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Eosinophils are myeloid effector cells whose main homing is the gastrointestinal tract. There, they take part in type I and type II immune responses. They also contribute to other non-immunological homeostatic functions like mucus production, tissue regeneration, and angiogenesis. In colorectal cancer (CRC), eosinophils locate in the center of the tumor and in the front of invasion and play an anti-tumoral role. They directly kill tumor cells by releasing cytotoxic compounds and eosinophil extracellular traps or indirectly by activating other immune cells via cytokines. As CRC progresses, the number of infiltrating eosinophils decreases. Although this phenomenon is not fully understood, it is known that some changes in the microenvironmental milieu and microbiome can affect eosinophil infiltration. Importantly, a high number of intratumoral eosinophils is a favorable prognostic factor independent from the tumor stage. Moreover, after immunotherapy, responding patients usually display eosinophilia, so eosinophils could be a good biomarker candidate to monitor treatment outcomes. Finally, even though eosinophils seem to play an interesting anti-tumoral role in CRC, much more research is needed to fully understand their interactions in the CRC microenvironment. This review explores the multifaceted roles of eosinophils in colorectal cancer, highlighting their anti-tumoral effects, prognostic significance, and potential as a biomarker for treatment outcomes.
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Neoplasias Colorrectales , Eosinófilos , Microambiente Tumoral , Humanos , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Eosinófilos/inmunología , Eosinófilos/metabolismo , Microambiente Tumoral/inmunología , Pronóstico , Animales , Inmunoterapia/métodos , Biomarcadores de Tumor/metabolismoRESUMEN
Introduction: Cytomegalovirus (CMV) is a common herpesvirus with a high prevalence worldwide. After the acute infection phase, CMV can remain latent in several tissues. CD8 T cells in the lungs and salivary glands mainly control its reactivation control. White adipose tissue (WAT) contains a significant population of memory T cells reactive to viral antigens, but CMV specificity has mainly been studied in mouse WAT. Therefore, we obtained blood, omental WAT (oWAT), subcutaneous WAT (sWAT), and liver samples from 11 obese donors to characterize the human WAT adaptive immune landscape from a phenotypic and immune receptor specificity perspective. Methods: We performed high-throughput sequencing of the T cell receptor (TCR) locus to analyze tissue and blood TCR repertoires of the 11 donors. The presence of TCRs specific to CMV epitopes was tested through ELISpot assays. Moreover, phenotypic characterization of T cells was carried out through flow cytometry. Results: High-throughput sequencing analyses revealed that tissue TCR repertoires in oWAT, sWAT, and liver samples were less diverse and dominated by hyperexpanded clones when compared to blood samples. Additionally, we predicted the presence of TCRs specific to viral epitopes, particularly from CMV, which was confirmed by ELISpot assays. Remarkably, we found that oWAT has a higher proportion of CMV-reactive T cells than blood or sWAT. Finally, flow cytometry analyses indicated that most WAT-infiltrated lymphocytes were tissue-resident effector memory CD8 T cells. Discussion: Overall, these findings postulate human oWAT as a major reservoir of CMV-specific T cells, presumably for latent viral reactivation control. This study enhances our understanding of the adaptive immune response in human WAT and highlights its potential role in antiviral defense.
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Infecciones por Citomegalovirus , Citomegalovirus , Animales , Ratones , Humanos , Receptores de Antígenos de Linfocitos T/genética , Epítopos , Tejido AdiposoRESUMEN
To reduce the environmental impacts from sodium silicate synthesis, a ceramic method was suggested, with sugarcane bagasse ash (SCBA) as the source of silicon dioxide and sodium carbonate. Although the production of sodium silicate is carried out on a large scale, it should be noted that its process requires temperatures above 1000 °C; it also requires the use of highly corrosive agents such as sodium hydroxide and chlorine gas to neutralize the remaining sodium hydroxide. In the present study, the synthesis temperatures were reduced to 800 °C with a reaction time of 3 h by pressing equimolar mixtures of previously purified SCBA and sodium carbonate; then, heat treatment was carried out under the indicated conditions. The resulting materials were analyzed with Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). Among the crystalline phases, calcium disodium silicate was identified, in addition to sodium silicate; thus, it was inferred that the other components of the ash can interfere with the synthesis of silicate. Therefore, in order to obtain the highest composition of sodium silicate, a leaching treatment of the SCBA is required.
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From birth, we perceive speech by hearing and seeing people talk. In adults cortical representations of visual speech are processed in the putative temporal visual speech area (TVSA), but it remains unknown how these representations develop. We measured infants' cortical responses to silent visual syllables and non-communicative mouth movements using functional Near-Infrared Spectroscopy. Our results indicate that cortical specialisation for visual speech may emerge during infancy. The putative TVSA was active to both visual syllables and gurning around 5 months of age, and more active to gurning than to visual syllables around 10 months of age. Multivariate pattern analysis classification of distinct cortical responses to visual speech and gurning was successful at 10, but not at 5 months of age. These findings imply that cortical representations of visual speech change between 5 and 10 months of age, showing that the putative TVSA is initially broadly tuned and becomes selective with age.
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Percepción del Habla , Adulto , Humanos , Lactante , Percepción del Habla/fisiología , Estimulación Acústica/métodos , Audición , Estimulación Luminosa/métodosRESUMEN
Early in life, infants exhibit motor overflow, which can be defined as the generation of involuntary movements accompanying purposeful actions. We present the results of a quantitative study exploring motor overflow in 4-month-old infants. This is the first study quantifying motor overflow with high accuracy and precision provided by Inertial Motion Units. The study aimed to investigate the motor activity across the non-acting limbs during goal-directed action. To this end, we used wearable motion trackers to measure infant motor activity during a baby-gym task designed to capture overflow during reaching movements. The analysis was conducted on the subsample of participants (n = 20), who performed at least four reaches during the task. A series of Granger causality tests revealed that the activity differed depending on the non-acting limb and the type of the reaching movement. Importantly, on average, the non-acting arm preceded the activation of the acting arm. In contrast, the activity of the acting arm was followed by the activation of the legs. This may be caused by their distinct purposes in supporting postural stability and efficiency of movement execution. Finally, our findings demonstrate the utility of wearable motion trackers for precise measurement of infant movement dynamics.
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Movimiento , Desempeño Psicomotor , Humanos , Lactante , Desempeño Psicomotor/fisiología , Movimiento/fisiología , Pierna , Movimiento (Física) , MotivaciónRESUMEN
Poly(ADP-ribose) polymerase-1 (PARP-1) is a protein involved in multiple physiological processes. Elevated PARP-1 expression has been found in several tumours, being associated with stemness and tumorigenesis. In colorectal cancer (CRC), some controversy among studies has been described. In this study, we analysed the expression of PARP-1 and cancer stem cell (CSC) markers in CRC patients with different p53 status. In addition, we used an in vitro model to evaluate the influence of PARP-1 in CSC phenotype regarding p53. In CRC patients, PARP-1 expression correlated with the differentiation grade, but this association was only maintained for tumours harbouring wild-type p53. Additionally, in those tumours, PARP-1 and CSC markers were positively correlated. In mutated p53 tumours, no associations were found, but PARP-1 was an independent factor for survival. According to our in vitro model, PARP-1 regulates CSC phenotype depending on p53 status. PARP-1 overexpression in a wild type p53 context increases CSC markers and sphere forming ability. By contrast, those features were reduced in mutated p53 cells. These results could implicate that patients with elevated PARP-1 expression and wild type p53 could benefit from PARP-1 inhibition therapies, meanwhile it could have adverse effects for those carrying mutated p53 tumours.
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Neoplasias Colorrectales , Células Madre Neoplásicas , Poli(ADP-Ribosa) Polimerasa-1 , Proteína p53 Supresora de Tumor , Humanos , Neoplasias Colorrectales/metabolismo , Células Madre Neoplásicas/metabolismo , Fenotipo , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Proteína p53 Supresora de Tumor/metabolismo , Poli(ADP-Ribosa) Polimerasa-1/metabolismoRESUMEN
Getting older affects both the structure of the brain and some cognitive capabilities. Until now, magnetic resonance imaging (MRI) approaches have been unable to give a coherent reflection of the cognitive declines. It shows the limitation of the contrast mechanisms used in most MRI investigations, which are indirect measures of brain activities depending on multiple physiological and cognitive variables. However, MRI signals may contain information of brain activity beyond these commonly used signals caused by the neurovascular response. Here, we apply a zero-spin echo (ZSE) weighted MRI sequence, which can detect heartbeat-evoked signals (HES). Remarkably, these MRI signals have properties only known from electrophysiology. We investigated the complexity of the HES arising from this sequence in two age groups; young (18-29 years) and old (over 65 years). While comparing young and old participants, we show that the complexity of the HES decreases with age, where the stability and chaoticity of these HES are particularly sensitive to age. However, we also found individual differences which were independent of age. Complexity measures were related to scores from different cognitive batteries and showed that higher complexity may be related to better cognitive performance. These findings underpin the affinity of the HES to electrophysiological signals. The profound sensitivity of these changes in complexity shows the potential of HES for understanding brain dynamics that need to be tested in more extensive and diverse populations with clinical relevance for all neurovascular diseases. Supplementary Information: The online version contains supplementary material available at 10.1140/epjs/s11734-022-00696-2.
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Individuals who have the disposition to identify with all humanity declare feeling close to people all over the world, caring about them, and perceiving them as an ingroup. However, never before were such declarations verified by measures of intergroup attitudes less direct than questionnaires, such as approach/avoidance tendencies or dynamical systems methods. Since individuals with higher dispositional identification with all humanity (IWAH) perceive people all over the world as ingroup members, we expected differences in the dynamic of inter-ethnic interactions (spatial distance, coordination, coupling, and leading), depending on a participant's level of IWAH. 227 participants fulfilled the IWAH scale, and those with the highest and lowest scores took part in a laboratory study, performing a task in inter-ethnic dyads. For the first time, an approach that combines a state-of-the-art tracking algorithm with a dynamical systems method was applied in such a context. Our results showed that those higher in IWAH kept a smaller distance from a partner, took a more leading role, and showed better coordination than those lower in IWAH. We found a similar trend for coupling. The results demonstrated the importance of IWAH for inter-ethnic relations and how it may shape non-verbal behaviors. Limitations are discussed.
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Etnicidad , Relaciones Interpersonales , Humanos , Actitud , Personalidad , Encuestas y CuestionariosRESUMEN
From early on, infants produce a variety of rhythmic behaviors-an ability that likely supports later social communication. However, it is unclear, how this rhythmic motor production changes with age. Here, we investigated the coupling between infants' arm movements across the first year of life in a social context of a rattle-shaking play with their mothers. Through longitudinal measurements at 4, 6, 9, and 12 months of age using wearable motion trackers placed on infants' arms, we show that infants (N = 40) are similarly motivated to attempt rattle-shaking across the first year of life. However, with age, they make more rattling movements with an increased frequency. Their left and right arm movements become more coupled during rattle-shaking, as shown by an increase in wavelet coherence. Infants produced more rattling movements when they were rattling alone than when their mothers were rattling or singing simultaneously. There were no differences between infants' individual and social rattling in between-arms coherence. Our results may help to understand rhythmic arm movements as precursors of motor social coordination.
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The role of parental behaviour in modulating infant learning during experimental studies has been rarely explored. Yet, multiple strands of research suggest that dyadic infant-parent interactions could be as important for infant learning and regulation during experimental studies with infants, as they are during their free, unconstrained play. Recently, we have developed a coding scheme for analysing the quantity and quality of various extraneous behaviours of both the parent and the infant during standard eye-tracking experiments. Here, we present a quantitative analysis of selected parental behaviours and their role in modulating infant task performance. We analysed whether parental looking (at the screen or at the infant), talking and pointing and physical contact change with the task that the infant is performing. The results showed subtle, systematic adjustments of parental behaviours in relation to the task. Moreover, parental behaviours were related to infant performance for tasks that involve learning (habituation task) and free viewing of visual stimuli, but not for those involving simple orienting responses (gap-overlap task). Additional dynamic analyses using Cross-Recurrence Quantification Analysis indicated that parents were closely following the infants' shifts, looking toward and away from the screen. Altogether, these results indicate that infant performance in eye-tracking tasks are associated with subtle adjustments of parental behaviours. This may suggest that early on infants perform learning tasks in coordination with parental behaviour as a dyadic unit of learning.
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Tecnología de Seguimiento Ocular , Padres , Lactante , Humanos , Aprendizaje , Relaciones InterpersonalesRESUMEN
Infants' attention to the mouth is thought to support language acquisition, yet this relation has been scantly tested longitudinally. This study assessed attention to the mouth and the eyes at 5.5 (n = 91; Polish, 49% females) and 11 months, between time-point changes and their associations with language development in infancy (11 months) and toddlerhood (24 months). Sex differences were also explored. Results showed an age-related increase in looking to the mouth, and the magnitude of this change was associated with productive language, but only in toddlerhood. By contrast, looking to the eyes did not change and its duration at 5.5 months correlated with language development at 2 years. Exploratory analyses showed that in females but not males, reduced mouth-looking was related to better language outcomes in toddlerhood. Thus, looking to the mouth in infancy likely plays a long-term role in language acquisition and is potentially modulated by participant sex.
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Lenguaje , Caracteres Sexuales , Lactante , Humanos , Femenino , Masculino , Desarrollo del Lenguaje , Boca , CaraRESUMEN
The paradigm of mast cells in type 2 diabetes is changing. Although they were first considered deleterious inflammatory cells, now they seem to be important players driving adipose tissue homeostasis. Here we have employed a flow cytometry-based approach for measuring the surface expression of 4 proteins (CD45, CD117, CD203c, and FcϵRI) on mast cells of omental (o-WAT) and subcutaneous white adipose tissue (s-WAT) in a cohort of 96 patients with morbid obesity. The cohort was split into three groups: non-T2D, pre-T2D, and T2D. Noteworthy, patients with T2D have a mild condition (HbA1c <7%). In o-WAT, mast cells of patients with T2D have a decrease in the surface expression of CD45 (p=0.0013), CD117 (p=0.0066), CD203c (p=0.0025), and FcϵRI (p=0.043). Besides, in s-WAT, the decrease was seen only in CD117 (p=0.046). These results indicate that T2D affects more to mast cells in o-WAT than in s-WAT. The decrease in these four proteins has serious effects on mast cell function. CD117 is critical for mast cell survival, while CD45 and FcϵRI are important for mast cell activation. Additionally, CD203c is only present on the cell surface after granule release. Taking together these observations, we suggest that mast cells in o-WAT of patients with T2D have a decreased survival, activation capacity, and secretory function.
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Diabetes Mellitus Tipo 2 , Obesidad Mórbida , Tejido Adiposo/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Antígenos Comunes de Leucocito , Mastocitos/fisiología , Obesidad Mórbida/complicaciones , Hidrolasas Diéster Fosfóricas , Proteínas Proto-Oncogénicas c-kit , Pirofosfatasas , Receptores de IgE/metabolismoRESUMEN
Infants' limb movements evolve from disorganized to more selectively coordinated during the first year of life as they learn to navigate and interact with an ever-changing environment more efficiently. However, how these coordination patterns change during the first year of life and across different contexts is unknown. Here, we used wearable motion trackers to study the developmental changes in the complexity of limb movements (arms and legs) at 4, 6, 9 and 12 months of age in two different tasks: rhythmic rattle-shaking and free play. We applied Multidimensional Recurrence Quantification Analysis (MdRQA) to capture the nonlinear changes in infants' limb complexity. We show that the MdRQA parameters (entropy, recurrence rate and mean line) are task-dependent only at 9 and 12 months of age, with higher values in rattle-shaking than free play. Since rattle-shaking elicits more stable and repetitive limb movements than the free exploration of multiple objects, we interpret our data as reflecting an increase in infants' motor control that allows for stable body positioning and easier execution of limb movements. Infants' motor system becomes more stable and flexible with age, allowing for flexible adaptation of behaviors to task demands.
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Visual search guides goal-directed action in humans and many other species, and it has been studied extensively in the past. Yet, no study has investigated the relative contributions of genes and environments to individual differences in visual search performance, or to which extent etiologies are shared with broader cognitive phenotypes. To address this gap, we studied visual search and general intelligence in 156 monozygotic (MZ) and 158 same-sex dizygotic (DZ) twin pairs. We found that different indexes of visual search performance (response latency and visual search efficiency) were moderately heritable. Phenotypic correlations between visual search and intelligence were small-to-moderate, and only a small proportion of the genetic variance in visual search was shared with genetic variance in intelligence. We discuss these findings in the context of the "generalist genes hypothesis" stating that different cognitive functions have a common genetic basis.
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Gemelos Dicigóticos , Gemelos Monocigóticos , Humanos , Inteligencia/genética , Fenotipo , Gemelos Dicigóticos/genética , Gemelos Monocigóticos/genéticaRESUMEN
In the 1st year of life, infants gradually gain the ability to control their eye movements and explore visual scenes, which support their learning and emerging cognitive skills. These gains include domain-general skills such as rapid orienting or attention disengagement as well as domain-specific ones such as increased sensitivity to social stimuli. However, it remains unknown whether these developmental changes in what infants fixate and for how long in naturalistic scenes lead to the emergence of more complex, repeated sequences of fixations, especially when viewing human figures and faces, and whether these changes are related to improvements in domain-general attentional skills. Here we tested longitudinally the developmental changes in the complexity of fixation sequences at 5.5 and 11 months of age using Recurrence Quantification Analysis. We measured changes in how fixations recur in the same location and changes in the patterns (repeated sequences) of fixations in social and non-social scenes that were either static or dynamic. We found more complex patterns (i.e., repeated and longer sequences) of fixations in social than non-social scenes, both static and dynamic. There was also an age-related increase in the length of repeated fixation sequences only for social static scenes, which was independent of individual differences in orienting and attention disengagement. Our results can be interpreted as evidence for fine-tuning of infants' visual scanning skills. They selectively produce longer and more complex sequences of fixations on faces and bodies before reaching the end of the 1st year of life.
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Type 2 diabetes (T2D) is a rising global health problem mainly caused by obesity and a sedentary lifestyle. In healthy individuals, white adipose tissue (WAT) has a relevant homeostatic role in glucose metabolism, energy storage, and endocrine signaling. Mast cells contribute to these functions promoting WAT angiogenesis and adipogenesis. In patients with T2D, inflammation dramatically impacts WAT functioning, which results in the recruitment of several leukocytes, including monocytes, that enhance this inflammation. Accordingly, the macrophages population rises as the WAT inflammation increases during the T2D status worsening. Since mast cell progenitors cannot arrive at WAT, the amount of WAT mast cells depends on how the new microenvironment affects progenitor and differentiated mast cells. Here, we employed a flow cytometry-based approach to analyze the number of mast cells from omental white adipose tissue (o-WAT) and subcutaneous white adipose tissue (s-WAT) in a cohort of 100 patients with obesity. Additionally, we measured the number of mast cell progenitors in a subcohort of 15 patients. The cohort was divided in three groups: non-T2D, pre-T2D, and T2D. Importantly, patients with T2D have a mild condition (HbA1c <7%). The number of mast cells and mast cell progenitors was lower in patients with T2D in both o-WAT and s-WAT in comparison to subjects from the pre-T2D and non-T2D groups. In the case of mast cells in o-WAT, there were statistically significant differences between non-T2D and T2D groups (p = 0.0031), together with pre-T2D and T2D groups (p=0.0097). However, in s-WAT, the differences are only between non-T2D and T2D groups (p=0.047). These differences have been obtained with patients with a mild T2D condition. Therefore, little changes in T2D status have a huge impact on the number of mast cells in WAT, especially in o-WAT. Due to the importance of mast cells in WAT physiology, their decrease can reduce the capacity of WAT, especially o-WAT, to store lipids and cause hypoxic cell deaths that will trigger inflammation.
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Tejido Adiposo/patología , Recuento de Células , Diabetes Mellitus Tipo 2/patología , Mastocitos/patología , Obesidad/patología , Adipogénesis , Tejido Adiposo/metabolismo , Tejido Adiposo Blanco/metabolismo , Tejido Adiposo Blanco/patología , Biomarcadores , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Inmunofenotipificación , Mucosa Intestinal/inmunología , Mucosa Intestinal/metabolismo , Neovascularización Fisiológica , Obesidad/metabolismoRESUMEN
In social animals, studying interactions with conspecifics is crucial for understanding even basic physiological, behavioral, and cognitive processes. Due to a visible "ecological turn" in behavioral research, we observe a rapid development of novel methods devoted to studying interaction. In this article, we offer a case study of an animal interactive behavior, which uses new methods of video-recorded motion capturing combined with time-series analysis called recurrence quantification analysis. We apply the method to the video-recorded behavioral sequence observed in Rattus norvegicus to evidence the fine-grained structure of this behavior. We show how such dynamical analyses can lead to insights about the processes behind such behavioral patterns and their change. Finally, we show how this approach can be successfully applied to other examples of highly coordinated behaviors in the animal world. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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Conducta Animal , Investigación Conductal , Animales , RatasRESUMEN
Multiple visual attention mechanisms are active already in infancy, most notably one supporting orienting towards stimuli and another, maintaining appropriate levels of alertness, when exploring the environment. They are thought to depend on separate brain networks, but their effects are difficult to isolate in existing behavioural paradigms. Better understanding of the contribution of each network to individual differences in visual orienting may help to explain their role in attention development. Here, we tested whether alerting and spatial cues differentially modulate pupil dilation in 8-month-old infants in a visual orienting paradigm. We found differential effects in the time course of these responses depending on the cue type. Moreover, using Principal Component Analysis (PCA) we identified two main components of pupillary response, which may reflect the alerting and orienting network activity. In a regression analysis, these components together explained nearly 40 % of variance in saccadic latencies in the spatial cueing condition of the task. These results likely demonstrate that both networks work together in 8-month-old infants and that their activity can be indexed with pupil dilation combined with PCA, but not with raw changes in pupil diameter.
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Atención/fisiología , Orientación/fisiología , Pupila/fisiología , Femenino , Humanos , Lactante , MasculinoRESUMEN
Autism spectrum disorder (ASD) is commonly conceived as the extreme end of a continuum. Research suggests that autistic individuals outperform typically developing controls in visual search. Thus, enhanced visual search may represent an adaptive trait associated with ASD. Here, using a large general population sample (N = 608, aged 9-14 years), we tested if higher levels of autistic traits are associated with enhanced visual search. Visual search was evaluated using both manual responses and eye movements, and autistic traits were measured using the Social Responsiveness Scale. Contrary to our hypothesis, no significant relation between autistic traits and visual search were observed. The theoretical implications of these results are discussed.
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Trastorno del Espectro Autista/fisiopatología , Movimientos Oculares , Adolescente , Niño , Femenino , Humanos , MasculinoRESUMEN
The analysis of parent-child interactions is crucial for the understanding of early human development. Manual coding of interactions is a time-consuming task, which is a limitation in many projects. This becomes especially demanding if a frame-by-frame categorization of movement needs to be achieved. To overcome this, we present a computational approach for studying movement coupling in natural settings, which is a combination of a state-of-the-art automatic tracker, Tracking-Learning-Detection (TLD), and nonlinear time-series analysis, Cross-Recurrence Quantification Analysis (CRQA). We investigated the use of TLD to extract and automatically classify movement of each partner from 21 video recordings of interactions, where 5.5-month-old infants and mothers engaged in free play in laboratory settings. As a proof of concept, we focused on those face-to-face episodes, where the mother animated an object in front of the infant, in order to measure the coordination between the infants' head movement and the mothers' hand movement. We also tested the feasibility of using such movement data to study behavioral coupling between partners with CRQA. We demonstrate that movement can be extracted automatically from standard definition video recordings and used in subsequent CRQA to quantify the coupling between movement of the parent and the infant. Finally, we assess the quality of this coupling using an extension of CRQA called anisotropic CRQA and show asymmetric dynamics between the movement of the parent and the infant. When combined these methods allow automatic coding and classification of behaviors, which results in a more efficient manner of analyzing movements than manual coding.