Mediation Analysis with Graph Mediator

This study introduces a mediation analysis framework when the mediator is a graph. A Gaussian covariance graph model is assumed for graph representation. Causal estimands and assumptions are discussed under this representation. With a covariance matrix as the mediator, parametric mediation models are imposed based on matrix decomposition. Assuming Gaussian random errors, likelihood-based estimators are introduced to simultaneously identify the decomposition and causal parameters. An efficient computational algorithm is proposed and asymptotic properties of the estimators are investigated. Via simulation studies, the performance of the proposed approach is evaluated. Applying to a resting-state fMRI study, a brain network is identified within which functional connectivity mediates the sex difference in the performance of a motor task

Uniaxial Tension Simulation Using Real Microstructure-based Representative Volume Elements Model of Dual Phase Steel Plate

AbstractDual-phase steels have become a favored material for car bodies. In this study, the deformation behavior of dual-phase steels under uniaxial tension is investigated by means of 2D Representative Volume Elements (RVE) model. The real metallographic graphs including particle geometry, distribution and morphology are considered in this RVE model. Stress and strain distributions between martensite and ferrite are analyzed. The results show that martensite undertakes most stress without significant strain while ferrite shares the most strain. The tensile failure is the result of the deforming inhomogeneity between martensite phase and ferrite phase, which is the key factor triggering the plastic strain localization on specimen section during the tensile test

Moderate mutation rate in the SARS coronavirus genome and its implications

BACKGROUND: The outbreak of severe acute respiratory syndrome (SARS) caused a severe global epidemic in 2003 which led to hundreds of deaths and many thousands of hospitalizations. The virus causing SARS was identified as a novel coronavirus (SARS-CoV) and multiple genomic sequences have been revealed since mid-April, 2003. After a quiet summer and fall in 2003, the newly emerged SARS cases in Asia, particularly the latest cases in China, are reinforcing a wide-spread belief that the SARS epidemic would strike back. With the understanding that SARS-CoV might be with humans for years to come, knowledge of the evolutionary mechanism of the SARS-CoV, including its mutation rate and emergence time, is fundamental to battle this deadly pathogen. To date, the speed at which the deadly virus evolved in nature and the elapsed time before it was transmitted to humans remains poorly understood. RESULTS: Sixteen complete genomic sequences with available clinical histories during the SARS outbreak were analyzed. After careful examination of multiple-sequence alignment, 114 single nucleotide variations were identified. To minimize the effects of sequencing errors and additional mutations during the cell culture, three strategies were applied to estimate the mutation rate by 1) using the closely related sequences as background controls; 2) adjusting the divergence time for cell culture; or 3) using the common variants only. The mutation rate in the SARS-CoV genome was estimated to be 0.80 – 2.38 × 10(-3 )nucleotide substitution per site per year which is in the same order of magnitude as other RNA viruses. The non-synonymous and synonymous substitution rates were estimated to be 1.16 – 3.30 × 10(-3 )and 1.67 – 4.67 × 10(-3 )per site per year, respectively. The most recent common ancestor of the 16 sequences was inferred to be present as early as the spring of 2002. CONCLUSIONS: The estimated mutation rates in the SARS-CoV using multiple strategies were not unusual among coronaviruses and moderate compared to those in other RNA viruses. All estimates of mutation rates led to the inference that the SARS-CoV could have been with humans in the spring of 2002 without causing a severe epidemic

The predictive value of T-cell chimerism for disease relapse after allogeneic hematopoietic stem cell transplantation

IntroductionChimerism is closely correlated with disease relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, chimerism rate is dynamic changes, and the sensitivity of different chimerism requires further research.MethodsTo investigate the predictive value of distinct chimerism for relapse, we measured bone marrow (BM), peripheral blood (PB), and T-cell (isolated from BM) chimerism in 178 patients after allo-HSCT.ResultsReceiver operating characteristic (ROC) curve showed that T-cell chimerism was more suitable to predict relapse after allo-HSCT compared with PB and BM chimerism. The cutoff value of T-cell chimerism for predicting relapse was 99.45%. Leukemia and myelodysplastic syndrome (MDS) relapse patients’ T-cell chimerism was a gradual decline from 2 months to 9 months after allo-HSCT. Higher risk of relapse and death within 1 year after allo-HSCT. The T-cell chimerism rates in remission and relapse patients were 99.43% and 94.28% at 3 months after allo-HSCT (P = 0.009), 99.31% and 95.27% at 6 months after allo-HSCT (P = 0.013), and 99.26% and 91.32% at 9 months after allo-HSCT (P = 0.024), respectively. There was a significant difference (P = 0.036) for T-cell chimerism between early relapse (relapse within 9 months after allo-HSCT) and late relapse (relapse after 9 months after allo-HSCT) at 2 months after allo-HSCT. Every 1% increase in T-cell chimerism, the hazard ratio for disease relapse was 0.967 (95% CI: 0.948–0.987, P<0.001).DiscussionWe recommend constant monitoring T-cell chimerism at 2, 3, 6, and 9 months after allo-HSCT to predict relapse

In-plane uniaxial pressure-induced out-of-plane antiferromagnetic moment and critical fluctuations in BaFe2_2As2_2

A small in-plane external uniaxial pressure has been widely used as an effective method to acquire single domain iron pnictide BaFe$_2$As$_2$, which exhibits twin-domains without uniaxial strain below the tetragonal-to-orthorhombic structural (nematic) transition temperature $T_s$. Although it is generally assumed that such a pressure will not affect the intrinsic electronic/magnetic properties of the system, it is known to enhance the antiferromagnetic (AF) ordering temperature $T_N$ ($<T_s$) and create in-plane resistivity anisotropy above $T_s$. Here we use neutron polarization analysis to show that such a strain on BaFe$_2$As$_2$ also induces a static or quasi-static out-of-plane ($c$-axis) AF order and its associated critical spin fluctuations near $T_N/T_s$. Therefore, uniaxial pressure necessary to detwin single crystals of BaFe$_2$As$_2$ actually rotates the easy axis of the collinear AF order near $T_N/T_s$, and such effect due to spin-orbit coupling must be taken into account to unveil the intrinsic electronic/magnetic properties of the system.Comment: 11 pages, 4 figures, Supplementary information is available upon reques

Bioengineered MSC-derived exosomes in skin wound repair and regeneration

Refractory skin defects such as pressure ulcers, diabetic ulcers, and vascular ulcers represent a challenge for clinicians and researchers in many aspects. The treatment strategies for wound healing have high cost and limited efficacy. To ease the financial and psychological burden on patients, a more effective therapeutic approach is needed to address the chronic wound. MSC-derived exosomes (MSC-exosomes), the main bioactive extracellular vesicles of the paracrine effect of MSCs, have been proposed as a new potential cell-free approach for wound healing and skin regeneration. The benefits of MSC-exosomes include their ability to promote angiogenesis and cell proliferation, increase collagen production, regulate inflammation, and finally improve tissue regenerative capacity. However, poor targeting and easy removability of MSC-exosomes from the wound are major obstacles to their use in clinical therapy. Thus, the concept of bioengineering technology has been introduced to modify exosomes, enabling higher concentrations and construction of particles of greater stability with specific therapeutic capability. The use of biomaterials to load MSC-exosomes may be a promising strategy to concentrate dose, create the desired therapeutic efficacy, and maintain a sustained release effect. The beneficial role of MSC-exosomes in wound healing is been widely accepted; however, the potential of bioengineering-modified MSC-exosomes remains unclear. In this review, we attempt to summarize the therapeutic applications of modified MSC-exosomes in wound healing and skin regeneration. The challenges and prospects of bioengineered MSC-exosomes are also discussed

The application and progress of tissue engineering and biomaterial scaffolds for total auricular reconstruction in microtia

Microtia is a congenital deformity of the ear with an incidence of about 0.8–4.2 per 10,000 births. Total auricular reconstruction is the preferred treatment of microtia at present, and one of the core technologies is the preparation of cartilage scaffolds. Autologous costal cartilage is recognized as the best material source for constructing scaffold platforms. However, costal cartilage harvest can lead to donor-site injuries such as pneumothorax, postoperative pain, chest wall scar and deformity. Therefore, with the need of alternative to autologous cartilage, in vitro and in vivo studies of biomaterial scaffolds and cartilage tissue engineering have gradually become novel research hot points in auricular reconstruction research. Tissue-engineered cartilage possesses obvious advantages including non-rejection, minimally invasive or non-invasive, the potential of large-scale production to ensure sufficient donors and controllable morphology. Exploration and advancements of tissue-engineered cartilaginous framework are also emerging in aspects including three-dimensional biomaterial scaffolds, acquisition of seed cells and chondrocytes, 3D printing techniques, inducing factors for chondrogenesis and so on, which has greatly promoted the research process of biomaterial substitute. This review discussed the development, current application and research progress of cartilage tissue engineering in auricular reconstruction, particularly the usage and creation of biomaterial scaffolds. The development and selection of various types of seed cells and inducing factors to stimulate chondrogenic differentiation in auricular cartilage were also highlighted. There are still confronted challenges before the clinical application becomes widely available for patients, and its long-term effect remains to be evaluated. We hope to provide guidance for future research directions of biomaterials as an alternative to autologous cartilage in ear reconstruction, and finally benefit the transformation and clinical application of cartilage tissue engineering and biomaterials in microtia treatment

Evidence-Based Software Engineering: A Checklist-Based Approach to Assess the Abstracts of Reviews Self-Identifying as Systematic Reviews

A systematic review allows synthesizing the state of knowledge related to a clearly formulated research question as well as understanding the correlations between exposures and outcomes. A systematic review usually leverages explicit, reproducible, and systematic methods that allow reducing the potential bias that may arise when conducting a review. When properly conducted, a systematic review yields reliable findings from which conclusions and decisions can be made. Systematic reviews are increasingly popular and have several stakeholders to whom they allow making recommendations on how to act based on the review findings. They also help support future research prioritization. A systematic review usually has several components. The abstract is one of the most important parts of a review because it usually reflects the content of the review. It may be the only part of the review read by most readers when forming an opinion on a given topic. It may help more motivated readers decide whether the review is worth reading or not. But abstracts are sometimes poorly written and may, therefore, give a misleading and even harmful picture of the review’s contents. To assess the extent to which a review’s abstract is well constructed, we used a checklist-based approach to propose a measure that allows quantifying the systematicity of review abstracts i.e., the extent to which they exhibit good reporting quality. Experiments conducted on 151 reviews published in the software engineering field showed that the abstracts of these reviews had suboptimal systematicity

Effect of Epoxy Adhesive on Nugget Formation in Resistance Welding of SAE1004/DP600/DP780 Steel Sheets

This study focused on the nugget formation in resistance welding of three dissimilar steel sheets influenced by different types and thicknesses of epoxy adhesive. An improved finite element model was employed to estimate the temperature distribution in three-sheet weld-bonding and was validated by the metallographic tests. Results showed that the weld initiation time and corresponding nugget size for weld-bonds would be earlier and larger than that of resistance spot welds in term of the same welding parameters. Compared to the adhesive Betamate Flex, the weld-bonding joint of three-sheets with adhesive Terokal 5089 would have a greater increment of the weld nugget sizes due to the increase of the static contact resistance brought by the interfaces between the steel sheets. However, the bond line thickness of the previously mentioned adhesive would take little effect on the weld sizes in weld-bonding of three dissimilar steel sheets

Analysis of Fracture Modes of Resistance Spot Welded Hot-Stamped Boron Steel

Fracture modes of resistance spot welded ultra-high strength hot-stamped boron steel via lap-shear test are different from that of the traditional advanced high strength steel due to the difference in geometrical size and material property of the spot welds. In this paper, lap-shear fracture modes of resistance spot welding joints were analyzed and joint characteristics that affecting the fracture behavior were discussed. Three fracture modes were found to change from interfacial fracture (IF) to pull-out fracture (PF) with the increase of nugget diameter. For PF I mode, the fracture initiated at the transition zone between the fusion zone and upper-critical heat affected zone (HAZ) and propagated along the thickness of the nugget. For PF II mode, during which the failure initiated at the sub-critical HAZ where the softest zone occurred, and it propagated to the base material. Obvious hardness decrease was observed in the transition zone with the formation of the delta ferrite at the fusion boundary due to the relatively high amount of alloying element in the hot-stamped boron steel, which could provide the reason for route of PF I extending along this zone. Fluctuation in the hardness in the transition zone led to the existence of both PF I and PF II at the same welding current