Interaction Patterns Research Articles

Chagas disease is a neglected tropical condition with limited treatment options, emphasizing the need for new antichagasic agents. Cruzipain (CZP), the main cysteine protease of Trypanosoma cruzi, is a validated target; however, achieving strong trypanocidal activity through CZP inhibition remains challenging. In this work, we report a series of novel triazole-based noncovalent CZP inhibitors designed by applying state-of-the-art molecular modeling techniques, showing good potency against isolated CZP combined with effective trypanocidal activity. Structure-activity relationships that define key pharmacodynamic features were elucidated, enabling analogues to translate enzymatic inhibition into cellular effects. The computer-aided design workflow combining molecular docking, molecular dynamics simulations, and binding free-energy calculations was key to reveal conserved interaction patterns within the oxyanion hole and the S1/S1' subsites (Gln19, His162, Trp184) of CZP for the most effective inhibitors. Overall, our findings introduce new 1,2,3-triazole-based antichagasic candidates and clarify molecular determinants influencing the translational gap between enzymatic and cellular activity, contributing with a predictive framework for the rational design of CZP-targeted inhibitors for Chagas disease therapy.

Recurrence related to poor prognosis is a leading cause of mortality in patients with breast cancer (BC). The MammaPrint (MP) genomic assay is designed to stratify recurrence risk and evaluate chemotherapy benefits for early-stage HR+/HER2- BC patients. However, MP fails to reveal spatial tumor morphology and is limited by high costs. In this study, a BC MP cohort is established and CPMP is developed, a weakly supervised agent-attention transformer model, to predict MP recurrence risk from annotation-free BC histopathological slides. CPMP achieves an AUROC of 0.824±0.03 in predicting MP risk groups. CPMP is further leveraged for spatial and morphological analyses to explore histological patterns associated with MP risk groups. The model reveals tumor spatial localization at the whole-slide level and highlights distinct intercellular interaction patterns of MP groups. It also characterizes the diversity in tumor morphology and uncovers MP high-specific, low-specific, and colocalized morphological phenotypes that differ in quantitative cellular composition. Prognostic evaluation in the external cohort exhibits significant stratification of distant metastasis risk (HR: 3.14, p-value=0.0014), underscoring the prognostic power of CPMP. These findings demonstrate the capability of CPMP in MP risk prediction, offering a flexible supplement to genomic risk assessment in early-stage BC.

Azoles are widely used in agriculture to combat fungal pathogens and protect crops. However, their increased use in recent years has raised concerns due to their endocrine-disrupting properties and other toxic effects, posing risks to human, animal, and environmental health. This study sought to characterize the interaction between selected azoles and the androgen receptor (AR) and to assess their impact on the receptor's normal activity. Molecular docking was performed with azoles and dihydrotestosterone (DHT) as reference ligand, followed by molecular mechanics/generalized born surface area (MM/GBSA) analysis of the docked complexes to evaluate their binding affinity with AR. ADMET analysis was conducted for all compounds along with density functional theory calculations, molecular dynamics simulations (MDS), and post-MDS MM/GBSA binding energy calculations for the top six azoles, including DHT, to assess their toxicity, chemical reactivity, structural and conformational stability, mobility, interaction patterns, and binding affinity. Additionally, experimental studies of the top six azoles, based on their affinity for AR, revealed that they inhibited the dimerization of DHT-bound ARs in the cytoplasm and suppressed DHT-induced AR expression. These findings underscore the importance of developing targeted strategies to mitigate the reproductive toxicity of azoles and promote environmental health.

A small-scale three-degree-of-freedom decompression launch experiment method is used to study the flow characteristics in a ventilated cavity at different transverse velocities. The study subjects are three typical head-shaped underwater vehicles: hemispherical, ellipsoidal, and conical. The evolution mechanism of the ventilated shoulder cavity in a vehicle under transverse velocity is investigated, and the effects of transverse velocity and vehicle head shape changes on the cavity are summarized. Research results show that the hemispherical-headed vehicle’s ventilated cavity is prone to cavity pre-positioning, thereby affecting the distribution of the confronted stream surface (CSS) cavity. As the transverse velocity increases, the cavity pre-positioning point disappears, and the degree of deflection in the vehicle’s trajectory increases. The difference between the opposing stream surface (OSS) and the CSS cavities decreases as the cavities shed. The drag effect of the shedding air mass causes a change in the cavity closure angle. At high transverse velocity (vt = 0.6 m/s), the cavity difference between the OSS and CSS of the ellipsoidal vehicle is the largest, and the amount of gas shed at the cavity’s end is the smallest. The initial angle of the closure angle at the cavity end is related to the ability of the air mass near the tube (AMNT) to be drawn in by the head shape of the vehicle. Under the influence of transverse velocity, the shedding cavity deflects toward the OSS. The interaction patterns between the shoulder and tail cavities on vehicles with different head shapes primarily include three modes.

Protein-based bioadhesives are emerging as sustainable alternatives to traditional adhesives, with potential applications in biomedicine, tissue engineering, and electronics. However, challenges such as low adhesive strength, poor substrate and environmental adaptability, and limited recyclability persist. Unlike previous studies that focused on replicating key chemical units, interaction patterns, liquid-liquid phase separation (LLPS), and nano/microscale structures in natural adhesives, a novel strategy is proposed that partially disrupts the noncovalent interactions between polyphenols and proteins through amino acid modulation. This approach facilitates the migration and enrichment of polyphenol adhesive molecules at substrate interfaces along with amino acid, where they synergistically enhance substrate adaptability. The high cohesion and dynamic nature of the resulting network, driven by noncovalent interactions, ensures both high adhesive strength and full recyclability of polyphenol-protein adhesives (PPA). Importantly, this strategy expands the PPA toolbox, incorporating proteins (gelatin, collagen, silk, keratin) and polyphenols (tannic acid, proanthocyanidins, epigallocatechin gallate), broadening their applications in daily-use adhesives, industrial products, and cultural relic restoration across both dry and wet environments. This work enhances the understanding of balancing adhesion and cohesion, providing insights for the design of high-performance bioadhesives.

Rapid environmental change is reshaping freshwater ecosystems, influencing food availability and predator–prey dynamics. This study examined interactions among four freshwater invertebrates—the cnidarian Hydra viridissima (HV), the turbellarians Polycelis felina (PF) and Dugesia gonocephala (DG), and the cladoceran Daphnia magna (DM)—under controlled microcosm conditions. We investigated the effects of temperature, light regime, and predator satiation on predation intensity, prey survival, and interspecific behavior during the 24 h period. DM served as a universal prey, with survival strongly affected by both temperature and predator feeding state. Predation was generally higher at 25 °C and among hungry individuals. HV proved to be the most efficient predator and competitor, whereas DG dominated among planarians by preying on PF and adopting its dark pigmentation—a potential camouflage strategy enabling mimicry of both prey and habitat. PF responded by forming defensive groups, highlighting species-specific behavioral adaptations. PF simultaneously exhibited traits of both predators and prey. These findings demonstrate that microcosm experiments can reproducibly capture natural freshwater interaction patterns. Moreover, this study provides the first evidence of a planarian predator exhibiting both prey mimicry and environmental camouflage, revealing a novel behavioral strategy in flatworm ecology.

Applying the Multiple Streams Framework to climate policy agenda-setting in the five Central Asian countries has strong explanatory power. The study finds that, under their political systems, the problem, policy, and politics streams do not operate independently; rather, the politics stream is dominant. Accordingly, this study offers an appropriate refinement of MSF and proposes a politics-stream-dominant coupling model. In this model, the politics stream comprises the ruling party’s executive will and governing philosophy, the catalytic influence of public sentiment, and the actions of interest groups. The problem stream encompasses climate-change-induced natural disasters and feedback from international climate conferences. The policy stream includes national climate-change plans, policy recommendations from experts and scholars, and lessons from relevant international organizations and other countries’ climate policies. However, within this model, the problem and policy streams must first be recognized, vetted, and absorbed by the politics stream before the policy window for climate-change agenda-setting opens, which gives the process a distinctly top-down character. Moreover, differences in political institutions, economic structures, and resource endowments yield unique interaction patterns among the three streams across country contexts. Looking ahead, agenda-setting for climate policy in these five countries will continue to face the challenge of uneven development among the streams; sustained deepening of their coupling is required to keep the policy window open. This study provides a theoretical touchstone and a practical reference for China and other developing countries as they pursue climate diplomacy.

The mechanism of wake formation behind two staggered in-phase pitching foils is numerically investigated over a range of Strouhal numbers (0.15<St<0.4), Reynolds numbers (1000<Re<10000), and horizontal (1c<h<3c) and vertical (0.5c<v<2c) foil separation distances, wherecis the foil chord. First, two flow patterns are identified, constituting merged and separated wakes. These are characterized in wake maps to explain the role of geometric and kinematic parameters in the wake formation. Relevant geometric thresholds for the formation of different wake topologies are identified, and their correspondence to kinematics is explained. This provides a wake evolution mechanism that explains the formation of these patterns. This mechanism is triggered by the interaction of upper and lower wakes, which results in the rearrangement of vortex pairs downstream. The interaction and resultant flow patterns change with the offset position of the upper wake, which is given by the horizontal and vertical placement of the upper foil. A wide range of separation distances in staggered foils enables, for the first time, the study of interactions between an external vortex and a vortex street. This allows the mechanisms of wake pattern formation triggered by this interaction to be explored. A novel wake model is proposed to explain this interaction, which consistently holds for different Reynolds numbers.

Introduction: Myocarditis, defined as an inflammatory injury to the myocardium, is irreversible with a 20% fatality rate in 2 years and a 50% fatality rate in 5 years. The most common causes of myocarditis are viruses, such as influenza A (IAV). IAV is a cardiotropic virus that can disseminate from the lungs to infect heart tissue, particularly during severe infections. Despite the implications for public health, little is known about the underlying mechanisms by which IAV causes heart pathology. Methods: To investigate the role of the novel E3 ligase TRIM47 in IAV-induced myocarditis, we utilized both in vitro and in vivo approaches. In vivo , wild-type (WT) and TRIM47 knockout (KO) mice were challenged intranasally with IAV to induce myocarditis. Survival, heart function (echocardiography), and cardiac pathology (histology, viral load by RT-PCR, cytokine levels by ELISA) were evaluated. In vitro , bone marrow-derived macrophages (BMDM) from WT and TRIM47 KO mice were infected with IAV and interferon production was detected by ELISA. To elucidate molecular mechanisms, co-immunoprecipitation and Western blotting were used to confirm TRIM47-MAVS interaction and ubiquitination patterns. Furthermore, recombinant protein expression, mutagenesis, and co-expression studies were used to map binding sites and identify specific ubiquitination types and sites on MAVS. Results: TRIM47 KO mice exhibited significantly reduced survival rates compared to WT controls following IAV infection, along with higher viral loads, diminished type I interferon levels, and increased histopathological damage in lungs and hearts. Consistently, TRIM47 KO BMDMs produced substantially lower interferon levels upon IAV challenge. Mechanistically, TRIM47 was found to directly bind MAVS at an endogenous level and promoted the ubiquitination of MAVS, facilitating its aggregation and subsequent activating downstream antiviral signaling pathways. Conclusions: Our findings establish macrophage expressed TRIM47 as a critical regulator of the innate immune response to IAV-induced myocarditis. This study provides the first in vivo evidence of TRIM47’s role in controlling IAV-induced myocarditis and highlights the TRIM47- MAVS axis as a promising therapeutic target for viral-associated cardiovascular diseases.

Abstract Sexual scripts operate at the levels of cultural scenarios with role expectations, interpersonal interaction patterns, and intrapsychic scripts that organize our personal desires. Importantly, these sexual expectations tend to be distinct for men and women. Religion also functions at these three levels to shape an adherent’s cosmology and cultural logic, templates for interpersonal behavioral, and personal ideals. Religious communities often promote very particular boundaries around sexual behavior and gender roles, yet despite these parallels, very little research has explored how religion relates to adopting gendered sexual scripts. This study addresses this gap by examining the relationship between religious factors and accepting male-centric sexual stereotypes. Data are drawn from the Public Discourse and Ethics Survey (PDES), which is a nationally representative study of adults in the United States. We find that higher levels of religiosity and identifying as Protestant or Catholic predict significantly higher agreement with male-centric sexual scripts compared to those who are not religiously affiliated. Religiosity has a more pronounced relationship to script agreement among women, while differences between religious groups are more pronounced among men. After controlling for marital gender traditionalism, our results suggest that Protestantism provides a unique source of male-centric sexual attitudes distinct from hierarchical gender thinking more generally.

Abstract This paper develops a credibility-weighted DeGroot-type agent model to examine how economic expectations evolve within directed, weighted networks. After reviewing key expectation types, it explores how unequal influence and the presence of opinion leaders shape collective dynamics. The model is tested on random and scale-free network structures with varying levels of connectivity, initial expectation distributions, and reliability indices. Results indicate that network topology is the dominant factor influencing aggregate outcomes. Dense networks tend to reach rapid consensus, while scale-free structures sustain persistent heterogeneity and slower convergence. Sparse networks display partial and delayed alignment of expectations. Opinion leaders meaningfully shift aggregate expectations only when both highly credible and well connected; otherwise, their influence remains localized. By linking micro-level interaction patterns to macro-level expectation outcomes, the study contributes to refining the understanding of opinion dynamics in an economic context and suggests potential implications for expectation modelling and policy communication in interconnected systems.

Patient interaction patterns with self-triage modules in mobile health apps during urgent direct-to-consumer telemedicine consultations remain underexplored, despite their critical role in optimizing virtual care pathways. This study aimed to analyze user navigation behaviors within the screen pathways of a symptom-based self-triage mobile app's algorithm during remote urgent care assessments. This observational, retrospective, single-center study analyzed data from users who were aged 18 years and older and who voluntarily sought virtual urgent care through the Einstein Conecta (version 2.0; iOS and Android) at a private Brazilian hospital between May 2022 and December 2023. Patients with incomplete connection records were excluded. User interactions were evaluated based on the number of distinct triage flows accessed per session, the number of screens viewed per flow, the frequency of returns to previous screens, and the time spent within the self-triage module. Descriptive statistical methods were applied for analysis. Data from 62,006 unique users with a mean age of 36.51 (SD 10.53) years, of whom 54.65% (33,889/62,006) were female, were analyzed. They initiated 194,976 self-triage flows. We found that 36.89% (22,875/62,006) of users completed 1 flow per session; 22.15% (13,734/62,006) users accessed 2 flows; and 27.93% (17,317/62,006) users accessed ≥4 flows (maximum 63 flows). Users receiving an initial emergency department referral recommendation were more likely to initiate subsequent flows than those recommended for virtual assessment. Returning to a previous screen was infrequent (used by 5277/62,006, 8% of users). The average time spent in the first flow was 70.95 (SD 65.26) seconds, with an average of 9.51 (SD 12.84) seconds per screen. In this cohort, most users explored alternative pathways beyond the initial self-triage recommendation, particularly when directed to the emergency department, while rarely backtracking within a flow. These findings underscore the need to refine self-triage mechanisms in telemedicine to better align with observed user navigation behaviors and preferences.

This study aimed to investigate the predictive influence of multimodal literacy instruction and students’ learning comfort on the classroom interaction of college students. Grounded in the increasing emphasis on multimodal pedagogies and affective learning environments, the study posits that both instructional modality and learner affect significantly shape interaction patterns within higher education classrooms. A quantitative research design employing a descriptive-correlational approach was utilized. Data were collected through stratified random sampling using standardized survey questionnaires. Descriptive statistics (mean and standard deviation), Pearson’s correlation coefficient (r), and multiple regression analysis were employed to analyze the data and address the study’s objectives. Findings indicated that the levels of multimodal literacy instruction, learning comfort, and classroom interaction were all rated as very high. Significant positive correlations were found between multimodal literacy instruction (r = 0.603, p &lt; 0.001) and learning comfort (r = 0.683, p &lt; 0.001) and classroom interaction. Moreover, regression analysis revealed that both multimodal literacy instruction (β = 0.280, t = 3.327, p &lt; 0.05) and learning comfort (β = 0.487, t = 5.653, p &lt; 0.05) were significant predictors of classroom interaction, jointly explaining 51.2% of its variance (R² = 0.512). The results highlight the crucial role of multimodal pedagogical strategies and learners’ affective states in promoting classroom engagement. These findings support instructional practices that enhance both multimodal comprehension and student comfort, thereby promoting enriched classroom interactions and increased learner participation.

In data visualization, users’ scanning patterns are as crucial as their reading patterns in text-based media. Yet, no systematic attempt exists to characterize this activity with basic features, such as reading speed and scanpaths, nor to relate them to data complexity and information disposition. To fill this gap, this paper proposes a model-based method to analyze and interpret those features from eye-tracking data. To this end, the bias-noise model is applied to a data visualization eye-tracking dataset available online, and enriched with areas of interest labels. The positive results of this method are as follows: (i) the identification of users’ reading styles like meticulous, systematic, and serendipitous; (ii) the characterization of information disposition as gathered or scattered, and of information complexity as more or less dense; (iii) the discovery of a behavioural pattern of efficiency, given that the more visualizations were read by a participant, the greater their reading speed, consistency, and predictability of reading; (iv) the identification of encoding and title areas of interest as the primary loci of attention in visualizations, with a peculiar back-and-forth reading pattern; (v) the identification of the encoding area of interest as the fastest to read in less dense visualization types, such as bars, circles, and lines charts. Future experiments involving participants from diverse cultural backgrounds could not only validate the observed behavioural patterns, but also enrich the experimental framework with additional perspectives.

Complex biological systems, like the brain, exhibit intricate multiway and multiscale interactions that drive emergent behaviors. In psychiatry, neural processes extend beyond pairwise connectivity, involving higher-order interactions critical for understanding mental disorders. Conventional brain network studies focus on pairwise links, offering insights into basic connectivity but failing to capture the complexity of neural dysfunction in psychiatric conditions. This study seeks to address this gap by utilizing a matrix-based entropy functional for estimating total correlation, which serves as a mathematical framework for capturing multivariate information. We apply this framework to fMRI-ICA-derived multiscale brain networks, enabling the investigation of multivariate interaction patterns within the human brain across multiple scales. Additionally, this approach holds significant promise for psychiatric research on schizophrenia, offering a novel framework for investigating higher-order triadic brain network interactions associated with the disorder. By examining both triple interactions and the latent factors underlying the triadic relationships among intrinsic brain connectivity networks through tensor decomposition, our study presents a novel approach to understanding changes in higher-order brain networks in schizophrenia. This framework not only advances our understanding of complex brain functions but also opens new avenues for investigating the pathophysiology of schizophrenia, potentially informing more targeted diagnostic and therapeutic strategies. Moreover, this method for analyzing multiway interactions is applicable across signal analysis domains. In this study, we apply this approach to neural signals in schizophrenia, demonstrating its ability to reveal complex multiway interaction patterns and provide new insights into brain connectivity beyond traditional pairwise analyses in the context of brain disorders.

Introduction: Adequate sleep is crucial for adolescent health because sleep deprivation can induce moodiness and frustration. Personality, encompassing introversion and extraversion, influences behavior and interaction patterns. Emotional intelligence pertains to the recognition and management of one’s own emotions and those of others. Methods: This study explored the relationships among sleep quality, personality type, and emotional intelligence among 5th and 7th semester students at the Faculty of Medicine, Hang Tuah University Surabaya, from 2024--2025. Using a descriptive analytic design and cross-sectional approach, 196 respondents were selected via purposive sampling. Data were collected via the Pittsburgh Sleep Quality Index, Personality Type Questionnaire, and Emotional Intelligence Questionnaire, which are distributed online. No personally identifiable information was collected, ensuring the full anonymity of the respondents. Results: Spearman’s correlation analysis revealed significant relationships between sleep quality and personality type (r = 0.235, p = 0.0005), between sleep quality and emotional intelligence (r = 0.212, p = 0.0005), and between personality type and emotional intelligence (r = 0.1476, p = 0.0005). Poor sleep quality was associated with lower emotional intelligence, indicating that sleep affects emotional awareness. Similarly, personality type was correlated with variations in emotional intelligence. Conclusion: This study revealed significant correlations between sleep quality, personality type, and emotional intelligence among medical students, suggesting that these factors play a key role in their emotional wellness.

In the context of media fragmentation and declining public trust in mainstream journalism, independent podcasts in Indonesia have emerged as alternative spaces for public discourse. These digital platforms enable marginalized voices and critical narratives to reach wider audiences, offering an avenue for civic engagement and grassroots activism. This study aims to explore how independent podcasts contribute to the formation of social awareness, identify the communication strategies used by podcasters, and map patterns of listener interaction as a form of participatory citizenship. Employing a qualitative approach, the research integrates digital ethnography, semi-structured interviews, and critical discourse analysis. Data were collected from 15 independent podcast channels, 12 in-depth interviews with podcasters and active listeners, and content analysis of 30 podcast episodes discussing social, political, and environmental themes. The findings reveal that independent podcasters act as organic intellectuals who use personal storytelling, emotional resonance, and ideological framing to raise social consciousness. The most common themes include human rights, labor issues, gender equality, and environmental justice. Audience engagement extends beyond listening—listeners share content, participate in discussions, donate, and even mobilize offline action. The study recommends supporting independent podcast production through funding, training in critical media literacy, and expanding accessibility to underserved communities. Independent podcasts represent not only an emerging media form but also a democratic communication model capable of reshaping public dialogue in Indonesia.

In animals, group living comes at the cost of increased pathogen exposure. In kin groups, social immune behaviours offset that cost and reach their most complex expression in eusocial insect societies. In the nests of these societies, collective social behaviours can modify the patterns of individual interactions across space, reducing the ability of pathogens to reach the reproductive core of the colony (organizational immunity). To be effective, these behaviours must separate infected and uninfected individuals; implying that the efficacy of social immune behaviours may depend upon nest structure. The role of nest space has received little attention, and most knowledge of social immune behaviour in social insects is based on the study of generalist entomopathogenic fungi. We examine the social immune behaviours involved in the interaction between the supercolonial, invasive tawny crazy ant (Nylanderia fulva) and its specialist, intracellular, microsporidian pathogen Myrmecomorba nylanderiae, to ask how nest structure influences social immunity. By manipulating nest structure, we demonstrate that preventing pathogen transmission to the colony core requires a multi-chambered nest. Without which, social immune function was lost, and disease transmission was universal. To understand how nest space enhances social immune efficacy, we first confirm that workers within tawny crazy ant nests form spatially and behaviourally segregated social sub-networks. We then find that infected ants introduced into the colony core migrate to the colony periphery, while uninfected ants do not. Behavioural tests indicate that, despite the infection being internal, uninfected ants can detect the infection status of a worker; thus, behaviours enforcing spatial segregation could be triggered by either party. Additionally, infected ants alter the behavioural tasks they perform, assuming more corpse removal tasks, particularly infected corpse removal, and reducing their efforts in foraging and brood care. With some exceptions, the social immune behaviours expressed by this supercolonial ant in response to microsporidian infection correspond to immune defence behaviours employed to defend against generalist entomopathogenic fungi. These behaviours appear to be conserved, generalized responses to pathogen infection among social insects.

Structure-function activity study of the unusual protein MAPK1-109aa encoded by the non-coding circular RNA hsa_circ_0004872.

DG-MSGAT: A Biologically-informed Differential Gene Multi-Scale Graph Attention Network for predicting neoadjuvant therapy response in rectal cancer.