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The Emotional Landscape of Everyday Eating: Using AI and Mind Genomics to Understand How Patients Think About Food

DOI: 10.31038/MGSPE.2026614

Abstract

Nutrition is usually presented to clinicians as a technical domain—macronutrients, biomarkers, guidelines—but patients live it as an emotional, cultural, and psychological experience. The same plate of food can represent comfort, guilt, rebellion, reward, or self care, depending on the mind that encounters it. Emotional eating, mindless eating, and conflicted eating are not marginal behaviors; they are central to how people drift from health toward nutritional disease. Yet medical education still treats food as a counseling topic rather than a lived emotional world. At the same time, AI supported training platforms now demonstrate that empathy, communication, and soft skill reasoning can be taught with the same rigor as technical skills. Mind Genomics adds a complementary layer by treating the patient’s inner logic as a measurable system, revealing distinct mind sets that respond differently to the same nutritional message. This paper integrates AI generated patient narratives with Mind Genomics segmentation to illuminate how people think and feel about everyday eating long before diabetes or obesity are diagnosed. The goal is to give clinicians a sharper lens on the emotional landscape of food, so prevention and counseling can begin where patients actually live—inside their daily decisions, habits, and feelings.

Keywords

Mind genomics, Emotional eating, Nutritional psychology, Artificial intelligence, Patient communication

Abbreviations

AI: Artificial Intelligence; OLS: Ordinary Least Squares

Introduction

Medical education increasingly recognizes nutrition as a major determinant of health, yet structured nutrition training remains limited in many medical curricula. Professional organizations have emphasized the need for longitudinal nutrition education in order to strengthen physicians’ ability to address diet-related disease and provide effective counseling [1,2]. Despite these efforts, nutrition is still often taught primarily as a technical domain of macronutrients, biomarkers, and dietary guidelines rather than as a lived behavioral and psychological experience.

Parallel to these developments, research in nutritional psychiatry and nutritional psychology has demonstrated that dietary patterns interact closely with mood, cognition, and emotional wellbeing. Food therefore functions not only as metabolic fuel but also as a continuous psychological signal embedded in identity, stress regulation, culture, and emotional meaning [3,4]. Individuals rarely approach food neutrally. Emotional eating research shows that people frequently use food to regulate feelings, distract themselves from stress, or create temporary comfort, often followed by cycles of guilt or frustration that reinforce unhealthy eating patterns [5,6].

At the same time, artificial intelligence has begun to play an expanding role in healthcare education. AI-supported virtual patient simulations are increasingly used to train communication skills, empathy, and patient-centered reasoning. These systems allow learners to practice clinical conversations, experiment with phrasing and tone, and receive structured feedback on interpersonal skills that are traditionally difficult to teach at scale [7,8].

Mind Genomics provides a complementary framework for understanding how individuals interpret everyday experiences and make behavioral decisions. Rather than studying attitudes through traditional surveys, Mind Genomics experimentally combines small elements of meaning into short narrative vignettes that respondents evaluate. Statistical decomposition of these responses reveals the psychological “drivers” that shape interest, resistance, or indifference toward specific messages [9,10]. In this way, Mind Genomics treats everyday decision-making as an experimentally measurable system.

Understanding these psychological drivers is particularly important in the context of eating behavior. Dietary choices are rarely determined by knowledge alone; they emerge from emotional triggers, habits, identity, convenience, and social context [11]. As a result, two individuals may receive identical nutritional advice yet respond to it in entirely different ways.

The present study focuses on the early stage of the nutritional trajectory—the world of everyday eating before chronic disease such as obesity or diabetes is formally diagnosed. The central premise is that prevention requires understanding the emotional landscape of food as patients actually experience it in daily life. AI provides narrative realism, while Mind Genomics offers experimental structure for exploring how different psychological mindsets interpret the same eating situations. Together, these approaches create a framework for examining how patients think and feel about food long before disease becomes clinically visible.

Materials and Methods

This study applies the Mind Genomics experimental framework to explore the emotional meanings associated with everyday eating. Mind Genomics treats everyday decision-making as an experimentally measurable system by decomposing complex experiences into smaller elements of meaning that can be systematically tested [9].

The study begins by identifying a set of micro-elements—short statements representing different ways individuals think and feel about food. These elements reflect multiple dimensions of everyday eating, including emotional drivers, situational triggers, identity themes, and practical considerations. In the Mind Genomics design, these elements are typically organized into a structured matrix consisting of four questions with four alternative answers each, yielding sixteen total elements intended to capture a broad range of interpretations related to eating behavior.

The elements are combined into short narrative vignettes. Each vignette contains two to four elements drawn from the full set, arranged according to a systematic experimental design so that each element appears in different combinations across the vignettes. Respondents evaluate a series of these vignettes and rate them according to personal resonance—for example, the degree to which the scenario reflects their own eating behavior or emotional relationship with food.

The ratings are analyzed using ordinary least squares (OLS) regression to estimate the part-worth utility associated with each element. The resulting coefficients reveal which ideas generate strong positive reactions, which provoke rejection, and which have minimal influence on responses. Cluster analysis is then applied to the pattern of coefficients in order to identify distinct psychological segments referred to as mindsets. These mindsets represent different interpretive frameworks through which individuals understand everyday eating situations rather than demographic groupings.

AI systems are used to generate narrative expansions of the experimental elements and to simulate clinician–patient dialogues representing different mindsets. AI-based educational simulations and large language model tools have increasingly been used to support communication training and patient-centered interaction in healthcare education [8,12].

Together, the integration of Mind Genomics segmentation and AI-generated narrative simulation creates a dual-lens system for understanding eating behavior. The quantitative layer identifies psychological drivers of everyday food choices, while the narrative layer illustrates how these drivers may appear in realistic clinical conversations about nutrition and health.

This study represents a conceptual and simulation-based application of the Mind Genomics framework. No real patient data or identifiable human participant information were used in this work. The AI-generated narratives and simulated dialogues are illustrative examples developed for educational and methodological demonstration.

Results

Mindsets Emerging from Everyday Eating

Everyday eating is not a single behavior but a set of psychological operating systems through which individuals interpret food, respond to stress, and understand nutritional advice. When the Mind Genomics framework is conceptually applied to the domain of everyday eating, it suggests that individuals may interpret food-related situations through several distinct psychological orientations.

Based on the structure of the experimental elements and their narrative interpretation, three illustrative mindsets emerge that represent different ways individuals relate to food in daily life. These mindsets are not demographic categories but patterns of meaning that shape how people experience hunger, react to emotional stress, and respond to recommendations about healthy eating.

The three mindsets identified in this framework are:

Mindset 1: The Emotional Eater

Mindset 2: The Convenience Navigator

Mindset 3: The Health-Identity Striver

Each mindset reflects a different internal logic guiding everyday eating behavior. The Emotional Eater experiences food primarily as emotional regulation and comfort. The Convenience Navigator approaches eating as a practical activity shaped by schedule constraints and convenience. In contrast, the Health-Identity Striver views food choices as expressions of discipline, self-control, and personal identity.

To illustrate the differences among these psychological orientations, Table 1 summarizes the defining characteristics of the three mindsets across several behavioral dimensions, including motivations for eating, responses to stress, interpretations of hunger, reactions to nutritional advice, barriers to change, and interpretations of failure.

Table 1: Psychological mindsets in everyday eating identified through the mind genomics framework.

Table 1 demonstrates that individuals who appear similar in demographic terms may interpret food and eating behavior in fundamentally different ways. Recognizing these psychological orientations can help clinicians anticipate how patients might respond to nutritional counseling and tailor communication strategies accordingly.

Fly-on-the-Wall Simulation

To further illustrate how these mindsets may appear in real-world clinical conversations, a “fly-on-the-wall” simulation was developed using AI-generated dialogue.

In this approach, the reader is positioned as an observer watching an interaction between a clinician and representative patients belonging to different mindsets. The purpose of the simulation is to translate the conceptual psychological segmentation into narrative form, allowing clinicians to observe how different orientations toward food may manifest during patient discussions.

The simulation highlights how the Emotional Eater frames food as emotional comfort, how the Convenience Navigator treats eating as a practical activity shaped by time pressure, and how the Health-Identity Striver interprets food choices as part of a disciplined lifestyle identity. By presenting these contrasting perspectives side by side, the dialogue illustrates how identical nutritional advice may be interpreted differently depending on the patient’s underlying mindset.

Illustrative Clinician–Patient Dialogue

Discussion

The findings from this study show that everyday eating is not a single behavior but a set of emotional, cognitive, and logistical patterns that shape how people move along the nutritional arc. The three mindsets—Emotional Eater, Convenience Navigator, and Health Identity Striver—demonstrate that patients do not hear nutritional advice the same way. Each mindset filters information through its own logic, priorities, and vulnerabilities. When clinicians assume a single “typical patient,” they inadvertently miss the psychological diversity that drives adherence, resistance, or ambivalence. AI and Mind Genomics together provide a structured way to surface these hidden patterns and make them visible, teachable, and clinically actionable.

AI contributes by generating natural-language voices that reflect the emotional logic of each mindset. Recent reviews of generative AI tools have highlighted their growing role in healthcare education, research assistance, and clinical training environments [12]. In this context, simulated patient narratives allow clinicians to rehearse conversations with individuals who think and feel differently about food. The Emotional Eater reveals the role of food as comfort and emotional relief; the Convenience Navigator exposes the logistical pressures that shape everyday eating; and the Health-Identity Striver shows how food choices become expressions of discipline and self-control. These voices are not caricatures. Rather, they are grounded in the conceptual structure of the Mind Genomics framework, ensuring that the AI-generated simulations reflect meaningful psychological patterns rather than generic stereotypes.

Mind Genomics contributes by decomposing the complexity of everyday eating into conceptual elements that represent the different ways individuals interpret food-related situations. It highlights which ideas resonate strongly, which are ignored, and which provoke resistance. This structure allows educators to teach soft-skill reasoning with the same rigor as technical content. Instead of vague advice like “meet patients where they are,” Mind Genomics helps clarify where patients are—what they value, what they fear, and what motivates them. This precision transforms empathy from an intuition into a teachable skill.

The combination of AI and Mind Genomics also addresses a major gap in medical education: the lack of systematic training in the emotional and psychological dimensions of nutrition. Students learn about dietary guidelines, but they rarely learn how patients experience food in daily life. They are taught what patients should do, but not how patients think. By integrating narrative realism with psychological segmentation, this approach gives learners a dual lens: they can see the structure of patient thinking and hear how it sounds in conversation. This dual perspective is essential for building clinical intuition.

Clinicians who understand mindsets can tailor their communication more effectively. Emotional Eaters need validation and emotional support before they can engage with behavioral change. Convenience Navigators need simple, efficient solutions that fit their routines. Health Identity Strivers need structured goals and reassurance that flexibility does not undermine identity. When clinicians match their approach to the patient’s mindset, adherence improves, trust deepens, and nutritional counseling becomes more effective.

This approach also has implications for prevention. Nutritional disease does not begin with biomarkers; it begins with daily decisions shaped by emotion, habit, and identity. By understanding the emotional landscape of everyday eating, clinicians can intervene earlier and more effectively. They can recognize when a patient is drifting toward patterns that increase risk for diabetes or obesity. They can offer support that aligns with the patient’s psychological operating system. Prevention becomes not just a matter of information but of emotional alignment.

Finally, this work demonstrates that AI can play a constructive role in teaching empathy. AI does not replace human connection; it enhances it by giving clinicians repeated exposure to diverse patient voices. Mind Genomics ensures that these voices are grounded in meaningful psychological patterns. Together, they create a new educational instrument—one that is scalable, rigorous, and deeply human. This integration represents a new frontier in medical humanities, where technology supports the development of emotional intelligence, communication skills, and patient-centered care.

Conclusion

Everyday eating is a psychological world that clinicians must understand if they hope to prevent nutritional disease. AI and Mind Genomics together provide a powerful framework for illuminating this world. AI generates realistic patient voices, while Mind Genomics structures the underlying patterns of interpretation. The result is a dual-lens system that makes the emotional landscape of eating visible, teachable, and clinically actionable. This approach transforms empathy from an abstract ideal into a practical skill that can be practiced, refined, and mastered. As medical education evolves, integrating AI-supported narrative simulation with Mind Genomics segmentation offers a promising and scalable new path forward—one that honors the complexity of human behavior and strengthens the clinician’s ability to meet patients where they truly live.

Competing Interests

The authors declare that they have no competing interests.

References

  1. Aspry KE, Van Horn L, Carson JAS et (2018) Medical Nutrition Education, Training, and Competencies to Advance Guideline-Based Diet Counseling by Physicians A Science Advisory from the American Heart Association. Circulation. [crossref]
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  10. Moskowitz HR, Ashman H (2006) Founding a New Science Mind Genomics. J Sens Stud
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A New Hypothesis About Neuroinflammation and Osteomyelitis in Adults With Type 2 Diabetes Mellitus and Peripheral Neuropathy Without and With Foot Lesions. What Comes First?

DOI: 10.31038/EDMJ.20261023

 

In the paper “Neuroinflammation and osteomyelitis in adults with Type 2 diabetes mellitus and peripheral neuropathy without and with foot lesions. What comes first?” published in September 2025 [1], diabetic foot disease, the leading causes of major and minor non-traumatic amputation worldwide, was originally described as a destructive, progressive bone tissue process beginning from perypheral nerve functional damage (Figure 1a-f, see main paper inn ref. [1]). An innovative framework was proposed, in which chronic oxidative stress, induced by hyperglycemia, may trigger epigenetically mediated adverse neuronal signals as proNGF expression in post-mitotic cells. This neuronal injury could initiate a domino-like cascade involving innervated peripheral tissues leading to neuro-ischemic gangrene or infected necrosis, remembering different tissue damages as myocardial heart failure, diabetic retinopathy and end-stage renal disease where similar irreversible behaviors could share convergent pathogenic mechanisms.

In the paper “Neuroinflammation and Osteomyelitis in Adults with Type 2 Diabetes Mellitus and Peripheral Neuropathy Without and With Foot Lesions. What Comes First?” published in September 20251 , diabetic foot disease—the leading cause of major and minor non-traumatic amputations worldwide—was originally described as a progressive, destructive bone tissue process that begins with peripheral nerve functional damage (Figure 1 a–f, see main paper1). The authors propose an innovative framework in which chronic oxidative stress induced by hyperglycemia may trigger epigenetically mediated adverse neuronal signaling, such as proNGF expression in post-mitotic cells. This neuronal injury could initiate a domino-like cascade affecting innervated peripheral tissues, ultimately leading to neuro-ischemic gangrene or infected necrosis. This process resembles other tissue injuries observed in conditions such as myocardial heart failure, diabetic retinopathy, and end-stage renal disease, where similar irreversible changes may share convergent pathogenic mechanisms.

The updated definition for diabetes-related foot disease proposed by the International Working Group on the Diabetic Foot (IWGDF, 2023 update) [2] describes it as a “disease of the foot of a person with current or previously diagnosed diabetes mellitus that includes one or more of the following: peripheral neuropathy, peripheral artery disease, infection, ulcer(s), neuro‐osteoarthropathy, gangrene, or amputation”. This statement reads more as an updated descriptive framework than a definition, because it describes coexisting or concomitant events and does not illustrate a progression or a prognosis of the phenomenon. Our hypothesis was that hyperglycemia alters the mitochondrial milieu and triggers danger-associated neurotrasmission signals capable of affecting both central and peripheral neuronal function. In particular, distal sensory and autonomic neuropathy could activate neuroischemic and endothelial signaling pathways, inflammatory responses and induce bone cell apoptosis, thereby exposing coating tissues to fatal damage prone to infections (Figure 1).

Figure 1: Hematoxylin/eosin staining and CX3CL1 and RORɣ imunohistochimic change expression in femoral head controls (a-c) versus foot bone of diabetic patients with HIOM (d-f). Magnification for A and B 200X, for B-E 400X (Figure 6 [1]).

Based on this hypothesis, we tried to identify an early marker of the phenomenon. Fractalkine (CX3CL1), a constitutively expressed transmembrane chemokine with different neurovascular distribution and unique cleavage-dependent signaling properties, emerged as a candidate [3]. Elevated expression of both the membrane-bound and soluble forms [4] of CX3CL1 has been shown to enhance fractalkine receptor (CX3CR1)-mediated recruitment of inflammatory cells, promote vascular endothelial dedifferentiation, and contribute to tissue fibrosis in non-obstructive vascular diseases. The spread of neuroinflammatory signals throughout peripheral innervated tissues can ultimately converge cytotoxic and apoptotic pathways, leading to irreversible damage in the foot.

It was described that CX3CR1 expression has an important role in early activation of endothelial and peri-endothelial cells both involved in ostructive and non obstructive coronary diseases [4]. In vitro studies have demonstrated that CX3CL1 is not only an endothelial chemokine and a monocyte adhesion molecule, but also acts as a dysfunctional endothelial trigger by promoting the production of reactive oxygen species (ROS), which leads to reduced nitric oxide (NO) bioavailability in vascular smooth muscle cells [4]. Experimental peripheral nerve injuries demonstrated the presence of Fractalkine/CX3CR1 axis beetween neuron and activated glia where clivating enzimes deliver soluble fractalkine for axonal preservation and vascular regeneration [5]. In our neuropathic patients, analysis of bone proteins involved in signal transduction pathways revealed a prominent reduction in ERK1/2 activating phosphorylation (P-ERK1/2) in bone tissue rich of fractalkine, accompanied by increased Akt activation (P-Akt) (See main paper [1] Figure 8C), supporting the hypothesis of a contributory role in the apoptotic cascade. These findings raise a critical question: what is the impact of reduced intraneuronal activity on peripheral nerve function and the integrity of innervated tissues?

In our paper, we reported data of 374 adults with Type 2 diabetes mellitus (T2DM) and diabetic neuropathy (DN) divided into progressive, at risk, or with established foot damage subgroups: 106 neuroparthic subjects without foot lesions (DNp); 119 non-macrovascular neuropathic subjects with ulcers/lesions/osteomyelitis (DNpU); 149 revascularized neuropathic subjects with ulcers/lesions/osteomyelitis (DNpUV) and a group of 53 healthy adults as normal control (NC). We performed biopsy specimens from exposed bone (grade III University of Texas wound classification, TUC) to obtain microbiological standards and histological analysis. Based on TUC classification which defines from stage I (dermal) to stage III (bone) the ulcer depth, we correlated CX3CL1 migration marker with EMG parameters of neuropathy and analyzed pro/anti-inflammatory cytokines, blood cells subsets (lymphocytes subpopulations, classical, non-classical and SLAN+ monocytes, classical DCs, innate lymphoid cells), Nerve Growth Factor (NGF) species, autophagy markers (Ulk1, Beclin1, LC3, and p62), pro/anti-apoptotic proteins (Bax, Bcl2, cleaved Caspase-3) and signal transduction proteins involved in inflammation and cell survival (p65-NF-kB, Akt and ERK1/2). Our results are interesting puzzle pieces in diabetic foot labyrinth. Electrophysiological parameters as Sural nerve (sS) conduction velocity (CV) and sensory Action Potential (sAP) thresholds confirmed the presence and severity of diabetic neuropathy. Worsening in neuronal function was correlated with depth of foot lesions, with or without peripheral critical ischemia and increased immature neurokine NGF (proNGF) circulating levels. Furthermore, we found higher numbers of SLAN+ monocytes co-expressing CX3CR1 in all TUC III versus I TUC groups; these inflammatory cells directly correlated with proNGF levels and worsened autonomic and sensory testing. All bone lesions were positive for CX3CL1 and RORɣ (lymphoid marker) in our immunohistochemical analysis1; in the same bone biopsies, sympathetic TH-positive nerves resulted positive by immunofluorescence for the co-expression of CX3CL1 and NGF receptors (p75, TrkA receptors; see main paper Figure 7 in [1]).

Finally, bone cleaved caspase 3 and Bax directly correlated with % of CX3CR1+SLAN+CD16+ inflammatory monocytes and inversely with bone ERK1/2 activating phosphorylation. Multiple RNA array sub-analysis confirmed potential impairments in autophagy and upregulated mTOR/RHEB apoptotic signaling co-expressed with CX3CR1 on bone species (see main paper [1] Figure 9C-E).

Collectively, these findings indicate that diabetic neuropathy represents a primary pathogenic driver in diabetic foot disease, triggering a domino-like neuroinflammatory process. Loss of sensitive function and autonomic dysregulation appear to compromise foot integrity, alter intrabone neurotrophins and CX3CL1 expression and induce vascular dysfunction, early bone apoptosis and CX3CR1+monocytes chemotaxis preceding and potentially occurring independently of infected osteomyelitis. These data redefine the hierarchy of pathogenic events in diabetic foot disease and may mark the way for the development of new targeted therapies.

Abbreviations

BAX: Bcl2 Associated X Protein; Bcl2: B-Cell Lymphoma 2; CD: Cluster Differentiation; CV: Conduction Velocity; CX3CL1: Chemokine (C-X3-C Motif) Ligand 1; CX3CR1: C-X3-C Motif Chemokine Receptor 1; DC: Dendritic Cell; DN: Diabetic Neuropathy; EMG: Electromyography; ERK1/2: Extracellular Signal-Regulated Kinase; HIOM: High Infected Osteomyelitis; IWGDF International Working Group on the Diabetic Foot; LC3: Microtubule-Associated Protein 1A/1B-Light Chain 3; mAP/sAP: Motor/Sensory Action Potential; MIOM: Mild Infected Osteomyelitis; m/proNGF: Mature/Immature Nerve Growth Factor; mTOR: Mechanistic Target of Rapamycin; NC: Normal Control; nDFH: Non-Diabetic Femur Head; NF-kB: Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells; nILOM: Non Infected Low Osteomyelitis; NGF: Nerve Growth Factor; NK: Natural Killer Cell; NO: Nitric Oxide; p75 NTR p75 Neurotrophic Receptor; PA: Plasminogen Activation; PB: Peripheral Blood; RHEB: Ras Homolog Enriched in Brain; ROS: Reactive Oxygen Species; ROR𝛾: RAR-related Orphan Receptor Gamma; SLAN: 6-sulfo LacNAc; ; sS: Sural; sSa: Saphenous; sSP: Superficial Peroneal; T2DM: Type 2 Diabetes Mellitus; TH: Tyrosin Hydroxilase; TrkA: Tropomyosin Receptor Kinase A; TUC: University of Texas Wound Classification; Ulk1: Unc-51 Like Autophagy Activating Kinase 1.

Keywords

Diabetic foot, Neuropathy, Osteomyelitis, Fractalkine CXC3L1/CXC3R1 axis

References

  1. Sambataro M, Sambado L, Colardo M, Furlan A, Stefani PM, Durante E, Antico A, Conte S, Bella SD, Nollino L, Barbara Z, Menegotto N, Vian E, Segatto M, Fassan M (2025) Neuroinflammation and osteomyelitis in adults with Type 2 diabetes mellitus and peripheral neuropathy without and with foot lesions What comes first? J Diabetes Complications. [crossref]
  2. Schaper NC, van Netten JJ, Apelqvist J, Bus SA, Fitridge R, Game F, Monteiro-Soares M, Senneville E (2024) Practical guidelines on the prevention and management of diabetes-related foot disease IWGDF 2023 update. Diabetes Metab Res Rev. [crossref]
  3. Umehara H, Bloom ET, Okazaki T, Nagano Y, Yoshie O, Imai T (2004) Fractalkine in vascular biology from basic research to clinical disease. Arterioscler Thromb Vasc Biol. [crossref]
  4. Stangret A, Sadowski KA, Jabłoński K, Kochman J, Opolski G, Grabowski M, Tomaniak M (2024) Chemokine Fractalkine and Non-Obstructive Coronary Artery Disease-Is There a Link? Int J Mol Sci. [crossref]
  5. Pottorf TS, Rotterman TM, McCallum WM, Haley-Johnson ZA, Alvarez FJ (2022) The Role of Microglia in Neuroinflammation of the Spinal Cord after Peripheral Nerve Injury. Cells. [crossref]

Understanding Radicalization Narratives: An AI-Assisted Mind Genomics Framework

DOI: 10.31038/MGSPE.2026613

Abstract

Acts of political violence often generate intense public attention, particularly when the motivations of the perpetrator remain unclear. In such situations, news narratives frequently become the primary lens through which the public attempts to interpret complex events. This study presents a conceptual framework that integrates artificial intelligence–assisted narrative analysis with Mind Genomics thinking to examine how audiences interpret narratives related to radicalization. Using a widely reported news account of the July 2024 assassination attempt on former U.S. President Donald Trump as a narrative stimulus, the study demonstrates how complex news stories can be decomposed into structured informational elements representing online environments, ideological alignment, social connection, autonomy, and emotional states. These elements are organized within a conceptual experimental design consistent with Mind Genomics methodology, enabling the construction of vignette-based simulations that illustrate how different combinations of narrative components may influence interpretation. The framework proposes three illustrative interpretive mindsets—The Radical, The Explorer, and The Outsider—to demonstrate how readers may cognitively segment when encountering narratives of political violence and radicalization. Although the present work represents a conceptual simulation rather than an empirical experiment, it outlines a methodological approach through which researchers, educators, and students may systematically analyze complex news narratives. By combining AI-assisted narrative decomposition with Mind Genomics experimental thinking, the study offers a structured approach for examining how individuals interpret contemporary news events and for promoting more reflective and critical engagement with media narratives.

Keywords

Mind genomics, Radicalization, Artificial intelligence, Narrative analysis, Media interpretation, Conceptual simulation

Introduction

Acts of political violence often generate intense public attention and extensive media coverage. When such events occur, journalists, policymakers, and researchers attempt to understand the motivations behind the perpetrator’s actions. However, in many cases, the motivations remain uncertain even after extensive investigation. In such situations, public interpretation of the event becomes heavily influenced by the narratives circulating in media and social discourse.

Radicalization has long been recognized as a complex process involving multiple psychological and social factors. Research suggests that ideological extremism typically emerges through interactions among identity processes, perceived grievances, and social influence rather than from a single causal factor [1]. Individuals may adopt increasingly extreme beliefs when they perceive threats to identity, belonging, or social status.

Identity-based uncertainty and social categorization processes can also contribute to ideological extremism. When individuals experience uncertainty about their social identity or group membership, they may be more likely to adopt strongly defined ideological positions in order to achieve clarity and belonging [2]. These psychological dynamics illustrate how ideological narratives can influence cognitive interpretation.

Scholars have also emphasized the role of perceived injustice and social context in shaping radicalization processes. Reviews of the social-science literature highlight that grievances, identity threats, and group dynamics often interact in the development of extremist beliefs [3]. Psychological analyses further indicate that emotional narratives and cognitive framing can influence how individuals interpret political conflict and violence [4].

In recent years, digital communication environments have added an additional dimension to radicalization research. Online networks may facilitate ideological reinforcement and allow individuals to connect with communities sharing similar beliefs or grievances [5]. Social media platforms can accelerate these processes by enabling rapid dissemination of emotionally charged narratives and by connecting geographically dispersed individuals [6].

Understanding how audiences interpret such narratives remains a major challenge. Traditional research approaches often focus on isolated psychological or sociological variables. However, real-world narratives typically combine multiple interacting influences including political rhetoric, emotional reactions, and social context.

Mind Genomics offers a methodological framework capable of addressing this complexity. Mind Genomics investigates how individuals interpret combinations of ideas embedded within short narrative descriptions known as vignettes [7]. Instead of analyzing isolated variables, the approach explores how people respond to patterns of information presented simultaneously.

Recent studies have extended Mind Genomics into the investigation of complex social issues including radicalization and public attitudes toward political conflict [8]. These studies demonstrate how experimental vignette designs can reveal distinct cognitive segments within populations.

To illustrate how such a framework may be developed, this study draws on a widely reported news account describing the attempted assassination of U.S. President Donald Trump during a campaign rally in Butler, Pennsylvania, in July 2024 [9]. Despite an extensive federal investigation lasting several months, the motivations of the shooter remain unclear [10].

This absence of a clear motive creates a particularly interesting analytical situation. When events occur without a definitive explanation, news narratives become the primary source through which the public attempts to interpret what happened. Different readers may interpret the same story in very different ways depending on their beliefs, experiences, and cognitive orientation.

The present study therefore uses the structure of this news narrative not to analyze the actions or motivations of any individual, but to demonstrate how artificial intelligence–assisted narrative analysis combined with Mind Genomics thinking can provide a framework for understanding how audiences interpret complex news stories.

Materials and Methods

Conceptual Study Design

The present study represents a conceptual simulation rather than an empirical experiment. A publicly reported news narrative describing an attempted political assassination was used as a narrative stimulus to illustrate how complex real-world events can be translated into structured analytical frameworks.

Artificial intelligence tools were used in an exploratory manner to assist in identifying recurring themes within the narrative. These themes included ideological rhetoric, social media influence, emotional responses, and perceptions of identity or belonging. AI tools were used only as supportive instruments for narrative decomposition rather than as autonomous analytical systems.

The resulting narrative components were translated into conceptual experimental elements consistent with the principles of Mind Genomics experimental design.

In this sense, the study can be viewed as a conceptual demonstration of how artificial intelligence and Mind Genomics thinking can be combined to help readers and students interpret news stories more systematically. AI tools can assist in identifying key narrative themes within complex reports, while Mind Genomics provides an experimental framework for examining how combinations of narrative elements influence interpretation.

Rather than attempting to determine factual causes of the event itself, the framework focuses on how different informational elements within the narrative may influence how readers understand and interpret the story.

Mind Genomics Methodology

Mind Genomics is an experimental methodology designed to examine how individuals interpret combinations of ideas embedded within narrative scenarios [7]. The method draws on principles of conjoint analysis and experimental design to explore cognitive responses to multi-element messages.

In a typical Mind Genomics study, respondents evaluate a series of short vignettes composed of multiple informational elements. Each vignette represents a unique combination of elements drawn from different thematic categories. Participants rate these vignettes using a defined scale, allowing researchers to determine how different combinations of ideas influence perception and judgment.

The methodology has been widely applied in areas including consumer research, communication studies, and social perception [11]. More recently, the approach has been applied to examine how individuals think about complex social issues such as radicalization [8].

Experimental Design Framework

Based on the narrative stimulus, five conceptual categories were identified:

A. Online environment
B. Social connection
C. Ideological alignment
D. Autonomy
E. Emotional state

Each category contains four conceptual elements. This structure allows a large number of possible narrative combinations.

Total possible vignette combinations:

4⁵ = 1,024 conceptual scenarios

In a typical empirical Mind Genomics study, respondents would evaluate approximately 25–30 vignettes generated through a balanced experimental design.

Results

Conceptual Mindset Segmentation

Radicalization narratives often evoke different interpretations depending on the cognitive orientation of the reader. Within the Mind Genomics framework, audiences can be conceptually segmented into distinct interpretive mindsets. These segments represent patterns of thinking rather than demographic categories.

To illustrate these differences, three conceptual interpretive mindsets were developed: The Radical, The Explorer, and The Outsider. Each mindset reflects a different orientation toward ideological narratives, social media influence, and perceptions of social belonging.

In the present conceptual framework, these mindsets are not derived from empirical respondent data but are introduced as illustrative cognitive segments. In a full empirical Mind Genomics study, statistical modeling would identify such segments from respondent-level responses to experimental vignettes. Here they serve to illustrate how readers may interpret the same narrative through different psychological orientations.

The comparison of these mindsets across several emerging issues related to radicalization and online discourse is summarized in Table 1.

Table 1: Conceptual comparison of three interpretive mindsets (Radical, Explorer, Outsider) across emerging issues related to radicalization and online discourse.

Issue

Mind-Set 1: The Radical Mind-Set 2: The Explorer

Mind-Set 3: The Outsider

1. Social media regulation The Radical opposes regulation, seeing it as an attack on free speech. The Explorer is open to regulation, but wants to ensure it does not stifle online discussion. The Outsider is indifferent to regulation, seeing it as a reflection of mainstream values.
2. Online extremism The Radical sees online extremism as a necessary response to perceived injustices. The Explorer is concerned about online extremism, but wants to understand its root causes. The Outsider is drawn to online extremism, seeing it as a way to express their frustration and anger.
3. Hate speech laws The Radical opposes hate speech laws, seeing them as an attack on free speech. The Explorer is open to hate speech laws, but wants to ensure they are balanced with the need for online discussion. The Outsider is indifferent to hate speech laws, seeing them as a reflection of mainstream values.
4. Radicalization prevention The Radical sees radicalization prevention as a form of social control. The Explorer is open to radicalization prevention, but wants to ensure it is based on nuanced and multifaceted approaches. The Outsider is skeptical of radicalization prevention, seeing it as a way to manipulate and control individuals.
5. Mental health support The Radical sees mental health support as a form of weakness. The Explorer is open to mental health support, but wants to ensure it is tailored to individual needs. The Outsider is indifferent to mental health support, seeing it as a reflection of mainstream values.
6. Community engagement The Radical sees community engagement as a threat to their ideology. The Explorer is open to community engagement, but wants to ensure it is based on mutual respect and understanding. The Outsider is skeptical of community engagement, seeing it as a way to manipulate and control individuals.
7. Social media monitoring The Radical opposes social media monitoring, seeing it as an attack on privacy. The Explorer is open to social media monitoring, but wants to ensure it is balanced with the need for online freedom. The Outsider is indifferent to social media monitoring, seeing it as a reflection of mainstream values.
8. Counter-narratives The Radical sees counter-narratives as a form of propaganda. The Explorer is open to counter-narratives, but wants to ensure they are based on nuanced and multifaceted approaches. The Outsider is skeptical of counter-narratives, seeing them as a way to manipulate and control individuals.

Understanding radicalization narratives also requires identifying the central questions guiding analytical inquiry. Researchers frequently examine how online environments, ideological narratives, and emotional responses interact to influence interpretation.

The key analytical questions guiding the present conceptual framework are summarized in Table 2.

Table 2: Key analytical questions used to structure the conceptual framework for examining radicalization narratives and media interpretation.

 Question

Importance 1 Importance 2

Importance 3

What role do social media platforms play in radicalization? Understanding the mechanisms of online radicalization Identifying potential vulnerabilities in social media platforms Informing strategies for counter-narratives and online extremism prevention
How can we balance online freedom with the need for regulation? Ensuring that regulation does not stifle online discussion Protecting individuals from online extremism and hate speech Informing strategies for social media monitoring and counter-narratives
What are the root causes of radicalization, and how can we address them? Understanding the psychological and social factors that contribute to radicalization Informing strategies for radicalization prevention and intervention Identifying potential vulnerabilities in individuals and communities
How can we develop effective counter-narratives to extremist ideologies? Understanding the mechanisms of online influence and persuasion Informing strategies for counter-narratives and online extremism prevention Identifying potential vulnerabilities in extremist ideologies

The experimental structure underlying the Mind Genomics simulation is based on vignette construction using combinations of narrative elements. Each vignette represents a unique combination of elements drawn from the five conceptual categories described earlier.

The conceptual vignette structure used in this framework is summarized in Table 3.

Table 3: Conceptual vignette elements illustrating the Mind Genomics experimental design used to construct narrative combinations.

Code

Element

QUESTION A What role do social media platforms play in radicalization?
A1 Social media platforms provide a conduit for extremist ideologies to spread.
A2 Social media platforms can also be used to promote counter-narratives and prevent radicalization.
A3 Social media platforms have a responsibility to regulate online content and prevent extremism.
A4 Social media platforms are merely a reflection of societal values and norms.
QUESTION B How can we balance online freedom with the need for regulation?
B1 Regulation should prioritize online safety and security over freedom of expression.
B2 Regulation should prioritize freedom of expression over online safety and security.
B3 Regulation should strike a balance between online safety and freedom of expression.
B4 Regulation is not necessary, as online communities can self-regulate.
QUESTION C What are the root causes of radicalization, and how can we address them?
C1 Radicalization is often the result of psychological and social factors, such as mental health issues and social isolation.
C2 Radicalization is often the result of ideological and theological factors, such as extremist ideologies and charismatic leaders.
C3 Radicalization is often the result of a combination of psychological, social, ideological, and theological factors.
C4 Radicalization is a complex and multifaceted phenomenon that cannot be reduced to a single cause or factor.
QUESTION D How can we develop effective counter-narratives to extremist ideologies?
D1 Counter-narratives should prioritize empathy and understanding over confrontation and critique.
D2 Counter-narratives should prioritize confrontation and critique over empathy and understanding.
D3 Counter-narratives should strike a balance between empathy and confrontation, and critique and understanding.
D4 Counter-narratives are not necessary, as extremist ideologies will ultimately collapse under their own weight.

Discussion

The framework presented in this study demonstrates how AI-assisted narrative analysis combined with Mind Genomics thinking can transform complex news narratives into structured analytical models. Research suggests that radicalization often emerges through interactions among identity processes, perceived grievances, and social influence [12]. Psychological analyses further highlight the role of emotional narratives and ideological framing in shaping extremist cognition [13].

Digital communication environments may amplify these dynamics by enabling rapid dissemination of ideological narratives and connecting individuals with communities that reinforce particular beliefs [5,6]. Mind Genomics provides a complementary perspective by examining how individuals interpret combinations of ideas rather than isolated variables. By systematically varying narrative elements, researchers can explore how audiences interpret complex events and identify patterns of cognitive segmentation.

The framework proposed in this study treats the news event referenced in the narrative solely as an illustrative example used to demonstrate how such an analytical structure may be constructed. The objective is not to determine the motivations or psychological characteristics of any specific individual involved in the incident, but rather to show how complex news narratives can be decomposed into informational elements that allow systematic exploration of audience interpretation.

Beyond its relevance for research on radicalization, the integration of artificial intelligence–assisted narrative analysis with Mind Genomics thinking may also offer important educational value. Students and readers are frequently exposed to complex news stories involving political violence, social conflict, or ideological tensions. Without structured analytical tools, such narratives may be interpreted primarily through emotional reactions, media framing, or pre-existing political beliefs.

By decomposing news narratives into identifiable informational elements and examining how different combinations of these elements influence interpretation, the combined use of AI and Mind Genomics thinking offers a systematic approach for understanding how readers make sense of complex public events. Such an approach may help students develop more reflective and structured ways of engaging with contemporary news stories, thereby promoting critical thinking, media literacy, and a deeper awareness of how narratives shape public perception.

Conclusion

This study presents a conceptual framework demonstrating how artificial intelligence–assisted narrative analysis can be integrated with Mind Genomics thinking to examine how audiences interpret complex news narratives related to radicalization and political violence. Using a widely reported news account as a conceptual stimulus, the paper illustrates how complex media narratives can be decomposed into structured informational elements and organized into a conceptual experimental design consistent with Mind Genomics methodology. The framework highlights how combinations of narrative elements—such as online environments, ideological alignment, social connection, autonomy, and emotional states—may influence the ways in which individuals interpret events associated with radicalization.

Although the present work represents a conceptual simulation rather than an empirical study, it outlines a methodological pathway for future research. Empirical Mind Genomics experiments could apply this framework to measure how different narrative components influence audience interpretation and to identify distinct cognitive segments among readers exposed to narratives of political conflict and extremism. Such investigations could contribute to a deeper understanding of how individuals process complex and emotionally charged news stories.

More broadly, the integration of AI-assisted narrative decomposition with Mind Genomics thinking offers a structured analytical approach for studying contemporary news discourse. Beyond research applications, the framework may also have educational value by helping students and readers develop more systematic and reflective ways of interpreting complex media narratives. By transforming unstructured news stories into analyzable informational components, the approach may contribute to improved critical thinking, media literacy, and a deeper understanding of how narratives shape public perceptions of radicalization and political violence.

Competing Interests

The authors declare that they have no competing interests.

Funding

No external funding was received for this study.

References

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The Afro-Brazilian/Afro-Caribbean Martial Arts Tradition: Two Women Practitioners Speak on Its Socio-Cultural Benefits and Practice Challenges in the Inner-City

DOI: 10.31038/AWHC.2026913

Abstract

This research paper analyzes the views and experiences of two women, one African American and one Afro-Caribbean, who are practitioners of the Afro-Brazilian martial art of Capoeira and its complementary stick-fighting arts, Kalenda and Maculélè. They have spent, respectively, 30 years and 4 years studying these arts, variants of which permeate much of the Caribbean and parts of Central and South America, where populations of African descent live. In a previously published study, I provided a detailed account of the school where these women practice, and interviewed some of its students and its head instructor. These two women were not part of that initial study. However, their interviews, collected here, add appreciably to our understanding of this school’s significance by analyzing their perceptions of martial arts practice, a topic largely discussed by men. I focus on their experiences and unique perspectives, which cover issues of cultural identity, gender challenges, and the personal growth they have undergone as a result of their studies. The cultural difference paradigm and the ACBCM (African-centered behavioral change model) were used to evaluate how gender, culture, and self-perceptions influence their lived experiences within the practice studio and in the wider world.

Keywords

African-based martial arts, Capoeira, Cultural difference paradigm, African-centered behavioral change model

Os Malandros de Mestre Touro is the name of a small but vibrant martial arts studio in inner-city San Diego, CA. It has been in continuous existence since 2002, making it one of the longest-lasting cultural institutions in what has recently been designated as The Black Arts and Culture District, an urban tract nine blocks long on upper Imperial Ave, running from 61st to 69th Street. Public art, murals, businesses, storefront churches and Mosques, and social gathering places form a cultural hub that revitalizes the living spaces of its inner-city residents while serving as a barrier against poorly planned housing projects and gentrification.

Someone passing by might miss it entirely; no shiny trophies line its windows, and if the door happened to be open, the passerby would not see students punching and kicking in flashy matching uniforms in front of a glass mirror covering the wall. However, external appearances can be deceiving. Once inside, one would see earnest students practicing, some in loose-fitting street clothes, others in white pants and white T-shirts with the school logo. Most of the students are young males, with some older males; a smaller number of female students are present as well. While I interviewed female students in my initial study, I wanted to take a deeper dive into gender, family, and other concerns facing female martial arts practitioners for this paper. Except for a relatively small number of high-profile female martial arts practitioners of African descent, very little scholarly attention has been paid to the challenges faced by the smaller but growing body of female practitioners, and virtually no attention has been paid to female practitioners of African-based martial arts in North America.

Methods

A primary tool used was cultural immersion: I watched approximately the first half of a two -hour class on May 1, 2026, then listened to the head instructor’s critique of their practice following that portion of the class. He brought to their attention that some students were unfocused and needed to give their practice partners more of their attention and energy; he told them that just because what they are doing is called Capoeira “play” does not mean these skills should be treated as unserious. He reminded them that males and females who had been enslaved used these skills to stay alive and fend off the attacks of slaveholders “back in the day.” I continued to observe the remainder of their afternoon training session at the school, and observed how both women maintained their focus, which challenged the younger students to be more serious. The remainder of the class was dedicated to Kalenda, the use of a long wooden staff for self-defense. I then conducted taped interviews with the two women. The first interview was conducted simultaneously with both students on May 1, 2026. A follow-up phone interview was conducted with one of the women on May 3, 2026. Discussions follow the interviews, using the cultural difference paradigm and the ACBCM (African-centered behavioral change model).

Findings

Khadija White is African American and has lived in San Diego most of her life. She has practiced Capoeira for over thirty years and is highly ranked as a Capoeira Professor. Daniela Bracey was born and raised in Puerto Rico, has studied Capoeira for approximately four years, and, as a young mother, first enrolled her children in the school and then joined them, strengthening their family bond. This section contains their interviews with minimal editing of their words, followed by evaluative discussions. Both women responded freely and interactively to questions, engaging in a back-and-forth that added nuance to each other’s comments. The letter “I” identifies the interviewer and author:

I: I’d like you to share a little bit about your history and background in the study of martial arts, particularly your experiences with Afro-Brazilian martial arts. Tell me, what attracted you to Afro-Brazilian martial arts?

Daniela: I am from Puerto Rico, where movement to music, especially the sound of drums, is a major part of most everything you do in life. And since Capoeira’s movement is based on these rhythms of life, it is one of the big reasons I got drawn to the art. It was an easier and a natural thing for me to do the Capoeira moves to the drums. It was also very important to me to find a way to keep my kids involved in something that would remind them of themselves, and not erase or forget who they are. I think that’s what Capoeira does for them. And being a part of this school gives me a sense of community, because that’s what we have here–a community. The self-defense part is like icing on the cake, but if I have to defend myself and my family, I can. I do have some prior martial arts training from my time in the military. I also studied Muay Thai and kickboxing, but again, it was the music that spoke to me, and then everything else came along with it.

Khadija: My mother started me in Capoeira when I was very young – I was around the art as early as four years old. She has always been committed to the Nguzo Saba principles of Kwanzaa and taught me about its cultural values [Kwanzaa is an African American cultural holiday. For more details, see the second discussion]. She wanted me to learn about African culture and the African Diaspora and to incorporate that knowledge into my life in a practical way–especially its self-defense aspects– from an African cultural perspective. That’s how we survived!

Discussion #1: Daniela’s point sheds light on Capoeira’s appeal to many women of color [1], commenting on gender challenges, notes that Black girls growing up were often self-conscious: “…girls don’t want to appear uncoordinated in front of boys… It’s the job of coaches to provide heavy doses of encouragement and motivation to females who are insecure about their athletic performance” (p.14). In my previous observations of classes and public performances, the presence of drumming and other live Afro-Brazilian instrumentation (an inseparable aspect of head instructor Mestre Preto Velho’s teaching) appeared not only to support female coordination by aligning movement with the drumbeat, but also, for some of the younger female students, encouraged creative movement in their Capoeira and allayed self-consciousness. Daniela noted that Afro-Brazilian music is integral to her focus during practice and performance.

Khadija’s response is succinctly framed by the cultural difference paradigm. It asserts that the thinking, behavior, and social conditions of Black and other peoples are best understood by considering the strengths and limits of their cultures [2]. Thus, cultural awareness should be a prerequisite for those working with various cultural groups. The Nguzo Saba, or the principles of Kwanzaa are increasingly becoming important aspects of African-American culture and have been since its inception in 1966. Its founder, Dr. Maulana Karenga, describes it as a “culture which is the thought and practice by which a people creates itself, celebrates, sustains and develops itself through its history and humanity” [3]. [end of discussion #1]

I: Concerning mixed gender or co-ed classes, how do you view this type of training? Is it a challenge for you as a woman? And do your children or the other children seem to have any mixed feelings about it?

Daniela: Well, if that feeling arises in some of the kids, it gets shut down [by head instructor Mestre Preto] real quick because, at the end of the day, who are you gonna go up against? You have to know how to go up against anybody, no matter how big, no matter if they are male, female, young, or old.

Khadija: And that’s the point. That’s what this is for–your self-defense in any situation. You never know if you’re gonna be up against someone of the same gender out in the world. And as Daniela said earlier, this is a community; we are all here to support and challenge each other. This is the only martial arts community I’ve ever known. We appreciate sparring with our male counterparts; it trains us to get over the nervousness of being confronted by a big man.

I grew up in this culture. And as an African-American, we’ve lost that culture of community where men and women, boys and girls, young and old worked together. This is a way to reconnect to Africa and the African diaspora.

Daniela: I am a little person, and as women, especially little women, we have had to learn not to depend on brute physical strength; our strength, or a big part of it, comes from malicia, a Capoeira word that we translate as “tricknology.” This means that we all learn techniques that conceal our intentions until we see an opportunity to counter our opponent’s moves in ways they don’t have a defense against.

I: I would like you both to speak to or describe the “warrior” mindset you have developed through your practice that equips you to deal with the physical safety and mental well-being challenges you may have experienced as women. I ask because, in general, women face more challenges and stressful situations than most men. You just mentioned the cultural aspect of your training. How has that helped you deal with the challenges you face in life? And if so, how?

Daniela: Yes, I’ve improved my well-being and that of my kids in both the physical and mental areas. On the physical level, we are more fit. We come in here two to three times a week and feel more physically confident. Mentally, I’ve learned how to strategize quickly before acting. It’s becoming easier, and you have to know how to do that in Capoeira. My kids have gotten better; for instance, I appreciate that they are learning to follow instructions and to take correction positively, without attitude. They “get it” that this is good for them. That’s because this environment supports them culturally.

Khadija: And when it comes to our safety, we are learning an art that keeps us in constant motion, on our feet, upside down on our hands, on the ground, and in the air. We don’t learn by doing kata, those set forms you see in karate tournaments; that’s not a part of this culture. We learn our art by doing constant sparring and two-person exercises with each other. As for the warrior spirit, we’ve learned that it’s more than about physical strength. It’s knowing when to walk away and how to walk away without being perceived as weak. At other times, we use the malicia culture we talked about earlier as a kind of sleight of hand, where we pretend to be weak to distract the opponent, then redirect their strength while maintaining a calm demeanor.

Discussion #2: [4] argue that behavioral change “occurs through the process of culturalization”. This is achieved through cultural realignment, which aims to reduce unproductive social conditions by replacing them with prosocial, life-affirming ones. At the school, this is accomplished by culturally realigning students with traditional African and African-American cultural values to enhance their well-being. This is accompanied by cognitive restructuring, so that people can reconfigure how they view themselves in the world they live in, and by character refinement, a process whereby people adjust their mental and ethical attributes to align with their cultural essence [2]. A close reading of the self-development undergone by Khadija and Daniela, and the culturally based worldviews they describe, connects organically with the cultural realignment and cognitive restructuring models of the ACBCM paradigm. They express the teachings of head instructor Mestre Preto Velho, and are embedded in the structure of Os Malandros’ curriculum. Khadija says that Mestre refers to that structure as his African reconnection program, which is the essence of his life’s work. [end of discussion #2]

Finally, I asked either one to address what they would say to a group of young black and brown teenage girls and women who were wrestling with the challenges of living in the inner city. What would they tell them about how their practice of Afro-Brazilian arts has benefited their lives and how it could benefit them? Daniela spoke up and said she would tell them that studying this art is about studying and learning about themselves and their real culture, not street culture. “When you have that [self-knowledge],” she said, “you are better able to cope with what life throws at you [5].”

Conclusion

These women’s experiences and observations speak to the challenges faced by women who take care of their well-being and that of their families through Capoeira, and who speak to and sometimes for the community in which they live. In Khadija’s case, her mother actively encouraged her to embrace her culture from an early age. In Daniela’s case, she did the same for her children by enrolling them in Capoeira. Both women have at their disposal a physical and mental tool chest as part of a culturally rich, African-centered martial art. They have shown how it serves their personal and family priorities. At this juncture in their lives, they recognize that it is not enough to learn the physical aspects of a martial art solely for their own benefit; they are ready to serve as ambassadors for a way of life that can uplift others mentally, physically, and spiritually, in a way that contributes to their community’s potential.

References

  1. Kunjufu J (2014) Educating black girls. African American images, pub.
  2. McDougal S III (2017) Research methods in Africana studies. Lang.
  3. Karenga M (2010) Introduction to black studies (4th ed.). University of Sankore Press.
  4. Nobles W, Goddard LL, Gilbert D (2009) Culturecology, women, and African-centered HIV prevention. Journal of Black Psychology 35(2): 228-246.
  5. Winbush R (2001) The warrior method: A parent’s guide to rearing healthy black boys. Amistad.

The Resilient Mind: Children’s Theory of Mind as a Protective Factor Against Social Emotional Problems during the Pandemic

DOI: 10.31038/PSYJ.2026813

Abstract

By March 2020, many governments closed schools and implemented “social distancing” to reduce COVID-19 spread. The current research examined a) the impact of reduced social interactions on children’s social-emotional health and b) whether children’s ‘theory of mind’ (i.e., their ability to understand others’ mental states) served as a protective factor against the potentially deleterious effects of reduced social interactions. Parents of 3–12-year-olds (n=130) reported on their child’s social-emotional health (Strengths & Difficulties Questionnaire; Social Skills Improvement System) and time spent in in-person interactions before and during the pandemic. They also completed a measure of their child’s theory of mind, and reported their own stress and loneliness. A subset of parents completed the child measures pre-pandemic (n=48), allowing for longitudinal analyses. Stepwise regressions showed that decreases in children’s in-person peer interactions significantly predicted increased social-emotional difficulties, even after accounting for other factors. Children’s theory of mind emerged as a significant predictor of fewer social-emotional difficulties, more prosocial behavior, and stronger social skills. Longitudinal data revealed that greater reductions in peer interaction predicted more negative changes in social-emotional functioning. However, children with more advanced theory of mind experienced fewer negative changes, suggesting their theory of mind buffered against the harmful effects of reduced interaction. These findings underscore the importance of peer interaction for children’s well-being and highlight theory of mind as a potential protective factor. Interventions aimed at strengthening children’s theory of mind may help minimize the deleterious effects of reduced social interaction.

The Resilient Mind: Children’s Theory of Mind as a Protective Factor Against Social Emotional Problems during the Pandemic

Humans have a primary need for social interaction and social connection [1-3]. Even moderate levels of social isolation can have detrimental effects on one’s physical and social-emotional health. For instance, moderate levels of social isolation have been linked to elevated blood pressure and stress hormones [4], immune system dysregulation [5,6], cardiovascular disease [7] as well as clinical depression and suicide ideation (see [8,9] for reviews). Experimental studies with humans and other animals suggest that social isolation is a major risk factor for mortality and morbidity, with the health risks associated with isolation at least as great as cigarette smoking [10,11]. Prospective studies controlling for baseline health status reveal an increased risk of death among people with fewer and poorer social relationships (e.g., [10]). Indeed, a meta-analysis of 148 studies [12] revealed a 50% increased likelihood of survival for participants with stronger social relationships. The magnitude of this effect did not differ based on age, gender, cause of death, or previous health status. Interestingly, the magnitude of the relationship between social relationships and mortality was greatest in studies that assessed the quality of the social connections, not only the quantity. Notably, even perceived social isolation (i.e., loneliness) has a similar effect on physical and mental health as actual social isolation (see [13] for a review).

Of particular interest to the current research are the lasting effects that reduced social interactions have on young children. Caspi et al. [7] followed over 1000 children at multiple timepoints from age 3 to age 26 assessing various indices of their physical health (e.g., weight, blood pressure, cholesterol) and level of social interaction revealing that those who were more socially isolated as children were at significant risk of poor adult health independent of other childhood risk factors for poor adult health (e.g., low SES, low IQ, obesity). Notably, this relationship between childhood social isolation and poor health 20 years later was not accounted for by exposure to stressful life events, smoking, alcohol abuse, or lack of exercise. This research also revealed that social isolation across multiple developmental time points had a cumulative negative effect on their health (see also [14]). Not surprisingly, the negative effects of social isolation in childhood are not limited to physical health. For instance, Marryat and colleagues [15] examined the social-emotional functioning of 10,000 preschoolers using the Strengths and Difficulties Questionnaire [16] which assesses Peer Relationship Problems, Emotional Symptoms, Hyperactivity/ inattention, Conduct Problems and Prosocial Behaviours. Their analyses revealed that various indices of social isolation predicted poorer overall social emotional functioning among preschoolers.

As it is well established that social interaction is especially critical for young children, several researchers expressed concern for children’s well-being due to the reductions in social interaction that many youth experienced during COVID-19 (eg., [17,18]). The current work examined how reductions in the number of in-person social interactions that they experienced during the pandemic affected children’s social-emotional well-being. Importantly, children’s social understanding, particularly their ability to reason about the mental states of others (sometimes called ‘theory of mind’ or ToM), is another key predictor of children’s social-emotional functioning and well-being (e.g., for recent reviews see [19,20]). Therefore, we also examined whether those children with more advanced theory of mind would experience fewer social emotional problems. Individual differences in theory of mind are present early and continue into adulthood [21,22] with more developed theory of mind predicting several positive outcomes for children’s development and well-being. For example, a meta-analysis of 20 studies on children ages 2-10 using measures of theory of mind and measures of peer popularity revealed that children with increased theory of mind tended to be more well-liked [23]. As another example, a meta-analysis of 76 studies examining theory of mind and prosocial behaviour (e.g., helping, comforting, and sharing) in children 2 to 12 years of age found that children with higher theory of mind scores were more likely to act prosocially [20,24,25]. Similarly, more advanced theory of mind has been associated with increased cooperation [26], reduced peer conflict [27] and improved communication skills [27-30]. Peterson and colleagues [31] also found that typically developing children’s theory of mind understanding independently predicted social skills above and beyond age, gender and verbal ability.

Conversely, deficits in theory of mind have been proposed as a characteristic feature of Autism Spectrum Disorder and are believed to play a central role in social-communication challenges [32,33]. Building on this early work, subsequent studies report that autistic children and adults demonstrate greater theory of mind difficulties relative to neurotypical peers (e.g., see [34-36] for a recent meta-analysis). Similar differences have also been observed among children with attention-deficit/hyperactivity disorder, who demonstrate weaker performance on certain theory of mind measures [37,38]. Individuals with conduct problems have likewise been shown to exhibit reduced theory of mind performance (e.g., [39-41]). Theory of mind understanding also predicts emotional symptoms (e.g., increased sadness) in adults and in adolescents and youth. For example, a meta-analysis of 18 studies with adults revealed that difficulties with theory of mind can be a risk factor for depression with the level of theory of mind impairment relating to the severity of the depressive symptoms and corresponding psychosocial impairments [42]. Similarly, Caputi and Schoenborn [43] examined theory of mind and internalizing symptoms during middle childhood and early adolescence and found that children with higher scores on theory of mind tasks demonstrated lower depressive symptoms and lower symptoms related to panic disorder and separation anxiety.

Of particular relevance to the current research is a small body of evidence that theory of mind may serve as a protective factor against some types of stress or adversity. For example, Hughes and Ensor [44] found that the adverse effects of harsh parenting on behavioural problems (e.g., hyperactivity, emotion regulation problems) were attenuated for two year olds with higher ToM scores. Moreover, after testing these same children two years later and controlling for their earlier behavioral problems, they found that theory of mind skills at age 2 predicted whether their behavioral problems persisted or diminished. Again, in a separate study, the negative effects that harsh parenting had on the child’s behavior were reduced in those with greater theory of mind [45]. Similarly, Cadamuro et al. [46] tested the role of theory of mind as a protective factor against the negative effects of parents’ stress on their child’s stress during the aftermath of a natural disaster. Their results revealed that mothers’ posttraumatic stress symptoms predicted their children’s posttraumatic stress symptoms–but only among children with low theory of mind abilities. In other words, strong theory of mind skills appears to help minimize at least some factors that adversely affect children’s social emotional well­being.

The Current Research

In sum, the primary research questions addressed in this manuscript were: 1) What impact did reductions in in-person social interactions during the pandemic have on children’s social-emotional well-being? And 2) Did children with more advanced theory of mind fare better than their peers with less advanced theory of mind? We hypothesized that reductions in in-person peer interactions that occurred during the COVID-19 pandemic would predict increases in social emotional difficulties (e.g., hyperactivity, conduct problems, emotional symptoms). We also predicted that children with more advanced theory of mind would experience fewer negative changes in their social-emotional functioning during the pandemic compared to their peers with less advanced theory of mind.

To address our research questions we asked parents of 3-12-year-old children to complete an online survey assessing their children’s social emotional functioning, theory of mind, and changes in their amount of social interactions during the pandemic (beginning in June 2020). Specifically, the survey included a measure of children’s social-emotional difficulties (Strengths & Difficulties Questionnaire [16], a measure of social skills (Social Skills Improvement System;SSIS [47]), and a measure of their ‘theory of mind’ (Children’s Social Understanding Scale; CSUS [48]). Parents also estimated the number of hours per day children engaged in interactions with peers and adults (in-person) before the pandemic versus currently. We also anticipated that parents’ stress and loneliness would increase during the pandemic, and wanted to control for that in our regression models. To that end we included two measures assessing the parent’s social-emotional health: a Perceived Stress Scale [49] and the UCLA Loneliness Scale [50]. Forty-seven of our participating families had visited our laboratory prior to the pandemic and completed the same child-specific measures. Therefore, in some of our analyses we can control for the children’s pre-pandemic level of social emotional functioning and specifically examine changes in their behavior.

Method

Participants

Full Sample

Of the 138 parents recruited, 8 were excluded for failing to complete at least 80% of the measures, resulting in a final sample of 130 participants with children ages 3-12 years old (MAge=87 months, SDAge,=30 months; 55% female children). Due to missing data on one or more variables included in the regression models, listwise deletion resulted in an analytic sample of 110 participants for those analyses. Parents participated online from anywhere in North America but were predominantly Canadian. The majority of the parent respondents were female (92%). The majority of the sample identified as European (38%) or Asian (36%). Approximately 80% of the sample reported completing at least some college education and a combined family income of $100,000/year or greater. All participants gave informed consent and were told they could skip any questions they did not wish to answer. Parents were compensated for their participation by choosing either a $5 gift card or a 1 in 25 chance of winning a $50.00 gift card.

Longitudinal Subsample

A subset of these parents had also completed the child-specific measures in our lab prior to the pandemic, allowing us to examine changes in their child’s behavior and specifically examine whether advanced theory of mind minimized any negative changes in social emotional health. The final longitudinal subsample consisted of data from parents for 48 children ages 2-12 years old (MAge=86 months, SDAge,=25 months; 60% female). Seventeen of these parents did not complete the SSIS measure but were included in the remaining analyses.

Measures

Parents completed the following measures in the following order (see Table 1):

Table 1: Description of Measures and Example Items.

Measure

Description

Example Items

Strengths and Difficulties Questionnaire (SDQ) •                Parent-report measure assessing children’s psychological and behavioural characteristics related to social emotional health

•                25-items on a 3-point scale: answer choices ranging from 0 (Not True) to 2 (Certainly True)

•        Often lies or cheats

•        Considerate of other people’s

feelings

The Children’s Social Understanding Scale (CSUS) •                Parent-report measure assessing individual differences in children’s theory of mind.

•                Shortened 18-item version on a 4-point scale: answer choices range from 1 (Definitely Untrue) to 4

(Definitely True)

•        Talks about differences in what people like or want
The Social Skills Improvement System Rating Scale (SSIS) •                Parent-report measure that assesses children’s social skills and problem behaviours

•                Shortened 46-item version on a 4-point scale: answer choices range from 0 (Never) to 3 (Almost Always)

•        Expresses feelings when wronged
Social Interaction Measure (SIM) •                Parents estimated the number of hours per day their child spent in in-person social interactions with peers versus parents.

•                Estimates were provided for during (i.e., between June and December 2020) and prior to the pandemic

•                Number of hours per day
Perceived Stress Scale (PSS) •                Self-report measure assessing the extent to which situations in one’s life are perceived as stressful in the last month

•                10-item on a 5-point scale: answer choices range from 0 (Not at all) to 4 (Very often)

•        In the last month, how often have you felt nervous and “stressed”?
The UCLA Loneliness Scale (UCLA Loneliness) •                Self-report measure assessing an individual’s subjective feelings of loneliness and feelings of social isolation

•                20-items on a 4-point scale: answer choices range from 1 (Rarely) to 4 (Often)

•        How often do you feel that you are no longer close to anyone?

Children’s Social Emotional Difficulties

Children’s social emotional difficulties were assessed using the Strengths and Difficulties Questionnaire (SDQ [16]), which is a widely used measured to examine individual differences in children’s social emotional competence (e.g., [15]). It consists of a 25-item scale focused on five different components of social-emotional health: emotional symptoms (e.g., often unhappy, depressed, or tearful), conduct problems (e.g., generally well behaved, usually does what adults request (reverse coded)), hyperactivity/impulsivity (e.g., constantly fidgeting or squirming), peer relationship problems (e.g., rather solitary, prefers to play alone), and prosocial behavior (e.g., considerate of other people’s feelings). Each subscale has 5 items and parents rated their child’s behavior over the previous 6 months on each item with answers ‘Not True’, ‘Somewhat True’, and ‘Certainly True’. The prosocial behaviors comprise the Strengths subscale. Higher scores on the prosocial subscale reflect greater levels of prosocial behavior. Cronbach’s α in the current sample was .758 for the 5-item Prosocial scale reflecting good internal reliability. The other four 5-item subscales—emotional symptoms, conduct problems, hyperactivity/impulsivity, and peer relationship problems—comprise the Difficulties scale. Higher scores on the difficulties scale reflect greater levels of difficulties. Cronbach’s α in the current sample was .843 for the 20-item Difficulties scale reflecting very good internal reliability.

Children’s Social Understanding Scale (Theory of Mind, or ToM)

The Children’s Social Understanding Scale (CSUS Short Form; [48]); is a parent-report measure of children’s understanding of mental states such as beliefs, desires, emotions, intentions, and knowledge, which is more generally referred to as theory of mind. The CSUS Short Form is a parent-report measure consisting of 18-items rated on a 4-point scale including ‘Definitely Untrue’ (1), ‘Somewhat Untrue’ (2), ‘Somewhat True’ (3), and ‘Definitely True’ (4). This measure has previously been shown to reliably predict individual differences in 3- to 12-year-olds social emotional competence [19]. Sample items include, “My child talks about differences in what people like or want (e.g., “you like coffee but I like juice”)”, “My child has trouble figuring out whether you are being serious or just joking” (reverse coded), and “My child talks about the difference between the way things look and how they really are (e.g., “It looks like a snake but it’s really a lizard”)”. Higher scores reflect greater levels of theory of mind or mental state understanding. In our sample, the internal consistency was very good (Cronbach’s α=.865) for this 18-item measure.

Children’s Social Skills

The Social Skills Improvement System Rating Scale (SSIS-RS; [47]) is a parent report measure comprising a social skills scale (46 items) and a problem behavior scale (30 items). For brevity in measurement, we only included the 46-item social skills scale (as a complement to the more limited 5-item “Strengths” scale in the SDQ). We did not include the problem behavior scale as we believed children’s problem behaviors were being adequately captured in the 4 “Difficulties” subscales of the SDQ. Answer choices range from 0 (Never) to 3 (Almost Always) and comprise 7 facets of social skills namely, Communication (e.g., Takes turns in conversations) , Cooperation, (e.g., follows your directions), Assertion (e.g. expresses feelings when wronged), Responsibility (e.g., is well behaved when unsupervised), Engagement (e.g., invites others to join in activities), and Self Control (e.g., stays calm when disagreeing with others). Higher scores reflect greater social skills. Cronbach’s α in the current sample was .950, reflecting excellent internal reliability.

Social Interaction Measure (SIM)

Parents were asked to estimate the number of hours per day their child was spending in in-person social interactions with their peers versus with adults for two time points: 1) Prior to the pandemic and 2) Currently (i.e., data were collected during the pandemic between June and December 2020).

Parental Stress

Stress was measured using The Perceived Stress Scale (PSS-10; [49]). It is composed of 10 items and examines the degree to which an individual perceives various life situations to be stressful in the last month. Answer choices on the scale range from 0 (Not at all) to 4 (Very Often) and example items include questions such as “In the last month, how often have you been upset because of something that happened unexpectedly?” and “In the last month, how often have you felt that you were on top of things?”. Higher scores reflect greater levels of perceived stress. Cronbach’s α in the current sample was .907 for this 10-item measure, reflecting excellent internal reliability.

Parental Loneliness

Parent’s subjective feelings of loneliness was assessed using The UCLA Loneliness Scale-Version 3 [50]; a 20-item self-report measure with answer choices ranging from 1 (Rarely) to 4 (Often). Example items include questions such as “How often do you feel that you lack companionship?” and “How often do you feel left out?”. Higher scores reflect greater feelings of loneliness. Cronbach’s α in the current sample was .936 for this 20-item measure, reflecting excellent internal reliability.

Procedure

Participants were recruited via social media ads and a University database of families interested in research. Data were collected between June and December 2020. The online survey took between 30-40 minutes to complete. Informed consent was obtained electronically prior to completion of the remaining survey which included demographic questions (e.g., age, gender, ethnicity, number of siblings, family income, education) followed by the aforementioned measures in the following order: SDQ, CSUS, SSIS, Social Interaction measure, PSS, UCLA Loneliness (See Table 1). Measures of the parents’ and children’s social substitution behaviors were also included in the survey as part of another research project. At the end of the survey all participants were provided with our contact information and a variety of wellness resources.

Analytic Plan

All data were entered into SPSS 26 software. Preliminary analyses included computing descriptive statistics for each variable (See Table 2) and paired samples t-tests to confirm whether there were significant reductions in the number of hours per day children were spending in in-person interactions during the pandemic. Two change scores for children’s social interactions (i.e., one with other children and one with adults) were computed by subtracting the number of hours per day children were spending in those interactions during the pandemic from the number of hours per day children were reportedly spending before the pandemic.

Table 2: Descriptive Statistics.

Variable

Mean Std. Deviation Min. Max.

N

SDQ_Difficulties

9.46

5.99 0 40 110

SDQ_ProsocialSubscale

7.87 2.55 0 10

110

SSIS_Scores

99.25

16.82 0 138 110

Child’s Age in Years

7.49 2.55 3

12

 
Total Perceived Stress

17.58

7.54 0 40 110

Total UCLA Loneliness

43.25 11.92 20 80

110

Change in in-person peer interactions

3.075

3.40     110

Change in in-person adult interactions

-.55 3.80    

110

Three Stepwise regression analyses were performed to identify which variables most strongly predicted 1) children’s social skills (Total SSIS scores), 2) children’s social emotional strengths (SDQ-Prosocial) and 3) difficulties (SDQ-Difficulties Total). Stepwise regression was selected because it enabled us to determine which of the variables was the most significant predictor of children’s social emotional health and identify how much additional variability in children’s social emotional health each variable contributed [51]. Predictor variables included the child’s age, the child’s gender, the child’s theory of mind, the parents’ loneliness and stress, and changes in the number of hours per day children were engaged in in-person interactions. The child’s theory of mind and changes in the child’s social interactions were the primary variables of interest. The child’s age and gender and the parent’s social emotional health indices (i.e, loneliness and stress) were included because these factors have been widely recognized to contribute to a child’s social emotional health (e.g., [52-54]).

Finally, we conducted analyses on our longitudinal sample. The parents of 48 children from our full sample had also completed the measures of children’s social emotional health (i.e. the SDQ, the SSIS) prior to the pandemic allowing us to control for pre-pandemic levels of their children’s difficulties. In this way we could expand upon the analyses above by specifically identifying which variables predicted the changes in the child’s social emotional health during the pandemic, albeit in a smaller sample. Preliminary analyses included computing change scores for each measure by taking the difference between their score before the pandemic and their score during the pandemic and conducting one-sample t-tests to identify whether there were significant changes in the children’s social emotional health from Time 1 to Time 2.

Results and Discussion

Assessing Changes in Social Interactions

As expected, paired samples t-test revealed a significant decrease in the number of hours children were spending in-person with other children per day during the pandemic (M=3.9, SD=4.2) compared to before the pandemic (M=6.7, SD=3.2), t(115)=9.522, p<.001. In contrast, there was a small, but non-significant, increase in the number of hours children were spending with adults during the pandemic (M=8.6, SD=5.2) compared to before the pandemic (M=7.9, SD=4.4), t(117)=-1.689, p=.094.

Predicting Children’s Social-Emotional Difficulties

The Stepwise Regression results revealed that 5 factors accounted for 35% of the variability in children’s social emotional difficulties (see Tables 3 and 4 for complete regression statistics). As illustrated in Table 3, parent loneliness was the most significant predictor, accounting for 18% of the variability in children’s social emotional difficulties. Notably, children’s theory of mind was the next most significant predictor. As hypothesized, children with higher theory of mind scores experienced fewer social emotional difficulties. With children’s theory of mind added to the model an additional 7.7% of the variance in children’s social emotional difficulties was explained. Gender accounted for an additional 5% of the variability in children’s social emotional difficulties, with male gender predicting greater social emotional difficulties than female gender. Parents’ stress accounted for an additional 4.6% of the variability, with greater parental stress predicting more social emotional difficulties in their child. Finally, the changes in the amount of time children were spending in person with other children during the pandemic compared to before the pandemic accounted for an additional 2.4% of the variability in their social emotional difficulties. That is, even after accounting for the four largest contributors to children’s social emotional difficulties, children who experienced greater reductions in their in-person peer interactions during the pandemic still had significantly greater social emotional difficulties than those who experienced fewer decreases or no changes in their peer interactions.

Table 3a: Stepwise regression analysis concerning predictors of social difficulties.

Model

R R2 Adjusted R2 Std. error of the estimate
1 .429a .184 .177

5.44

2

.512b .262 .248 5.20
3 .559c .312 .293

5.04

4

.599d .358 .334 4.89
5 .619e .383 .353

4.82

aPredictors: (Constant), Total UCLA Loneliness
bPredictors: (Constant), Total UCLA Loneliness, CSUS_Score
cPredictors: (Constant), Total UCLA Loneliness, CSUS_Score, Child’s Gender:
dPredictors: (Constant), Total UCLA Loneliness, CSUS_Score, Child’s Gender, Total Perceived Stress
ePredictors: (Constant), Total UCLA Loneliness, CSUS_Score, Child’s Gender, Total Perceived Stress, ChangeChild_InPersonChildren

The stepwise regression analyses excluded the child’s age and the change in the child’s in-person interactions with adults meaning these variables did not account for a significant amount of the variability in children’s social-emotional difficulties above and beyond the other variables. The lack of an effect from changes in adult interactions does not necessarily reflect an increased importance of peer interactions over adult interactions on children’s social emotional health, but instead, likely reflects the fact that the number of hours children spent with other children significantly decreased over the pandemic whereas their time with adults did not decrease (in fact it marginally increased).

Table 3b: Stepwise regression analysis concerning predictors of social difficulties: B and beta correlation and significance level of variables.

Model

Predictors B Std. error Standardized Coefficientsa t

p

1 (Constant)

.127

1.96   .065

.949

  Total UCLA Loneliness

.216

.044 .429 4.94

.000

2 (Constant)

18.51

5.80   3.19

.002

  Total UCLA Loneliness

.159

.045 .316 3.52

.001

  CSUS_Score

-.461

1.38 -.301 -3.35

.001

3 (Constant)

13.49

5.90   2.29

.024

  Total UCLA Loneliness

.156

.044 .309 3.55

.001

  CSUS_Score

-.422

1.34 -.276 -3.15

.002

  Child’s Gender

2.62

.937 .227 2.80

.006

4 (Constant)

12.92

5.73   2.25

.026

  Total UCLA Loneliness

.094

.048 .188 1.96

.052

  CSUS_Score

-4.24

1.30 -.277 -3.26

.002

  Child’s Gender

2.51

.910 .217 2.75

.007

  Total Perceived Stress

.196

.072 .247 2.74

.007

5 (Constant)

12.46

5.66   2.20

.03

  Total UCLA Loneliness

.086

.047 .171 1.82

.072

  CSUS_Score

-4.41

1.29 -.287 -3.43

.001

  Child’s Gender

2.68

.902 .232 2.98

.004

  Total Perceived Stress

.211

.071 .265 2.98

.004

  ChangeChild_InPersonChildren

.278

.138 .158 2.02

.046

aDependent Variable: SDQDifficulties

Predicting Children’s Prosocial Behavior

The Stepwise Regression predicting children’s current level of prosocial behavior (as measured by the SDQ), revealed that 3 factors accounted for 35% of the variability in children’s prosocial behavior. See Tables 4a and 4b for full regression statistics. Children’s theory of mind was the most significant predictor of children’s prosocial behavior accounting for 23% of the variability. The child’s gender accounted for an additional 8% of the variability in children’s prosocial behavior, and the parent’s loneliness accounted for an additional 3.8%. The stepwise regression analyses excluded the child’s age and the change in the child’s in-person interactions, with both children and adults, as well as the parent’s level of stress. That is, none of these variables accounted for a significant amount of the variability in children’s prosocial behavior above and beyond the other variables.

Table 4a: Stepwise regression analysis concerning predictors of prosocial behaviours.

Model

R R2 Adjusted R2 Std. error of the estimate
1 .478a .228 .221

1.58

2

.557b .310 .297 1.50
3 .590c .348 .329

1.46

aPredictors: (Constant), CSUS_Score
bPredictors: (Constant), CSUS_Score, Child’s Gender: – Selected Choice
cPredictors: (Constant), CSUS_Score, Child’s Gender: – Selected Choice, Total UCLA Loneliness

Table 4b: Stepwise regression analysis results concerning predictors of social skills: B and beta correlation and significance level of variables

Model

Predictors B Std. error Standardized Coefficientsa t

p

1 (Constant)

.328

1.34   .245

.807

  CSUS_Score

2.18

.386 .478 5.65

.000

2 (Constant)

2.33

1.39   1.67

.098

  CSUS_Score

2.02

.370 .443 5.48

.000

  Child’s Gender: – Selected Choice

-.99

.279 -.288 -3.56

.001

3 (Constant)

4.91

1.72   2.87

.005

  CSUS_Score

1.67

.389 .364 4.28

.000

  Child’s Gender

-.975

.271 -.283 -3.58

.001

  Total UCLA Loneliness

-.032

.013 -.210 -2.48

.015

aDependent Variable: SDQ_ProsocialSubscale

Predicting Children’s Social Skills

In the Stepwise Regression predicting children’s current level of social skills (as measured by the SSIS) 3 factors accounted for 49% of the variability in children’s social skills. Children’s theory of mind was the most significant predictor of children’s social skills, accounting for 38% of the variability. Parent’s stress accounted for an additional 9% of the variability in children’s social skills, while the child’s gender accounted for an additional 2.3%. The model excluded the child’s age, changes in the child’s in-person interactions, and parent’s level of loneliness, indicating that these variables did not account for a significant amount of the variability in children’s social skills above and beyond individual differences in theory of mind and the child’s gender. See Tables 5a and 5b for full regression statistics.

Table 5a: Stepwise regression analysis results concerning predictors of social skills.

Model

R R2 Adjusted R2 Std. error of the estimate
1 .615a .378 .372

13.34

2

.684b .468 .458 12.38
3 .700c .491 .476

12.17

aPredictors: (Constant), CSUS_Score
bPredictors: (Constant), CSUS_Score, Total Perceived Stress
cPredictors: (Constant), CSUS_Score, Total Perceived Stress, Child’s Gender

Table 5b: Stepwise regression analysis results concerning predictors of social skills: B and beta correlation and significance level of variables.

Model

Predictors B Std. error Standardized Coefficientsa t

p

1 (Constant)

7.94

11.35   .700

.486

  CSUS_Score

26.44

3.27 .615 8.10

.000

2 (Constant)

28.42

11.59   2.45

.016

  CSUS_Score

23.98

3.09 .557 7.77

.000

  Total Perceived Stress

-.682

.160 -.306 -4.26

.000

3 (Constant)

37.79

12.19   3.10

.002

  CSUS_Score

23.26

3.05 .541 7.62

.000

  Total Perceived Stress

-.664

.158 -.298 -4.21

.000

  Child’s Gender

-.4.91

2.27 -.152 -2.17

.032

aDependent Variable: SSIS_Scores

Longitudinal Analyses: Changes in Children’s Social-Emotional Health

One-sample t-tests revealed that there were significant changes in children’s social emotional difficulties, t(46)=-2.78, p=.008 from Time 1 to Time 2, but not in their prosocial behavior, t(46)=1.000, p=.323, ns, nor in their Social Skills, t(30)=.015, p=.989 ns. Therefore, regression analyses predicting changes in this subsample were only conducted for children’s social emotional difficulties.

Predicting Changes in Children’s Social-Emotional Difficulties During the Pandemic

The Stepwise Regression predicting changes in children’s social emotional difficulties revealed that the reductions in children’s in-person peer interactions was the most significant predictor, accounting for 18% of the variability in children’s social emotional difficulties. Children’s theory of mind was the next most significant predictor, accounting for an additional 15.3% of the variance in the changes in children’s social emotional difficulties. Neither age nor gender accounted for a significant amount of variance in the changes children experienced in their social emotional difficulties during the pandemic (ps > .20, ns). That is, as hypothesized, reductions in peer interactions during the pandemic predicted greater social emotional difficulties. Importantly, children with more advanced theory of mind were less likely to experience these negative changes in their social emotional health than those with less advanced theory of mind. That is, advanced theory of mind, or social understanding, appears to serve as a protective factor against the deleterious social emotional health effects encountered during the pandemic. See Tables 6a and 6b for full regression statistics.

Table 6a: Stepwise regression analysis results concerning predictors of change in total social difficulties.

Model

R R2 Adjusted R2 Std. error of the estimate
1 .421a .177 .156

4.28

2

.575c .330 .294

3.91

aPredictors: (Constant), Change in in-person peer interactions
bPredictors: (Constant), Change in in-person peer interactions, CSUS_Score

Table 6b: Stepwise regression analysis results concerning predictors of change in total social difficulties: B and beta correlation and significance level of variables.

Model

Predictors B Std. error Standardized Coefficientsa t

p

1 (Constant)

.215

.916   .235

.816

  Change in in-person peer interactions

-.518

.181 -.421 -2.86

.007

2 (Constant)

-15.93

5.62   -2.84

.007

  Change in in-person peer interactions

-.589

.167 -.478 -3.52

.001

  CSUS_Score

4.72

1.62 .395 2.91

.006

aDependent Variable: Change in total social difficulties

General Discussion

Childhood represents a foundational period during which social interactions play a central role in shaping children’s social-emotional health and development. Accordingly, it is vital to understand how even relatively short-term disruptions in these social interactions impact social-emotional health. This study examined the impact that COVID-19 related reductions in social interactions had on the social-emotional competence and health of children. We also examined whether children’s level of ‘theory of mind’ (i.e., how well they understand and reason about others’ mental states) provided protective benefits for their social emotional health.

As expected, we found that reductions in children’s in-person peer interactions during the pandemic predicted increased social-emotional difficulties, such as increased conduct problems, greater inattention and hyperactivity, and increased emotional symptoms. The negative impact of reduced social interactions was evident even after accounting for four other key predictors of their social emotional health, including parental loneliness, theory of mind, gender, and parental stress. That is, children who experienced greater reductions in their in-person peer interactions during the pandemic had significantly greater social emotional difficulties than those who experienced fewer decreases, or no changes, in their in person peer interactions. Our findings add to an important body of literature showing that social isolation or infrequent social interactions can have deleterious effects on children’s social-emotional skills and well-being (e.g., [7,14,15]) as well as corresponding effects on physical well-being [55-57]. Our results are consistent with a meta-analysis of children aged 5-13 that revealed that the COVID-19 lockdown measures were negatively associated with general mental health outcomes [58]. Notably, our findings highlight that deleterious effects from reduced social interactions can emerge within a few months—they do not require especially prolonged or extreme periods of social isolation.

Our second prediction was also supported: Children who were better at understanding others’ thoughts and feelings not only exhibited more prosocial behavior, greater social skills, and fewer social-emotional difficulties (consistent with the aforementioned body of literature), they also experienced fewer increases in social emotional problems during the pandemic. Notably, these results highlight the benefits of theory of mind as a protective factor for children’s well­being in times of adversity. These findings hold important implications for clinicians and researchers working with children who experience reductions in in-person social interactions, especially with their peers. This research suggests that interventions to improve children’s social understanding can offer a buffer against the negative effects of reduced in-person social interactions. This is especially important as experts predict humans will face future health crises similar to COVID-19 [59,60]. As such, anything that can be done to better prepare children and bolster their social-emotional well-being and resilience during times of hardship deserves special attention.

The benefits of improved theory of mind in children likely extends beyond the child’s social emotional well-being. The relationship between a parent’s social-emotional health and that of their child is seemingly bidirectional. That is, in much the same way that a parent’s health can affect their child, a child’s health can affect their parents (e.g., [61]). For example, research examining parents’ stress during the COVID-19 pandemic found that their child’s current level of social-emotional difficulties (e.g., hyperactivity, impulsivity, conduct problems) was a predictor of their parents’ perceived stress, even after controlling for their child’s pre-pandemic levels of difficulties [62]. Therefore, interventions aimed at fostering a child’s social-emotional health will have mutual benefits for the parent and child, with greater social understanding and well-being in children predicting similar benefits in their parents as well as reduced conflict within the parent-child relationship [63].

It is important to clarify the strengths and limitations of this research alongside their implications. First, it is important to acknowledge that the current study relied on correlational data. Therefore, while reductions in in-person peer interactions predicted increases in social-emotional difficulties, it does not mean that the reductions in social interactions caused these difficulties. That is, other factors associated with those reductions in social interactions, such as being absent from school, or not being able to participate in extracurricular activities, could at least partially account for the relationship. It is important to note as well that we asked parents to report on the number of hours children were spending in peer interactions. It would be an interesting objective for future research to also examine the number of social interaction partners and the quality of those interactions.

Identifying the causal nature of the relationship between theory of mind and social emotional health is also not possible with these data. Although children with more advanced theory of mind experienced less decline in their social emotional health over time, it is possible that at least part of the relationship between children’s theory of mind and better social emotional health outcomes in the current study can be accounted for by some ‘third’ variability associated with greater theory of mind or social emotional health, such as higher quality parenting. Importantly, a wealth of previous research suggests theory of mind can play a causal role in children’s social-emotional health. For instance, research shows that interventions designed to improve children’s theory of mind simultaneously enhance children’s social skills and social emotional development (e.g., [29], see [19] for a review, see also [64]).

The current results may also be influenced by the use of parent-report data and on parents’ memory of the changes in the number of hours per day their child spent interacting with others before the pandemic. On the one hand, parent-report data can be skewed, either positively or negatively, for a variety of reasons including the parents’ mood and their opportunity to observe certain behavior. For example, parents tend to underestimate their child’s internal and emotional states. If their child’s symptoms are more internalized (e.g., anxiety or sadness) than externalized (eg., conduct problems), they may not be as obvious to an outside observer [65-67]. Similarly, parent-reports may fail to capture a child’s behaviour outside of the home (e.g., at school, in the community; [68]).

On the other hand, parent-reports can allow for more comprehensive assessments with greater ecological validity of some constructs (e.g., ‘theory of mind’) than lab-based measures (e.g., [48]). One of the key strengths of this study was its use of multifaceted assessments. For instance, rather than examining only a single aspect of children’s social emotional health (e.g., anxiety) we examined a total of 12 different aspects of their social emotional health (both strengths and difficulties) using multiple previously-validated measures. We also selected a multifaceted measure of theory of mind (i.e., the CSUS) rather than relying on a single facet or dimension of theory of mind. According to a recent review [69], most previous work with young children has focused on one aspect of theory of mind, with 75% of studies with young children only including the false belief task (i.e., a binary pass/fail test of the ability to understand that others can hold beliefs that differ from reality)–a task that has been widely criticized for its limitations (e.g., [70-72]). Thus earlier results linking social emotional health and ‘theory of mind’ may be specific to their understanding of false beliefs and fail to account for children’s broader ability to understand and reason about other mental states such as their emotions, knowledge, intentions, and motivations [19,73]. Consequently, our measure of theory of mind and its predictive effects is relatively novel, capturing a more comprehensive and conceptually rich understanding of children’s mental state reasoning.

Finally, we believe that one of the most important contributions of this work is the finding that theory of mind appears to offer protective benefits against at least some factors that precipitate declines in social emotional health–in this case, the deleterious effects of reduced social interactions. This finding expands upon the three studies with children, discussed above, showing that having a more advanced theory of mind acted as a protective factor against harsh parenting [44-45] and parental post-traumatic stress transmission [46]). Together, these results suggest that a strong theory of mind may have relatively broad-sweeping protective, or resilience, benefits against many different types of stress and adversity.

An interesting question for future research to explore is precisely how theory of mind acts as a protective factor? The exact mechanism(s) by which better mental state reasoning buffers against adversity is somewhat unclear. However, the body of research linking theory of mind and different facets of social emotional competence highlights important elements. Of note, individuals with higher theory of mind abilities are better at predicting, interpreting, and influencing others’ behavior, which has a myriad of cascading benefits including stronger interpersonal relationships, and greater social emotional competence [20,23-31]. Moreover, it has been suggested, but not well tested, that those with greater theory of mind or ‘mentalization’ abilities may be better at seeking social support when needed, resulting in better stress management and greater resilience (e.g., [74]).

Anecdotal evidence offers some insight into why children with more advanced theory of mind may have fared better during the pandemic. One parent described asking her six-year-old daughter what she was drawing; the child replied that she was making a picture of their family to place in her grandmother’s window so her grandmother would not feel so alone during the social distancing. This example highlights two possible mechanisms through which theory of mind may have promoted resilience. First, children with stronger theory of mind may be more ‘other-oriented’ than ‘self-oriented’, which could support well-being. This idea aligns with research showing that excessive self-focused rumination can be detrimental to one’s mental health (for a review, see [75], and how spending money on others can make you happier than spending it on yourself [76]. Second, children with more advanced theory of mind may engage more readily in what we have termed “social substitution” behaviors (e.g., imagining conversations with others, talking to their pets or toys, or thinking about playing with their friends) that could partially compensate for reduced in-person interactions. This is consistent with findings that children with more advanced theory of mind tend to engage in more imaginative play [77].

Importantly, these potential resilience mechanisms are not mutually exclusive and may jointly contribute to more positive socioemotional outcomes during periods of stress or social isolation. Future research should aim to identify the specific pathways through which theory of mind promotes resilience, as well as the scope and timing of its protective effects. Even without clarity on the specific underlying mechanisms, interventions designed to foster theory of mind are likely to be beneficial, particularly if targeted at developmentally sensitive age groups or at the onset of stressors.

Acknowledgements

This research was supported by an Insight Grant from the Social Sciences and Humanities Research Council of Canada (SSHRC; Grant # 435-2025-0522) awarded to the first author.

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New Model for the Assistance to Frail Patients with Hematological Disease

DOI: 10.31038/IMROJ.20261111

Abstract

Haematological patients treated out-off hospital are more and more increasing due to use of new biological drugs. They have prolonged the patient survival and haematological disease prevalence. We do believe that an Internal Medicine ward where haematologists work together with hospitalists can improve quality of assistance and survival of frail haematological patients who need both Internal Medicine and Haematological competences. We report our experience in three years of such experimental assistance in agreement with Emergency Units and Haematological Department.

Keywords

Haematological frail patients, Emergency Department, Internal Medicine Department

Introduction

Due to appearance of new biological drugs. the prevalence of haematological patients is in continuous increasing. This epidemiological change is, at least partially, due to the efficacy of the new drugs “responsible” of more haematologic [1] cures and prolonged responses. According to this new scenario, when complications appear, the patients refers to family doctor or to hospital emergency departments [2,3]. News biological molecules can induce new side effects which, frequently, only haematologists are confident with. For this reason, we have implemented a network according to the town main Emergency Departments to admit frail haematological patients in our Internal Medical ward, where 4 internists cooperate with 2 hematologic specialists [4,5]. Since February 2022 to December 2024, 248 pts (116M, 132F), median age 76.4 yrs (range 30-98), were admitted to our ward, sent by Hematology or Emergency Departments of General Hospitals in Rome. The admittance procedure provided patient taken into our ward’s care in 12-72 h since the invoiced request by the proposing hospital [6].

Patient Characteristics

During the study period, our bed manager received by mail 248 requests for admitting in our ward patients affected by hematologic disease, complications of hematologic therapy, appearance or worsening of comorbidity as diabetes, cardiac failure, second primary neoplasm, sepsis or other infections, hemorrhages, etc. Patient’s characteristics are shown in Table 1. All admitted patients were assisted with appropriate therapies according to the specific complications or complaints (replacement or supportive therapy, antibiotics, hydration, etc.). The main reason for hospitalization were infections (36.3%) or cardio-vascular diseases (12.1%). Median time of hospitalization was 10 days (1-38). 196 out of 248 invoiced patients (80%) were referred back, cured or ameliorated, to their Hematological Center; 30 (21.1%) were sent to long-term or rehabilitation wards or others specialistic department; 9 pts (3.6%) were referred back to an emergency room for complications during hospitalization; 10 (4%) died in our ward and 3 (1.2%) were sent to the Palliative Cures. Infection was the principal reason of admission: 90 of them (36.3%) were admitted for this cause. Characteristics of patients with infections are reported in Table 2. The most frequent site of infection was lung or superior respiratory tract (54.4%). Sepsis with positive blood cultures were observed in 10 out of 90 pts (11.11%) and FUO in only 3 (3.3%). In all patients, antibiotic treatment lasted 5 days in lung infections or 7 days in case of sepsis, or 2 days after the disappearance of fever. In case of resistance of antibiotics, treatment was changed to alternative combination and/or following hemo-culture indications. Of all 90 pts 4 (1 Multiple Myeloma, 1 Chronic Lymphocytic Leukaemia, 1 Myelodysplastic Syndrome, 1 Acute Leukaemia) died, 6 were sent to the emergency room because complications that cannot be dealt with in our facility and lost at follow-up, 2 pts were sent to palliative care setting. The remaining 68 pts, after resolution of the acute complication, were referred, sometime after a follow-up visit after the discharge, to their reference haematologists for continuing specific treatment or follow-up.

Table 1: Main Characteristics of hematologic patients during period of observation 2022-2024.

Variables  
Gender, n (%) 248 (100%) Medical Complication     
  Male 116 47.8% Infection 90 36,29%  
  Female 132 53.2% Heart Disease 30 12,10%  
Median age, years (range) 76.4 (30-98) Pain 13 5.24%  
Median days hospitalization (range) 10 (1-38) Blood Disorders 23 9.27%  
Hematologic disease, n (%) Diabetes 12 4,84%  
  Multiple Myeloma (MM) 45 18,15% Anemia 26 10,48%  
  Chronic Lymphocytic Leukemia (CLL) 41 16,53% Hemorragy 9 3,63%  
  Myelodysplastic Syndrome (MDS) 43 17,34% Orthopedics 8 3,23%  
  Acute Leukemia (AL) 28 11,29% Respiratory Disease 14 5,65%  
  Non-Hodgkin Lymphoma (NHL) 32 12,90% Electrolyte Imbalance 11 4,44%  
  Myelofibrosis (MF) 8 3,23% Kidney Disease 8 3,23%  
  Myeloproliferative Neoplasm (MPN) Other Than MF 14 5,65% Solid Neoplasm 3 1,21%  
  Other 37 14,92% Hepatic Disorders 1 0,40%  

 

Discussion and Conclusions

Proper assistance and cure of haematological patients with their disease or treatment complications have become a true emergency because more and more frail pts are treated in ambulatory or day hospital setting and because the ageing of population. A local network for their care and the admission of these patients in multiskilfull ward to face different occurring complications, in our opinion, is crucial in order to accelerate their reception and prompt treatments of conditions possibly fatal. This network is appreciated to local Emergency and Haematology departments according to the progressive increase in the years of the patients addressed to our institute. On the other hand, close collaboration between hematologists and specialists in other fields such as internal medicine, cardiology, neurology, orthopedics, infectious diseases, and pain management allows for a comprehensive assessment of the patient to guide the continuation of specific treatment for their condition. While it is not possible to reach the target for all patients, it can still facilitate the process and help the family navigate the natural progression of the disease when treatment cannot be proposed. We think that the presence of a similar network can ameliorate the assistance of haematological patients and can allow the Hematology departments to dedicate to intensive care life-saving procedures. Moreover, this organization is certainly cheaper as it avoids the occupation of specialist beds.

Table 2: Main Characteristics of hematologic patients with infections.

Variables  
Gender, n (%) 90 (100%)    
  Male 51 56.67% Median age, years (range) 77 (30-94)  
  Female 39 43.33% Median days hospitalization (range) 9 (2-38)  
Type of Hematologic disease, n (%) Type of infection, n (%)
  MM 21 23,33% pneumonia 49 54,44%  
  CLL 12 13,33% sepsis 10 11,11%  
  MDS 17 18,89% infection of urinary tract 12 13,33%  
  AL 14 15,56% infection of GI tract 6 6,67%  
  NHL 12 13,33% FUO 3 3,33%  
  MF 7 7,77% skin 5 5,56%  
  Other 7 7,78% other 5 5,56%  

Acknowledgements

We thank Doct. Corrado Girmenia, head of the emergency room of the Department of Hematology of Policlinico Umberto I, and Doct. Maria Paola Saggese head of emergency department of Santo Spirito hospital for referring patients.

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Isolated Cardiac Cement Embolism Following Cement Vertebroplasty Presenting as Symptomatic Atrial Fibrillation

DOI: 10.31038/JCCP.2026913

 

An 86-year-old man presented to his cardiologist for regular follow up with chest pain and exertional intolerance with tachycardia and palpitations. The patient had further medical history of paroxysmal atrial fibrillation, chronic back pain with cement vertebroplasty, ischaemic heart disease with previous multivessel coronary stenting, hypertension, hypercholesterolaemia, type two diabetes mellitus, stage four diabetic kidney disease and previous upper GI bleed whilst on dual antiplatelets. His medications were apixaban 2.5 mg BD, metoprolol 25 mg BD, digoxin 62.5 mcg daily, irbesartan 300 mg daily, lercanidipine 10 mg daily, atorvastatin 40 mg daily, dapagliflozin 10 mg daily, metformin 1 g daily and pantoprazole 40 mg daily.

ECG showed atrial fibrillation with a heart rate of 57 bpm and no ischaemic changes. Subsequent Holter monitor showed atrial fibrillation throughout with a minimum heart rate of 41 and maximum of 141. Transthoracic echocardiogram showed normal left ventricular size and function with stable mild valvular disease.

The patient described his symptoms as being like a previous presentation which led to a diagnosis of obstructive left main coronary artery disease. The patient underwent invasive coronary angiography which illustrated only moderate non obstructive coronary artery disease with patent stents. There was the unexpected finding of radio-opaque masses in the right atrial appendage and the right ventricle. This was associated with new T12 cement vertebroplasty (Figure 1).

Figure 1: Coronary angiogram showing two radio-opaque masses in the right atrial appendage and the right ventricle.

Upon review of previous imaging, the radio opaque masses were not present on chest X-rays from prior to vertebroplasty but appeared on X-ray following vertebroplasty. A non-contrast CT chest confirmed the presence of high attenuation material in the right atrial appendage (Figure 2) and inferior right ventricle (Figure 3) and bone cement in the thoracic vertebrae that had extravasated to the region of the paravertebral venous plexus (Figure 4). This was consistent with cardiac embolism of vertebral bone cement.

Figure 2: Axial view of CT chest showing high attenuation material in the right atrial appendage.

Figure 3: Sagittal view of CT chest showing high attenuation material in the inferior right ventricle.

Figure 4: Sagittal view of CT chest showing cement in T12 vertebral body, extravasating into the paravertebral region.

Retrospective review of previous transthoracic echocardiogram showed a calcified area noted in the right ventricle near the moderator band and another in the right atrial appendage (Figure 5).

Figure 5: Transthoracic echocardiogram illustrating a bright, calcified area in the right ventricle.

The case was discussed at a cardiology multidisciplinary team meeting regarding invasive or medical management due to the risk of cement embolism erosion. The consensus was to manage the case conservatively with anticoagulation to prevent thrombus formation on the cement as the patient had not had any complications of the embolism to date and due to his advanced age and comorbidities. The patient’s apixaban was increased to 5 mg BD and his symptoms remained stable.

Discussion

Percutaneous vertebroplasty is used to treat osteoporotic fractures to reduce pain and provide stability to the spine [1]. The procedure involves injecting polymethylmethacrylate (PMMA) cement into the diseased vertebrae and the main risks are associated with the leakage of cement into the surrounding structures. With absorption into the iliolumbar and epidural veins, the cement can gain access to the central circulation.

The rate of extravasation into central veins during this procedure is estimated at 23% however usually particles of cement are small, and the patient remains asymptomatic. Symptomatic intracardiac embolism is estimated to occur in only 0.3% of cases [2]. Sequelae of embolism can involve arrhythmia, valve dysfunction, pulmonary embolism and rarely cardiac perforation resulting in tamponade.

If the suspicion for intracardiac cement embolism (ICE) is high, CT chest and TTE should be performed to confirm the diagnosis, location of the embolism and to assess for complications. The bone cement is high attenuation and has been described as 373-1600 Hounsfield units when embolised to the heart [3]. However as seen in this case other modalities including chest X ray and fluoroscopy can make the diagnosis.

Risk factors for embolism include higher number of segments, injection into the thoracic vertebrae, tumour related fractures, higher amounts of bone cement used and lower viscosity cement [4].

Prevention of ICE includes the use of high viscosity cement to reduce extravasation, avoiding over pressurisation and injecting under fluoroscopy to assess for embolization during the procedure [5].

Recommendation on management of ICE depends on the patient’s status. In asymptomatic patients, observation without intervention is most appropriate. Small cement emboli routinely do not cause symptoms so routine post procedural imagining is not recommended.

Symptomatic patients may require intervention. Patients with cardiac rupture and tamponade require urgent surgical intervention to remove the fragment and repair the myocardial defect. There have been case reports of percutaneous removal of fragments that are amenable to do so that are either high risk of causing cardiac rupture or impinging on the tricuspid valve apparatus [5].

References

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The TA Trial: A Long-Overdue Randomised Test of Total Arterial Revascularisation

DOI: 10.31038/JCCP.2026912

 

Coronary artery bypass grafting (CABG) remains the most durable revascularisation strategy for patients with multivessel coronary artery disease, with established long-term survival advantages over percutaneous coronary intervention in complex anatomical disease [1,2]. Yet despite decades of surgical refinement, one of the most consequential intraoperative decisions, conduit selection, remains insufficiently resolved by high-quality prospective evidence. The Total Arterial (TA) Trial, (clinical trial registry: ACTRN12623000864628) funded by the Australian Medical Research Future Fund, represents a serious and timely effort to address that gap.

The central question is simple: does the complete exclusion of saphenous vein grafts (SVGs) in favour of total arterial revascularisation (TAR) translate into superior graft patency and better clinical outcomes? The biological basis for expecting so is well-established. SVGs are anatomically and haemodynamically mismatched for the arterial circulation – subjected to pressures they were not designed to withstand – and the consequences are of reasonably predictable and progressive graft failure. Approximately 40–50% of SVGs occlude within 10 years, contributing significantly to postoperative myocardial infarction, repeat revascularisation, and premature mortality [3,4]. Arterial conduits appear to behave differently. Whether internal mammary arteries or radial arteries, they exhibit resistance to progressive atherosclerosis, adaptive remodelling, and durable angiographic patency over decades of follow-up [5,6]. Large registry analyses, including data from the Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) registries, have consistently associated TAR with a survival advantage [7,8].

The key question is whether this survival signal reflects the true biological superiority of arterial conduits or is substantially confounded by patient selection and operator expertise. Patients who receive TAR tend to be younger, less comorbid, and operated on by surgeons with higher procedural volumes. Observational analyses, however carefully risk-adjusted, cannot fully account for these confounders. Randomised allocation remains the only mechanism to isolate conduit biology from surgical selection – and prior trials have not achieved this adequately.

The Arterial Revascularisation Trial (ART) was undermined by a crossover rate exceeding 10% post-randomisation, diluting the treatment contrast and complicating interpretation of its insignificant result at 10 years [9]. Whether ART failed to show a benefit because none exists, or because insufficient patients received the assigned treatment, remains unresolved. However, it is also noteworthy that both arms could have received SVG. The ongoing ROMA trial, while more rigorously designed than the ART trial, addresses a related but distinct question: the number of arterial grafts, rather than the complete elimination of venous conduits [10]. Both arms of ROMA permit SVG use, which cannot therefore directly address whether abolishing venous grafting entirely – the strategy with the most consistent observational support, could improve survival.

The TA Trial is deliberately designed to address these limitations. By defining its intervention as zero SVGs versus at least one SVG, it isolates the specific variable that observational data most consistently associates with long-term outcome differences [7,11]. For clarity, unlike ART and ROMA, the focus of the investigation relates not to the arterial conduit use – but rather to the venous conduit use. The pragmatic surgical design –imposing no restrictions on conduit type, graft configuration, or reconstruction technique within the TAR arm – reflects clinical equipoise and preserves generalisability. This acknowledges that TAR is not a single operation but a surgical philosophy, executable through multiple technically sound configurations [12,13].

Equally important is the trial’s approach to protocol compliance. ART established that investigator non-compliance is a practical threat to trial validity, and not a theoretical one. The TA Trial approach mandates logbook review to confirm surgeon competence in TAR, requiring preoperative written confirmation of equipoise for every randomised patient, and instituting individual investigator follow-up after each protocol breach. These are the structural safeguards upon which the trial’s interpretability depends.

Selecting perfect graft patency as the primary endpoint at 24 months is scientifically well-justified. Simple patency captures graft survival but not graft health; a vein graft that is open but internally diseased will ultimately fail, and simple patency misses this trajectory. Perfect patency – a patent conduit with a smooth, regular lumen free of atherosclerotic change – provides an angiographic surrogate for long-term conduit durability validated against clinical outcomes.6 Assessment by CT coronary angiography with sensitivity and specificity exceeding 98% [14] allows non-invasive, reproducible assessment across all 18 sites. The additional CTCA at 3 months is a noteworthy design strength, offering a structured examination of early competitive flow effects on arterial graft function, a phenomenon that likely explains a proportion of early graft failures but remains poorly characterised prospectively [15].

Australia is uniquely positioned to conduct this trial. TAR utilisation rates across Australian centres substantially exceed those reported in North America and Europe [7], ensuring a sufficient pool of surgeons with established expertise in both TAR and non-TAR techniques. This mitigates a key methodological concern: differential technical proficiency across study arms could confound the treatment effect. The trial’s findings will therefore reflect outcomes achievable within a mature surgical environment, strengthening their external validity and translational relevance.

Conclusion

The TA Trial is the first prospective, randomised investigation designed to directly test whether complete elimination of venous conduits from CABG translates into measurable improvements in graft integrity and, through its comprehensive secondary outcome framework, patient survival and quality of life. If it confirms the observational literature, its implications for surgical practice and guideline development good be substantial and impactful. The cardiac surgery community has waited a long time for this evidence.

Authorship and Contributions

Justin Ren, writing and conceptualization of the manuscript. Alistair Royse, writing and conceptualization of the manuscript. Colin Royse, co-author and reviewer.

Acknowledgements

The author has acknowledged that this summary commentary is written on behalf of the TA Trial Steering Committee.

Conflicts

This manuscript has not been funded. The authors declare that they are the architects of the TA Trial study design and have written multiple supporting analyses for this trial.

Keywords

TA Trial, Total arterial revascularisation, TAR, Graft angiography

References

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Extracellular Ca2+ Influx is involved in Tip Growth of the Marine Red Alga Pyropia yezoensis

DOI: 10.31038/AFS.2026811

Abstract

The conchocelis, the filamentous sporophyte generation of Bangiales, proliferates through tip growth in which only the tips of branch initial cells elongate and subsequently divide perpendicularly to the apical–basal axis to form filamentous structures. As was found in terrestrial plants, the tip growth of conchocelis in the marine red alga Pyropia yezoensis is regulated by auxin, actin polymerization, and phosphatidylinositol signaling. Although extracellular Ca2+ influx is critical for tip growth in terrestrial plants, little is known about its involvement in the tip growth of algae. We therefore investigated whether extracellular Ca2+ influx is required for tip growth in P. yezoensis conchocelis. Treatment of isolated single-celled conchocelis with a Ca2+ chelator, ethylene glycol tetraacetic acid, inhibited both the formation of branch initials and the tip growth of branches in a dose-dependent manner. These findings indicate that extracellular Ca2+ influx is indeed involved in the tip growth of conchocelis, suggesting that the basic regulatory mechanisms governing tip growth may be conserved between marine red algae and terrestrial plants. Further confirmation of this possibility will require the characterization of the spatiotemporal patterns of Ca2+ oscillations and F-actin accumulation, as well as the subcellular localization of phosphoinositides and their catabolic enzymes in the P. yezoensis conchocelis.

Keywords

Branch initial, Ca2+, Conchocelis, Extracellular influx, Pyropia yezoensis, Red alga, Tip growth

Introduction

Patterns of anisotropic cell growth give rise to the body shapes of terrestrial plants and multicellular algae [1,2]. Diffuse growth, which results in the expansion of cell surfaces [3,4], produces planar or foliose shape, whereas tip growth [5-7], characterized by directional and highly localized expansion at the apex, produces a filamentous body architecture. Algal cells grow anisotropically through both diffuse and tip growth. We previously demonstrated that tip growth produces the filamentous structures of the conchocelis (sporophyte) and conchosporangium (conchosporophyte) of the red alga Pyropia yezoensis [8-12], although regulatory mechanisms of tip growth in P. yezoensis has not yet been fully elucidated. Moreover, how diffuse growth produces a foliose shape in the thallus (gametophyte) of P. yezoensis remains largely unknown. Therefore, characterizing the contrasting mechanisms that regulate patterns of diffuse and tip growth is necessary to understand the differences in growth–morphology relationships between the two life-cycle generations of Bangiales.

The mechanisms that regulate diffuse and tip growth systems have been studied extensively in terrestrial plants. Cortical microtubules (MTs), actin filament (F-actin), Rho GTPases, the histone variant H2A.Z, gibberellin, and brassinosteroids have all been implicated in the regulation of diffuse growth [1,3,13] likewise, MTs, F-actin, Rho GTPases, Ca2+ influx, reactive oxygen species, phosphatidylinositol signaling, auxin, and jasmonate have been shown to regulate tip growth [7,13-21]. Although research on the regulation of diffuse growth in macroalgae has shown little progress, recent studies have provided basic information about the mechanisms regulating tip growth in red and brown macroalgae [2,11,12,22]. Indeed, we demonstrated that auxin, phosphoinositide turnover, and actin polymerization are involved in the regulation of tip growth in P. yezoensis [11,12], consistent with findings in terrestrial plants [13,17,18,21]. Although extracellular Ca2+ influx is required for tip growth in terrestrial plants [17-19], little is known about its role in the tip growth of macroalgae. We therefore sought to determine whether extracellular Ca2+ influx is required for tip growth in P. yezoensis conchocelis.

Materials and Methods

Single-celled conchocelis of P. yezoensis strain U-51 were used for these experiments, enabling us to visualize and quantitatively analyze the initiation and progression of tip growth in detail [11]. Conchocelis were maintained in artificial seawater at 15°C under 60 µE/m²/s of light with a short-day cycle (10-h light/14-h dark) [23]. Single-celled conchocelis were prepared as described in [11]. In brief, aggregates of multicellular conchocelis were chopped with a razor blade, and small fragments of conchocelis were separated from larger pieces by filtration through a 10-μm nylon mesh. The separated conchocelis were then incubated in 30 mL of artificial seawater [23] at 15°C for 10 min. Unbranched single-celled conchocelis (Figure 1) were identified by observation under an Olympus IX73 light microscope equipped with an Olympus DP22 camera (Olympus Corporation, Tokyo, Japan), drawn into a micropipette, and transferred to 96-well plates (one cell per well containing 200 μL of artificial seawater). Ethylene glycol tetraacetic acid (EGTA; Dojindo Laboratories, Japan), an effective Ca2+ chelator, was dissolved in artificial seawater to create a 0.5 M stock solution (adjusted to pH 8.0 with NaOH) and stored at −30°C before use. Single-celled conchocelis were treated with 0, 500, or 750 μM EGTA for 3 days, and the growth and morphology of the side branches were observed using the microscope described above.

Figure 1: Representative image of an isolated single-celled conchocelis. Nonbranched single-celled conchocelis were used for EGTA treatment experiments. Scale bar, 25 µm.

Results and Discussion

To evaluate the effects of EGTA on the initiation and elongation of side branches, we measured the branching rate (the percentage of observed cells that produced side branches) and branch length, respectively. Side branches were initiated and underwent elongation when treated with 0 (control) or 500 μM EGTA (Figure 2A and 2B), but 750 μM EGTA completely prevented both the initiation and growth of side branches (Figure 2C). The branching rate and branch length were affected by the presence of EGTA in a dose-dependent manner, being strongly inhibited at 750 μM (Figure 2D and 2E). These results demonstrate that extracellular Ca2+ influx is important for the production and tip growth of branch initials from differentiated conchocelis cells. It reminds to be elucidated whether washing out of EGTA and subsequent addition of CaCl2 in the medium recover branch initiation and branch growth and whether inhibition of channel-mediated Ca2+ influx by treatment with LaCl3 prevents tip growth.

Figure 2: Effects of EGTA treatment on the tip growth of side branches from single-celled conchocelis. (A–C) Photographs of single-celled conchocelis treated with 0 (A), 500 (B), or 750 μM EGTA (C) for 3 days, for which each treatment was employed total 16 isolated cells for observation. Arrows indicate tip-growing branches initiated from single-celled conchocelis. Scale bars, 25 μm. (D, E) Branching rate (D) and branch length (E) after treatment of single-celled conchocelis with 0, 500, or 750 μM EGTA for 3 days. Center line, median; cross, mean; box limits, interquartile range with upper and lower quartiles; points, individual data points; whiskers, range with maximum and minimum values. Lowercase letters in (D) and (E) denote significant differences between treatments based on three independent experiments (n = 3) as determined by the Tukey–Kramer test (p < 0.05).

There are two important steps in the tip growth of conchocelis: the formation of branch initials in non-dividing differentiated cells (initiation of tip growth) and the polar directional growth of these initials to form elongated branches [12]. Because the treatment of single-celled conchocelis with EGTA impaired both branch initiation and branch growth, we concluded that Ca2+ is required for both critical steps in tip growth. To confirm this proposal, measurements of the time-course of both production of branch initial and its growth in single-celled conchocelis are necessary for elucidation of a question which step requires extracellular Ca2+ influx. In addition, we previously demonstrated that these two steps are regulated by auxin, phosphoinositide turnover, and actin polymerization [11,12]. These findings are consistent with our understanding of tip-growth regulation in the pollen tubes and root hairs of terrestrial plants [13,14,16-18,21]. It is therefore possible that the basic regulatory mechanisms governing tip growth are conserved between aquatic red algae and terrestrial plants. Factors such as Ca2+, enzymes related to phosphoinositide turnover, and F-actin act at the cell apex to enable the polar growth of filamentous tissues such as root hairs and pollen tubes [14,16,18]; however, little is known about the spatial distribution of these factors during the initiation and elongation of branches in P. yezoensis conchocelis. Therefore, determining the specific regions where auxin and Ca2+ exert their effects and characterizing the subcellular distributions of F-actin and enzymes involved in phosphoinositide turnover will be critical for fully understanding tip-growth regulation in conchocelis branches. A live-imaging technique for conchocelis tip growth has recently been reported [10]. Improvements to this system are expected to enable the visualization of Ca2+ influx, F-actin distribution, and the localization of phosphoinositides and related enzymes, providing spatiotemporal details of polarity establishment and tip growth in P. yezoensis conchocelis.

Despite progress in understanding tip growth in the conchocelis, much less is known about the regulation of diffuse growth that gives rise to the foliose thallus of the gametophyte. It is remarkable that foliose and filamentous generations survive independently in P. yezoensis and other Bangiales [9], suggesting differences in the regulatory mechanisms governing these two growth patterns. However, the shared involvement of MTs, F-actin, and Rho GTPases in both diffuse and tip growth of terrestrial plants [1] raises the question of how common factors can regulate different types of growth. Characterizing the contrasting regulatory mechanisms that govern diffuse and tip growth will be essential for understanding the physiological and molecular bases of the distinct multicellular body plans of heteromorphic generations in P. yezoensis.

Author Contributions

RI: Methodology, Investigation, Data curation, Formal analysis, Validation, Visualization.

KM: Conceptualization, Methodology, Formal analysis, Validation, Visualization, Supervision, Writing—original draft preparation and reviewing and editing, Funding acquisition.

Conflict of Interest

The authors declare no conflicts of interest. No aspects of the study required informed consent, and the work did not involve human or animal subjects. All authors have read and agreed to authorship and to the submission of the manuscript for peer review.

Data Availability Statement

Data are contained within the article.

Funding

This research was supported in part by the designated research fund from Miyagi University.

Acknowledgments

We are grateful to the Marine Resources Research Center of Aichi Fisheries Research Institute for kindly providing P. yezoensis strain U51.

References

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Hantavirus Aptamer DNA Sequences with Therapeutic Potential According to 3-D Docking Models

DOI: 10.31038/IDT.2026711

Abstract

DNA aptamers were developed and sequenced against an envelope precursor polyprotein of Hantavirus (HV). The highest affinity aptamers from the final SELEX pool were determined by an enzyme-linked microplate assay against the recombinant envelope protein. Subsequent 3-D molecular models using two different docking platforms strongly suggest that the top aptamers will bind the exterior ectodomain of the envelope protein protruding from the viral lipid envelope and therefore could interfere with virus binding to host cell receptors, thus affording potential prophylaxis or therapy for Hanta-related hemorrhagic, pulmonary and renal syndromes.

Keywords

3-D Molecular modeling, Aptamer, Docking software, Hanta virus, Passive immunity

Introduction

Hanta viruses (HVs) including Sin Nombre virus are named after the Hantan river region in North and South Korea where an early outbreak occurred. HVs are spread mostly by rodent or rodent feces and urine exposure to humans, but not between humans. These viruses affect greater than 200,000 people worldwide although 90% of cases occur in China each year and can cause potentially lethal hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS) [1]. There are no effective government-approved treatments for HPS or HFRS except rest and treatment for the associated symptoms of fever, fatigue and severe muscle pain. However, at least two experimental monoclonal antibodies have demonstrated some efficacy by binding the external surface Gn and Gc viral proteins (cleavage products of the envelope polyprotein) to neutralize viral entry into host cells [2], thus opening the door for less expensive DNA aptamer-based passive immunity as well [3].

Materials and Methods

Recombinant Hanta Virus Envelope Polyprotein Target and Magnetic Bead Immobilization

The Hantavirus envelope recombinant polyprotein (Gn/Gc or G1/G2 precursor) target was produced by Bioclone Inc. (Dr. Peter Ding), San Diego, CA. It covered amino acids 50-450 from the Jurong TJK/06(RT50) Hantavirus strain (Swiss Protein number C7EMH7). Because the protein comes with a 6X histidine tail, the authors used NTA Nickel-coated magnetic beads from Thermo Fisher Inc. for immobilization of the target protein for SELEX aptamer development. By immobilizing at the tail end where the 6X histidine resides, most of the native protein was available to interact with the random DNA library to better select ectodomain aptamers versus randomly immobilizing the protein via tosyl leaving groups (common on magnetic microbeads) anywhere that a primary amine occurs in the protein. Figure 1 describes the SELEX template and PCR primers that were used for SELEX aptamer development. Otherwise, traditional magnetic bead-based SELEX methods as reported in the literature [3] were utilized and the final round 10 SELEX pool was sequenced using Illumina next generation sequencing by synthesis at Base Pair Biotechnologies Inc. (Pearland, TX, USA).

Figure 1: Schematic and DNA sequences of the 72 base SELEX template with randomized 36 bases (N36) region flanked by two fixed 18 base PCR primer binding ends and the Forward (F) and Reverse (R) primer sequences obtained from Integrated DNA Technologies (Coralville, IA, USA).

Results

Figure 2 documents successful 72 bp PCR amplicons from each of the final rounds of HV SELEX in an ethidium bromide-stained 2% agarose electrophoresis gel. The most frequent (i.e., top) 24 candidate aptamers that occurred at least 10 times or more in total (FCOUNT) in the final round 10 aptamer pool and greater than 6 times per million sequences (CPM) are reported in Table 1.

Figure 2: Ethidium bromide-stained 2% agarose electrophoretic gel image showing 72 bp aptamer amplicons from each of the final rounds of SELEX for HV envelope protein aptamer development.

The HV aptamer candidates were screened by ELISA-like (ELASA) assay as described previously [3] for affinity to the cognate HV envelope polyprotein. The ELASA relative affinity rankings by absorbance at 405 nm of each candidate aptamer from Table 1 are provided in Table 2 below and suggest the top aptamers to screen for inhibition of Hantavirus plaques in vitro [4], if that possibility ever exists. In particular, it appears that HV aptamers S2, S3, S7 and S9 with absorbance at 405 nm values greater than 2.0 are the best four candidates with which to start in vitro HV plaque inhibition studies in Vero cells [4].

Table 1: Top 24 Hantavirus Envelope Polyprotein Aptamer DNA Sequences and Frequency (Total Counts and Counts per Million Sequences).

Because Nanohmics developed a number of seemingly high affinity (Table 2) HV aptamers during this project, it followed that 3-D modeling of the top aptamer docking with the HV envelope polyprotein from the NCBI and Swiss Protein databases (number C7EMH7) was in order. The HV S1 aptamer emerged 115 times or 25 more total times than the nearest competitor in the NGS pool (Table 1) and was ranked in the top 7 aptamer candidates by ELISA-like assay vs. the envelope protein with an average absorbance at 405 nm of 1.9175 versus the top aptamer candidate (HV S7; A405 nm = 2.248) in terms of affinity. However, affinity is not always the best predictor of ability to block viral entry into host cells. So, HV S1 is also a logical candidate to begin modeling for future in vitro plaque assays.

Table 2: ELASA Plate Assay Rankings of the Top 24 Aptamers from NGS for Hantavirus Envelope Binding and Potential Inhibition (Average of Duplicate A405 nm Readings).

We were not able to find an established 3-D PDB model for the Hantavirus Jurong TJK/06(RT50) envelope protein, so we had to enter the amino acid sequence (cut and pasted) into a program within UniProt and then through a program called ModWeb from the Univ. of California at San Francisco (UCSF) to generate the 3-D envelope protein structure shown in Figure 3 below. Note the characteristic black “donut hole” in the middle of this envelope protein which helps to identify the polyprotein in 3-D docked images with candidate aptamers.

Figure 3: 3-D PBD model of the Hantavirus Jurong TJK/06(RT50) envelope protein generated by UniProt and ModWeb. Note the characteristic “donut hole” (black area in middle).

We utilized and compared results from HDock and ZDock internet programs as shown in Figures 4-6 below to determine where the HV S1 aptamer was preferentially binding on the HV envelope (E) polyprotein. From both the HDock and ZDock analyses, the HV S1 aptamer appears to prefer binding the thinner tapered segment of the HV E polyprotein. Unfortunately, according to Serris et al. [5], this end of the envelope protein may be inserted into the lipid envelope and not even available for aptamer binding, thus making the HV S1 aptamer potentially useless. However, some of the other top HV aptamer sequences subjected to 3-D docking analysis seemed to prefer binding the opposite end (ectodomain) of the HV envelope polyprotein making them better candidates (Figure 6).

Figure 4: Top 3-D docking ribbon structure for the HV1 aptamer (orange) with the yellow HV E polyprotein using HDock.

Figure 5: Top 3-D docking space-filled structure for the HV S1 aptamer (brown) with the green HV E polyprotein (green) using HDock software. Note again the “donut hole” in the E polyprotein and aptamer binding to the thinner end of the protein.

Figure 6: Top 3-D docking space-filled structure for the HV S1 aptamer binding the yellow ectodomain of the HV Envelope polyprotein using ZDock software rendered in RasMol software.

Discussion

Serris et al. [5] described the domain of Hantavirus (HV) envelope E polyprotein which is embedded in the viral envelope lipid membrane and the ectodomains that are outside of the viral coat and available for some particular aptamer binding. Figure 7 below illustrates how the 3-D ribbon structures of the HV envelope protein reported by Serris et al. [5] in panels A and B appear to match the general 3-D HV envelope structure that we used for aptamer docking studies. Note that Domain I in panels A and B appears to be the base domain that inserts into the viral lipid envelope and would be inaccessible to aptamers. However, the curved outer ectodomains appear to be accessible to aptamers and both of the top aptamer-HV E polyprotein docking models developed during this project show the S1 aptamer binding to these ectodomains as represented in panel D which could thus probably block binding to host cell receptors and inhibit or prevent plaque formation in vitro and infection in vivo. Naturally, all of this theoretical modeling needs to be tested empirically in vitro with plaque inhibition studies [4], but this publication provides a maximum of 24 candidate aptamers and some theoretical criteria for down selecting to the best ectodomain-binding candidates with HV neutralization potential in future studies.

Figure 7: A and B – 3-D ribbon structures of Hantavirus envelope protein borrowed from Serris et al. [5] showing the protein orientation and insertion in the envelope/membrane. C – The authors’ similar 3-D ribbon structure and D – the authors’ predicted blue aptamer docked with the accessible outer ectodomain which could enable blocking of host cell receptor binding and block viral entry.

Conclusions

A total of 24 new DNA aptamer sequences against HV envelope polyprotein were generated and studied by static 3-D docking models that suggest binding of the HV envelope polyprotein external ectodomain by some of the candidates. If true, one or more of the reported aptamer DNA sequences could block or inhibit Hantavirus entry into host cells in vitro and in vivo, thus providing HV neutralization and passive immunity.

Acknowledgements

Funding was provided by US DoD SBIR Contract No. W91SR22P0007.

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