From Digital Human Modeling to Human Digital Twin: Framework and Perspectives in Human Factors

The human digital twin(HDT)emerges as a promising human-centric technology in Industry 5.0,but challenges remain in human modeling and simulation.Digital human modeling(DHM)provides solutions for modeling and simulating human physical and cognitive aspects to support ergonomic analysis.However,it has limitations in real-time data usage,personalized services,and timely interaction.The emerging HDT concept offers new possibilities by integrating multi-source data and artificial intelligence for continuous monitoring and assessment.Hence,this paper reviews the evolution from DHM to HDT and proposes a unified HDT framework from a human factors perspective.The framework comprises the physical twin,the virtual twin,and the linkage between these two.The virtual twin integrates human modeling and AI engines to enable model-data-hybrid-enabled simulation.HDT can potentially upgrade traditional ergonomic methods to intelligent services through real-time analysis,timely feedback,and bidirectional interactions.Finally,the future perspectives of HDT for industrial applications as well as technical and social challenges are discussed.In general,this study outlines a human factors perspective on HDT for the first time,which is useful for cross-disciplinary research and human factors innovation to enhance the development of HDT in industry.

Establishment of a humanized ST6GAL1 mouse model for influenza research

Background:This study aimed to construct and characterize a humanized influenza mouse model expressing hST6GAL1.Methods:Humanized fragments,consisting of the endothelial cell-specific K18 promoter,human ST6GAL1-encoding gene,and luciferase gene,were microinjected into the fertilized eggs of mice.The manipulated embryos were transferred into the oviducts of pseudopregnant female mice.The offspring were identified using PCR.Mice exhibiting elevated expression of the hST6GAL1 gene were selectively bred for propagation,and in vivo analysis was performed for screening.Expression of the humanized gene was tested by performing immunohistochemical(IHC)analysis.Hematologic and biochemical analyses using the whole blood and serum of humanized hST6GAL1 mice were performed.Results:Successful integration of the human ST6GAL1 gene into the mouse genome led to the overexpression of human SiaT ST6GAL1.Seven mice were identified as carrying copies of the humanized gene,and the in vivo analysis indicated that hST6GAL1gene expression in positive mice mirrored influenza virus infection characteristics.The IHC results revealed that hST6GAL1 was expressed in the lungs of humanized mice.Moreover,the hematologic and biochemical parameters of the positive mice were within the normal range.Conclusion:A humanized influenza mouse model expressing the hST6GAL1 gene was successfully established and characterized.

Humanization for neurological disease modeling:A roadmap to increase the potential of Drosophila model systems

Neuroscience and neurology research is dominated by experimentation with rodents.Around 75%of neurology disease-associated genes have orthologs in Drosophila mel-anogaster,the fruit fly amenable to complex neurological and behavioral investiga-tions.However,non-vertebrate models including Drosophila have so far been unable to significantly replace mice and rats in this field of studies.One reason for this situ-ation is the predominance of gene overexpression(and gene loss-of-function)meth-odologies used when establishing a Drosophila model of a given neurological disease,a strategy that does not recapitulate accurately enough the genetic disease condi-tions.I argue here the need for a systematic humanization approach,whereby the Drosophila orthologs of human disease genes are replaced with the human sequences.This approach will identify the list of diseases and the underlying genes that can be adequately modeled in the fruit fly.I discuss the neurological disease genes to which this systematic humanization approach should be applied and provide an example of such an application,and consider its importance for subsequent disease modeling and drug discovery in Drosophila.I argue that this paradigm will not only advance our un-derstanding of the molecular etiology of a number of neurological disorders,but will also gradually enable researchers to reduce experimentation using rodent models of multiple neurological diseases and eventually replace these models.

Model-Based Systems Engineering Approach to Design a Human Settlement to Better Serve Displaced People

The challenge of transitioning from temporary humanitarian settlements to more sustainable human settlements is due to a significant increase in the number of forcibly displaced people over recent decades, difficulties in providing social services that meet the required standards, and the prolongation of emergencies. Despite this challenging context, short-term considerations continue to guide their planning and management rather than more integrated, longer-term perspectives, thus preventing viable, sustainable development. Over the years, the design of humanitarian settlements has not been adapted to local contexts and perspectives, nor to the dynamics of urbanization and population growth and data. In addition, the current approach to temporary settlement harms the environment and can strain limited resources. Inefficient land use and ad hoc development models have compounded difficulties and generated new challenges. As a result, living conditions in settlements have deteriorated over the last few decades and continue to pose new challenges. The stakes are such that major shortcomings have emerged along the way, leading to disruption, budget overruns in a context marked by a steady decline in funding. However, some attempts have been made to shift towards more sustainable approaches, but these have mainly focused on vague, sector-oriented themes, failing to consider systematic and integration views. This study is a contribution in addressing these shortcomings by designing a model-driving solution, emphasizing an integrated system conceptualized as a system of systems. This paper proposes a new methodology for designing an integrated and sustainable human settlement model, based on Model-Based Systems Engineering and a Systems Modeling Language to provide valuable insights toward sustainable solutions for displaced populations aligning with the United Nations 2030 agenda for sustainable development.

The generation and properties of human cortical organoids as a disease model for malformations of cortical development

As three-dimensional“organ-like”aggregates,human cortical organoids have emerged as powerful models for studying human brain evolution and brain disorders with unique advantages of humanspecificity,fidelity and manipulation.Human cortical organoids derived from human pluripotent stem cells can elaborately replicate many of the key properties of human cortical development at the molecular,cellular,structural,and functional levels,including the anatomy,functional neural network,and interaction among different brain regions,thus facilitating the discovery of brain development and evolution.In addition to studying the neuro-electrophysiological features of brain cortex development,human cortical organoids have been widely used to mimic the pathophysiological features of cortical-related disease,especially in mimicking malformations of cortical development,thus revealing pathological mechanism and identifying effective drugs.In this review,we provide an overview of the generation of human cortical organoids and the properties of recapitulated cortical development and further outline their applications in modeling malformations of cortical development including pathological phenotype,underlying mechanisms and rescue strategies.

ChatModeler:基于大语言模型的人机协作迭代式需求获取和建模方法

需求获取和建模是需求工程中的关键步骤,影响后续系统设计与实现.传统的需求获取和建模方法通常由需求提供者、需求分析师等多类干系人共同协作、反复迭代完成,需要耗费大量的人力.如何减轻需求提供者与需求分析师的负担、提高获取和建模的效率有着重要意义.现有工作中有的使用知识库来提供更多知识,以辅助获取或者建模,有的利用自然语言处理等技术对获取或者建模过程进行自动化,但是它们并没有减轻需求提供者的负担.利用大语言模型(large language models,LLMs)的生成能力,提供了一种人机协作的迭代式需求获取和建模框架ChatModeler.具体来说,根据真实世界中需求团队的分工及协作关系,将部分需求提供者、需求分析师等角色的工作由大语言模型承担,而需求提供者只需要进行确认.为大语言模型扮演的各种角色进行了提示词设计,该提示词会随需求的元模型而变化.ChatModeler在7个需求案例上与3种需求模型的自动建模方法进行了14组对比实验,证明了ChatModeler在降低需求提供者的负担和生成高质量需求模型2个方面上的优越性.

Human Settlement Evaluation in Mountain Areas Based on Remote Sensing,GIS and Ecological Niche Modeling

The Qinghai-Tibet Plateau is the word＇s highest and largest plateau. Due to increasing demands for environment exploration and tourism, a large transitional area is required for altitude adaptation. Hehuang valley, which locates in the transition zone between the Loess Plateau and the Qinghai-Tibet Plateau, has convenient transportation and relatively low elevation. Our question is whether the geographic conditions here are appropriate for adapted stay before going into the Qinghai-Tibet Plateau. Therefore, in this study, we examined the potential use of ecological niche modeling （ENM） for mapping current and potential distribution patterns of human settlements. We chose the Maximum Entropy Method （Maxent）, an ENM which integrates climate, remote sensing and geographical data, to model distributions and assess land suitability for transition areas. After preprocessing and selection, the correlation between variables and spatial auto- correlation input data were removed and 106 occurrence points and 9 environmental layers were determined as the model inputs. The threshold- independent model performance was reasonable according to lO times model running, with the area under the curve （AUC） values being 0.917± 0.01, and 0.923±0.002 for test data. Cohen＇s kappa coefficient of model performance was 0.848. Results showed that 82.22% of the study extent was not suitable for human settlement. Of the remaining areas, highly suitable areas aceounted for 1.19%, moderately for 5.3% and marginally for 11.28%. These suitable areas totaled 418.79 km2, and 86.25% of the sample data was identified in the different gradient of suitable area.The decisive environmental factors were slope and two climate variables： mean diurnal temperature range and temperature seasonality. Our model showed a good performance in mapping and assessing human settlements. This study provides the first predicted potential habitat distribution map for human settlement in Ledu County, which could also help in land use management.

Characterization of Gallic Acid Interaction with Human Serum Albumin by Spectral and Molecular Modeling Methods

The binding of drugs with human serum albumin（HSA） is a crucial factor influencing the distribution and bioactivity of drugs in the body.To understand the action mechanisms between gallic acid（GA,3,4,5-trihydroxybenzoic acid） and HSA,the binding of GA with HSA was investigated by a combined experimental and computational approach.The fluorescence properties of HSA and the binding parameters of GA collectively indicate that the binding is characterized by static quenching mechanism at one high affinity binding site.According to the estimated molecular distance between the donor（HSA） and the acceptor（GA）,the binding is related to the fluorescence resonance energy transfer.As indicated by the thermodynamic parameters,hydrophobic interaction plays a major role in the GA-HSA complex.Further,the experimental results reveal that GA is bound in the large hydrophobic cavity of subdomain IIA in the site I of HSA,which is well approved by molecular docking.

Human pluripotent stem cell-derived kidney organoids:Current progress and challenges

Human pluripotent stem cell(hPSC)-derived kidney organoids share similarities with the fetal kidney.However,the current hPSC-derived kidney organoids have some limitations,including the inability to perform nephrogenesis and lack of a corticomedullary definition,uniform vascular system,and coordinated exit path-way for urinary filtrate.Therefore,further studies are required to produce hPSC-derived kidney organoids that accurately mimic human kidneys to facilitate research on kidney development,regeneration,disease modeling,and drug screening.In this review,we discussed recent advances in the generation of hPSC-derived kidney organoids,how these organoids contribute to the understanding of human kidney development and research in disease modeling.Additionally,the limitations,future research focus,and applications of hPSC-derived kidney organoids were highlighted.

A Survey on Deep Learning-Based 2D Human Pose Estimation Models

In this article,a comprehensive survey of deep learning-based(DLbased)human pose estimation(HPE)that can help researchers in the domain of computer vision is presented.HPE is among the fastest-growing research domains of computer vision and is used in solving several problems for human endeavours.After the detailed introduction,three different human body modes followed by the main stages of HPE and two pipelines of twodimensional(2D)HPE are presented.The details of the four components of HPE are also presented.The keypoints output format of two popular 2D HPE datasets and the most cited DL-based HPE articles from the year of breakthrough are both shown in tabular form.This study intends to highlight the limitations of published reviews and surveys respecting presenting a systematic review of the current DL-based solution to the 2D HPE model.Furthermore,a detailed and meaningful survey that will guide new and existing researchers on DL-based 2D HPE models is achieved.Finally,some future research directions in the field of HPE,such as limited data on disabled persons and multi-training DL-based models,are revealed to encourage researchers and promote the growth of HPE research.

Biomechanical modeling for the response of human thorax to blast waves

A simplified finite element model of a human thorax had been developed for probing into the mechani- cal response in simple and complex blast environments. The human thorax model was first created by CT images with blast loading applied via a coupled arbitrary Lagrangian- Eulerian method, allowing for a variety of loads to be considered. The goal is to analyze the maximum stress distri- butions of lung tissue and peak inward thorax wall velocity and to know the possible regions and levels of lung injury. In parallel, a mathematical model has been modified from the Lobdell model to investigate the detailed percentage of lung injury at each level. The blast loadings around the human tho- rax were obtained from the finite element model, and were then applied in the mathematical model as the boundary con- ditions to predict the normalized work of the human thorax lung. The present results are found in agreement with the modified Bowen curves and the results predicted by Axels- son＇s model.

Effects of coal mining and tunnel excavation on groundwater flow system in karst areas by modeling:A case study in Zhongliang Mountain,Chongqing,Southwest China

A karst groundwater system ranks among the most sensitive and vulnerable types of groundwater systems.Coal mining and tunnel excavation can greatly change the natural hydrogeological flow system,groundwater-dependent vegetation,soil,as well as hydrology of surface water systems.Abandoned coal mine caves and proposed highway tunnels may have significant influences on groundwater systems.This study employs MODFLOW,a 3D finite-difference groundwater model software,to simulate the groundwater system's response to coal mining and tunnel excavation impact in Zhongliang Mountain,Chongqing,from 1948 to 2035.The results show a regional decline in groundwater levels within the study area following mining and tunnel construction.The groundwater flow system in the study area evolves from the Jialing River groundwater flow system to encompass the Jialing River,Moxinpo highway tunnel,Moxinpo,and the Liujiagou coal mine cave groundwater flow systems between 1948 and 2025.With the completion of tunnel construction,the groundwater level at the top of the tunnel is gradually restored to the water level in the natural state.The model also predicts groundwater level variations between 2025 and 2035.The groundwater level will rise further initially,however,it may take about 10 years for the system to stabilize and reach a new equilibrium.In light of these findings,it is advised that changes in groundwater flow systems caused by tunnel construction should be modeled prior to the practical construction.This approach is crucial for evaluating potential engineering and environmental implications.

Influence of Human Activity Intensity on Habitat Quality in Hainan Tropical Rainforest National Park,China

Due to long-term human activity interference,the Hainan Tropical Rainforest National Park(HTRNP)of China has experienced ecological problems such as habitat fragmentation and biodiversity loss,and with the expanding scope and intensity of human activity impact,the regional ecological security is facing serious challenges.A scientific assessment of the interrelationship between human activity intensity and habitat quality in the HTRNP is a prerequisite for achieving effective management of ecological disturbances caused by human activities and can also provide scientific strategies for the sustainable development of the region.Based on the land use change data in 2000,2010,and 2020,the spatial and temporal variations and the relationship between habitat quality(HQ)and human activity intensity(HAI)in the HTRNP were explored using the integrated valuation of ecosystem services and trade-offs(InVEST)model.System dynamics and land use simulation models were also combined to conduct multi-scenario simulations of their relationships.The results showed that during 2000–2020,the habitat quality of the HTRNP improved,the intensity of human activities decreased each year,and there was a negative correlation between the two.Second,the system dynamic model could be well coupled with the land use simulation model by combining socio-economic and natural factors.The simulation scenarios of the coupling model showed that the harmonious development(HD)scenario is effective in curbing the increasing trend of human activity intensity and decreasing trend of habitat quality,with a weaker trade-off between the two compared with the baseline development(BD)and investment priority oriented(IPO)scenarios.To maintain the authenticity and integrity of the HTRNP,effective measures such as ecological corridor construction,ecological restoration,and the implementation of ecological compensation policies need to be strengthened.

Establishment and Application of A Human Primary Keratinocyte Inflammation Model for Cosmetic Raw Material Screening

Using inducers to induce cells to produce inflammatory response is a common in vitro experimental method to study inflammation.However,there are relatively few inflammatory models developed for the cosmetic industry,and there are also great differences in the control of model induction,the selection of inflammatory indicators,and the concentration of inducers.Therefore,in this paper,by systematically studying the effects of Lipopolysaccharide(LPS)on the cell viability,the levels of IL-1α,IL-8 and ROS of human primary keratinocytes,a skin inflammation model based human primary keratinocyte was developed.The results showed that 0.01~100μg/mL LPS had no significant effect on the cell viability of human primary keratinocytes,while 100μg/mL LPS could simultaneously induce human primary keratinocytes to produce large amounts of IL-1αand IL-8,and 0.01μg/mL LPS could induce plentiful ROS.Therefore,a skin inflammation model for differential induction of different inflammatory indicators was established,and the sample OSM2021041301 was tested with this model,it was found that sample OSM2021041301 could significantly inhibit LPS-induced elevated IL-1αand IL-8 levels,the inhibitory effect on LPS-induced elevated ROS level was weak.The results indicated that OSM2021041301 has certain anti-inflammatory effect on inflammation caused by the increase of IL-1α,IL-8 and ROS induced by LPS and its analogues.

Progress,implications,and challenges in using humanized immune system mice in CAR-T therapy-Application evaluation and improvement

In recent years,humanized immune system(HIS)mice have been gradually used as models for preclinical research in pharmacotherapies and cell therapies with major breakthroughs in tumor and other fields,better mimicking the human immune system and the tumor immune microenvironment,compared to traditional immunodeficient mice.To better promote the application of HIS mice in preclinical research,we se-lectively summarize the current prevalent and breakthrough research and evaluation of chimeric antigen receptor(CAR)-T cells in various antiviral and antitumor treat-ments.By exploring its application in preclinical research,we find that it can better reflect the actual clinical patient condition,with the advantages of providing high-efficiency detection indicators,even for progressive research and development.We believe that it has better clinical patient simulation and promotion for the updated design of CAR-T cell therapy than directly transplanted immunodeficient mice.The characteristics of the main models are proposed to improve the use defects of the existing models by reducing the limitation of antihost reaction,combining multiple models,and unifying sources and organoid substitution.Strategy study of relapse and toxicity after CAR-T treatment also provides more possibilities for application and development.

How can we establish animal models of HIV-associated lymphoma?

Human immunodeficiency virus(HIV)infection is strongly associated with a height-ened incidence of lymphomas.To mirror the natural course of human HIV infection,animal models have been developed.These models serve as valuable tools to inves-tigate disease pathobiology,assess antiretroviral and immunomodulatory drugs,ex-plore viral reservoirs,and develop eradication strategies.However,there are currently no validated in vivo models of HIV-associated lymphoma(HAL),hampering progress in this crucial domain,and scant attention has been given to developing animal models dedicated to studying HAL,despite their pivotal role in advancing knowledge.This re-view provides a comprehensive overview of the existing animal models of HAL,which may enhance our understanding of the underlying pathogenesis and approaches for malignancies linked to HIV infection.

An Improved CREAM Model Based on DS Evidence Theory and DEMATEL

Cognitive Reliability and Error Analysis Method(CREAM)is widely used in human reliability analysis(HRA).It defines nine common performance conditions(CPCs),which represent the factors thatmay affect human reliability and are used to modify the cognitive failure probability(CFP).However,the levels of CPCs are usually determined by domain experts,whichmay be subjective and uncertain.What’smore,the classicCREAMassumes that the CPCs are independent,which is unrealistic.Ignoring the dependence among CPCs will result in repeated calculations of the influence of the CPCs on CFP and lead to unreasonable reliability evaluation.To address the issue of uncertain information modeling and processing,this paper introduces evidence theory to evaluate the CPC levels in specific scenarios.To address the issue of dependence modeling,the Decision-Making Trial and Evaluation Laboratory(DEMATEL)method is used to process the dependence among CPCs and calculate the relative weights of each CPC,thus modifying the multiplier of the CPCs.The detailed process of the proposed method is illustrated in this paper and the CFP estimated by the proposed method is more reasonable.

Rapid 3D human body modeling based on Kinect technology

The 3D shape of the human body is useful for applications in fitness, games and apparel. Accurate body scanners, howev- er, are expensive, limiting the availability of 3D body models. In this paper, we focus on the human body 3D modeling using one Kinect sensor modeling method. To get the human body model fast, three steps in rapid modeling of the human body are carried out. Firstly, according to anthropometric parameters, the standard model is parameterized; Secondly, the Kinect depth image of the human body model is gotten through, then, by using the PCL library the point cloud data is processed and matched, and the human body model is optimized; Finally, the realistic human body model is obtained with the rapid integration of the standard model and PCL library.

Analysis and FDTD Modeling of the Influences of Microwave Electromagnetic Waves on Human Biological Systems

The interactions of electromagnetic waves with the human body are complex and depend on several factors related to the characteristics of the incident wave, including its frequency, its intensity, the polarization of the tissue encountered, the geometry of the tissue and its electromagnetic properties. That’s to say, the dielectric permittivity, the conductivity and the type of coupling between the field and the exposed body. A biological system irradiated by an electromagnetic wave is traversed by induced currents of non-negligible density;the water molecules present in the biological tissues exposed to the electromagnetic field will begin to oscillate at the frequency of the incident wave, thus creating internal friction responsible for the heating of the irradiated tissues. This heating will be all the more important as the tissues are rich in water. This article presents the establishment from a mathematical and numerical analysis explaining the phenomena of interaction and consequences between electromagnetic waves and health. Since the total electric field in the biological system is unknown, that is why it can be determined by the Finite Difference Time Domain FDTD method to assess the electromagnetic power distribution in the biological system under study. For this purpose, the detailed on the mechanisms of interaction of microwave electromagnetic waves with the human body have been presented. Mathematical analysis using Maxwell’s equations as well as bio-heat equations is the basis of this study for a consistent result. Therefore, a thermal model of biological tissues based on an electrical analogy has been developed. By the principle of duality, an electrical model in the dielectric form of a multilayered human tissue was used in order to obtain a corresponding thermal model. This thermal model made it possible to evaluate the temperature profile of biological tissues during exposure to electromagnetic waves. The simulation results obtained from computer tools show that the temperature in the biological tissue is a linear function of the duration of exposure to microwave electromagnetic waves.

Risk identification and safety assessment of human-computer interaction in integrated avionics based on STAMP

To solve the problem of risk identification and quantitative assessment for human-computer interaction(HCI)in complex avionics systems,an HCI safety analysis framework based on system-theoretical process analysis(STPA)and cognitive reliability and error analysis method(CREAM)is proposed.STPACREAM can identify unsafe control actions and find the causal path during the interaction of avionics systems and pilot with the help of formal verification tools automatically.The common performance conditions(CPC)of avionics systems in the aviation environment is established and a quantitative analysis of human failure is carried out.Taking the head-up display(HUD)system interaction process as an example,a case analysis is carried out,the layered safety control structure and formal model of the HUD interaction process are established.For the interactive behavior“Pilots approaching with HUD”,four unsafe control actions and35 causal scenarios are identified and the impact of common performance conditions at different levels on the pilot decision model are analyzed.The results show that HUD's HCI level gradually improves as the scores of CPC increase,and the quality of crew member cooperation and time sufficiency of the task is the key to its HCI.Through case analysis,it is shown that STPACREAM can quantitatively assess the hazards in HCI and identify the key factors that impact safety.