Pattern Mining-Based Pig Behavior Analysis for Health and Welfare Monitoring.

The increasing popularity of pigs has prompted farmers to increase pig production to meet the growing demand. However, while the number of pigs is increasing, that of farm workers has been declining, making it challenging to perform various farm tasks, the most important among them being managing the pigs' health and welfare. This study proposes a pattern mining-based pig behavior analysis system to provide visualized information and behavioral patterns, assisting farmers in effectively monitoring and assessing pigs' health and welfare. The system consists of four modules: (1) data acquisition module for collecting pigs video; (2) detection and tracking module for localizing and uniquely identifying pigs, using tracking information to crop pig images; (3) pig behavior recognition module for recognizing pig behaviors from sequences of cropped images; and (4) pig behavior analysis module for providing visualized information and behavioral patterns to effectively help farmers understand and manage pigs. In the second module, we utilize ByteTrack, which comprises YOLOx as the detector and the BYTE algorithm as the tracker, while MnasNet and LSTM serve as appearance features and temporal information extractors in the third module. The experimental results show that the system achieved a multi-object tracking accuracy of 0.971 for tracking and an F1 score of 0.931 for behavior recognition, while also highlighting the effectiveness of visualization and pattern mining in helping farmers comprehend and manage pigs' health and welfare.

A systems approach to assist policy action to prevent falls among community-dwelling older people in Australia.

OBJECTIVES: While systems thinking has gained recognition as an important approach in health policy and prevention research, its application in the context of fall prevention among community-dwelling older adults has been underutilised. Here, we build on the guiding principles of the systemic lens component of the Prevention System Change Framework to assess and identify potential changes that are required to facilitate policy action in the field of falls prevention. METHODS: We conducted a desktop search to identify policy documents encompassing falls prevention among community-dwelling older adults in Australia. Documents were considered eligible if they were published in the last 10 years and were authored or endorsed by federal or state government bodies. We collaboratively examined eligible documents to gain insights into the current policy landscape in falls prevention and to illustrate opportunities for action and the potential for strengthening partnerships. RESULTS: There is no current national policy on preventing falls in older adults in Australia. While we identified eight policy documents, none focused exclusively on falls prevention, indicating that falls are currently not perceived as a public health issue that warrants a dedicated policy framework. We identified a need for a comprehensive national policy that draws upon insights from various disciplines, suggests intersectoral collaboration, addresses health inequities and involves meaningful engagement with key stakeholders. Future falls prevention policies may benefit from clear governance structures and specific targets, along with mechanisms for monitoring and evaluating outcomes. CONCLUSION: Falls prevention is a pressing public health concern that requires dedicated policy resources. Adopting a systems-oriented approach can help reduce falls and their associated burdens on individuals and the healthcare system. Acknowledging the urgency and complexity of this challenge is a first, essential step toward crafting a comprehensive national falls prevention policy.

Lessons Learned from Cross-Systems Approach to COVID-19 Pandemic Response in Juvenile Justice System, Colorado, USA.

The global COVID-19 pandemic illustrates the importance of a close partnership between public health and juvenile justice systems when responding to communicable diseases. Many setting-specific obstacles must be navigated to respond effectively to limit disease transmission and negative health outcomes while maintaining necessary services for youth in confinement facilities. The response requires multidisciplinary expertise and collaboration to address unique considerations. Public health mitigation strategies must balance the risk for disease against the negative effects of restrictions. Key aspects of the COVID-19 response in the juvenile justice system of Colorado, USA, involved establishing robust communication and data reporting infrastructures, building a multidisciplinary response team, adapting existing infection prevention guidelines, and focusing on a whole-person health approach to infection prevention. We examine lessons learned and offer recommendations on pandemic emergency response planning and managing a statewide public health emergency in youth confinement settings that ensure ongoing readiness.

Systems approach in planetary health education for medical students: a mixed methods study.

BACKGROUND: Introducing students to the "planetary health lenses" perspective is crucial. Comprehensive strategies for teaching this perspective are lacking, especially in the domains of "interconnection within nature (IWN)" and "systems thinking/complexity." There is also a scarcity of studies assessing medical students' opinions on planetary health and evaluating teaching strategies. OBJECTIVE: To understand Brazilian medical students' perceptions and knowledge of planetary health (PH) and evaluate the application of the educational material "Patient and Clinic through the Lens of Planetary Health," which addresses "IWN" and "complexity" through the sociological lens of Actor-Network Theory, in an integrative course at a medical school in Brazil. METHODS: A mixed-methods, quasi-experimental design involving two medical student classes during 2022/2023. Participants completed a questionnaire on sociodemographic data; pre- and post-intervention closed-ended questions about perceptions related to PH, and an open-ended questionnaire on experience and learning. Each student group presented a portfolio under the planetary health lenses regarding a real patient, developing a network diagram that described the social network involving both human and non-human actors with which this person is interconnected. The cohorts participated in "IWN" activities: a contemplative trail or reflection on belonging to the planet. RESULTS: Ninety-six students and 9 professors participated. The majority of students (66.7%) reported significant or extremely significant learning from the sessions. There was an increase in perception of the need for physicians to incorporate PH into their clinical practice (p = 0.002; r = 0.46) and an intensification of the sense of interconnection with the environment (p = 0.003; r = 0.46). There was a gain in knowledge about how many diseases were related to PH (p < 0.02 for all 13 listed diseases). The majority (83%) found the sessions relevant or highly relevant and commented on their impact, both professionally and personally. CONCLUSIONS: Teaching PH in a medical school allowed students to learn from the patient's perspective, considering psychosocial and environmental determinants, about the intrinsic interdependence between population's health and PH. This strategy made a significant contribution by proposing pioneering didactics and offering valuable insights into the challenges and nuances of teaching PH.

PERSIST: a pre-post study to assess an educational methodology to enhance youth climate literacy and systems thinking ability.

BACKGROUND: Education has a pivotal role in preparing society to address the forthcoming health impacts of the climate crisis. Education provides the tools necessary to instil both individual and collective attitudes for mitigating climate change, fosters the development of adaptive skills and mindsets, and promotes a critical understanding of climate change. The aim of the PERSIST project was to assess the effectiveness of a school educational intervention to strengthen literacy on the climate crisis, pro-environmental behaviours, and systems thinking in high school students (aged 14-18 years). METHODS: Three meetings were carried out in a scientific high school in the suburbs of Rome (Italy) between March 21, and April 12, 2023, using complex systems models, group activities, and collective discussions. Pre-intervention and post-intervention questionnaires were administered to students to record knowledge, climate-related emotions, and pro-environmental behaviours. Questionnaires that were complete were considered valid. The anonymously collected data were processed using descriptive statistics and t test. FINDINGS: A total of 273 students in ten different classes attending between grades 1 and 4 took part in the project. 78 (36%) participants were female, 133 (62%) were male, and four (2%) did not disclose their gender. The mean age was 15 years. We received 211 pairs of valid pre-intervention and post-intervention questionnaires. The preliminary analysis showed an average increase of 19% in correct responses to knowledge questions, a 21·2% increase in pro-environmental behaviours, and no discernible differences in climate-related emotions between pre-intervention and post-intervention questionnaires. INTERPRETATION: An interactive approach and the use of complex systems might improve students' literacy and attitudes towards the climate crisis, without increasing negative ecological emotions. This pilot project can guide similar, repeatable programmes in other schools and countries and it represents the first measure of climate-related emotions after school intervention. FUNDING: None.

Temporal meta-optimiser based sensitivity analysis (TMSA) for agent-based models and applications in children's services.

With current and predicted economic pressures within English Children's Services in the UK, there is a growing discourse around the development of methods of analysis using existing data to make more effective interventions and policy decisions. Agent-Based modelling shows promise in aiding in this, with limitations that require novel methods to overcome. This can include challenges in managing model complexity, transparency, and validation; which may deter analysts from implementing such Agent-Based simulations. Children's Services specifically can gain from the expansion of modelling techniques available to them. Sensitivity analysis is a common step when analysing models that currently has methods with limitations regarding Agent-Based Models. This paper outlines an improved method of conducting Sensitivity Analysis to enable better utilisation of Agent-Based models (ABMs) within Children's Services. By using machine learning based regression in conjunction with the Nomadic Peoples Optimiser (NPO) a method of conducting sensitivity analysis tailored for ABMs is achieved. This paper demonstrates the effectiveness of the approach by drawing comparisons with common existing methods of sensitivity analysis, followed by a demonstration of an improved ABM design in the target use case.

Systematic analysis of cuproptosis abnormalities and functional significance in cancer.

BACKGROUND: Cuproptosis is a recently discovered type of cell death, but the role and behavior of cuproptosis-related genes (CuRGs) in cancers remain unclear. This paper aims to address these issues by analyzing the multi-omics characteristics of cancer-related genes (CuRGs) across various types of cancer. METHOD: To investigate the impact of somatic copy number alterations (SCNA) and DNA methylation on CRG expression, we will analyze the correlation between these factors. We developed a cuproptosis index (CPI) model to measure the level of cuproptosis and investigate its functional roles. Using this model, we assessed the clinical prognosis of colorectal cancer patients and analyzed genetic changes and immune infiltration features in different CPI levels. RESULTS: The study's findings indicate that the majority of cancer-related genes (CuRGs) were suppressed in tumors and had a positive correlation with somatic copy number alterations (SCNA), while having a negative correlation with DNA methylation. This suggests that both SCNA and DNA methylation have an impact on the expression of CuRGs. The CPI model is a reliable predictor of survival outcomes in patients with colorectal cancer and can serve as an independent prognostic factor. Patients with a higher CPI have a worse prognosis. We conducted a deeper analysis of the genetic alterations and immune infiltration patterns in both CPI positive and negative groups. Our findings revealed significant differences, indicating that CuRGs may play a crucial role in tumor immunity mechanisms. Additionally, we have noticed a positive correlation between CuRGs and various crucial pathways that are linked to the occurrence, progression, and metastasis of tumors. CONCLUSIONS: Overall, our study systematically analyzes cuproptosis and its regulatory genes, emphasizing the potential of using cuproptosis as a basis for cancer therapy.

Systems analysis of innate and adaptive immunity in Long COVID.

Since the onset of the COVID-19 pandemic, significant progress has been made in developing effective preventive and therapeutic strategies against severe acute SARS-CoV-2 infection. However, the management of Long COVID (LC), an infection-associated chronic condition that has been estimated to affect 5-20% of individuals following SARS-CoV-2 infection, remains challenging due to our limited understanding of its mechanisms. Although LC is a heterogeneous disease that is likely to have several subtypes, immune system disturbances appear common across many cases. The extent to which these immune perturbations contribute to LC symptoms, however, is not entirely clear. Recent advancements in multi-omics technologies, capable of detailed, cell-level analysis, have provided valuable insights into the immune perturbations associated with LC. Although these studies are largely descriptive in nature, they are the crucial first step towards a deeper understanding of the condition and the immune system's role in its development, progression, and resolution. In this review, we summarize the current understanding of immune perturbations in LC, covering both innate and adaptive immune responses, and the cytokines and analytes involved. We explore whether these findings support or challenge the primary hypotheses about LC's underlying mechanisms. We also discuss the crosstalk between various immune system components and how it can be disrupted in LC. Finally, we emphasize the need for more tissue- and subtype-focused analyses of LC, and for enhanced collaborative efforts to analyze common specimens from large cohorts, including those undergoing therapeutic interventions. These collective efforts are vital to unravel the fundaments of this new disease, and could also shed light on the prevention and treatment of the larger family of chronic illnesses linked to other microbial infections.

Tailoring functional two-dimensional nanohybrids: A comprehensive approach for enhancing photocatalytic remediation.

Photocatalysis is gaining prominence as a viable alternative to conventional biohazard treatment technologies. Two-dimensional (2D) nanomaterials have become crucial for fabricating novel photocatalysts due to their nanosheet architectures, large surface areas, and remarkable physicochemical properties. Furthermore, a variety of applications are possible with 2D nanomaterials, either in combination with other functional nanoparticles or by utilizing their inherent properties. Henceforth, the review commences its exploration into the synthesis of these materials, delving into their inherent properties and assessing their biocompatibility. Subsequently, an overview of mechanisms involved in the photocatalytic degradation of pollutants and the processes related to antimicrobial action is presented. As an integral part of our review, we conduct a systematic analysis of existing challenges and various types of 2D nanohybrid materials tailored for applications in the photocatalytic degradation of contaminants and the inactivation of pathogens through photocatalysis. This investigation will aid to contribute to the formulation of decision-making criteria and design principles for the next generation of 2D nanohybrid materials. Additionally, it is crucial to emphasize that further research is imperative for advancing our understanding of 2D nanohybrid materials.

The importance of incorporating systems thinking and One Health in global health classrooms: findings from a One Health simulation activity.

There are several challenges and opportunities in health education in global health. Given the field's rapid expansion, demand for including systems thinking and One Health (a unifying approach that considers human, animal, and environmental health) in global health courses has recently increased. Simulation activities provide an avenue to attain and assess learning objectives that foster critical and systems thinking. This study carried out a One Health simulation activity in an undergraduate global health course, conducted a focus group discussion, and obtained responses from written questionnaires from students who participated in the activity. Data were analyzed using thematic analysis. Results show that the One Health simulation was instrumental for students to understand the complex interactions between different actors and stakeholders in global health systems. The One Health simulation also improved class dynamics, peer-to-peer interactions, and collaborations in the remaining part of the course. The activity helped assess two of the critical thinking learning objectives of the course, and there was some evidence that student agency and confidence may have been improved. Evidence shows that the activity helped students understand the principles of systems thinking and apply them in complex scenarios. Findings support including interactive simulation activities in global health courses to include elements of system science and One Health into classroom activities innovatively and engagingly.

Sex Workers in Canada Face Unequal Access to Healthcare: A Systems Thinking Approach.

OBJECTIVES: Despite Canada's universal health system, sex workers across the country face an alarmingly high number of barriers when they seek to healthcare services. This has resulted in unmet healthcare needs and substantially poorer health outcomes than the general Canadian population. The objective of this study was to use a systems thinking approach to gain an in-depth understanding of the barriers sex workers face and how access could be improved. METHODS: The analysis was conducted using a systems thinking methodology, which incorporates systems tools and inquiry processes. The methodology comprised 2 domains of inquiry: (1) Problem Landscape, (2) Solutions Landscape. Systems tools and methods, such as causal loop diagrams, iceberg diagram, and systems mapping, investigated the problem landscape for understanding the interconnected nature of the issue, alongside review of both published and gray literature. An environmental scan explored the current solutions landscape. These methods connected through systemic inquiry processes, including ongoing review and application of diverse perspectives, boundary judgments, interrelationships; enabled gaps and levers of change to be determined. RESULTS: The main barriers sex workers face are stigma, criminalization, accessibility, and cost of healthcare. The stigma of sex work stems from otherization, paternalism, and moralistic, faith-based beliefs. The barriers unique to sex work are stigma and criminalization; both of which surface as avoidance, dislike, and/or fear of medical professionals. Five gaps each with a lever of change to improve access were identified: (1) Stigma - Collectivization and external collaboration, (2) Criminal status of sex work - Decriminalization, (3) Lack of adequate education - Improved healthcare professional training and anti-discriminatory health policies, (4) Lack of support - Increased community-based healthcare services, (5) Cost of healthcare - Universal coverage of "secondary" healthcare components. CONCLUSION: Through reducing the stigma surrounding sex work, making changes that improve the healthcare services that sex workers receive, and collaboration between involved parties, sex workers can be prevented from falling through the cracks of the Canadian healthcare system; lessening the health inequities sex workers face and improving their health outcomes.

Adoption of C-reactive protein rapid tests for the management of acute childhood infections in hospitals in the Netherlands and England: a comparative health systems analysis.

BACKGROUND: The adoption of C-reactive protein point-of-care tests (CRP POCTs) in hospitals varies across Europe. We aimed to understand the factors that contribute to different levels of adoption of CRP POCTs for the management of acute childhood infections in two countries. METHODS: Comparative qualitative analysis of the implementation of CRP POCTs in the Netherlands and England. The study was informed by the non-adoption, abandonment, spread, scale-up, and sustainability (NASSS) framework. Data were collected through document analysis and qualitative interviews with stakeholders. Documents were identified by a scoping literature review, search of websites, and through the stakeholders. Stakeholders were sampled purposively initially, and then by snowballing. Data were analysed thematically. RESULTS: Forty-one documents resulted from the search and 46 interviews were conducted. Most hospital healthcare workers in the Netherlands were familiar with CRP POCTs as the tests were widely used and trusted in primary care. Moreover, although diagnostics were funded through similar Diagnosis Related Group reimbursement mechanisms in both countries, the actual funding for each hospital was more constrained in England. Compared to primary care, laboratory-based CRP tests were usually available in hospitals and their use was encouraged in both countries because they were cheaper. However, CRP POCTs were perceived as useful in some hospitals of the two countries in which the laboratory could not provide CRP measures 24/7 or within a short timeframe, and/or in emergency departments where expediting patient care was important. CONCLUSIONS: CRP POCTs are more available in hospitals in the Netherlands because of the greater familiarity of Dutch healthcare workers with the tests which are widely used in primary care in their country and because there are more funding constraints in England. However, most hospitals in the Netherlands and England have not adopted CRP POCTs because the alternative CRP measurements from the hospital laboratory are available in a few hours and at a lower cost.

In silico agent-based modeling approach to characterize multiple in vitro tuberculosis infection models.

In vitro models of Mycobacterium tuberculosis (Mtb) infection are a valuable tool for examining host-pathogen interactions and screening drugs. With the development of more complex in vitro models, there is a need for tools to help analyze and integrate data from these models. To this end, we introduce an agent-based model (ABM) representation of the interactions between immune cells and bacteria in an in vitro setting. This in silico model was used to simulate both traditional and spheroid cell culture models by changing the movement rules and initial spatial layout of the cells in accordance with the respective in vitro models. The traditional and spheroid simulations were calibrated to published experimental data in a paired manner, by using the same parameters in both simulations. Within the calibrated simulations, heterogeneous outputs are seen for bacterial count and T cell infiltration into the macrophage core of the spheroid. The simulations also predict that equivalent numbers of activated macrophages do not necessarily result in similar bacterial reductions; that host immune responses can control bacterial growth in both spheroid structure dependent and independent manners; that STAT1 activation is the limiting step in macrophage activation in spheroids; and that drug screening and macrophage activation studies could have different outcomes depending on the in vitro culture used. Future model iterations will be guided by the limitations of the current model, specifically which parts of the output space were harder to reach. This ABM can be used to represent more in vitro Mtb infection models due to its flexible structure, thereby accelerating in vitro discoveries.

A novel framework for human factors analysis and classification system for medical errors (HFACS-MES)-A Delphi study and causality analysis.

The healthcare system (HCS) is one of the most crucial and essential systems for humanity. Currently, supplying the patients' safety and preventing the medical adverse events (MAEs) in HCS is a global issue. Human and organizational factors (HOFs) are the primary causes of MAEs. However, there are limited analytical methods to investigate the role of these factors in medical errors (MEs). The aim of present study was to introduce a new and applicable framework for the causation of MAEs based on the original HFACS. In this descriptive-analytical study, HOFs related to MEs were initially extracted through a comprehensive literature review. Subsequently, a Delphi study was employed to develop a new human factors analysis and classification system for medical errors (HFACS-MEs) framework. To validate this framework in the causation and analysis of MEs, 180 MAEs were analyzed by using HFACS-MEs. The results showed that the new HFACS-MEs model comprised 5 causal levels and 25 causal categories. The most significant changes in HFACS-MEs compared to the original HFACS included adding a fifth causal level, named "extra-organizational issues", adding the causal categories "management of change" (MOC) and "patient safety culture" (PSC) to fourth causal level", adding "patient-related factors (PRF)" and "task elements" to second causal level and finally, appending "situational violations" to first causal level. Causality analyses among categories in the HFACS-MEs framework showed that the new added causal level (extra-organizational issues) have statistically significant relationships with causal factors of lower levels (Φc≤0.41, p-value≤0.038). Other new causal category including MOC, PSC, PRF and situational violations significantly influenced by the causal categories of higher levels and had an statistically significant effect on the lower-level causal categories (Φc>0.2, p-value<0.05). The framework developed in this study serves as a valuable tool in identifying the causes and causal pathways of MAEs, facilitating a comprehensive analysis of the human factors that significantly impact patient safety within HCS.

Functional connectivity and complexity analyses of resting-state fMRI in pre-adolescents demonstrating the behavioral symptoms of ADHD.

Attention deficit hyperactivity disorder (ADHD) has been characterized by impairments among distributed functional brain networks, e.g., the frontoparietal network (FPN), default mode network (DMN), reward and motivation-related circuits (RMN), and salience network (SAL). In the current study, we evaluated the complexity and functional connectivity (FC) of resting state fMRI (rsfMRI) in pre-adolescents with the behavioral symptoms of ADHD, for pathology-relevant networks. We leveraged data from the Adolescent Brain and Cognitive Development (ABCD) Study. The final study sample included 63 children demonstrating the behavioral features of ADHD and 92 healthy control children matched on age, sex, and pubertal development status. For selected regions in the relevant networks, ANCOVA compared multiscale entropy (MSE) and FC between the groups. Finally, differences in the association between MSE and FC were evaluated. We found significantly reduced MSE along with increased FC within the FPN of pre-adolescents demonstrating the behavior symptoms of ADHD compared to matched healthy controls. Significant partial correlations between MSE and FC emerged in the FPN and RMN in the healthy controls however the association was absent in the participants demonstrating the behavior symptoms of ADHD. The current findings of complexity and FC in ADHD pathology support hypotheses of altered function of inhibitory control networks in ADHD.

Healthy together Victoria and childhood obesity study: effects of a large scale, community-based cluster randomised trial of a systems thinking approach for the prevention of childhood obesity among secondary school students 2014-2016.

BACKGROUND: Healthy Together Victoria (HTV) was a Victorian Government initiative that sought to reduce the prevalence of overweight and obesity through targeting chronic disease risk factors including physical activity, poor diet quality, smoking, and harmful alcohol use. The intervention involved a boosted workforce of > 170 local-level staff in 12 communities; employed to deliver system activation around health and wellbeing for individuals, families and communities. A cluster randomised trial (CRT) of a systems thinking approach to obesity prevention was embedded within HTV. We present the two-year changes in overweight and obesity and associated behaviours among secondary school students across Victoria, Australia. METHODS: Twenty-three geographically bounded areas were randomised to intervention (12 communities) or comparison (11 communities). Randomly selected secondary schools within each community were invited to participate in the trial in 2014 and 2016. Students in Grade 8 (aged approximately 13-15 years) and Grade 10 (aged approximately 15-16 years) at participating schools were recruited using an opt-out approach across July-September 2014 and 2016. Primary outcomes were body mass index (BMI) and waist circumference. Secondary outcomes were physical activity, sedentary behaviour, diet quality, health-related quality of life, and depressive symptoms. Linear mixed models were fit to estimate the intervention effect adjusting for child/school characteristics. RESULTS: There were 4242 intervention children and 2999 control children in the final analysis. For boys, the two-year change showed improvement in intervention versus control for waist circumference (difference in change: - 2.5 cm; 95% confidence interval [CI]: - 4.6, - 0.5) and consumption of sugar-sweetened beverages per day (< 1 serve: 8.5 percentage points; 95% CI: 0.6, 16.5). For girls, there were no statistically significant differences between conditions. CONCLUSIONS: HTV seemed to produce favourable changes in waist circumference and sugar-sweetened beverage consumption for boys, however, no effect on BMI was observed. Although the HTV intervention was cut short, and the period between data collection points was relatively short, the changes observed in HTV contribute to the growing evidence of whole-of-community interventions targeting childhood obesity. TRIAL REGISTRATION: This trial is unregistered. The intervention itself was a policy setting delivered by government and our role was the collection of data to evaluate the effect of this natural experiment. That is, this study was not a trial from the classical point of view and we were not responsible for the intervention.

Quantifying collective motion patterns in mesenchymal cell populations using topological data analysis and agent-based modeling.

Fibroblasts in a confluent monolayer are known to adopt elongated morphologies in which cells are oriented parallel to their neighbors. We collected and analyzed new microscopy movies to show that confluent fibroblasts are motile and that neighboring cells often move in anti-parallel directions in a collective motion phenomenon we refer to as "fluidization" of the cell population. We used machine learning to perform cell tracking for each movie and then leveraged topological data analysis (TDA) to show that time-varying point-clouds generated by the tracks contain significant topological information content that is driven by fluidization, i.e., the anti-parallel movement of individual neighboring cells and neighboring groups of cells over long distances. We then utilized the TDA summaries extracted from each movie to perform Bayesian parameter estimation for the D'Orsgona model, an agent-based model (ABM) known to produce a wide array of different patterns, including patterns that are qualitatively similar to fluidization. Although the D'Orsgona ABM is a phenomenological model that only describes inter-cellular attraction and repulsion, the estimated region of D'Orsogna model parameter space was consistent across all movies, suggesting that a specific level of inter-cellular repulsion force at close range may be a mechanism that helps drive fluidization patterns in confluent mesenchymal cell populations.

Agent-based modeling of the prostate tumor microenvironment uncovers spatial tumor growth constraints and immunomodulatory properties.

Inhibiting androgen receptor (AR) signaling through androgen deprivation therapy (ADT) reduces prostate cancer (PCa) growth in virtually all patients, but response may be temporary, in which case resistance develops, ultimately leading to lethal castration-resistant prostate cancer (CRPC). The tumor microenvironment (TME) plays an important role in the development and progression of PCa. In addition to tumor cells, TME-resident macrophages and fibroblasts express AR and are therefore also affected by ADT. However, the interplay of different TME cell types in the development of CRPC remains largely unexplored. To understand the complex stochastic nature of cell-cell interactions, we created a PCa-specific agent-based model (PCABM) based on in vitro cell proliferation data. PCa cells, fibroblasts, "pro-inflammatory" M1-like and "pro-tumor" M2-like polarized macrophages are modeled as agents from a simple set of validated base assumptions. PCABM allows us to simulate the effect of ADT on the interplay between various prostate TME cell types. The resulting in vitro growth patterns mimic human PCa. Our PCABM can effectively model hormonal perturbations by ADT, in which PCABM suggests that CRPC arises in clusters of resistant cells, as is observed in multifocal PCa. In addition, fibroblasts compete for cellular space in the TME while simultaneously creating niches for tumor cells to proliferate in. Finally, PCABM predicts that ADT has immunomodulatory effects on macrophages that may enhance tumor survival. Taken together, these results suggest that AR plays a critical role in the cellular interplay and stochastic interactions in the TME that influence tumor cell behavior and CRPC development.