Rigidity percolation uncovers a structural basis for embryonic tissue phase transitions.

Embryo morphogenesis is impacted by dynamic changes in tissue material properties, which have been proposed to occur via processes akin to phase transitions (PTs). Here, we show that rigidity percolation provides a simple and robust theoretical framework to predict material/structural PTs of embryonic tissues from local cell connectivity. By using percolation theory, combined with directly monitoring dynamic changes in tissue rheology and cell contact mechanics, we demonstrate that the zebrafish blastoderm undergoes a genuine rigidity PT, brought about by a small reduction in adhesion-dependent cell connectivity below a critical value. We quantitatively predict and experimentally verify hallmarks of PTs, including power-law exponents and associated discontinuities of macroscopic observables. Finally, we show that this uniform PT depends on blastoderm cells undergoing meta-synchronous divisions causing random and, consequently, uniform changes in cell connectivity. Collectively, our theoretical and experimental findings reveal the structural basis of material PTs in an organismal context.

A simplicial epidemic model for COVID-19 spread analysis.

Networks allow us to describe a wide range of interaction phenomena that occur in complex systems arising in such diverse fields of knowledge as neuroscience, engineering, ecology, finance, and social sciences. Until very recently, the primary focus of network models and tools has been on describing the pairwise relationships between system entities. However, increasingly more studies indicate that polyadic or higher-order group relationships among multiple network entities may be the key toward better understanding of the intrinsic mechanisms behind the functionality of complex systems. Such group interactions can be, in turn, described in a holistic manner by simplicial complexes of graphs. Inspired by these recently emerging results on the utility of the simplicial geometry of complex networks for contagion propagation and armed with a large-scale synthetic social contact network (also known as a digital twin) of the population in the U.S. state of Virginia, in this paper, we aim to glean insights into the role of higher-order social interactions and the associated varying social group determinants on COVID-19 propagation and mitigation measures.

X-ray 3D imaging-based microunderstanding of granular mixtures: Stiffness enhancement by adding small fractions of soft particles.

This research focuses on performing ultrasound propagation measurements and micro-X-ray computed tomography (µXRCT) imaging on prestressed granular packings prepared with biphasic mixtures of monodisperse glass and rubber particles at different compositions/fractions. Ultrasound experiments employing piezoelectric transducers, mounted in an oedometric cell (complementing earlier triaxial cell experiments), are used to excite and detect longitudinal ultrasound waves through randomly prepared mixtures of monodisperse stiff/soft particles. While the fraction of the soft particles is increasing linearly from zero, the effective macroscopic stiffness of the granular packings transits nonlinearly and nonmonotonically toward the soft limit, remarkably via an interesting stiffer regime for small rubber fractions between 0.1 ≲ ν ≲ 0.2. The contact network of dense packings, as accessed from µXRCT, plays a key role in understanding this phenomenon, considering the structure of the network, the chain length, the grain contacts, and the particle coordination. While the maximum stiffness is due to surprisingly shortened chains, the sudden drop in elastic stiffness of the mixture packings, at ν ≈ 0.4, is associated with chains of particles that include both glass and rubber particles (soft chains); for ν ≲ 0.3, the dominant chains include only glass particles (hard chains). At the drop, ν ≈ 0.4, the coordination number of glass and rubber networks is approximately four and three, respectively, i.e., neither of the networks are jammed, and the chains need to include particles from another species to propagate information.

A model-based assessment of social isolation practices for COVID-19 outbreak response in residential care facilities.

BACKGROUND: Residential aged-care facilities (RACFs, also called long-term care facilities, aged care homes, or nursing homes) have elevated risks of respiratory infection outbreaks and associated disease burden. During the COVID-19 pandemic, social isolation policies were commonly used in these facilities to prevent and mitigate outbreaks. We refer specifically to general isolation policies that were intended to reduce contact between residents, without regard to confirmed infection status. Such policies are controversial because of their association with adverse mental and physical health indicators and there is a lack of modelling that assesses their effectiveness. METHODS: In consultation with the Australian Government Department of Health and Aged Care, we developed an agent-based model of COVID-19 transmission in a structured population, intended to represent the salient characteristics of a residential care environment. Using our model, we generated stochastic ensembles of simulated outbreaks and compared summary statistics of outbreaks simulated under different mitigation conditions. Our study focuses on the marginal impact of general isolation (reducing social contact between residents), regardless of confirmed infection. For a realistic assessment, our model included other generic interventions consistent with the Australian Government's recommendations released during the COVID-19 pandemic: isolation of confirmed resident cases, furlough (mandatory paid leave) of staff members with confirmed infection, and deployment of personal protective equipment (PPE) after outbreak declaration. RESULTS: In the absence of any asymptomatic screening, general isolation of residents to their rooms reduced median cumulative cases by approximately 27%. However, when conducted concurrently with asymptomatic screening and isolation of confirmed cases, general isolation reduced the median number of cumulative infections by only 12% in our simulations. CONCLUSIONS: Under realistic sets of assumptions, our simulations showed that general isolation of residents did not provide substantial benefits beyond those achieved through screening, isolation of confirmed cases, and deployment of PPE. Our results also highlight the importance of effective case isolation, and indicate that asymptomatic screening of residents and staff may be warranted, especially if importation risk from the outside community is high. Our conclusions are sensitive to assumptions about the proportion of total contacts in a facility accounted for by casual interactions between residents.

The role of vaccine status homophily in the COVID-19 pandemic: a cross-sectional survey with modelling.

BACKGROUND: Vaccine homophily describes non-heterogeneous vaccine uptake within contact networks. This study was performed to determine observable patterns of vaccine homophily, as well as the impact of vaccine homophily on disease transmission within and between vaccination groups under conditions of high and low vaccine efficacy. METHODS: Residents of British Columbia, Canada, aged ≥ 16 years, were recruited via online advertisements between February and March 2022, and provided information about vaccination status, perceived vaccination status of household and non-household contacts, compliance with COVID-19 prevention guidelines, and history of COVID-19. A deterministic mathematical model was used to assess transmission dynamics between vaccine status groups under conditions of high and low vaccine efficacy. RESULTS: Vaccine homophily was observed among those with 0, 2, or 3 doses of the vaccine. Greater homophily was observed among those who had more doses of the vaccine (p < 0.0001). Those with fewer vaccine doses had larger contact networks (p < 0.0001), were more likely to report prior COVID-19 (p < 0.0001), and reported lower compliance with COVID-19 prevention guidelines (p < 0.0001). Mathematical modelling showed that vaccine homophily plays a considerable role in epidemic growth under conditions of high and low vaccine efficacy. Furthermore, vaccine homophily contributes to a high force of infection among unvaccinated individuals under conditions of high vaccine efficacy, as well as to an elevated force of infection from unvaccinated to suboptimally vaccinated individuals under conditions of low vaccine efficacy. INTERPRETATION: The uneven uptake of COVID-19 vaccines and the nature of the contact network in the population play important roles in shaping COVID-19 transmission dynamics.

Analysis of Correlation Effects of Double Mutations in Enzymes: A Revised Residual-Contact Network Clique Model.

The relationship between amino acid mutations and enzyme bioactivity is a significant challenge in modern bio-industrial applications. Despite many successful designs relying on complex correlations among mutations at different enzyme sites, the underlying mechanisms of these correlations still need to be explored. In this study, we introduced a revised version of the residual-contact network clique model to investigate the additive effect of double mutations based on the mutation occurrence topology, secondary structures, and physicochemical properties. The model was applied to a set of 182 double mutations reported in three extensively studied enzymes, and it successfully identified over 90% of additive double mutations and a majority of non-additive double mutations. The calculations revealed that the mutation additivity depends intensely on the studied mutation sites' topology and physicochemical properties. For example, double mutations on irregular secondary structure regions tend to be non-additive. Our method provides valuable tools for facilitating enzyme design and optimization. The code and relevant data are available at Github.

Estimating contact network properties by integrating multiple data sources associated with infectious diseases.

To effectively mitigate the spread of communicable diseases, it is necessary to understand the interactions that enable disease transmission among individuals in a population; we refer to the set of these interactions as a contact network. The structure of the contact network can have profound effects on both the spread of infectious diseases and the effectiveness of control programs. Therefore, understanding the contact network permits more efficient use of resources. Measuring the structure of the network, however, is a challenging problem. We present a Bayesian approach to integrate multiple data sources associated with the transmission of infectious diseases to more precisely and accurately estimate important properties of the contact network. An important aspect of the approach is the use of the congruence class models for networks. We conduct simulation studies modeling pathogens resembling SARS-CoV-2 and HIV to assess the method; subsequently, we apply our approach to HIV data from the University of California San Diego Primary Infection Resource Consortium. Based on simulation studies, we demonstrate that the integration of epidemiological and viral genetic data with risk behavior survey data can lead to large decreases in mean squared error (MSE) in contact network estimates compared to estimates based strictly on risk behavior information. This decrease in MSE is present even in settings where the risk behavior surveys contain measurement error. Through these simulations, we also highlight certain settings where the approach does not improve MSE.

Circulation of Respiratory Viruses in the City: Towards an Agent-Based Ecosystem model.

Mathematical models play an important role in management of outbreaks of acute respiratory infections (ARI). While such models are generally used to study the spread of a solitary virus, in reality multiple viruses co-circulate in the population. These viruses have been studied in detail, including the course of infection and immune defense mechanisms. We developed an agent-based model, called ABM-ARI, assimilating heterogeneous data and theoretical knowledge into a biologically motivated system, that allows to reproduce the seasonal patterns of ARI incidence and simulate interventions. ABM-ARI uses city-specific data to create a synthetic population and to construct realistic contact networks in different activity settings. Characteristics of infection, immune protection and non-specific resistance were varied between individuals to account for the population heterogeneity. For the calibration, we minimised the normalised mean absolute error between simulated and observed epidemic curves. ABM-ARI was built based on the quantitative assessment of features of predominant respiratory viruses and epidemiological characteristics of the population. It provides a good fit to the observed epidemic curves for different age groups and viruses. We also simulated one-week school closures when student absences were at or above 10%, 20% or 30% and found that only 10% and 20% thresholds resulted in a reduction of the incidence. ABM-ARI has a great potential in tackling the challenge of emerging infections by simulating and evaluating the effectiveness of various interventions.

Behavioral Propagation Based on Passionate Psychology on Single Networks with Limited Contact.

Passionate psychology behavior is a common behavior in everyday society but has been rarely studied on complex networks; so, it needs to be explored in more scenarios. In fact, the limited contact feature network will be closer to the real scene. In this paper, we study the influence of sensitive behavior and the heterogeneity of individual contact ability in a single-layer limited-contact network, and propose a single-layer model with limited contact that includes passionate psychology behaviors. Then, a generalized edge partition theory is used to study the information propagation mechanism of the model. Experimental results show that a cross-phase transition occurs. In this model, when individuals display positive passionate psychology behaviors, the final spreading scope will show a second-order continuous increase. When the individual exhibits negative sensitive behavior, the final spreading scope will show a first-order discontinuous increase In addition, heterogeneity in individuals' limited contact capabilities alters the speed of information propagation and the pattern of global adoption. Eventually, the outcomes of the theoretic analysis match those of the simulations.

Pathogen transmission modes determine contact network structure, altering other pathogen characteristics.

Pathogen traits can vary greatly and heavily impact the ability of a pathogen to persist in a population. Although this variation is fundamental to disease ecology, little is known about the evolutionary pressures that drive these differences, particularly where they interact with host behaviour. We hypothesized that host behaviours relevant to different transmission routes give rise to differences in contact network structure, constraining the space over which pathogen traits can evolve to maximize fitness. Our analysis of 232 contact networks across mammals, birds, reptiles, amphibians, arthropods, fish and molluscs found that contact network topology varies by contact type, most notably in networks that are representative of fluid-exchange transmission. Using infectious disease model simulations, we showed that these differences in network structure suggest pathogens transmitted through fluid-exchange contact types will need traits associated with high transmissibility to successfully proliferate, compared to pathogens that transmit through other types of contact. These findings were supported through a review of known traits of pathogens that transmit in humans. Our work demonstrates that contact network structure may drive the evolution of compensatory pathogen traits according to transmission strategy, providing essential context for understanding pathogen evolution and ecology.

Contact networks in RNA: a structural bioinformatics study with a new tool.

Base pairing in RNA are significantly rich and versatile due to the potential non-canonical base pairing amongst nucleotides. Not only that, one base in RNA can pair with more than one bases simultaneously. This opens up a new dimension of research to detect such types of base-base pair networks in RNA and to analyze them. Even if a base do not form a pair, it may have significant extent of [Formula: see text]-[Formula: see text] stacking overlap that can stabilize the structures. In this work, we report a software tool, called BPNet, that accepts a mmCIF or PDB file and computes the base-pair/[Formula: see text]-[Formula: see text] contact network components using graph formalism. The software can run on Linux platform in both serial and parallel modes. It generates several information in suitable file formats for visualization of the networks. This paper describes the BPNet software and also presents some interesting results obtained by analyzing several RNA structures by the software to show its effectiveness.

Generating function approach to the effective degree SIR model.

The effective degree SIR model describes the dynamics of diseases with lifetime acquired immunity on a static random contact network. It is typically modeled as a system of ordinary differential equations describing the probability distribution of the infection status of neighbors of a susceptible node. Such a construct may not be used to study networks with an infinite degree distribution, such as an infinite scale-free network. We propose a new generating function approach to rewrite the effective degree SIR model as a nonlinear transport type partial differential equation. We show the existence and uniqueness of the solutions the are biologically relevant. In addition we show how this model may be reduced to the Volz model with the assumption that the infection statuses of the neighbors of an susceptible node are initially independent to each other. This paper paves the way to study the stability of the disease-free steady state and the disease threshold of the infinite dimensional effective degree SIR models.

Contact network analysis of COVID-19 Delta variant outbreak in urban China -based on 2,050 confirmed cases in Xi'an, China.

BACKGROUND: The purpose of this paper is to study how the Delta variant spread in a China city, and to what extent the non-pharmaceutical prevention measures of local government be effective by reviewing the contact network of COVID-19 cases in Xi'an, China. METHODS: We organize the case reports of the Shaanxi Health Commission into a database by text coding and convert them into a network matrix. Then we construct a dynamic contact network for the corresponding analysis and calculate network indicators. we analyze the cases' dynamic contact network structure and intervals between diagnosis time and isolation time by using data visualization, network analysis method, and Ordinary Least Square (OLS) regression. RESULTS: The contact network for this outbreak in Xi'an is very sparse, with a density of less than 0.0001. The contact network is a scale-free network. The average degree centrality is 0.741 and the average PageRank score is 0.0005. The network generated from a single source of infection contains 1371 components. We construct three variables of intervals and analyze the trend of intervals during the outbreak. The mean interval (interval 1) between case diagnosis time and isolation time is - 3.9 days. The mean of the interval (interval 2) between the infector's diagnosis time and the infectee's diagnosis time is 4.2 days. The mean of the interval (interval 3) between infector isolation time and infectee isolation time is 2.9 days. Among the three intervals, only interval 1 has a significant positive correlation with degree centrality. CONCLUSIONS: By integrating COVID-19 case reports of a Chinese city, we construct a contact network to analyze the dispersion of the outbreak. The network is a scale-free network with multiple hidden pathways that are not detected. The intervals of patients in this outbreak decreased compared to the beginning of the outbreak in 2020. City lockdown has a significant effect on the intervals that can affect patients' network centrality. Our study highlights the value of case report text. By linking different reports, we can quickly analyze the spread of the epidemic in an urban area.

Transmission characteristic and dynamic analysis of COVID-19 on contact network with Tianjin city in China.

The outbreak of 2019 novel coronavirus pneumonia (COVID-19) has had a profound impact on people's lives around the world, and the spread of COVID-19 between individuals were mainly caused by contact transmission of the social networks. In order to analyze the network transmission of COVID-19, we constructed a case contact network using available contact data of 136 early diagnosed cases in Tianjin. Based on the constructed case contact network, the structural characteristics of the network were first analyzed, and then the centrality of the nodes was analyzed to find the key nodes. In addition, since the constructed network may contain missing edges and false edges, link prediction algorithms were used to reconstruct the network. Finally, to understand the spread of COVID-19 in the network, an individual-based susceptible-latent-exposed-infected-recover (SLEIR) model is established and simulated in the network. The results showed that the disease peak scale caused by the node with the highest centrality is larger, and reducing the contact infection rate of the infected person during the incubation period has a greater impact on the peak disease scale.

Sequence and Structure-Based Analyses of Human Ankyrin Repeats.

Ankyrin is one of the most abundant protein repeat families found across all forms of life. It is found in a variety of multi-domain and single domain proteins in humans with diverse number of repeating units. They are observed to occur in several functionally diverse proteins, such as transcriptional initiators, cell cycle regulators, cytoskeletal organizers, ion transporters, signal transducers, developmental regulators, and toxins, and, consequently, defects in ankyrin repeat proteins have been associated with a number of human diseases. In this study, we have classified the human ankyrin proteins into clusters based on the sequence similarity in their ankyrin repeat domains. We analyzed the amino acid compositional bias and consensus ankyrin motif sequence of the clusters to understand the diversity of the human ankyrin proteins. We carried out network-based structural analysis of human ankyrin proteins across different clusters and showed the association of conserved residues with topologically important residues identified by network centrality measures. The analysis of conserved and structurally important residues helps in understanding their role in structural stability and function of these proteins. In this paper, we also discuss the significance of these conserved residues in disease association across the human ankyrin protein clusters.

A knowledge graph-based method for epidemic contact tracing in public transportation.

Contact tracing is an effective measure by which to prevent further infections in public transportation systems. Considering the large number of people infected during the COVID-19 pandemic, digital contact tracing is expected to be quicker and more effective than traditional manual contact tracing, which is slow and labor-intensive. In this study, we introduce a knowledge graph-based framework for fusing multi-source data from public transportation systems to construct contact networks, design algorithms to model epidemic spread, and verify the validity of an effective digital contact tracing method. In particular, we take advantage of the trip chaining model to integrate multi-source public transportation data to construct a knowledge graph. A contact network is then extracted from the constructed knowledge graph, and a breadth-first search algorithm is developed to efficiently trace infected passengers in the contact network. The proposed framework and algorithms are validated by a case study using smart card transaction data from transit systems in Xiamen, China. We show that the knowledge graph provides an efficient framework for contact tracing with the reconstructed contact network, and the average positive tracing rate is over 96%.

Transmission networks and ectoparasite mite burdens in Oecomys paricola (Rodentia: Cricetidae).

The host contact network structure results from the movement and behaviour of hosts (e.g. degree of sociability; vagility and greater or lesser fidelity of shelters), which can generate heterogeneity in the transmission of parasites and influence the parasitic burden of individual hosts. In the current study, we tested the hypothesis that the burdens of Gigantolaelaps oudemansi mites are related to the characteristics of the transmission networks of individuals of Oecomys paricola, a solitary rodent. The study was carried out in a savannah habitat in north-eastern Brazil. In the dry season, the rodent network presented sub-groups of rodent individuals interacting with each other, whereas in the wet season, no modules were formed in the network. Mite burden was positively related to the number of connections that an individual host had with other host individuals in the dry season. The pairwise absolute difference between the mean mite burdens among individual rodents was negatively correlated with the similarities of node interactions. No relationships were observed during the wet season. There was a higher heterogeneity of mite burden among hosts in the dry season compare to that in the wet season. In solitary species, spatial organization may show seasonal variation, causing a change in the opportunities of host contacts, thereby influencing the transmission and dispersion of their ectoparasite burdens.

COVID-19 Lockdowns May Reduce Resistance Genes Diversity in the Human Microbiome and the Need for Antibiotics.

Recently, much attention has been paid to the COVID-19 pandemic. Yet bacterial resistance to antibiotics remains a serious and unresolved public health problem that kills hundreds of thousands of people annually, being an insidious and silent pandemic. To contain the spreading of the SARS-CoV-2 virus, populations confined and tightened hygiene measures. We performed this study with computer simulations and by using mobility data of mobile phones from Google in the region of Lisbon, Portugal, comprising 3.7 million people during two different lockdown periods, scenarios of 40 and 60% mobility reduction. In the simulations, we assumed that the network of physical contact between people is that of a small world and computed the antibiotic resistance in human microbiomes after 180 days in the simulation. Our simulations show that reducing human contacts drives a reduction in the diversity of antibiotic resistance genes in human microbiomes. Kruskal-Wallis and Dunn's pairwise tests show very strong evidence (p < 0.000, adjusted using the Bonferroni correction) of a difference between the four confinement regimes. The proportion of variability in the ranked dependent variable accounted for by the confinement variable was η2 = 0.148, indicating a large effect of confinement on the diversity of antibiotic resistance. We have shown that confinement and hygienic measures, in addition to reducing the spread of pathogenic bacteria in a human network, also reduce resistance and the need to use antibiotics.

Individual Specialization and Multihost Epidemics: Disease Spread in Plant-Pollinator Networks.

Many parasites infect multiple species and persist through a combination of within- and between-species transmission. Multispecies transmission networks are typically constructed at the species level, linking two species if any individuals of those species interact. However, generalist species often consist of specialized individuals that prefer different subsets of available resources, so individual- and species-level contact networks can differ systematically. To explore the epidemiological impacts of host specialization, we build and study a model for pollinator pathogens on plant-pollinator networks, in which individual pollinators have dynamic preferences for different flower species. We find that modeling and analysis that ignore individual host specialization can predict die-off of a disease that is actually strongly persistent and can badly over- or underpredict steady-state disease prevalence. Effects of individual preferences remain substantial whenever mean preference duration exceeds half of the mean time from infection to recovery or death. Similar results hold in a model where hosts foraging in different habitats have different frequencies of contact with an environmental reservoir for the pathogen. Thus, even if all hosts have the same long-run average behavior, dynamic individual differences can profoundly affect disease persistence and prevalence.

Optimizing COVID-19 surveillance in long-term care facilities: a modelling study.

BACKGROUND: Long-term care facilities (LTCFs) are vulnerable to outbreaks of coronavirus disease 2019 (COVID-19). Timely epidemiological surveillance is essential for outbreak response, but is complicated by a high proportion of silent (non-symptomatic) infections and limited testing resources. METHODS: We used a stochastic, individual-based model to simulate transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) along detailed inter-individual contact networks describing patient-staff interactions in a real LTCF setting. We simulated distribution of nasopharyngeal swabs and reverse transcriptase polymerase chain reaction (RT-PCR) tests using clinical and demographic indications and evaluated the efficacy and resource-efficiency of a range of surveillance strategies, including group testing (sample pooling) and testing cascades, which couple (i) testing for multiple indications (symptoms, admission) with (ii) random daily testing. RESULTS: In the baseline scenario, randomly introducing a silent SARS-CoV-2 infection into a 170-bed LTCF led to large outbreaks, with a cumulative 86 (95% uncertainty interval 6-224) infections after 3 weeks of unmitigated transmission. Efficacy of symptom-based screening was limited by lags to symptom onset and silent asymptomatic and pre-symptomatic transmission. Across scenarios, testing upon admission detected just 34-66% of patients infected upon LTCF entry, and also missed potential introductions from staff. Random daily testing was more effective when targeting patients than staff, but was overall an inefficient use of limited resources. At high testing capacity (> 10 tests/100 beds/day), cascades were most effective, with a 19-36% probability of detecting outbreaks prior to any nosocomial transmission, and 26-46% prior to first onset of COVID-19 symptoms. Conversely, at low capacity (< 2 tests/100 beds/day), group testing strategies detected outbreaks earliest. Pooling randomly selected patients in a daily group test was most likely to detect outbreaks prior to first symptom onset (16-27%), while pooling patients and staff expressing any COVID-like symptoms was the most efficient means to improve surveillance given resource limitations, compared to the reference requiring only 6-9 additional tests and 11-28 additional swabs to detect outbreaks 1-6 days earlier, prior to an additional 11-22 infections. CONCLUSIONS: COVID-19 surveillance is challenged by delayed or absent clinical symptoms and imperfect diagnostic sensitivity of standard RT-PCR tests. In our analysis, group testing was the most effective and efficient COVID-19 surveillance strategy for resource-limited LTCFs. Testing cascades were even more effective given ample testing resources. Increasing testing capacity and updating surveillance protocols accordingly could facilitate earlier detection of emerging outbreaks, informing a need for urgent intervention in settings with ongoing nosocomial transmission.