In this perspective, we highlight recent developments in collecting electrospun nanofibers as aligned arrays and then illustrate how the aligned nanofibers can be utilized to manipulate cell migration.Cell migration plays an important role in a wide variety of biological processes, including embryogenesis, wound healing, inflammation, cancer metastasis, and tissue repair. Electrospun nanofibers have been extensively explored as scaffolds to manipulate cell migration owing to their unique characteristics in mimicking the hierarchical architecture of extracellular matrix. In particular, aligned arrays of electrospun nanofibers are capable of guiding and promoting the directional migration of cells. The physical parameters and properties of the aligned nanofibers, including their size, modulus, and surface chemistry, can all affect the migratory behaviors of cells, while the controlled release of growth factors and drugs from the nanofibers can also be utilized to influence cell migration. By manipulating cell migration, electrospun nanofibers have been applied to promote tissue repair and help eradicate tumors  I.4 In the case of tissue repair, for example, the recruitment and migration of desirable cells to the defect site is key to the construction and regeneration process. For instance, the regeneration of skin includes re-establishment of the dermis structure, which can be accelerated by triggering the directional migration of epithelial cells and fibroblasts to the wound area.2 On the other hand, the deregulation of cell migration can lead to pathological conditions such as impaired healing and cancer metastasis.7Cell migration plays a central role in a wide variety of biological processes, as exemplified in embryogenesis, inflammatory responses, wound healing, and tissue repair.1010 The leader cells are polarized under stimulation by interacting with the underlying substrate and surrounding soluble factors such as growth factors and drugs. At the front of each cell, cytoskeletal rearrangements lead to the formation of membrane protrusions such as filopodia and lamellipodia, serving as the main engine for movement. The microtubule network and components of the intracellular membrane also organize in a polarized manner along the direction of migration, as illustrated in 11 In principle, the types and locations of cues determine which type of directed cell migration is engaged.12 For instance, haptotaxis refers to cell migration toward a substrate-bound agent, whereas chemotaxis involves directed migration toward a soluble cue in the environment. Durotaxis describes cell migration in response to mechanical signals, and electrotaxis is the response to an electric field. With a growing understanding of the mechanism involved in cell migration, there is an increased effort to develop substrates capable of recapitulating key features of the ECM, which directly controls the migration of cells.Cell migration is a dedicated process that involves cell adhesion, polarization, and forward movement, and its direction and speed are regulated by the intricate interactions between the cells and their microenvironments.13 Specifically, microfluidic devices with various types of channels have been fabricated using soft lithography. The microfluidic channels are able to physically confine cells and provide guidance to their migration.14 The channels can also be coated or filled with ECM proteins to generate bioactive cues or integrated with protein gradients to offer chemoattractant for controlling the migration of cells.15 With the use of multiple channels, parallel measurements of cell migration under different experimental conditions can be performed simultaneously.16 The microfluidic channels, however, cannot closely mimic the structure and composition of native ECM because they are limited in terms of materials, configurations, and feature size. On the other hand, e-beam lithography scans a focused beam of electrons across a surface covered with an electron-sensitive film or resist to generate patterned features, and it has been applied to fabricate nanostructures as small as 5 nm for controlling cell migration.17 However, e-beam writing needs a dedicated, expensive instrument, and only a limited number of materials are suitable for use as the substrates.13 Typically, the structures can only be patterned over a relatively small area. In comparison, electrospinning is a simple technique that offers more flexibility in terms of materials. It can be used to generate continuous fibers with diameters ranging from tens of nanometers to several micrometers and, more important, fibrous structures resembling native ECM.19 Recent progress in fabricating electrospun fibers with complex compositions  and well-controlled alignment have made the fibers a class of attractive substrates for controlling the migration of cells. As another major advantage over the microfluidic channels and lithographically patterned surfaces, electrospun fibers can be made free-standing and further implanted as scaffolds in vivo to recruit cells for tissue regeneration or cancer treatment.Various types of micro/nano-structured surfaces or substrates have been fabricated to manipulate the migration of cells. The most prominent technologies include soft lithography, nanolithography , and electrospinning.18 The properties of the as-spun nanofibers  can be easily tuned to match those of native ECM by adjusting the properties of the polymer solution and the parameters of the electrospinning process. The surfaces of the nanofibers can also be functionalized with ECM proteins or bioactive agents through post-treatment. By mimicking native ECM in this way, electrospun nanofibers are able to manipulate the migration of cells ranging from normal cells to stem cells and tumor cells. Additionally, when the nanofibers are assembled as aligned arrays, they can guide and promote the directional migration of cells. Furthermore, due to contact guidance, the cytoskeletons of cells on the aligned nanofibers also show aligned architectures, causing the cells to produce a highly aligned collagen matrix, which is desirable for repairing tissues with anisotropic anatomies such as tendon, cardiac, and nerve tissues.21 The understanding of how nanofibers affect cell migration has progressed substantially in recent years. In this perspective, we highlight both recent findings and future expectations in regulating cell migration by aligned arrays of electrospun nanofibers.Electrospinning relies on the electrostatic repulsion between surface charges to draw nanofibers from a viscoelastic fluid. When a polymer solution is pumped out through a spinneret connected to a high voltage, a conical structure known as “Taylor cone” is formed, and a jet emanates from the apex of the cone toward a grounded collector. The jet continues to decrease in diameter as a result of stretching caused by electrostatic repulsion, whipping, and solvent evaporation until the jet is solidified and deposited on the collector.II.22Due to the chaotic trajectory of an electrospinning jet, the nanofibers collected on a flat, grounded collector are typically deposited as a non-woven mat with no orientation, as shown by the scanning electron microscopy (SEM) image of polycaprolactone (PCL) nanofibers in 23 The rotating speed of the mandrel determines the degree of alignment. To obtain uniformly aligned nanofibers, the mandrel must be rotated at a speed in accordance with the velocity of the electrospinning jet.Uniaxially aligned nanofibers can be produced using a high-speed rotating mandrel  and natural  polymers. For the in vivo recruitment of cells, besides biocompatibility, the scaffolds made of electrospun fibers also need to offer additional properties, such as suitable biodegradation rate and mechanical property for supporting the cells. In this regard, it is challenging to find a single polymer that meets all these requirements. As a potential solution, multiple polymers are often used to generate blended or core-sheath electrospun fibers.20Electrospinning has been successfully applied to generate aligned nanofibers from a large number of different types of natural and synthetic polymers. For III.28 The migratory behavior of cells can be characterized by examining the distance and speed of migration over a certain period of time using metrics such as the total migration distance , linear migration speed , net migration distance , effective migration speed , and migration persistence .As shown by the schematic in A.29 Micrographs of a 3T3 fibroblast on the nanofiber are shown in μm in diameter, the 3T3fibroblast displayed high directionality and migrated at a linear speed of approximately 40 μm/h. When the cell encountered multiple fibers, as shown in The migratory behavior of cells on suspended individual nanofibers is distinct from that on fibrous mats consisting of densely packed nanofibers. B.30 Similar phenomena were observed for astrocytes and L929 cells on mats composed of electrospun PLA and PCL nanofibers, respectively.32 The migration of stem cells can also be accelerated by aligned nanofibers; for a similar fiber diameter, human neural progenitor cells and mesenchymal stem cells (MSCs) both showed higher migration speeds on uniaxially aligned nanofibers compared to the case of random nanofibers.34On a two-dimensional mat composed of nanofibers with a high packing density rather than suspended, individual nanofibers, the fiber alignment primarily affects the migratory direction and speed of the cells. The cells rely on membrane protrusions such as filopodia and lamellipodia to move. On random nanofibers, the cells migrate randomly in all directions without preferred directionality. Each cell has a large number of junctions, resulting in small cell translocation since the cells are constrained to follow the direction of the nanofibers and thereby may change direction in a typical trajectory. However, on aligned nanofibers, due to contact guidance, the cells orient and migrate in linear paths corresponding to the direction of fiber orientation, leading to an enhancement in migration speed. Taking the migration of 3T3 fibroblasts on thermoplastic polyurethane nanofibers as an example, for a similar nanofiber diameter, the migration speed of cells cultured on uniaxially aligned nanofibers was approximately two times that of cells cultured on random nanofibers.35 When the scaffold was warmed from 30 °C to 37 °C, the unidirectional alignment of the nanofibers was dynamically increased, leading to a change in cell motility from non-polarized to polarized along the fiber alignment with increased cell migration speed.The effect of fiber alignment on cell migration was further demonstrated in dynamic systems. A nanofibrous scaffold was electrospun from a shape-memory polymer, in which the fiber alignment could be changed on command by thermal triggering, and used to study cell migration.C.36 On uniaxially aligned PLA fibers with different diameters , the Schwann cells migrated the farthest on the large fibers and the shortest on the small nanofibers.37 The authors stated that the fibers with a large diameter were more densely packed than those with intermediate and small diameters. The densely packed fibers acted as barriers to impede the Schwann cells from crossing onto nearby fibers. On the intermediate and small fibers, the spacing between the fibers was large; thus, these fibers could not provide sufficient topographical cues to direct the migration of Schwann cells. However, the influence of fiber diameter on cell migration can be different depending on polymer compositions and cell types. In one study, the migratory behavior of glioblastoma cells on uniaxially aligned chitosan-PCL fibers with diameters of 200 nm, 400 nm, and 1.1 μm was separately monitored.38 The traces of the cells migrating on the fibers with different diameters over 15–24 h are shown in μm/h, similar to that reported for cells invading along microvessels in vivo. On the aligned fibers with a diameter of 400 nm, the cells expressed higher values of invasion-related genes than those on the fibers with a diameter of 1.1 μm, indicating that higher curvature of the fibers promoted the migratory behavior. In another study, uniaxially aligned silk fibroin nanofibers with a diameter of 400 nm exhibited a better ability to direct MSC migration than the fibers with diameters of 800 nm and 1200 nm.33 The size of the electrospun fibers used forfacilitating the cell migration should be optimized based on the intended application and the type of cells.A correlation between the fiber diameter and the migratory behavior of cells has also been reported.D.In vivo, tissue modulus ranges widely from 0.5 kPa (adipose tissue) to 20 MPa (bone) and changes both during development and in different diseases.39 Numerous studies have demonstrated the role of substrate modulus in regulating cell motility.44 When nanofibers are used as substrates, the migratory behavior of cells can also be regulated by the nanofiber modulus. In one study, fibrous mats with different surface moduli were fabricated using the co-axial electrospinning method.45 Different polymers  were employed as the core to modulate the fiber moduli, while PCL was used as the sheath to conserve surface chemistry. μm/h for PCL nanofibers with a modulus of ca. 8 MPa); slower migration speeds were observed on the nanofibers with low modulus  and high modulus . The sensitivity of cells to the fiber modulus can be attributed to a cellular sensing process often referred to as the “catch-bond formation” mechanism,46 by which larger traction forces generated by cells can be evoked to promote their migration.The fiber modulus is another critical factor that affects cell migration. E.47 Thus, optimal focal adhesion turnover  is required for good cell motility. Bioactive agents such as proteins and growth factors can be coated on the surface of the fibers through physical adsorption, ionic bonding, or covalent bonding to tune the interactions between the cells and the underlying fibers. For example, when laminin was grafted onto the surface of electrospun PLGA nanofibers, the migration of Schwann cells was greatly accelerated.48The surface chemistry of the fibers also affects the migratory behavior of cells because cell migration is a balance between cell adhesion and cell movement on the fibers. While weak adhesion is not sufficient to stabilize the cell front, leading to impaired motility, overly strong adhesion also results in impaired motility due to the inability of the cells to break rear adhesion.49 A collector consisting of a central point electrode and a peripheral ring electrode was developed to collect nanofibers oriented in a radial fashion. ex vivo model, dura tissues were separately cultured on scaffolds composed of radially aligned nanofibers and random nanofibers to allow the migration of dural fibroblasts from the surrounding tissues to the scaffolds. After incubation for four days, the entire surface of the scaffold composed of radially aligned nanofibers was covered by the cells [50 Modifying the nanofiber’s surface with polydopamine further enhanced the migration speed of the cells by presenting a favorable surface for cell adhesion.In addition to migration along the uniaxial direction, in some cases, it is desirable to induce the radial migration of cells from the periphery toward the center or vice versa. For instance, to facilitate the regeneration of dura mater after a neurosurgical procedure, the synthetic dural substitute must favor the adhesion of dural fibroblasts and simultaneously promote their migration from the periphery of the substitute toward the center. Radially aligned fibers have shown promise for this purpose.he cells ; by conthe cells . After t51 The variations in adhesion strength between the cells and graded cue on the fibers also attribute to cell migration. When the cells attach to the fibers more tightly at one end, the imbalance in adhesive force will lead to the movement of cells toward the direction of increasing adhesion.52Compared to a uniform coating of bioactive agents on the surface of nanofibers, a gradient cue on the nanofibers is more effective for accelerating cell migration along the direction of concentration increase. This occurs via the haptotaxis of cells in response to migratory cues, including graded adhered agents on the surface or anchored factors within the substrate. The first response of cells to a gradient is polarization, by which chemosensory signaling receptors are redistributed. If cellular polarization persists in one direction, cell migration will occur in succession.53 In one study, a gradient of vascular endothelial growth factor (VEGF) over 1.125 mm was constructed on the surface of uniaxially aligned hyaluronic acid nanofibers by overlaying a microfluidic gradient generator on the nanofibers.28 It was found that the motility of human umbilical vein endothelial cells was maximized in the presence of the VEGF gradient along the direction of fiber alignment. Interestingly, when nanofibers were aligned perpendicular to the VEGF gradient, no effect of the VEGF gradient was observed, indicating that topographical cues were more influential than chemical cues in this case. A major drawback of this approach is that it requires a considerable volume of solution containing the expensive bioactive agent to generate a large-area gradient along the nanofibers. Additionally, the conditions for generating the gradient need be scrutinized for different types of bioactive agents and nanofiber compositions.Various strategies have been used to integrate bioactive agents with concentration gradient on nanofibers. The simplest way to generate a gradient is to vary the contact time of the bioactive agent on the nanofiber’s surface along the direction of fiber alignment.54 As shown in 55 By constantly increasing the volume of the BSA solution introduced into a container with a center-raised fibrous scaffold placed in the upright or upside-down configuration, a divergent or convergent BSA gradient was generated along the radially aligned nanofibers, respectively. A countercurrent, circular gradient of bioactive protein could then be produced. Compared to the scaffold composed of nanofibers uniformly coated with laminin, the circular gradient of laminin, which increased in concentration from the periphery to the center along the radially aligned PCL nanofibers, significantly accelerated the migration of fibroblasts from the periphery toward the center. Similar results were observed for the migration of keratinocytes on scaffold composed of radially aligned PCL nanofibers with a circular gradient of the epidermal growth factor on the surface.To solve these problems, a simple method was developed for creating gradients through a graded mask of bovine serum albumin (BSA).56 By applying the ring collector to fabricate radially aligned nanofibers for a certain collection time, the nanofiber density can be controlled to gradually increase from the periphery to the center. After immobilizing CBD-fused stromal cell-derived factor-1α (SDF1α) in the collagen domains of the PCL-collagen blend nanofibers, a continuous gradient of SDF1α was formed along the radially aligned nanofibers, leading to the accelerated migration of neural stem cells from the periphery toward the center.Bioactive agents can also be immobilized on the surface of nanofibers based on high-affinity interactions in the presence of specifically recognized domains. For example, collagen-binding domain (CBD)-fused proteins can be selectively immobilized on the collagen domains of PCL-collagen blend nanofibers.57 Using a scaffold made of uniaxially aligned nanofibers as the substrate, this strategy can be further applied to manipulate cell migration.In addition to forming single layers of bioactive agents on the surfaces of nanofibers, bioactive agents can also be constructed into particles or immobilized on particles and then deposited onto thesurface of nanofibers with a gradient. A linear gradient of protein-encapsulated PLGA microparticles was generated across a glass substrate by spatially varying the deposition time (during which the substrate was exposed to the electrosprayed microparticles).F.59 For example, leukocytes are drawn to the site of injury by chemotactic influences. Bioactive agents can be functionalized in scaffolds composed of aligned fibers through various means, such as directly blended in the nanofibers,60 contained within the core of core-sheath nanofibers,61 and included within microspheres that are co-electrospun to the surface or within the fibers.62 Depending on the encapsulation method of the bioactive agents and biodegradation rate of the fibers, release profiles ranging from an immediate burst release to sustained release over the course of several weeks can be realized. For example, the release of recombinant human VEGF from polyethylene oxide-PCL core-sheath fibers could significantly improve the migration of endothelial cells compared to plain nanofibers.63 By incorporating Cu2S particles into nanofibrous mats made of a blend of poly-DL-lactic acid and PCL, Cu ions could be released from the nanofibers, significantly accelerating the migration of endothelial cells.64 These studies collectively indicate that, by tailoring the properties of the electrospun fibers, the migratory behavior of different types of cells can be manipulated, as summarized in The controlled, localized release of soluble bioactive agents from nanofibers is another important tool to encourage cell migration by taking advantage of the chemotaxis of cells. Chemotaxis is a phenomenon that enables cells to sense the concentrations of certain chemical species in their microenvironment by comparing the asymmetric activation of the receptors at the different ends of the cell and move toward chemically favorable regions.IV.in vivo.67 To promote tissue repair, it is necessary to facilitate the directional migration and proliferation of reparative cells at the wound site. To this end, in one study, a tri-component nanofibrous scaffold was developed, which was able to release multiple factors in a temporal sequence to direct cell migration for connective tissue repair in a meniscus damage model.68 Water-soluble poly(ethylene oxide) nanofibers were used as a sacrificial fraction to first deliver a burst of matrix-degrading enzyme  to the wound interface in an effort to reduce local ECM density and stiffness, thus allowing cell migration and increasing interfacial cellularity.69 The slower-degrading hyaluronic acid nanofibers then delivered a chemoattractant , providing an exogenous chemoattractive gradient to recruit cells to the wound site and accelerate repair. The remaining population of stable PCL nanofibers acted as a physical template to provide mechanical integrity and instruction for organized ECM synthesis upon cell arrival. Even though random nanofibers were utilized in this study, it is promising to extend this concept to aligned nanofibers to foster tissue formation that recapitulates the structural and mechanical anisotropies of the native organized connective tissues.70The manipulation of cell migratory behavior using electrospun nanofibers has been applied to tissue repair. Unlike cell migration on a surface, cells must overcome the biophysical resistance of their microenvironment, including the high matrix stiffness and limited pore size in order to move V.71 A broad spectrum of migration mechanisms can be involved for both the individual and collective migration of cancer cells.72 Electrospun nanofibers have been applied as substrates to examine the migration behavior of cancer cells .45 Furthermore, electrospun nanofibers can serve as “tumor guides”to move primary intracorticals tumor to extracortical locations, making it possible to “manage” the growth of tumors by giving them a preferred and pre-specified escape route. To this end, a tumor guidance conduit was constructed from two components: a PCL-polyurethane conduit containing a uniaxially aligned PCL nanofibrous mat with a thickness of 10 μm, and a cyclopamine-conjugated collagen hydrogel that served as an apoptotic “tumor sink.”73 As shown in in vivo migration of tumor cells in the empty conduit and the conduit containing the nanofibrous mat. Compared with the empty conduit, more tumor cells migrated into the conduit containing the aligned nanofibrous mat, and tumor cells were distributed along the entire length of the conduit. After guiding the invasive tumor cells away from the primary tumor site to the extracortical collagen hydrogel, the tumor cells underwent apoptosis, and the tumor volume in the brain was also significantly reduced.The manipulation of cell migratory behavior using electrospun nanofibers has also been applied to cancer treatment. The electrospun nanofibers can be used to construct models that accurately mimic the microenvironment of invading cancer cells to better understand the migration of cancer cells and test potential anti-migration therapies of cancer cells. Cancer is a disease of uncontrolled cell growth along with uncontrolled cell migration.VI.In conclusion, electrospun fibers are capable of manipulating cell migration, and this capability can be tailored and optimized for applications in tissue repair and cancer treatment. For these applications, it is necessary to take a full consideration on the desired properties of the fiber substrate, the required bioactive agents, and the specific function and structure of the target tissue to optimize the migration and recruitment of cells.Along with the developments toward the electrospinning technique, there are also many forward-looking aspects in applying the aligned fibers to manipulate cell migration. While the alignment, size, composition, mechanical strength, and surface chemistry of the fibers have all been tailored to manipulate cell migration, the following potential developments are envisioned in the near future.74 For instance, as a prime directional cue, electric fields at strengths equal to those detected endogenously at wounds have been reported to direct cell migration during wound healing.77 Clinically, for wound healing management, it is highly desirable to develop reliable technologies that exploit electric signaling.76 Therefore, combing electrospun nanofibers with an electrical signal is a promising method to promote cell migration and thus tissue repair.Endowing electrospun fibers with electrical signals. Electrotaxis plays an important role in regulating cell migration. Motile cells exposed to an external DC electric field will reorient and migrate along the direction of the electric potential.in vivo likely encounter multiple types of cues that they must simultaneously evaluate and prioritize to achieve an appropriate physiological response. Chemotactic, haptotactic, durotactic, and galvanotactic cues all play important roles, and these cues also affect each other. For example, chemotaxis can be modulated by substrate stiffness; higher cell chemotaxis is observed on softer substrates.78 To construct a niche for facilitating cell migration and tissue repair, an ideal scaffold should possess characteristic features of natural ECMs to allow different types of cues to act in concert. The architecture, composition, size, and mechanical strength of the electrospun fibers should all be carefully adjusted to achieve multi-functionality. Moreover, rather than two-dimensional mats, three-dimensional scaffolds with aligned topographical cues are desirable for tissue repair. A gas-foaming technique followed by freeze-drying has been developed to generate three-dimensional electrospun fibrous scaffolds with highly ordered structures.79 This technique can be further combined with the construction of graded surface to support cell migration in three-dimension. Furthermore, apart from sensitization to one type of growth factor, cell chemotaxis can be promoted by the synergy of multiple chemokines. The controlled release of multiple bioactive agents in a defined sequence from the scaffold is highly promising for promoting cell migration. In addition, during tissue repair, more than one type of cell migrates toward the defect site. Current studies are mostly restricted to one type of cell line. Thus, it is necessary to establish a system that incorporates multiple types of cells to involve the role of cell-cell interactions during cell migration on fibers. A better understanding of the mechanism of cell migration is also required to instruct the design of fibrous scaffolds.Integrating different types of cues into one scaffold to optimize cell migration and thus tissue repair. It is important to note that cells engaged in directed migration 80 Any uncontrolled differentiation of stem cells will be a disaster. Therefore, when using electrospun fibers for manipulating the migration of stem cells, it is crucial to simultaneously evaluate and control the differentiation of stem cells.Simultaneously manipulating the migration and differentiation of stem cells using electrospun fibers. Manipulating the migration of stem cells is of great importance for accelerating tissue repair and controlling cancer metastasis. Due to the multi-lineage differentiation potential of stem cells, the properties of the fibers affect not only the migration but also the phenotype of the cells.Although electrospun fibers have shown great potential for manipulating cell migration, the electrospinning technique still faces a set of challenges. For example, it is still difficult to precisely control the structural parameters of electrospun fibers. The diameters of the fibers are typically distributed over a certain range. To ensure both homogeneity and reproducibility for the fibers, it is necessary to precisely control the electrospinning parameters, as well as the properties of the polymer solution during an electrospinning process. Currently, the fabrication of aligned fibers is mainly restricted to the laboratory setting in a relatively small volume due to the use of a single spinneret only. Although industrial lines based on multiple needles or needleless electrospinning have enabled the production of electrospun fibers on a large scale, it still remains a challenge to continuously collect the fibers with well-controlled alignment. In addition, when the fibers are electrospun from polymer solutions, it is required to completely remove any residual solvent in the fibers to avoid the potential toxicity to cells and human body. These challenges also represent the future directions and opportunities to push forward the development of electrospinning technique. The ultimate goal is to move the electrospun fibers toward applications from laboratory to industry and from bench to bedside.


Ship trajectory prediction is a key requisite for maritime navigation early warning and safety, but accuracy and computation efficiency are major issues still to be resolved. The research presented in this paper introduces a deep learning framework and a Gate Recurrent Unit (GRU) model to predict vessel trajectories. First, series of trajectories are extracted from Automatic Identification System (AIS) ship data . Secondly, main trajectories are derived by applying the Density-Based Spatial Clustering of Applications with Noise (DBSCAN) algorithm. Next, a trajectory information correction algorithm is applied based on a symmetric segmented-path distance to eliminate the influence of a large number of redundant data and to optimize incoming trajectories. A recurrent neural network is applied to predict real-time ship trajectories and is successively trained. Ground truth data from AIS raw data in the port of Zhangzhou, China were used to train and verify the validity of the proposed model. Further comparison was made with the Long Short-Term Memory (LSTM) network. The experiments showed that the ship’s trajectory prediction method can improve computational time efficiency even though the prediction accuracy is similar to that of LSTM. AIS data provide real-time trajectory data which can be used to monitor ship’s navigation status and trigger alert mechanisms for ship collision avoidance, maritime monitoring, trajectory clustering, ship traffic flow predicting, and maritime accident investigations . The mosIn sea areas or ports with high traffic density and complicated conditions, a key issue is to improve the safety of ships sailing at sea. Vessel Traffic Service (VTS), whose objective is to accurately and effectively monitor and predict ship trajectories and real-time ship trajectories, provides a valuable technical support for early warning of marine traffic accidents . To imprIn a related work, a Bayesian probability trajectory prediction model based on a Gaussian process is introduced. A K-order multivariate Markov chain is applied to establish a state transition matrix to train a large amount of data and support short-term prediction of ship positions, but this approach is still sensitive to previous ship positions this resulting in low accuracy . A singlThe research presented in this paper introduces a deep learning theoretical framework and a Gate Recurrent Unit (GRU) model to predict vessel trajectories. The approach is based on an integration, clustering, and correction of maritime navigation trajectories. A recurrent neural network is applied to predict and train real-time ship trajectories. Ground truth data from AIS raw data in the port of Zhangzhou, China were used to train and verify the validity of the proposed model. Further comparison was made with the Long Short-Term Memory (LSTM) network that has been widely used in the field of deep learning. The rest of the paper is organized as follows. Trajectory prediction methods based on statistical methods are commonly used in the ship field, including Gaussian process regression models, which are the most common. Anderson  took timThe Kalman filter implements this algorithm in the form of recursion. Its advantage is that it occupies less storage space during the calculation process and can realize short-term trajectory prediction. The disadvantage is that the initial state of the model and the assumptions under ideal conditions have a significant impact on the accuracy of prediction.Neural networks are computing systems with interconnected nodes that work similar to neurons in the human brain. Using algorithms, they can recognize hidden patterns and correlations in raw data, cluster and classify them, and—over time—continuously learn and improve . Neural Brian  proposedMao  proposedA “sequence-to-sequence” recurrent neural network model has been developed to mesh and serialize a ship trajectory into a neural network model, in order to predict the main trajectory and arrival time . A LSTM The prediction model framework consists of four parts: data preprocessing, clustering analysis, similarity measurement, and model analysis . Data prThe AIS is an essential component of modern vessel navigation systems, which are installed and widely used on vessels to enhance the ability to identify targets and mark the location. Raw AIS data are used to build a reference dataset and define a matrix of historic AIS data as follows:Algorithm 1: Data preprocessingOutput: Trajectories Input: Original dataset 1: Connect to the database.2: Get 3: if Return:4: then Optimization  is a type of recurrent neural network that takes sequence data as an input while cyclic units are connected in a chain  and thatLet us introduce more formally the principles of the GRU neural network. For the hidden layer of the GRU neural network, given the input value  at t is :(15)rt=σEquations (9)–(12) show that the weight matrices at time “GRU merges the forgotten gate layer The vessel trajectory datasets are classified after DBSCAN clustering, using the clusters of the north–south routes as the experimental dataset, which is divided into three parts: the training set, validation set, and test set. The training set is used to train the model. In the training process, the validation set is used to verify the performance of the model to improve its generalization ability . The tesThe result of output processed by the neural network in the interval To evaluate the results of GRU in vessel traffic flow prediction, LSTM is constructed as comparative experiments, and Mean Square Error (MSE) is selected as the model error analysis index during the training process as followed.The selection of parameters is crucial for recurrent neural networks. Generally speaking, the more hidden layers are included in the GRU recurrent neural network, the stronger is the model’s performance and learning ability. The Adam optimizer , which iThe selection of parameters such as the neurons is shown in After several experimental tests and parameter comparisons, the GRU construct consists of the following parts: fully connected layer, an activation layer, two GRU layers, and a method of drop out to construct the GRU recurrent neural network. The second layer gru_1 and fourth layer gru_2 are the GRU layers, each containing 120 hidden units; the third and fifth layers are the drop out method, which can not only ensure that the model maintains the robustness of the model when information is lost during training, but it can also be used for regularization, reducing the weight connection, increasing the robustness of the network model in the event of missing individual connection information; and the fifth layer is a fully connected layer, which contains two neurons. The visualization of the GRU neural network is shown in In the training process, as shown in The model training is shown in A total of 330 sets of trajectory data was used to predicted using LSTM, Extended Kalman Filter (EKF), and GRU models as shown in A vessel trajectory is selected from the historical AIS data of Zhangzhou Port, China, visualized in the Electronic Chart Display and Information System (ECDIS), as shown in This paper introduces a ship trajectory prediction framework based on a recurrent neural network. One of the peculiarities of our approach is to take into account vessel navigation errors due to receiving and sending data processes. The vessel trajectory prediction model is divided into data preprocessing, clustering analysis, similarity measurement, and model analysis. The objective of the first three modules is to extract high-quality datasets. The model was tested with a series of real data and different parameter combinations within a reasonable range o train the neural network and predict vessel trajectories is the most valuable way. A comparative experiment was conducted with LSTM that is considered as a valuable solution. The experiments showed that the vessel trajectory prediction model based on the GRU model has good prediction accuracy similar to that of LSTM, but it has the advantage of being computationally more efficient. It is more suitable for the requirements of immediate and early warnings of maritime navigation and can provide appropriate decisions for intelligent vessel navigation systems and VTS. LSTM is similar to GRU, and it is less effective in long-distance trajectory prediction. On the basis of improving the calculation efficiency, if the accuracy of long-distance trajectory prediction can be improved, it will be of great help to the early warning of ship navigation hazards. While current trajectory prediction model is based on a recursive call model, long-distance vessel trajectories are still computationally expensive , which will be considered in further work.


This study aims to determine the prevalence, severity, and nature of the motor abnormalities seen in children with autism spectrum disorder (ASD) as well as to elucidate the associated developmental profiles. The short-form of the Bruininks-Oseretsky Test of Motor Proficiency, Second Edition (BOT-2) was used to assess various aspects of the motor performance of 119 children with ASD and 30 typically developing children (age range: 6–12 years) from three Gulf states. The results revealed the high prevalence of motor abnormalities among the ASD group when compared with the normative data derived from the BOT-2 manual as well as with the data concerning the typically developing group. The results also indicated that the motor performance of the children with ASD fell within the below-average range according to the BOT-2 cut-off score. Further, the results suggested that the age variable may influence the overall motor performance of children with ASD, since the children’s motor abnormalities may decrease with maturation. The results concerning the specific motor dysfunction profiles seen in individuals with ASD could help practitioners, parents, and educators to better understand the nature of the motor deficits exhibited by children with ASD, which could assist with the design and implementation of treatment and rehabilitation programs for such children. Overall, motor performance represents an important aspect that should be considered during the clinical evaluation of ASD and that should not be ignored during early interventions. Motor skills are associated with “activities that require a chain of sensory , central (brain and nervous systems), and motor mechanisms whereby the performer is able to maintain constant control of the sensory input and in accordance with the goal of the movement” . The chiASD affects every domain of human existence. An impairment in the motor domain can have profound effects on a child’s development in areas such as schooling, socialisation, and communication ,7. It haMotor dysfunction represents an important neurological symptom in those with ASD. A growing body of evidence illustrates the motor difficulties experienced by children with ASD when compared with their typically developing peers ,11,12,13The only motor abnormalities currently included in the diagnostic criteria for ASD are stereotypical and repetitive behaviours . HoweverLittle is currently known about the underlying neurobiology of ASD-related motor problems, although the disruptions observed in those with ASD may stem from abnormal brain connectivity ,21. SomeConsiderable ambiguity persists regarding the nature of such motor abnormalities and whether they are universal and specific to ASD. Some findings indicate that motor impairments constitute a cardinal feature of ASD ,26,27,28Some preliminary evidence indicates that motor impairments represent an essential part of a broader autistic phenotype , althougJeste 2011) offers a number of justifications for investigating motor dysfunction in individuals with ASD [11 offersAge might be a critical factor in determining the nature of the motor dysfunction seen in individuals with ASD. However, the available research concerning the developmental acquisition of motor skills by children with ASD is limited. Evidence suggests that the different subsystems supporting motor development mature at different times and rates, which results in nonlinear development ; therebyNo firm conclusions regarding the stability or instability of motor performance can yet be drawn in relation to ASD. Some longitudinal studies indicate the persistent and constant nature of impaired motor performance in children with ASD . FurtherA growing body of evidence gathered in Western contexts suggests motor abnormalities to be a marker of clinical severity and an important therapeutic target in children with ASD ,36,47. HThe present study had three main aims. First, to determine the ratio of motor impairments seen in children with ASD, as identified using the short form of the Bruininks-Oseretsky Test of Motor Proficiency, Second Edition (BOT-2) . It was This observational study applied a quantitative research approach that entailed the use of a cross-sectional design to characterize the motor proficiency levels of the participants at a given point in time. There were a number of reasons why this particular research approach was chosen. First, the study relied on a quantitative measurement instrument  that provided a numerical evaluation of various aspects of the participants’ motor performance, which meant that it was possible to objectively assess the performance of the study sample. Second, due to the nature of the research aims, outcomes in the form of numerical values were required to allow for comparisons between the ASD population and the corresponding BOT-2 norms and/or those children without ASD, as well as to reflect the relationship between the participants’ age and their test outcomes.Data for the present study were collected in Bahrain, Saudi Arabia, and the United Arab Emirates (UAE). The participants comprised children who were participating in an ongoing large-scale study evaluating neurobehavioral problems in children with ASD. They were recruited through purposive sampling on a voluntary basis.n = 180) and typically developing (TD) (n = 55) groups. Among them, 61 children with ASD and 25 TD children were excluded from the final sample. The recruitment process is illustrated in The initial sample consisted of 235 children, who were divided into the ASD , a partially inclusive school , or a specialised ASD school or centre .All the children with ASD  had received a formal diagnosis prior to their recruitment for the present study. They attended three different types of educational settings, namely a fully inclusive school . Second, they all met the diagnostic criteria for level 1 of the ASD severity scale included within the DSM-5, indicating that they had mild symptoms and required support . Third, The exclusion criterion for the ASD group was the presence of comorbid affective and/or behavioural symptoms . The absence of such comorbidities was verified by the researcher through interviewing the parents and reviewing the children’s medical records.The comparison (non-ASD or TD) group comprised 30 TD children  recruited from mainstream primary schools. The exclusion criteria were (i) a history of any psychiatric, neurological, or developmental disorder, (ii) a family history of ASD, (iii) a need to regularly use any psychotropic medication, (iv) a physical disability that hinders motor performance, and/or (v) undergoing physical therapy to address motor issues. One obstacle to recruiting a sufficient number of TD participants concerns parents’ reluctance to permit their children to participate in research. This reluctance could indicate that parents are concerned about their children’s assessment results. Data collection can prove particularly challenging in the Arab context due to recognised delays in certain developmental skills and the potential for stigmatisation.p < 0.05) with regard to any factor relevant to the comparison outcome variables.All the participants  were group-wise matched according to their gender, chronological age, handedness (rated using the Edinburgh Handedness Inventory (EHI) , non-verThis study relied on two types of instruments, namely screening questionnaires, and assessment measures.Gilliam Autism Rating Scale—Third Edition (GARS-3) : After oMichigan Autism Spectrum Questionnaire (MASQ) : The MASThe Clinician-Rated Severity of Autism Spectrum and Social Communication Disorders (CRSASSC) : This twThe following three screening questionnaires were used to verify the participant’s clinical diagnosis and to determine the severity of their autistic symptoms. The first two measures were completed by at least one parent of each participant with ASD, while the third measure was used by the researcher to independently assess the severity of the ASD symptoms.There are a number of different tools available to assist clinicians and researchers with the evaluation and measurement of different aspects of motor skills development and their contribution to motor performance ,56. ThisBruininks-Oseretsky Test of Motor Proficiency, Second Edition : The BOThe BOT-2 SF exhibited strong psychometric properties. Its high internal consistency was determined using the stratified alpha method with regard to each composite and the split-half method with regard to each subtest . The alpIn terms of the validity of the measure, the internal structure of the BOT-2 has been examined using the correlations among the subtest scale scores and the composite scores . The valAll the involved procedures were carried out in accordance with the ethical standards of the Queensland University of Technology, the research ethics committee of which approved the study protocol. The children involved in this project participated with the full written informed consent of their parents and legal guardians after the study procedures were explained; however, it was also important that the child participants were asked to give their verbal assent to participate. The parents of children with ASD provided information about the severity of their child’s autism by answering the questions on the GARS-3 and MASQ. In addition, the children with ASD underwent an assessment based on the CRSASSC scale that was conducted by the researcher in order to determine the level of severity. Each child was individually evaluated according to the BOT-2 by the researcher in a noise- and distraction-free room at their school. The verbal instructions given were adapted to fit each child’s level of language ability. The instructions for the test were also accompanied by photos of a child performing the main components of the test. All scores were recorded and converted into standardised scores according to the procedure described in the test manual. The assessment sessions were scheduled according to the times suggested by the children’s parents and teachers. The children were all given adequate praise throughout the test. At the start of the testing session, the children were informed that they could cease to participate at any time and for any reason.All the data analyses in the present study were performed using the Statistical Package for the Social Sciences (SPSS) version 23.0 . A one-sample z-test was performed to determine whether the mean of the motor scores of the ASD group statistically differed from the corresponding normative mean derived from the standardisation sample, as available in the BOT-2 manual. Further, the BOT-2 cut-off score (40 or less) was used to calculate the proportions of the actual clinical scores .t-test.Descriptive statistics were calculated concerning the raw scores for all the BOT-2 subtests. The overall differences between the raw scores of the children with ASD on the BOT-2 and those of the typically developing children were analysed by means of an independent samples p = 0.006.Generally speaking, when performing multiple comparisons using the same data set, the risk of a type I error occurring increases. To overcome this problem, the probabilities were not maintained at the chosen level (0.05), while a Bonferroni adjustment was made to control the overall type I error rate. When performing a Bonferroni adjustment, the alpha is estimated by taking the desired alpha level (0.05) and then dividing it by the number of comparisons being conducted. In the present study, for the multiple comparison analysis of the eight BOT-2 subtests, the significance level was set at The effect sizes were expressed using Cohen’s d . Accordip < 0.01 in order to avoid type I errors.Further, the effect of the age variable on the participants’ motor performance was investigated using a regression analysis, with age being considered the predictor variable and the total raw score for each child’s motor performance being considered the outcome of interest. The level of statistical significance was set as For linear regression, the effect size was calculated using Cohen’s ƒ2. According to Cohen’s guidelines (1988) concerning the interpretation of the magnitude of the R-squared value, the values of Cohen’s ƒ2 = 0.02, 0.13 and 0.26 are considered to be small, medium, and large effect size, respectively. The equation to compute Cohen’s effect size is (ƒ2 = R2/1 – R2) .The results of this study are presented in three stages according to the sequence of the research objectives:The BOT-2 standardized test was used in this study in order to evaluate motor proficiency in the child participants. Lower scores on the BOT-2 items are considered to be indicative of lower motor performance. On the short form of the BOT-2, the subtests are administered to find the raw scores. Each raw score for the subtests was then converted into a point score using the graded scale provided. The point scores are summed to give the total point score (max = 88), which is in turn converted into the standard score considering age and sex (ranging from 20 to 80), with a mean of 50 (SD = 10). A total composite standard score of 40 or less (one standard deviation below) is classified as indicative of motor impairment. This total motor composite can be reported as a categorical variable with five descriptive categories: well above average “≥70”, above average “60–69”, average “41–59”, below average “31–40”, and well below average “≤30”. Based on this process, the overall score, which is the sum of the eight subscales, was compared with the BOT-2 norms. p < 0.001) statistically deviated from the norm with a large effect size; thereby, indicating the presence of motor impairment within the overall level of motor proficiency. In light of the cut-off score set out in the BOT-2 guidelines, 88% of participants with ASD scored below the normal threshold when compared with the normative BOT-2 data. Based on the descriptive standard scoring categories detailed in the BOT-2 guidelines, the children with ASD were classified as displaying a motor performance deficit that fell within the below-average range.As shown in t-test found significant differences in terms of all the BOT-2 short-form subtests and the total score when comparing the children with ASD and the typically developing children. All the differences are significant at the p < 0.001 level, with the size effects on the eight BOT-2 subtests ranging from 1.16 to 2.66 and the total motor composite equalling 2.71 (Cohen’s d). This indicates that the children with ASD performed more poorly on the BOT-2 items than the TD controls. The performance on the eight motor subtests was variable. The children with ASD scored their lowest point scores on the strength element of all the subtests (Cohen’s d = 2.66), while Fine Motor Integration was associated with their highest point scores (Cohen’s d = 1.16).The independent samples β = 0.52, p ≤ 0.001, 2R = 0.26, Cohen’s ƒ2 = 0.36). This correlation pattern indicated that the children with ASD exhibited fewer deficits during the performance of motor tasks as they aged.The relationship between the ASD participants’ age and their overall motor performance was examined using linear regression analyses. The results indicated the significant main effect of age, which suggested that the children with ASD exhibited age-related gains in terms of their overall motor performance. Indeed, positive correlation was noted between their overall motor performance and their age  . The majSecond, a lack of opportunities to engage in physical activity/practice responding to physical stimuli could stem from various familial factors. The negative relationship between motor development and insufficient physical activity has been confirmed in the literature ,71. The Additionally, children living in the Gulf region tend to only rarely engage in physical activities out in the natural environment. Prior research evidence has suggested that the physical environment that we inhabit can offer both opportunities and barriers in terms of engaging in physical activities . For exaFinally, children with ASD typically lack exercise partners of the same age and are frequently isolated from their peers, which means that they generally lack opportunities to engage in social interactions. Unfortunately, children with ASD are particularly susceptible to social exclusion due to both the stigma experienced by their families  and the rejection and lack of acceptance shown by their peers . Some families attempt to keep their children’s condition a secret, and hence prevent their children from attending social events and engaging in social interactions with their peers. It has been reported that the lack of a peer exercise partner represents one of the key barriers to physical activity experienced by children with ASD . Such noThis study also sought to examine the differences between the motor performance, as assessed using the BOT-2, of children with ASD and typically developing children. The results demonstrated that the children with ASD exhibited weaker motor skills performance than the typically developing children, which indicated deficits in their motor proficiency. The results, therefore, support the findings of prior studies concerning motor behaviours, which indicated a general impairment of motor functioning in individuals with ASD ,11. The When considering all eight subscales used to evaluate the overall motor proficiency of the children with ASD, it appears that the identified motor deficits manifested with different degrees of severity. For instance, fine motor precision tasks require precise control over finger and hand movements. Our results indicated that the children with ASD experienced difficulties drawing lines through paths and folding paper. This finding is in accordance with the notion that individuals with ASD experience difficulties completing tasks that require the planning and sequencing of movement . As someFine motor integration skills require the capacity to integrate visual stimuli with motor control. This kind of integration is commonly referred to as “visual motor integration”. Our results indicated that the children with ASD were generally unable to perform the hand-eye coordination tasks. This finding is in line with prior evidence that some individuals with ASD exhibit underlying deficits in visual-motor integration . Such deOur findings also revealed the impaired performance of the children with ASD on the manual dexterity subtest, which is in line with the results of prior studies ,14,81,82The bilateral coordination subtest concerns the capacity to use both sides of the body in a controlled and organized manner to accomplish a functional task . The resThe balance subtest evaluates the motor control skills integral to an individual’s posture when standing. Balance is necessary for both movement and stillness, which is why it is sometimes referred to as postural control ,87. The The running speed and agility subtest includes activities that require both speed and agility. Hopping is defined as the elevation of the body off the ground and the subsequent landing on a single foot . It appeThe upper-limb coordination (ULC) subtest consists of activities designed to measure visual tracking with coordinated arm and hand movements. Our results revealed that the children with ASD exhibited ULC difficulties, which is consistent with prior evidence that individuals with ASD exhibit poor ULC during visuomotor activities . The resThe strength subtest is intended to assess the trunk flexor muscles and the upper and lower extremity strength. It involves activities such as push-ups and sit-ups. Our results indicated that the children with ASD showed an insufficient level of strength during such activities. They were able to complete fewer push-up and sit-up repetitions than the typically developing children. This is in line with the results obtained by Pan (2014), who found individuals with ASD to be able to complete fewer push-ups and sit-ups than age-matched peers without ASD . The inaThe final aim of this study was to determine whether the chronological age of the children with ASD affected their overall motor performance. Ultimately, it was determined that age did impact the motor performance of the children with ASD. The total score for motor performance was positively related to the age of the children with ASD. In general, the present results indicate that children with ASD demonstrated fewer deficits during motor tasks with age. This finding is consistent with the general pattern of the developmental acquisition of motor skills with age ,48. RelaThe present study outlined the prevalence of motor impairments in children with ASD, as well as the nature of the motor abnormalities seen in school-aged children with ASD when compared to typically developing children, through the use of a standardized test so as to facilitate a better understanding of the motor profiles associated with ASD. An additional focus of the study was the exploration of the relationship between motor performance ability and age. Based on the impairment cut-off detailed in the BOT-2 guidelines, the majority of children with ASD in our sample showed mild to extremely negative deviation from population norms, and therefore were classified as exhibiting a motor performance deficit. This study also found evidence that the children with ASD performed significantly poorer than the typically developing children in relation to all the items of the BOT-2. In addition, the study demonstrated the existence of a positive relationship between age and motor performance ability, which indicated that motor skills may improve as children grow older.The overall findings of this study served to reinforce and extend the results of prior studies concerning motor abnormalities in those with ASD. In particular, the present findings contributed significantly to our understanding of such motor characteristics in non-Western individuals diagnosed with ASD.A strength of this study is related to the use of a standardised assessment of motor impairment , which is one of the most commonly applied means of evaluating and discriminating motor function in children. However, only the short form of the chosen motor proficiency test (SFBOT-2) was used in this study, which limited our interpretation of the subcategories. However, the use of the SFBOT-2 can be justified based on the findings of our unpublished pilot study, which revealed both the difficulty and the high time requirements associated with applying the full version of the test. Additionally, a number of comorbid psychiatric disorders, including anxiety, could potentially impact children’s performance during a motor task ,104. HowAnother limitation of the present study is related to the cross-sectional methodological approach chosen to explore the impact of chronological age on the motor difficulties exhibited by children with ASD, which limited our ability to interpret the findings from a developmental perspective. Future studies should employ a longitudinal design so as to be better able to investigate the developmental trajectories of motor impairments in children with ASD and to provide us with further insights into the mechanisms that underlie such motor disruptions. The final limitation of this study concerned the study sample. Only children with ASD who exhibited an average or above-average IQ were included in the study. Therefore, the findings are limited to that group, and hence are not representative of individuals with ASD who exhibit lower cognitive function. Additionally, the fact that the sample of typically developing children included in the study was relatively small should be considered. Indeed, the typically developing participants in this study may not be representative of the population as a whole.Despite the above-mentioned limitations, the findings of the present study have a number of important implications for practice. First, the results reported here suggested that motor abnormalities represent a prevalent feature of ASD. However, such problems do not typically form part of the assessments for ASD nor are they typically included in intervention programs. Therefore, the inclusion of a motor assessment in the evaluation protocols associated with ASD should prove highly useful. Second, although motor deficits are present from very early on in the development of children with ASD and may actually reflect an underlying brain deficit, they do not generally represent a key focus for either parents or professionals. It is recommended that motor functioning should be considered during the clinical assessment and management of ASD, and it should not be ignored during early interventions. Further, it is recommended that additional research be undertaken in this regard so as to ensure greater clinical recognition of motor dysfunctions among children with ASD.Moreover, the wide-ranging implications of poor motor performance on the part of individuals with ASD can extend beyond the motor domain and into the educational, social, cognitive, and behavioural domains. Hence, motor functioning represents another area that we should be mindful of in the clinical context. The identification of motor abnormalities could be a potentially valuable marker of the degree and the nature of the other defining clinical features of ASD. Finally, the results of the present study highlighted the need for increased efforts to improve the clinical surveillance process in order to better identify potential developmental delays or deficits in terms of motor performance, as well as to implement intervention strategies intended to address motor problems, in children with ASD. Early identification and proper intervention with regard to motor problems in children with ASD may lead to such children experiencing improved self-confidence and self-esteem, increased performance quality, and enhanced occupational engagement and social participation.


In the last decade, the public concern over environmental problems has led to the emergence of environmental regulations in firms’ information disclosure on environmental practice, especially in some developing countries such as China. Based on a panel dataset composed of the listed manufacturing firms in China during 2006–2016, this paper uses the difference-in-differences (DID) model and the propensity score matching (PSM) method to investigate whether the Environmental Information Disclosure Measure  affects the firm value. The results show that EIDMT exerts a significant impact on the listed manufacturing firms’ value. In consideration of the firm’s ownership, EIDMT plays a more important role in the firm value of non-state-owned firms than state-owned firms. Furthermore, using a PSM–DID model for eastern, central, and western China, we find that EIDMT significantly affects the firm value in eastern and western China but has little impact on central China. As the world’s most populous country and the fourth largest in area, China’s economy is growing at a faster rate than any major nation. However, its environmental problems are getting worse ,2. ChinaThe firm contributes to the development of economy. However, it also leads to severe environmental problems. Accordingly, firms are increasingly required to be responsible for the impact of their activities on the environment . A varieWe wonder whether or not the EID policy impacts firm value. Therefore, we explore the impact of EID on the firm value based on EID Measure , which is the most vital EID policy in China. In this paper, we use the quasi-natural experiment to explore the net impact of EIDMT on firm value of state-owned and non-state-owned firms. Based on the difference-in-differences (DID) model and propensity score matching (PSM) model, we also discuss whether there is different results due to different regions. Moreover, we alter the dependent variable and EIDMT samples respectively to exam the robustness of the benchmark results.In this paper, we mainly have two contributions. First, EDIMT is not only one of the most important and meaningful EID policies, but also the first normative and comprehensive departmental regulation on EID in China. This is the first paper that explores the impact of EID on the firm value, based on EIDMT. Besides, we discuss the net impact of EIDMT on the firm value with a quasi-experimental framework by applying the PSM–DID method. It avoids the endogeneity of the EID policy and diminishes selection bias of the sample firms. With various robust checks, the results are quite convincing.The remainder of this paper is organized as follows: In terms of environmental regulation policies, many countries have gone through the first two stages—adopting legal control alone and introducing market tools (such as tradable emission permits and sewage charge), and entered the third stage, that is, adopting environmental, society, and governance (ESG) policies to control environmental pollution. In 1989, Norsk Hydro released the world’s first environmental development report in Norway. Then, many countries and international organizations started to pay attention to ESG. A growing number of firms disclosed their environmental information, which awakened public awareness of ESG issues. Thus, how to effectively control the environmental pollution became one of the most important issues. As a vital way for the public and investors to understand the environmental protection status quo of firms, EID aroused social attention and become a great hit in theoretical researches. However, the laws and regulations related to EID were not that adequate in China. Therefore, the market effect of rewarding and punishing information disclosure cannot be well generated.To establish and perfect the pollution source monitoring and information disclosure system, China started to adopt EID policies to regulate the pollution from firms since the 1990s. In 2003, Chinese government made regulations on the EID of the administrative departments for the first time. However, it was principled but lacking in binding and practicality. Securities Law of the People’s Republic of China (2005 Amendment) announced that if environmental information has had a significant impact on the stock’s trading price and the investor has not been informed, an interim report should be submitted. In 2008, the China Securities Regulatory Commission issued a regulation on the initial public offering (IPO) of firms in environmentally sensitive industries, stipulating that the IPO application documents of firms in environmentally sensitive industries must provide the investigation opinions of the national environmental protection agency. The China Securities Regulatory Commission will not approve an IPO application without investigation. In the same year, the ministry of environmental protection issued the EIDMT, which is a milestone in China’s legal science in EID. The EIDMT not only stipulated the definition and principle of EID, but also clarified the contents and procedural requirements of EID for firms. It is the first normative policy to regulate Chinese firms on EID, and it is also the first comprehensive departmental regulation on EID in China.The EIDMT, by disclosing the environmental information of enterprises, gives extra “punishment” to enterprises violating environmental laws in addition to legal punishment. Firms with poor environmental performance will suffer from public boycotts, government fines and other penalties, and their development prospects are bleak. If the firm is forced to close because of environmental accidents, investors may be in a disastrous situation. Firms with strong environmental management abilities and good environmental performance have a comparative competitive advantage. From the EID by the firm, external capital providers can understand the environmental behavior and performance of the firm and make effective investment decisions. However, in existing literature, the scholars may pay more attention to the relation between EID and corporate financial performance, based on the regression method ,15,16. TThe book-to-market ratio is the ratio of a stock’s book value to its market value. It is believed that stocks with high book-to-market ratios earn higher average returns than stocks with low book-to-market ratios. According to previous literature, the book-to-market ratio is always used to forecast the firm’s value by predicting stock returns. Accounting-based valuation theory asserts that the firm’s value is a combination of the book value and market expectations of future earnings. In addition, many scholars use the book-to-market ratio to explain the cross-sectional variation in stock returns ,18,19. KGenerally, EID can positively affect CFP by inducing firms to innovate and diminishing the information asymmetry in the firms. According to the Porter hypothesis, properly designed EID policies induce firms to break inefficient operational inertia and innovate, which allows firms to improve their productivity and profitability ,7,8. TheHowever, many empirical results also show a negative or no significant relation between EID and CFP. Palmer et al. (1995) assert that market competition forces firms to improve operational efficiency and innovate even without environmental regulation. In addition, the exogenous regulation affects firm profit maximization, which decreases the firm profits . Hou  uses Tobin’s Q to measure firm value, and he reports that the CEO power that is driven by product market competition has a positive effect on the firm value . Many stThe media plays a vital role in the financial market by disseminating information about firms, and firms are sensitive to the media reports by influencing the reputation capital of firms . Wang etFirms also provide information disclosure through financial reports, which include financial statements, notes to the financial statements, and management discussion and analysis. The firm’s financial accounting quality can weaken its information risk and hence lower the firm’s cost of equity capital . ZimmermEarly studies examining the relation between EID and firm value often focus on the impact of specific environmental issues, such as Union Carbide’s chemical leak in Bhopal, India in 1984  and SupeIn contrast, some scholars believe that more improved environmental disclosure leads to more precise earnings forecasts by analysts, which reduces expected future cash flow and cost of equity capital (COEC) through a reduction in information risk ,16. ThusHypothesis 1:There is a statistically significant positive association between EID and the firm value.Many studies have documented that corporate governance mechanisms can affect the firm’s information disclosure through ownership, board mechanisms, audit committee quality, governor independence, and so on ,41,42,43Hypothesis 2:EIDMT plays a more important role in the firm value of non-state-owned firms than state-owned firms.It is widely accepted that the DID is the best method for studying quasi-natural experiments . Bertran treat=0 ; Tt is aDifferent listed companies have heterogeneity. Therefore, when using the DID method, the listed companies, which have similar characteristics to the treatment group but do not have environmental information disclosure, should be selected as the control group. The DID method can solve the endogeneity, but it is difficult to solve the sample deviation problem, which can result in a nonrandom policy’s implementation. While the PSM method can solve the sample selection deviation. The EIDMT is an EID policy with a quasi-experimental framework. To measure the net impact of policy operation, we used the PSM method to statistically compare the sample with a diminished systematic difference based on the propensity scores ,49,50,51The PSM provides the propensity score, which implies the probability of the implementation of EIDMT, which can be calculated based on the logit regression as Equation (2):To comprehensively measure the impact of environmental information disclosure on the firm value, we needed to exclude the impact of other factors on the firm value. Therefore, we combined the PSM method with the DID method to solve the endogenous problem, to estimate the effects of external shocks on the impact of EIDMT. Data relating to these firms were collected from the CSMAR financial and trading database, and the initial observation samples were screened according to the following four principles: (1) the manufacturing firms listed in the Shanghai stock exchange and the Shenzhen stock exchange from 2005 to 2011 were selected as the research samples; (2) because the regulatory system and statement structure of financial listed companies were quite different from those of other industries, we excluded the samples from the financial industry based on the general treatment methods of previous studies; (3) Special Treatment (ST) samples were excluded; and (4) the continuous variables were winsorized at the level of 1%.Finally, 6066 “firm-panel” observations were grouped as unbalanced panel data, among which 5266 were labeled as the control group and 800 as the treatment group. The descriptive statistics of variables are shown in Chinese firms usually count on the support from local governments . TherefoTo overcome systematic differences in the listed manufacturing firms we selected and to reduce the bias of the DID estimation, we used the PSM method to match the EID firms with non-EID firms. First, we used both logit and probit regression to estimate the propensity scores of the listed manufacturing firms in China. Then, we selected the non-EID firms whose individual characteristics were similar to the EID firms, according to kernel matching. To avoid bias, we used the Gaussian, Biweight, Uniform, and Tricube algorithms to examine the results and the results are provided in p-value of the cash flow after applying the PSM method was more than 10%, which indicates that there was no significant difference between the EID firms and non-EID firms, consisting with the result of the sample selected from 2002 to 2016 in Based on Equation (3), we obtained the results of the differences of the characteristic variables before and after using the kernel matching in p-value, the standardized difference of the sample after matching was smaller than that before matching, which indicates that the systematic difference between the EID firms and matched non-EID firms was effectively avoided. The result based on the sample between 2002 and 2016 in The results of sample comparison before and after using the PSM method are reported in p-values were greater than the 10% level, indicating that in 2007, EIDMT did not affect the firms’ value. The result was consistent with the result based on the sample from 2002 to 2016 in Placebo test is a kind of counterfactual test that makes contrary assumptions about the impact of a policy or event. In this paper, we conducted it to examine the robustness of the results above. We set the date of EID in advance, by multiplying the year dummy variables and Treat to establish two new interaction terms. Although we measured the firm value by the book-to-market ratio, there are also other means to measure the firm value. Therefore, we adopted share price returns as the dependent variable, using a bootstrap self-sampling 500 times to estimate the effect of EIDMT. Since the PSM–DID method can be more convincing that it diminishes the sample selection bias, we applied it instead of the sore DID method. The results are provided in As discussed, our study focused on the impact of EIDMT on the firm value of listed manufacturing firms from 2006 to 2016. To provide further assurance of the results, we investigated the robustness of our results with the firms in heavy polluting industries. The results based on the PSM–DID method are shown in Through one of the most important EID policies in China, this study investigated the impact of EIDMT on the firm value by applying the PSM–DID method. The key conclusions were drawn as follows: (1) EIDMT exerted a significant impact on the listed manufacturing firms’ value in China. After we altered the EIDMT samples, the results show that EIDMT also had a positive effect on the firms in heavy polluting industries. A possible reason is that EID plays a monitoring role in diminishing information asymmetry so they can attract more investors. Besides, EIDMT gives extra punishment to firms with poor EID by public boycotts and government fines so firms with good environmental disclosure have a comparative competitive advantage. (2) EIDMT played a more important role in the firm value of non-state-owned firms, rather than state-owned firms. State-owned firms are bound to take more responsibility for environmental protection because of their ownership. (3) The findings’ region-based regressions proved that EIDMT significantly affected the firm value in eastern and western China but had little impact on central China. Since most of the non-state-owned listed manufacturing firms were in eastern China; the number of state-owned firms was much higher than the non-state-owned firms in western China.The contributions of this paper to the previous literature were as follows. First, the existing researches on the relation between environmental policies and the firm value mainly concentrate on corporate social responsibility (CSR) and environmental, social, and governance (EGS) disclosure, but lacks discussions of EID. This paper is the first study focusing on the net impact of EIDMT on the firm value. Second, this paper used the PSM–DID method to provide rigorous empirical results on the net effect of EID, which avoids exogenous shocks automatically.From the perspective of the government, we provided a rigorous reference for relevant policymaking to maximize the impact of environmental policies by considering the current situation of listed companies in China. This is also of certain guiding significance to the development of environmental protection in China. From the perspective of the firms, our contribution is to provide an empirical reference for the listed firms. We found that firms with EID had a better firm value, which gave firms an extra chance to promote their value and corporate financial performance.There were some potential limitations in this study. First, this paper investigated whether EIDMT affects the firm value and what the impact is, but did not well discuss how EIDMT affects the firm value . Future


Segmentation of the hippocampus (HC) in magnetic resonance imaging (MRI) is an essential step for diagnosis and monitoring of several clinical situations such as Alzheimer’s disease (AD), schizophrenia and epilepsy. Automatic segmentation of HC structures is challenging due to their small volume, complex shape, low contrast and discontinuous boundaries. The active contour model (ACM) with a statistical shape prior is robust. However, it is difficult to build a shape prior that is general enough to cover all possible shapes of the HC and that suffers the problems of complicated registration of the shape prior and the target object and of low efficiency. In this paper, we propose a semi-automatic model that combines a deep belief network (DBN) and the lattice Boltzmann (LB) method for the segmentation of HC. The training process of DBN consists of unsupervised bottom-up training and supervised training of a top restricted Boltzmann machine (RBM). Given an input image, the trained DBN is utilized to infer the patient-specific shape prior of the HC. The specific shape prior is not only used to determine the initial contour, but is also introduced into the LB model as part of the external force to refine the segmentation. We used a subset of OASIS-1 as the training set and the preliminary release of EADC-ADNI as the testing set. The segmentation results of our method have good correlation and consistency with the manual segmentation results. The shape and volume of the hippocampus (HC) is altered in cases of Alzheimer’s disease (AD), schizophrenia and epilepsy, among other conditions . AtrophyHippocampal segmentation methods include but are not limited to image-based methods, active contour models (ACM) , active The active contour model with prior information  embedded into the external term ,11 is roHowever, a common drawback of the traditional solution methods for ACM is poor efficiency, rendering its utilization for time-critical applications problematic. Recently, the lattice Boltzmann (LB) method has attracted the attention of researchers for its natural parallel characteristics and clear physical meaning . The parUsing limited training samples, DBN can model shapes of HC. The combination of DBN and LB is patient specific and can get accurate segmentation results without a complex network structure. The shape prior inferred from DBN can solve the problem of boundary leakage caused by an ambiguous boundary, while the initial contour can reduce iterations for segmentation. Compared with the statistical shape prior, our method does not need label alignment and shape prior registration with the object to be segmented. The segmentation accuracy of the DBN-LB_joint is higher than using the DBN and LB methods independently, and it is higher than the PCA-LB_joint and the cRBM  -LB_joinThe block diagram of the proposed method is depicted in We utilize and train a DBN as depicted in This DBN is trained layer by layer in an unsupervised way by stacking RBMs. The error minimized during this unsupervised training is the reconstruction error of the visible input. The result obtained from the previous RBM is used as “visible” input for the next RBM. The supervised training begins only at the top RBM, when the segmentation label t; it is treated as the mass of sub-pixels. In LB methods are usually composed of two steps: Collision and streaming steps. The collision step is shown in During the collision step, In the streaming step, the gray level on each sub-pixel is updated by the gray level from neighboring sub-pixels. Because In order to improve computing efficiency, we choose the D2Q5 lattice as shown in I as the image gray level. s represents the shape mask inferred from the DBN. H is the Heaviside function, The flowchart of the LB segmentation model is depicted in The energy function is:Since the distance function Comparing Equations (8) and (16), we get:The lattice Boltzmann method in image segmentation can be interpreted as the curve evolution process of the iso-density line  under the action of the internal force  and the external force . The procedure of DBN driven LB method for image segmentation is shown in Algorithm 1 below.Algorithm 1. DBN Driven LB Method for Image SegmentationC and defining level set function where 1: Setting the initial position of evolving curve 2: Initialize local equilibrium distribution function 3: Compute the external force term and discretize it with Equation (20)4: Updating the evolving curve and 5: If the segmentation is not done, jump back to step (2)6: Output the segmentation resulthttp://www.oasis-brains.org/) as the training set of DBN. This dataset was chosen to cover the entire age span of the subjects and to include subjects with different degrees of dementia. A professional radiologist provided manual segmentations of this subset, which are offered publicly [http://www.hippocampal-protocol.net/) and has manual segmentation over a subset (N = 100). There are 34 patients with MCI, 29 normal control subjects and 37 patients with AD.We use a subset of OASIS-1  Core (TM) i5 3230M processor with a clock speed of 2.6 GHz and 4 GB of RAM. The parameters in Equation (16) are Firstly, to show the positive effect of shape prior on segmentation results, we subjectively compare the previous LB model and the DRLS method with our method. Secondly, in order to verify that the segmentation method is sensitive to changes of the shape and size of the object, we carry out experiments on the synthetic fishes and HC images. Synthetic fish images have different shapes and sizes. HC images included groups of AD, MCI and NC with different HC volumes. To verify our method and can segment objects with occlusion or missing parts, we carry out experiments on the synthetic ellipse images. Synthetic ellipse images includes partially occluded ellipse and partially missing ellipse. We also compare the segmentation results with ground truth and show the segmentation results of 20 subjects. Thirdly, we use the Dice coefficient as a measure and compare our method with several other methods. Finally, we study the correlation and consistency between several different methods and the ground truth.To prove the positive effect of shape prior, we randomly choose three samples from EADC-ADNI and subjectively compare the segmentation results of the proposed method with the previous LB method proposed in  and the The segmentation results of ellipses are shown in To verify the sensitivity of our method to HC structural changes, we segmented images of the AD, MCI and NC groups of EADC-ADNI. We chose the largest HC on the sagittal plane and calculated the average area of three groups, separately. A is the estimated volume and B is the actual volume.In Execution time is an important factor that determines the performance of a segmentation method. PCA-LB_joint, cRBM-LB_joint, DBN-LB_jonit and DRLS can be regarded as the active contour converging to the target boundary. DBN based segmentation is only a part of our proposed method, which is used for rough segmentation. The execution time of the above methods is directly compared in this paper. In our method, the initial contour is very close to the HC edge to be segmented, and the shape prior guides the contour evolution, so the number of convergence iterations is less. Compared with DBN, the shape prior generated from cRBM is not so close to the HC to be segmented, so the cRBM-LB_joint method needs more iterations to converge. The PCA-LB_joint method needs the registration between the shape prior and the HC to be segmented, and the registration process accounts for a large proportion of the total time consumption. DBN-based segmentation is only a part of our proposed method, which is used for rough segmentation, so it does not need an iterative process and takes the shortest time. A comparison of computational cost for the above methods is shown in Furthermore, the agreement between the automatically and manually segmented volumes was studied with the use of Bland–Altman analysis . cRBM-LBDRLS and LB models without shape prior cannot segment HC correctly because its boundaries present rich, poor and missing gradient regions. Our model uses both the global constraint of shape and the local information of the target image. Global constraint ensures our model can deal with different types of images including partial occlusion, missing parts, weak boundaries. Local information ensures our model has the ability to deal with objects with shape and scale variance.Experiments on synthetic image and an HC image show our model is sensitive to shape and scale change and can segment objects with partial occlusion and missing parts. While the effect of this method in the segmentation of HC in patients with severe brain atrophy is little worse, the statistical results are satisfactory. We are confident of solving this problem by increasing the number of hidden layers and selecting training samples reasonably.That the segmentation accuracy of the DBN-LB_joint is higher than using DBN and the LB method independently means that this combination is effective. That the segmentation accuracy of our method is higher than PCA-LB_joint and cRBM-LB_joint means the shape prior generated from DBN is superior to those generated from PCA and cRBM. The reason for this is that PCA methods extract several principal components from a set of training images as a shape prior, which inevitably loses useful information. The cRBM lacks the ability to receive feedback from a higher layer to a lower layer and might generate a sub-optimal shape model. Compared with cRBM, DBN can capture more global information of the HC shape. The segmentation results of our method are worse than the atlas based method because the latter has mature template.We proposed a DBN-driven LB model for HC segmentation. Compared with the statistical shape prior, the shape prior inferred from the DBN is patient specific. Our method does not need train label alignment, shape prior or target object registration. Our method is sensitive to the changes of the HC structure and has good correlation and consistency with the results of manual segmentation. While satisfactory segmentation results were achieved in this paper, there are several directions deserving further study. (1) We will study a method that can automatically locate the HC to generate the training set of DBN; (2) the number of layers and units in the hidden layer of DBN are determined manually. We will study an optimization method that can automatically determine the above parameters. (3) Considering the natural parallelism of the LB method, we plan to apply it directly to 3D HC segmentation in the future. (4) Furthermore, we plan to use the generative model such as RBM, DBN or DBM to get the occlusion sensitive map of organs, which plays an important role in medical image analysis.