Integrated Model Research Articles

Bayesian Multilayered Mediation Analysis for Cancer Pharmacogenomics

ABSTRACTMultiomic data from multilevel biological systems are becoming common and motivate integrative modelling approaches to decipher within‐ and cross‐platform dependencies. Mediation analysis aims to identify mediating mechanisms that regulate the effect of an exposure on an outcome. In multiomic contexts, identification of genomic mediators of disease outcomes provides a deeper understanding of mechanisms of disease and corresponding therapeutic targets. While there has been significant work on joint modelling of high‐dimensional potential mediators, approaches that can identify individual mediators in presence of high‐dimensional potential mediators are lacking. We posit that the multiomic data are interrelated following multilayered Gaussian graphical models that include undirected and directed acyclic graphs as special cases. We develop a Bayesian inferential framework for multilayered mediation analysis with continuous, binary, and ordinal outcomes using probit models. As opposed to existing approaches focusing on identifying joint mediation effects, we decompose the joint effect into effects attributable to individual mediators in the framework of interventional mediation analysis. Simulations demonstrate our method outperforms other existing approaches to identify mediators that have nonzero indirect effects to the outcome. We apply our method to multiomic analysis on drug sensitivity outcomes of palbociclib and agents for endocrine therapy, standard care for breast cancer.

Performance and economic analysis of various geothermal power plant systems: Case study for the Chingshui geothermal field in Taiwan

Geothermal power plants are a source of sustainable energy. However, their performance is influenced by various factors, including production temperature and well locations, and few studies have investigated the relationships between these factors. To address this research gap, the present study developed integrated models of a geothermal reservoir and a variety of power plant systems. By using COMSOL and MATLAB, we conducted simulations for the Chingshui geothermal field in Taiwan to investigate the performance and economic feasibility of five common types of geothermal power plant systems over their operational lifetime under different well configurations. The key findings of this investigation are as follows. First, the locations of production wells are a primary factor influencing production temperature. Constructing wells in low-permeability zones results in considerable increases in the pressure differential in the injection pump; thus, wells should not be constructed in such zones. Second, as system flow rate and well depth decrease, production temperature remains relatively stable, net power output decreases, and system efficiency increases. This efficiency increase is caused by decreases in pumping power requirements at lower flow rates and shallower well depths. Finally, among the investigated systems, the organic Rankine cycle system had the lowest electricity production cost and shortest payback period within the enthalpy range of 500–1000 kJ/kg. Double-flash (DF) and DF–binary systems are also viable options when the mass flow rate is 10–20 kg/s and the enthalpy is 700–800 kJ/kg. Overall, the results of this study offer valuable insights for the design of geothermal power plants, thereby contributing to the optimization of renewable energy systems.

Integrated study of hydraulic/CO2 fracturing and production coupled with a THM-D process in ultra-shallow shale reservoirs

To explore fracturing technology for vertical wells in ultra-shallow shale gas reservoirs, a coupled thermo-hydro-mechanical-damage (THM-D) fracturing and production integration model is established in this study. In addition, a new coupled hydro-mechanical damage model is established to calculate fracture evolution. These two models are validated through theoretical models and field data, respectively. Based on these models, the quality of fracturing under different geological parameters, fracturing parameters, and fracturing technology is compared and analyzed. The results show that the distribution of natural fractures significantly influences fracturing and production. In addition, due to the high leak-off in the ultra-shallow shale reservoir, the total fracture length and cumulative production after 720 days of carbon dioxide fracturing are only 70.35% and 77.26% of the values achieved by hydraulic fracturing, respectively. Therefore, it is necessary to consider reducing carbon dioxide leak-off in the design of carbon dioxide fracturing in ultra-shallow shale reservoirs. Fracturing efficiency also should be considered when designing fracturing time. When the injection rate is 5 m3/min, the efficiency drops sharply if the fracturing time exceeds 67.45 min. The production of hydraulic fracturing and carbon dioxide fractured wells has also been studied when fracturing methods without proppant are used. This study found that a satisfactory production rate can also be achieved in ultra-shallow shale gas reservoirs when fracturing without proppant.

Transferable skills in tourism and hospitality

A multi-stage, multi-method approach using participatory research methodology that considers the perspectives of tourism and hospitality professionals, and academic experts is used to develop an integrated model of transferable skills gained by working in the industry. Grounded in career construction theory, this study is anticipated to provide a comprehensive understanding of essential skills in the tourism and hospitality industry. It also aims to reshape the image of working in the industry into a more positive one, emphasizing the opportunities of the sector not only as a career but also as a steppingstone to learn transferable skills needed in different sectors, and ultimately contribute to the long-term and sustainable development of the tourism and hospitality sector.

Integrative Multi-Omics Approach for Improving Causal Gene Identification.

Transcriptome-wide association studies (TWAS) have been widely used to identify thousands of likely causal genes for diseases and complex traits using predicted expression models. However, most existing TWAS methods rely on gene expression alone and overlook other regulatory mechanisms of gene expression, including DNA methylation and splicing, that contribute to the genetic basis of these complex traits and diseases. Here we introduce a multi-omics method that integrates gene expression, DNA methylation, and splicing data to improve the identification of associated genes with our traits of interest. Through simulations and by analyzing genome-wide association study (GWAS) summary statistics for 24 complex traits, we show that our integrated method, which leverages these complementary omics biomarkers, achieves higher statistical power, and improves the accuracy of likely causal gene identification in blood tissues over individual omics methods. Finally, we apply our integrated model to a lung cancer GWAS data set, demonstrating the integrated models improved identification of prioritized genes for lung cancer risk.

Multi-digit touch II: perceptual weighting during integration follows a leading-finger priority.

When we run our hand across a surface, each finger typically repeats the sensory stimulation that the leading finger has already experienced. Because of this redundancy, the leading finger may attract more attention and contribute more strongly when tactile signals are integrated across fingers to form an overall percept. To test this hypothesis, we re-analysed data collected in a previous study (Arsanova et al., 1), where two probes were moved in different directions on two different fingerpads and participants reported the probes' average direction. Here, we evaluate the relative contribution of each finger to the percept and examine whether multi-digit integration gives priority to the leading finger. Although the hand actually remained static in these experiments, a 'functional leading finger' could be defined with reference to the average direction of the stimuli, and the direction of hand-object relative motion that this implied. When participants averaged the motion direction across fingers of the same hand, the leading finger received a higher weighting than the non-leading finger, even though this biased estimates of average direction. Importantly, this bias disappeared when averaging motion direction across the two hands. Both the reported average direction and its systematic relation to the difference between the individual stimulus directions were explained by a model of motion integration in which the sensory weighting of stimuli depends on the directions of the applied stimuli. Our finding supports the hypothesis that the leading finger, which often receives novel information in natural hand-object interactions, is prioritized in forming our tactile perception.

Gather "Round": An Integrated Care Model for the Emergency Department Multi-Visit Patient.

Emergency departments (EDs) are a vital component of the United States healthcare system and care for over 130 million patient visits annually. Nonurgent ED visits can contribute to crowding, delays in care, and adverse effects. Many high-utilizing ED patients may present with complex medical, behavioral, and social needs that are not necessarily emergent or urgent in nature. The authors created an Integrated Care Model, called the Multi-Visit Patient (MVP) program, for patients with 5 or more visits to the ED in a rolling 12-month period. The MVP program incorporated an interdisciplinary group of ED leadership and case management (CM) to identify, engage, and intervene with ED MVPs, aiming to improve their ED utilization. Patients received comprehensive screenings for depression, falls, alcohol use disorder, caregiver support, social determinants of health, and more. Based on these screenings, the CM team implemented interventions such as connecting patients with outpatient specialists and linking patients to community-based organizations to optimize stability, wellness, and reduce ED utilization. The collaboratively developed MVP program was implemented in the ED of a large, suburban, tertiary care academic hospital. The MVP program identified 221 MVP patients over a 20-month period and successfully connected with 89% of them. Of these 221 patients, 78% (172 patients) chose to engage in the MVP program, with 160 completing their engagement with an outcome. Among the patients who completed their engagement and for whom the study could match separate utilization data (151 patients), the study observed a 57% reduction in ED visits. Case managers play a crucial role in the effectiveness of the MVP program by coordinating comprehensive care for high-utilizing ED patients. The MVP program includes transition of care initiatives designed to improve patient outcomes. Through screenings and targeted interventions, case managers identify and address the complex medical, behavioral, and social needs of MVP patients. This collaborative, interdisciplinary approach underscores the importance of timely and coordinated care, benefiting both patients and the health system. The MVP program exemplifies the critical role of case managers in reducing unnecessary ED visits and enhancing overall patient care.

Exploring Thailand as a gastronomic tourism destination: A structural equation model approach

This study aims to construct an integrative model for understanding the factors that shape Chinese tourists’ intentions to visit Thailand as a gastronomic tourism destination. In detail, we investigate the relationships among cognitive experiences, emotional experiences, cultural experiences, affective destination image, cognitive destination image, and the intention to visit Thailand for culinary experiences. Utilizing an online survey method to gather 562 Chinese tourists who have experienced Thai gastronomy, this study continues to use structural equation model to process data. The findings reveal that cognitive, emotional, and cultural experiences significantly influence tourists’ affective and cognitive destination images, positively impacting their intention to visit Thailand for its culinary offerings. The affective and cognitive destination images act as crucial mediators, intricately linking these experiences with travel intentions. This approach improves our understanding of the dynamics involved. It also provides practical insights for developing targeted marketing strategies.

Calibration of a dual-robot collaborative system for drilling tasks on spacecraft core cabins

Purpose This study aims to propose a calibration method to enhance the positioning accuracy in dual-robot collaborative operations, aiming to address the challenge of drilling hole spacing errors in spacecraft core cabin brackets that require an accuracy of less than 0.5 mm. Design/methodology/approach Initially, the cooperative error of dual robots is defined. Subsequently, an integrated model is constructed that encompasses the kinematic model errors of the dual robots, as well as the establishment errors of the base and tool frames. A calibration method for optimizing the cooperative accuracy of dual robots is proposed. Findings The application of the proposed method satisfies the collaborative drilling requirements for the spacecraft core cabin. The average cooperative positioning error of the dual robots was reduced from 0.507 to 0.156 mm, with the maximum value and standard deviation decreasing from 1.020 and 0.202 mm to 0.603 and 0.097 mm, respectively. Drilling experiments conducted on a core cabin simulator demonstrated that after calibration, the maximum hole spacing error was reduced from 1.219 to 0.403 mm, with all spacing errors falling below the 0.5 mm threshold, thus meeting the requirements. Originality/value This paper addresses the drilling accuracy requirements for spacecraft core cabins by using a calibration method to reduce the cooperative error of dual robots. The algorithm has been validated through experiments using ER 220 robots, confirming its effectiveness in fulfilling the drilling task requirements.

Integrative prognostic modeling for stage III lung adenosquamous carcinoma post-tumor resection: machine learning insights and web-based implementation.

The prognostic landscape of stage III Lung Adenosquamous Carcinoma (ASC) following primary tumor resection remains underexplored. A thoughtfully developed prognostic model has the potential to guide clinicians in patient counseling and the formulation of effective therapeutic strategies. Utilizing data from the Surveillance, Epidemiology, and End Results database spanning 2000 to 2018, this study identified independent prognostic factors influencing Overall Survival (OS) in ASC using Boruta analysis. Employing Gradient Boosting, Random Forest, and Neural Network algorithms, predictive models were constructed. Model performance was assessed through key metrics, including Area Under the Receiver Operating Characteristic Curve (AUC), calibration plot, Brier score, and Decision Curve Analysis (DCA). Among 241 eligible patients, seven clinical parameters-age, sex, primary tumor size, N stage, primary tumor site, chemotherapy, and systemic therapy-were identified as significant predictors of OS. Advanced age, male gender, larger tumor size, absence of chemotherapy, and lack of systemic therapy were associated with poorer survival. The Random Forest model outperformed others, achieving 3- and 5-year AUCs of 0.80/0.79 (training) and 0.74/0.65 (validation). It also demonstrated better calibration, lower Brier scores (training: 0.189/0.171; validation: 0.207/0.199), and more favorable DCA. SHAP values enhanced model interpretability by highlighting the impact of each parameter on survival predictions. To facilitate clinical application, the Random Forest model was deployed on a web-based server for accessible prognostic assessments. This study presents a robust machine learning model and a web-based tool that assist healthcare practitioners in personalized clinical decision-making and treatment optimization for ASC patients following primary tumor resection.

Research on the Impact and Strategies of Rail Transit Network Integration in the Context of Metropolitan Area Development: A Case Study of the Wuhan Metropolitan Area

The metropolitan area is one of the key focal points in the construction and development of China’s new urbanization. Urban integration is an emerging trend in metropolitan areas. This paper explores the traffic demand characteristics and economic aspects of rail transit within metropolitan regions and argues that the construction of an integrated urban rail transit network is an effective approach to support their development. Rail transit in metropolitan areas offers both technical and economic advantages, improving the efficiency of time and space resource utilization, fostering economic cooperation, and ultimately contributing to an integrated development model. However, the integration of rail transit networks faces several challenges, including road network planning, technical standards, and operational organization. Using the Wuhan metropolitan area as a case study, this paper analyzes the challenges of rail transit network integration and proposes strategic solutions for development.

On the rate-limiting dynamics of force development in muscle.

Skeletal muscles produce forces relatively slowly compared with the action potentials that excite them. The dynamics of force production are governed by multiple processes, such as calcium activation, cycling of cross-bridges between myofilaments, and contraction against elastic tissues and the body. These processes have been included piecemeal in some muscle models, but not integrated to reveal which are the most rate limiting. We therefore examined their integrative contributions to force development in two conventional types of muscle models: Hill-type and cross-bridge. We found that no combination of these processes can self-consistently reproduce classic data such as twitch and tetanus. Rather, additional dynamics are needed following calcium activation and facilitating cross-bridge cycling, such as for cooperative myofilament interaction and reconfiguration. We provisionally lump such processes into a simple first-order model of 'force facilitation dynamics' that integrate into a cross-bridge-type muscle model. The proposed model self-consistently reproduces force development for a range of excitations including twitch and tetanus and electromyography-to-force curves. The model's step response reveals relatively small timing contributions of calcium activation (3%), cross-bridge cycling (3%) and contraction (27%) to overall force development of human quadriceps, with the remainder (67%) explained by force facilitation. The same set of model parameters predicts the change in force magnitude (gain) and timing (phase delay) as a function of excitatory firing rate, or as a function of cyclic contraction frequency. Although experiments are necessary to reveal the dynamics of muscle, integrative models are useful for identifying the main rate-limiting processes.

Constructing a picture of fatigue in the context of cancer: assessment of construct overlap in common fatigue scales.

Individuals diagnosed with cancer experience multiple inter-related short- and long-term side effects. Chief among such symptomology is cancer-related fatigue (CRF), which, if left unmanaged, can become chronic and result in increased disability and healthcare utilization. A growing number of self-report scales have been developed to measure CRF symptoms based on various theoretical conceptualizations with the aim of promoting targeted assessment and intervention efforts. It may be, however, unwise to assume that the various measures are conceptually similar (i.e., that they assess for the same constructs). Accordingly, we aimed to characterize item content among nine self-report scales, using a Jaccard index to quantify content overlap among scales. We characterized construct assessment among nine self-report scales recommended to assess CRF by a recent clinical practice guideline, and used a Jaccard index to quantify content overlap among scales. Analysis of 208 items across nine rating scales resulted in 20 distinct symptoms of CRF assessed. The most common symptoms were energy level (captured in all nine scales), cognitive function, impaired task performance (in eight scales), sleepiness, and physical function (in seven scales). Mean overlap among all scales was low (Jaccard index = 0.455). Only one construct (duration of fatigue; 5.0%) was captured by a single scale, and one symptom (energy level; 5.0%) was common across all scales. The PFS, MFSI, and BFI each captured at least one symptom from each of the NCCN domains of CRF. CRF scales are heterogeneousin the content they measure, critically impairing integration of knowledge across studies using disparate scales. Future work is urgently needed to build more integrated theoretical and/or computational models of CRF based on relevant mechanisms.

Fatherhood in the context of preterm birth: A narrative review of contemporary research evidence

AbstractLong focused on maternal roles in infancy, research is now exploring fathers' contributions to child development. Current public policy emphasizes early prevention and intervention for child and parent well‐being, especially for at‐risk infants such as those born prematurely. A literature review was conducted following the approach of a narrative review, to examine fatherhood in the context of preterm birth, highlighting the stress and emotional vulnerability experienced by fathers of preterm infants. Promoting early paternal presence and involvement in infant care helps fathers cope with this emotionally challenging experience. Despite limited data on premature fatherhood, fathers are active partners in dyadic interactions and play a significant role in their infant's neonatal intensive care unit journey and family dynamics. The discussion underscores the importance of father‐focused interventions and the paternal contribution to child development, framed within the authors' proposed integrative and developmental model of the family triad.

Development of a spinopelvic complex finite element model for quantitative analysis of the biomechanical response of patients with degenerative spondylolisthesis.

Research on degenerative spondylolisthesis (DS) has focused primarily on the biomechanical responses of pathological segments, with few studies involving muscle modelling in simulated analysis, leading to an emphasis on the back muscles in physical therapy, neglecting the ventral muscles. The purpose of this study was to quantitatively analyse the biomechanical response of the spinopelvic complex and surrounding muscle groups in DS patients using integrative modelling. The findings may aid in the development of more comprehensive rehabilitation strategies for DS patients. Two new finite element spinopelvic complex models with detailed muscles for normal spine and DS spine (L4 forwards slippage) modelling were established and validated at multiple levels. Then, the spinopelvic position parameters including peak stress of the lumbar isthmic-cortical bone, intervertebral discs, and facet joints; peak strain of the ligaments; peak force of the muscles; and percentage difference in the range of motion were analysed and compared under flexion-extension (F-E), lateral bending (LB), and axial rotation (AR) loading conditions between the two models. Compared with the normal spine model, the DS spine model exhibited greater stress and strain in adjacent biological tissues. Stress at the L4/5 disc and facet joints under AR and LB conditions was approximately 6.6 times greater in the DS spine model than in the normal model, the posterior longitudinal ligament peak strain in the normal model was 1/10 of that in the DS model, and more high-stress areas were found in the DS model, with stress notably transferring forwards. Additionally, compared with the normal spine model, the DS model exhibited greater muscle tensile forces in the lumbosacral muscle groups during F-E and LB motions. The psoas muscle in the DS model was subjected to 23.2% greater tensile force than that in the normal model. These findings indicated that L4 anterior slippage and changes in lumbosacral-pelvic alignment affect the biomechanical response of muscles. In summary, the present work demonstrated a certain level of accuracy and validity of our models as well as the differences between the models. Alterations in spondylolisthesis and the accompanying overall imbalance in the spinopelvic complex result in increased loading response levels of the functional spinal units in DS patients, creating a vicious cycle that exacerbates the imbalance in the lumbosacral region. Therefore, clinicians are encouraged to propose specific exercises for the ventral muscles, such as the psoas group, to address spinopelvic imbalance and halt the progression of DS.

From entry to transformation: exploring AI integration in teachers’ K–12 assessment practices

ABSTRACT This study explores the role of artificial intelligence (AI) in K–12 student assessment practices, focusing on educators’ use of AI tools. Through content analysis of active Facebook groups dedicated to AI in education, the authors examined how educators integrate AI into assessment across various grade levels and subjects. Using the Technology Integration Model, they analysed posts to evaluate the use of AI across subjects and grade levels. The findings revealed a progression from initial interest and experimentation with AI to more advanced, adaptive uses in assessment creation and grading. Educators reported positive experiences with AI-driven tools, especially in automating tasks and gamifying assessments. However, challenges such as ensuring reliable, context-specific feedback persist. Overall, the research highlights AI’s potential to enhance student-centred assessment practices and provides insights for educators, administrators and policymakers on AI’s evolving role in education.

Optimal Arrangements and Local Anisotropy of {100} Guinier-Preston (GP) Zones by Parametric Dislocation Dynamics (PDD) Simulations.

Stress-oriented precipitation and the resulting mechanical anisotropy have been widely studied over the decades. However, the local anisotropy of precipitates with specific orientations has been less thoroughly investigated. This study models the interaction between an edge dislocation source and {100} variants of Guinier-Preston (GP) zones in Al-Cu alloys using the parametric dislocation dynamics (PDD) method. Concentric geometrically necessary dislocation (GND) loops were employed to construct a line integral model for thin platelets. The simulations, conducted with our self-developed code based on Green's function method and Eshelby inclusion theory revealed distinct strengthening behavior along the strong and weak directions for 60° GP zones, demonstrating anisotropic strengthening from the perspective of elastic interactions. Furthermore, the optimal inclined arrangement of the GP zone array was determined through elastic energy calculations, and these results were corroborated by TEM observations.

Mind-body medicine and altered states of consciousness in Homo

The mind-body relationship has long been a subject of inquiry from both philosophical and scientific perspectives. Ancient Greek philosophers such as Pythagoras and Plato posited dualistic models, where the mind and body are distinct substances. In contrast, modern approaches in Mind-Body Medicine (MBM) offer integrative models that emphasize the interconnectedness of mental and physical states and the proactive role of the patient in their own healing process. This review examines the evolutionary roots of altered states of consciousness (ASC) as a precursor to current MBM techniques. By tracing ASC to early hominins and their cognitive development, it posits that the ability to enter various ASC—such as those used in rituals, meditation, and other mind-body practices—provided evolutionary advantages, influencing both individual fitness and social cohesion. Moreover, this review discusses tonic immobility in animals as a survival mechanism and explores parallels in human and non-human primate behaviors involving ASC. Additionally, neurochemical pathways that govern ASC, such as serotonergic and dopaminergic regulation, are explored for their roles in promoting social behaviors, cognitive flexibility, and emotional regulation. Furthermore, the role of the default mode network is investigated in relation to psychotropic and mood altering substances and altered states of consciousness. This integrated perspective offers new insights into the origins of MBM and underscores the significance of ASC in both evolutionary and contemporary contexts.

Longitudinal liquid biopsy predicts clinical benefit from immunotherapy in advanced non-small cell lung cancer

High heterogeneity in clinical benefit characterizes the use of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). We prospectively enrolled 113 advanced NSCLC patients treated with ICIs and performed liquid biopsy at the time of ICI start (T1), after 3 weeks (T2) and at the time of radiological evaluation (T3). Molecular variables were associated with outcome endpoints: cfDNA quantification, its dynamic change (∆T2–T1), variant allele frequency (VAF) of the gene with the highest frequency detected at baseline with NGS (maxVAF) and its dynamic change (∆T2–T1). At multivariate analysis, PD-L1 negativity, T1 cfDNA, cfDNA increase (∆T2–T1), and T2 VAF were significantly associated with shorter progression-free survival (PFS); PD-L1 negativity, squamous histology, T1 cfDNA, cfDNA (∆T2–T1) increase, and T2 maxVAF affected overall survival (OS). Among high PD-L1 expressing patients treated in first-line, elevated T2 maxVAF and cfDNA increase (∆T2–T1) correlated with worse PFS; higher T2 maxVAF and cfDNA increase (∆T2–T1) with worse OS. Derived integrated models were used to build nomograms and categorize different risk groups.

Improving weather forecast skill of the Korean Integrated Model by assimilating Soil Moisture Active Passive soil moisture anomalies

Improving weather forecast skill of the Korean Integrated Model by assimilating Soil Moisture Active Passive soil moisture anomalies