Multimodal N-of-1 trials: A Novel Personalized Healthcare Design

N-of-1 trials aim to estimate treatment effects on the individual level and can be applied to personalize a wide range of physical and digital interventions in mHealth. In this study, we propose and apply a framework for multimodal N-of-1 trials in order to allow the inclusion of health outcomes assessed through images, audio or videos. We illustrate the framework in a series of N-of-1 trials that investigate the effect of acne creams on acne severity assessed through pictures. For the analysis, we compare an expert-based manual labelling approach with different deep learning-based pipelines where in a first step, we train and fine-tune convolutional neural networks (CNN) on the images. Then, we use a linear mixed model on the scores obtained in the first step in order to test the effectiveness of the treatment. The results show that the CNN-based test on the images provides a similar conclusion as tests based on manual expert ratings of the images, and identifies a treatment effect in one individual. This illustrates that multimodal N-of-1 trials can provide a powerful way to identify individual treatment effects and can enable large-scale studies of a large variety of health outcomes that can be actively and passively assessed using technological advances in order to personalized health interventions

RhoA/ROCK-dependent moesin phosphorylation regulates AGE-induced endothelial cellular response

<p>Abstract</p> <p>Background</p> <p>The role of advanced glycation end products (AGEs) in the development of diabetes, especially diabetic complications, has been emphasized in many reports. Accumulation of AGEs in the vasculature triggers a series of morphological and functional changes in endothelial cells (ECs) and induces an increase of endothelial permeability. This study was to investigate the involvement of RhoA/ROCK-dependent moesin phosphorylation in endothelial abnormalities induced by AGEs.</p> <p>Methods</p> <p>Using human dermal microvascular endothelial cells (HMVECs), the effects of human serum albumin modified-AGEs (AGE-HSA) on the endothelium were assessed by measuring monolayer permeability and staining of F-actin in HMVECs. Activations of RhoA and ROCK were determined by a luminescence-based assay and immunoblotting. Transfection of recombinant adenovirus that was dominant negative for RhoA (RhoA N19) was done to down-regulate RhoA expression, while adenovirus with constitutively activated RhoA (RhoA L63) was transfected to cause overexpression of RhoA in HMVECs. H-1152 was employed to specifically block activation of ROCK. Co-immunoprecipitation was used to further confirm the interaction of ROCK and its downstream target moesin. To identify AGE/ROCK-induced phosphorylation site in moesin, two mutants pcDNA3/HA-moesinT^558Aand pcDNA3/HA-moesinT^558Dwere applied in endothelial cells.</p> <p>Results</p> <p>The results showed that AGE-HSA increased the permeability of HMVEC monolayer and triggered the formation of F-actin-positive stress fibers. AGE-HSA enhanced RhoA activity as well as phosphorylation of ROCK in a time- and dose-dependent manner. Down-regulation of RhoA expression with RhoA N19 transfection abolished these AGE-induced changes, while transfection of RhoA L63 reproduced the AGE-evoked changes. H-1152 attenuated the AGE-induced alteration in monolayer permeability and cytoskeleton. The results also confirmed the AGE-induced direct interaction of ROCK and moesin. Thr558 was further identified as the phosphorylating site of moesin in AGE-evoked endothelial responses.</p> <p>Conclusion</p> <p>These results confirm the involvement of RhoA/ROCK pathway and subsequent moesin Thr558 phosphorylation in AGE-mediated endothelial dysfunction.</p

Indigo: a natural molecular passivator for efficient perovskite solar cells

Organic–inorganic hybrid lead halide perovskite solar cells have made unprecedented progress in improving photovoltaic efficiency during the past decade, while still facing critical stability challenges. Herein, the natural organic dye Indigo is explored for the first time to be an efficient molecular passivator that assists in the preparation of high-quality hybrid perovskite film with reduced defects and enhanced stability. The Indigo molecule with both carbonyl and amino groups can provide bifunctional chemical passivation for defects. In-depth theoretical and experimental studies show that the Indigo molecules firmly binds to the perovskite surfaces, enhancing the crystallization of perovskite films with improved morphology. Consequently, the Indigo-passivated perovskite film exhibits increased grain size with better uniformity, reduced grain boundaries, lowered defect density, and retarded ion migration, boosting the device efficiency up to 23.22%, and ˜21% for large-area device (1 cm2). Furthermore, the Indigo passivation can enhance device stability in terms of both humidity and thermal stress. These results provide not only new insights into the multipassivation role of natural organic dyes but also a simple and low-cost strategy to prepare high-quality hybrid perovskite films for optoelectronic applications based on Indigo derivatives.Peer ReviewedPostprint (author's final draft

Expert Consensus on Microtransplant for Acute Myeloid Leukemia in Elderly Patients -Report From the International Microtransplant Interest Group

Recent studies have shown that microtransplant (MST) could improve outcome of patients with elderly acute myeloid leukemia (EAML). To further standardize the MST therapy and improve outcomes in EAML patients, based on analysis of the literature on MST, especially MST with EAML from January 1st, 2011 to November 30th, 2022, the International Microtransplant Interest Group provides recommendations and considerations for MST in the treatment of EAML. Four major issues related to MST for treating EAML were addressed: therapeutic principle of MST (1), candidates for MST (2), induction chemotherapy regimens (3), and post-remission therapy based on MST (4). Others included donor screening, infusion of donor cells, laboratory examinations, and complications of treatment

Feasibility-Based Design Model For Road Vertical Alignment

Road vertical alignment design is a multi-objective design problem that needs to consider multiple constraints. Intelligent design based on optimization algorithms cannot wholly solve problems, such as multi-objective, uncertainty, and constraint dynamics. The article proposes a model of dynamically transforming design constraints into feasible regions as the design develops, to provide decision information before design actions rather than performing constraint evaluation after the design that reduces the empirical estimation. The design actions are divided into new design actions and modifying design actions, and corresponding feasible regions derived from constraints of design specifications and control elevations are established, respectively. Geometrical equations and program algorithms of feasible regions are described in the graphic environment, which is applied to the vertical alignment design to improve the design efficiency and decision-making level

Research on Vibration Characteristics of an Underground Powerhouse of Large Pumped-Storage Power Station

With the rapid development of pumped storage, the vibration problems caused by the operation of power stations have become increasingly prominent. In this paper, a large-scale pumped-storage power station is taken as the research object, and a three-dimensional refined finite element model of the underground powerhouse including the surrounding rock mass is established. Based on the analysis of the vibration source of the powerhouse and the water diversion pipeline, the modal and dynamic response analysis of the underground powerhouse of the hydropower station is carried out, and the distribution law of the larger vibration displacement position is revealed. The calculation results show that under the premise that the vibration source is selected reasonably and the numerical model is accurate, the main frequency of the underground powerhouse structure can be obtained more accurately. After optimizing the design of the underground powerhouse based on the calculation results, the resonance problem of the underground powerhouse of the hydropower station can be avoided. The dynamic elastic modulus of the rock mass around the underground powerhouse has little influence on the mode shape of the powerhouse, but has a great influence on its fundamental frequency. When the dynamic elastic modulus of the rock mass increases by 50%, the fundamental frequency of the plant increases by about 29%. At the same time, the mode shape of each order of the underground powerhouse structure does not change much, mainly manifested as the vibration of the beam system structure, which is mainly caused by the stiffness of the beam system components being much smaller than the structural stiffness of the windshield, machine pier, and mass concrete around the volute. The research results can provide references for the design of underground powerhouses of large-scale pumped-storage power stations and the analysis of vibration problems

RAGE Plays a Role in LPS-Induced NF-κB Activation and Endothelial Hyperpermeability

Endothelial functional dysregulation and barrier disruption contribute to the initiation and development of sepsis. The receptor for advanced glycation end products (RAGE) has been demonstrated to be involved in the pathogenesis of sepsis. The present study aimed to investigate the role of RAGE in lipopolysaccharide (LPS)-induced nuclear factor-κB (NF-κB) activation in endothelial cells and the consequent endothelial hyperpermeability. LPS-induced upregulation of RAGE protein expression in human umbilical vein endothelial cells (HUVECs) was detected by western blotting. Activation of NF-κB was revealed using western blotting and immunofluorescent staining. LPS-elicited endothelial hyperpermeability was explored by transendothelial electrical resistance (TER) assay and endothelial monolayer permeability assay. The blocking antibody specific to RAGE was used to confirm the role of RAGE in LPS-mediated NF-κB activation and endothelial barrier disruption. We found that LPS upregulated the protein expression of RAGE in a dose- and time-dependent manner in HUVECs. Moreover, LPS triggered a significant phosphorylation and degradation of IκBα, as well as NF-κB p65 nuclear translocation. Moreover, we observed a significant increase in endothelial permeability after LPS treatment. However, the RAGE blocking antibody attenuated LPS-evoked NF-κB activation and endothelial hyperpermeability. Our results suggest that RAGE plays an important role in LPS-induced NF-κB activation and endothelial barrier dysfunction

Research on Vibration Characteristics of an Underground Powerhouse of Large Pumped-Storage Power Station

With the rapid development of pumped storage, the vibration problems caused by the operation of power stations have become increasingly prominent. In this paper, a large-scale pumped-storage power station is taken as the research object, and a three-dimensional refined finite element model of the underground powerhouse including the surrounding rock mass is established. Based on the analysis of the vibration source of the powerhouse and the water diversion pipeline, the modal and dynamic response analysis of the underground powerhouse of the hydropower station is carried out, and the distribution law of the larger vibration displacement position is revealed. The calculation results show that under the premise that the vibration source is selected reasonably and the numerical model is accurate, the main frequency of the underground powerhouse structure can be obtained more accurately. After optimizing the design of the underground powerhouse based on the calculation results, the resonance problem of the underground powerhouse of the hydropower station can be avoided. The dynamic elastic modulus of the rock mass around the underground powerhouse has little influence on the mode shape of the powerhouse, but has a great influence on its fundamental frequency. When the dynamic elastic modulus of the rock mass increases by 50%, the fundamental frequency of the plant increases by about 29%. At the same time, the mode shape of each order of the underground powerhouse structure does not change much, mainly manifested as the vibration of the beam system structure, which is mainly caused by the stiffness of the beam system components being much smaller than the structural stiffness of the windshield, machine pier, and mass concrete around the volute. The research results can provide references for the design of underground powerhouses of large-scale pumped-storage power stations and the analysis of vibration problems

E3W—A Combined Model Based on GreedySoup Weighting Strategy for Chinese Agricultural News Classification

With the continuous development of the internet and big data, modernization and informatization are rapidly being realized in the agricultural field. In this line, the volume of agricultural news is also increasing. This explosion of agricultural news has made accurate access to agricultural news difficult, and the spread of news about some agricultural technologies has slowed down, resulting in certain hindrance to the development of agriculture. To address this problem, we apply NLP to agricultural news texts to classify the agricultural news, in order to ultimately improve the efficiency of agricultural news dissemination. We propose a classification model based on ERNIE + DPCNN, ERNIE, EGC, and Word2Vec + TextCNN as sub-models for Chinese short-agriculture text classification (E3W), utilizing the GreedySoup weighting strategy and multi-model combination; specifically, E3W consists of four sub-models, the output of which is processed using the GreedySoup weighting strategy. In the E3W model, we divide the classification process into two steps: in the first step, the text is passed through the four independent sub-models to obtain an initial classification result given by each sub-model; in the second step, the model considers the relationship between the initial classification result and the sub-models, and assigns weights to this initial classification result. The final category with the highest weight is used as the output of E3W. To fully evaluate the effectiveness of the E3W model, the accuracy, precision, recall, and F1-score are used as evaluation metrics in this paper. We conduct multiple sets of comparative experiments on a self-constructed agricultural data set, comparing E3W and its sub-models, as well as performing ablation experiments. The results demonstrate that the E3W model can improve the average accuracy by 1.02%, the average precision by 1.62%, the average recall by 1.21%, and the average F1-score by 1.02%. Overall, E3W can achieve state-of-the-art performance in Chinese agricultural news classification