up to 5.43 ± 1.14 MPa). Moreover, CPT hydrogels had good antibacterial, antioxidant, and hemostatic activities and could substantially promote wound healing in a rat model of full-thickness skin defect by regulating inflammatory responses and promoting collagen deposition and blood vessel formation. Therefore, this work provides a useful strategy to fabricate novel multifunctional CPT hydrogels with excellent mechanical, antibacterial, antioxidant, hemostatic, and biocompatible properties. CPT hydrogels could be promising candidates for wound healing.
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Hemostáticos , Ratos , Animais , Hemostáticos/farmacologia , Antioxidantes/farmacologia , Antioxidantes/química , Hidrogéis/farmacologia , Hidrogéis/química , Cicatrização/fisiologia , Antibacterianos/farmacologia , Antibacterianos/química , Quitina/farmacologiaRESUMO
Infections caused by bacteria have long constituted a major threat to human health and the economy. Therefore, there is an urgent need to design broad-spectrum antibacterial materials possessing good biocompatibility to treat such infections. Herein, inspired by the good biocompatibility of chitin and antibacterial properties of imidazolium salts, a polysaccharide-based material, imidazolium salt chitin (IMSC), was homogeneously prepared using a facile method with epichlorohydrin as a chemical crosslinker to combine chitin with imidazole to enhance Staphylococcus aureus (S. aureus)-infected wound healing. The characteristics, antimicrobial properties, and biosafety of IMSC were evaluated. The results demonstrated successful grafting of imidazole onto chitin. Furthermore, IMSC exhibited good water solubility, broad-spectrum antimicrobial activity, hemocompatibility, and biocompatibility. Moreover, IMSC enabled complete healing of S. aureus-infected wound in Sprague-Dawley rats within 15 days of application, thus demonstrating that IMSC could reduce wound inflammation and remarkably accelerate wound healing owing to its efficient antibacterial activity and ability to promote collagen deposition in and around the wound area. Therefore, this study provides a promising and potential therapeutic strategy for infected wound healing by synthesizing a water-soluble and broad-spectrum antimicrobial material exhibiting good biocompatibility.
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Anti-Infecciosos , Infecção dos Ferimentos , Ratos , Animais , Humanos , Staphylococcus aureus , Ratos Sprague-Dawley , Escherichia coli , Cicatrização , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antibacterianos/química , Quitina/farmacologia , Quitina/uso terapêutico , Quitina/química , Cloreto de Sódio , Água/química , Infecção dos Ferimentos/tratamento farmacológicoRESUMO
Low-temperature curable negative-tone photosensitive polyimide (n-LTPI) viscous solutions were prepared by dissolving photo-crosslinkable poly (amic ester) (pc-PAE) resin, photophotocrosslinker, photoinitiator, and the heteroaromatic base as curing catalysts, and other additives in organic solvents. Among them, the pc-PAE resin was synthesized by polycondensation of aromatic diacid chloride and diester of 2-ethoxymathacrylate, aromatic diamines in aprotic solvents. After being spun-coated on a silicon wafer surface, soft-baked, exposed to UV light, and developed, the n-LTPI with 2% of imidazole (IMZ) as a curing catalyst produced high-quality photo-patterns with line via resolution of 5 µm at 5 µm film thickness. The photo-patterned polymer films thermally cured at 230 °C/2 h in nitrogen showed 100% of the imidization degree (ID) determined by in situ FT-IR spectroscopy. The thermally cured polymer films exhibited great combined mechanical and thermal properties, including mechanical properties with tensile strength of as high as 189.0 MPa, tensile modulus of 3.7 GP, and elongation at breakage of 59.2%, as well as glass transition temperature of 282.0 °C, showing great potential in advanced microelectronic packaging applications.
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More than 70% of catastrophic landslides were previously unknown and brought tremendous losses to human life and property in urban regions; therefore, there is an urgent need for early identification of active landslides to eliminate landslide risk at the early stage. However, early identification of landslides has always been a worldwide challenge due to high concealment, steep topography, inaccessible location, and sudden onset. This work suggests a new set of comprehensive criteria for the early identification of landslides by integrating surface deformation, geological, topographic, geomorphological, and disaster-failure features. This set of criteria is universally applicable with no use of the prior knowledge of landslide locations (blind identification) and is successfully validated by a field survey. This work selects the Xuecheng region, a hard-hit area of landslides, as the study area and employs multisource data (seismic, geological, topographic, meteorological, SAR, and optical remote sensing data) and time-series InSAR technology to identify active landslides and reveal their deformation rules. Some new viewpoints are suggested. (1) The new comprehensive criteria synthesize the surface deformation, disaster-controlling, and disaster-inducing characteristics and achieve relatively high accuracy by field validation. (2) Forty-seven active landslides are identified in Xuecheng with no use of the prior knowledge of landslides. The soft rocks or soft-hard interbeddings, tectonic movement, fluvial undercutting and eroding, precipitation, earthquakes, and human engineering activity control or induce the development of these active landslides. (3) Two giant landslides that significantly threaten human lives and properties and exhibit different movement modes are selected to highlight the deformation rules of active landslides under the coupled action of poor lithologic condition, tectonic movement, river erosion, precipitation, and human engineering activity. The suggested new criteria can be applied to other landslide hard-hit urban regions and contribute to the timely and effective prevention and control of catastrophic landslides, reduction of enormous disaster losses, and rational management of the environment.
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Desastres , Terremotos , Deslizamentos de Terra , Humanos , Medição de Risco , RiosRESUMO
Hyperspectral band selection aims to identify an optimal subset of bands for hyperspectral images (HSIs). For most existing clustering-based band selection methods, they directly stretch each band into a single feature vector and employ the pixelwise features to address band redundancy. In this way, they do not take full consideration of the spatial information and deal with the importance of different regions in HSIs, which leads to a nonoptimal selection. To address these issues, a region-aware hierarchical latent feature representation learning-guided clustering (HLFC) method is proposed. Specifically, in order to fully preserve the spatial information of HSIs, the superpixel segmentation algorithm is adopted to segment HSIs into multiple regions first. For each segmented region, the similarity graph is constructed to reflect the bands-wise similarity, and its corresponding Laplacian matrix is generated for learning low-dimensional latent features in a hierarchical way. All latent features are then fused to form a unified feature representation of HSIs. Finally, k -means clustering is utilized on the unified feature representation matrix to generate multiple clusters from which the band with maximum information entropy is selected to form the final subset of bands. Extensive experimental results demonstrate that the proposed clustering method can achieve superior performance than the state-of-the-art representative methods on the band selection. The demo code of this work is publicly available at https://github.com/WangJun2023/HLFC.
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Catastrophic landslides have much more frequently occurred worldwide due to increasing extreme rainfall events and intensified human engineering activity. Landslide susceptibility evaluation (LSE) is a vital and effective technique for the prevention and control of disastrous landslides. Moreover, about 80% of disastrous landslides had not been discovered ahead and significantly impeded social and economic sustainability development. However, the present studies on LSE mainly focus on the known landslides, neglect the great threat posed by the potential landslides, and thus to some degree constrain the precision and rationality of LSE maps. Moreover, at present, potential landslides are generally identified by the characteristics of surface deformation, terrain, and/or geomorphology. The essential disaster-inducing mechanism is neglected, which has caused relatively low accuracies and relatively high false alarms. Therefore, this work suggests new synthetic criteria of potential landslide identification. The criteria involve surface deformation, disaster-controlling features, and disaster-triggering characteristics and improve the recognition accuracy and lower the false alarm. Furthermore, this work combines the known landslides and discovered potential landslides to improve the precision and rationality of LSE. This work selects Chaya County, a representative region significantly threatened by landslides, as the study area and employs multisource data (geological, topographical, geographical, hydrological, meteorological, seismic, and remote sensing data) to identify potential landslides and realize LSE based on the time-series InSAR technique and XGBoost algorithm. The LSE precision indices of AUC, Accuracy, TPR, F1-score, and Kappa coefficient reach 0.996, 97.98%, 98.77%, 0.98, and 0.96, respectively, and 16 potential landslides are newly discovered. Moreover, the development characteristics of potential landslides and the cause of high landslide susceptibility are illuminated. The proposed synthetic criteria of potential landslide identification and the LSE idea of combining known and potential landslides can be utilized to other disaster-serious regions in the world.
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Desastres , Deslizamentos de Terra , Humanos , Sistemas de Informação Geográfica , Geologia , Aprendizado de MáquinaRESUMO
The single-beam bathymetric light detection and ranging (LiDAR) system 1 (SBLS-1), which is equipped with a 532-nm-band laser projector and two concentric-circle receivers for shallow- and deep-water echo signals, is a lightweight and convenient prototype instrument with low energy consumption. In this study, a novel LiDAR bathymetric method is utilized to achieve single-beam and dual-channel bathymetric characteristics, and an adaptive extraction method is proposed based on the cumulative standard deviation of the peak and trough, which is mainly used to extract the signal segment and eliminate system and random noise. To adapt the dual-channel bathymetric mechanism, an automatic channel-selection method was used at various water depths. A minimum half-wavelength Gaussian iterative decomposition is proposed to improve the detection accuracy of the surface- and bottom-water waveform components and ensure bathymetric accuracy and reliability. Based on a comparison between the experimental results and in situ data, it was found that the SBLS-1 obtained a bathymetric accuracy and RMSE of 0.27 m and 0.23 m at the Weifang and Qingdao test fields. This indicates that the SBLS-1 was bathymetrically capable of acquiring a reliable, high-efficiency waveform dataset. Hence, the novel LiDAR bathymetric method can effectively achieve high-accuracy near-shore bathymetry.
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Total and fine mode aerosol optical depth (AODT and AODF), as well as the fine mode fraction (FMF = AODF/AODT), are critical variables for climate change and atmospheric environment studies. The retrievals with high accuracy from satellite observations, particularly FMF and AODF over land, remain challenging. This study aims to improve the Moderate-resolution Imaging Spectro-radiometer (MODIS) land dark target (DT) algorithm for retrieving AODT, AODF, and FMF on a global scale. Based on the fact that the underestimated surface reflectance (SR) could overestimate the AODT and underestimate the aerosol size parameter in the DT algorithm, two robust schemes were developed to improve SR determination: the first (NEW1 DT) used the top of the atmosphere reflectance instead of SR at 2.12 µm; the second (NEW2 DT) used eleven-year MODIS data to establish a monthly spectral SR relationship model (2.12-0.47 and 2.12-0.65 µm) database at pixel-by-pixel scale. Then a novel lookup table approach based on the physical process was proposed to retrieve the AODF and FMF. The new MODIS AODT, FMF, and AODF were compared to AERosol RObotic NETwork (AERONET) retrievals. Results showed that the root mean square error (RMSE) was 0.096-0.103, 0.098-0.099, and 0.167-0.180 for the new AODTs, AODFs, and FMFs, respectively, which were better than that of the Collection 6.1 (C6.1) DT (0.117, 0.235, and 0.426) in the validation by global AERONET sites. From the validation results, NEW2 DT provided better AODT and coarse mode AOD retrievals, while NEW1 DT had better AODF and FMF performances. The spatial patterns of AODF, FMF, and AODC of the new DT algorithms were comparable to those of the Polarization and Directionality of the Earth's Reflectances aerosol product. Hence, the new algorithms have the potential to provide global AODT, FMF, and AODF products over land to the scientific community with high accuracy using long-term MODIS data.
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PURPOSE: To evaluate the clinical characteristics and treatment outcomes of Chinese children with advanced stage anaplastic large cell lymphoma (ALCL) who were treated with the low-intensity APO regimen. METHODS: Clinical data from children newly diagnosed with advanced stage ALCL and treated with the APO regimen were reviewed. RESULTS: Altogether 22 eligible patients with advanced stage ALCL were recruited in this study. 18 (81%) patients achieved complete response (CR) after the initial induction, and 4 experienced relapse. Among patients with relapsed or refractory ALCL, CR was achieved in 3 (50%) who received the BFM95 R3/R4 regimen. Besides, 2 patients received the targeted therapy with crizotinib and were still alive. The 5-year OS and EFS rates were 82 ± 8.7% and 68.2 ± 9.4%%, respectively. According to our results, the elevated LDH level and bone marrow involvement were identified as the poor prognostic factors for EFS (p=0.035 and 0.048, respectively). During APO treatment, only 23% patients experienced grade 3-4 hematologic toxicity. CONCLUSIONS: In this study, bone marrow involvement and elevated serum LDH levels were identified as the poor prognostic factors for EFS. In resource-limited regions, patients with advanced stage ALCL can also achieve comparable outcomes to those in high-income regions, and the BFM95 R3/R4 regimen can take the role of salvage treatment for patients with relapsed or refractory disease. Nonetheless, new therapeutic strategy is still needed.