A data-driven computational model for obesity-driven diabetes onset and remission through weight loss

Obesity is a major risk factor for the development of type 2 diabetes (T2D), where a sustained weight loss may result in T2D remission in individuals with obesity. To design effective and feasible intervention strategies to prevent or reverse T2D, it is imperative to study the progression of T2D and remission together. Unfortunately, this is not possible through experimental and observational studies. To address this issue, we introduce a data-driven computational model and use human data to investigate the progression of T2D with obesity and remission through weight loss on the same timeline. We identify thresholds for the emergence of T2D and necessary conditions for remission. We explain why remission is only possible within a window of opportunity and the way that window depends on the progression history of T2D, individual's metabolic state, and calorie restrictions. These findings can help to optimize therapeutic intervention strategies for T2D prevention or treatment.</p

FAIR compliant database development for human microbiome data samples

IntroductionSharing microbiome data among researchers fosters new innovations and reduces cost for research. Practically, this means that the (meta)data will have to be standardized, transparent and readily available for researchers. The microbiome data and associated metadata will then be described with regards to composition and origin, in order to maximize the possibilities for application in various contexts of research. Here, we propose a set of tools and protocols to develop a real-time FAIR (Findable. Accessible, Interoperable and Reusable) compliant database for the handling and storage of human microbiome and host-associated data.MethodsThe conflicts arising from privacy laws with respect to metadata, possible human genome sequences in the metagenome shotgun data and FAIR implementations are discussed. Alternate pathways for achieving compliance in such conflicts are analyzed. Sample traceable and sensitive microbiome data, such as DNA sequences or geolocalized metadata are identified, and the role of the GDPR (General Data Protection Regulation) data regulations are considered. For the construction of the database, procedures have been realized to make data FAIR compliant, while preserving privacy of the participants providing the data.Results and discussionAn open-source development platform, Supabase, was used to implement the microbiome database. Researchers can deploy this real-time database to access, upload, download and interact with human microbiome data in a FAIR complaint manner. In addition, a large language model (LLM) powered by ChatGPT is developed and deployed to enable knowledge dissemination and non-expert usage of the database

Depinning of Drops on Inclined Smooth and Topographic Surfaces: Experimental and Lattice Boltzmann Model Study

In this study, the dynamics of initially stationary liquid drops on smooth and topographic inclined silicon surfaces was investigated experimentally and by lattice Boltzmann simulations. The transient contact angles and the critical angle of inclination were measured systematically for different liquids, drop sizes, and surfaces having different wettability and surface roughness. In general, the critical angle of inclination is larger for hydrophilic than for hydrophobic surfaces, irrespective of the liquids, and increases with increasing contact angle hysteresis and decreasing drop sizes. A two-phase liquid–vapor lattice Boltzmann model based on the Shan and Chen approach was developed for two dimensions which incorporates the wetting and topographic characteristics of the surface. The simulation results matched the experimentally found features quantitatively and allowed one to explore the roll-off behavior even in cases that can hardly be accessed experimentally

Using picoliter droplet deposition to track clonal competition in adherent and organoid cancer cell cultures

Abstract Clonal growth and competition underlie processes of key relevance in etiology, progression and therapy response across all cancers. Here, we demonstrate a novel experimental approach, based on multi-color, fluorescent tagging of cell nuclei, in combination with picoliter droplet deposition, to study the clonal dynamics in two- and three-dimensional cell cultures. The method allows for the simultaneous visualization and analysis of multiple clones in individual multi-clonal colonies, providing a powerful tool for studying clonal dynamics and identifying clonal populations with distinct characteristics. Results of our experiments validate the utility of the method in studying clonal dynamics in vitro, and reveal differences in key aspects of clonal behavior of different cancer cell lines in monoculture conditions, as well as in co-cultures with stromal fibroblasts

Scar formation from the perspective of complexity science: A new look at the biological system as a whole

A burn wound is a complex systemic disease at multiple levels. Current knowledge of scar formation after burn injury has come from traditional biological and clinical studies. These are normally focused on just a small part of the entire process, which has limited our ability to sufficiently understand the underlying mechanisms and to predict systems behaviour. Scar formation after burn injury is a result of a complex biological system-wound healing. It is a part of a larger whole. In this self-organising system, many components form networks of interactions with each other. These networks of interactions are typically non-linear and change their states dynamically, responding to the environment and showing emergent long-term behaviour. How molecular and cellular data relate to clinical phenomena, especially regarding effective therapies of burn wounds to achieve minimal scarring, is difficult to unravel and comprehend. Complexity science can help bridge this gap by integrating small parts into a larger whole, such that relevant biological mechanisms and data are combined in a computational model to better understand the complexity of the entire biological system. A better understanding of the complex biological system of post-burn scar formation could bring research and treatment regimens to the next level. The aim of this review/position paper is to create more awareness of complexity in scar formation after burn injury by describing the basic principles of complexity science and its potential for burn care professionals. Declaration of interest: The authors gratefully acknowledge financial support from the Dutch Burns Foundation (DBF), Beverwijk, project 19.105. The authors have no conflicts of interest to declare

Scar formation from the perspective of complexity science: a new look at the biological system as a whole

A burn wound is a complex systemic disease at multiple levels. Current knowledge of scar formation after burn injury has come from traditional biological and clinical studies. These are normally focused on just a small part of the entire process, which has limited our ability to sufficiently understand the underlying mechanisms and to predict systems behaviour. Scar formation after burn injury is a result of a complex biological system-wound healing. It is a part of a larger whole. In this self-organising system, many components form networks of interactions with each other. These networks of interactions are typically non-linear and change their states dynamically, responding to the environment and showing emergent long-term behaviour. How molecular and cellular data relate to clinical phenomena, especially regarding effective therapies of burn wounds to achieve minimal scarring, is difficult to unravel and comprehend. Complexity science can help bridge this gap by integrating small parts into a larger whole, such that relevant biological mechanisms and data are combined in a computational model to better understand the complexity of the entire biological system. A better understanding of the complex biological system of post-burn scar formation could bring research and treatment regimens to the next level. The aim of this review/position paper is to create more awareness of complexity in scar formation after burn injury by describing the basic principles of complexity science and its potential for burn care professionals

The future of burn care from a complexity science perspective

Healthcare is undergoing a profound technological and digital transformation and has become increasingly complex. It is important for burns professionals and researchers to adapt to these developments which may require new ways of thinking and subsequent new strategies. As Einstein has put it: 'We must learn to see the world anew'. The relatively new scientific discipline "Complexity science" can give more direction to this and is the metaphorical open door that should not go unnoticed in view of the burn care of the future. Complexity sciences studies 'why the whole is more than the sum of the parts'. It studies how multiple separate components interact with each other and their environment and how these interactions lead to 'behavior of the system'. Biological systems are always part of smaller and larger systems and exhibit the behavior of adaptivity, hence the name complex adaptive systems. From the perspective of complexity science, a severe burn injury is an extreme disruption of the 'human body system'. But this disruption also applies to the systems at the organ and cellular level. All these systems follow principles of complex systems. Awareness of the scaling process at multilevel helps to understand and manage the complex situation when dealing with severe burn cases. The aim of this paper is to create awareness of the concept of complexity and to demonstrate the value and possibilities of complexity science methods and tools for the future of burn care through examples from preclinical, clinical, and organizational perspective in burn care

Continuous clonal labeling reveals uniform progenitor potential in the adult exocrine pancreas

The tissue dynamics that govern maintenance and regeneration of the pancreas remain largely unknown. In particular, the presence and nature of a cellular hierarchy remains a topic of debate. Previous lineage tracing strategies in the pancreas relied on specific marker genes for clonal labeling, which left other populations untested and failed to account for potential widespread phenotypical plasticity. Here we employed a tracing system that depends on replication-induced clonal marks. We found that, in homeostasis, steady acinar replacement events characterize tissue dynamics, to which all acinar cells have an equal ability to contribute. Similarly, regeneration following pancreatitis was best characterized by an acinar self-replication model because no evidence of a cellular hierarchy was detected. In particular, rapid regeneration in the pancreas was found to be driven by an accelerated rate of acinar fission-like events. These results provide a comprehensive and quantitative model of cell dynamics in the exocrine pancreas