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1.
Dev Psychopathol ; : 1-13, 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38602091

ABSTRACT

Exposure to early life adversity (ELA) is hypothesized to sensitize threat-responsive neural circuitry. This may lead individuals to overestimate threat in the face of ambiguity, a cognitive-behavioral phenotype linked to poor mental health. The tendency to process ambiguity as threatening may stem from difficulty distinguishing between ambiguous and threatening stimuli. However, it is unknown how exposure to ELA relates to neural representations of ambiguous and threatening stimuli, or how processing of ambiguity following ELA relates to psychosocial functioning. The current fMRI study examined multivariate representations of threatening and ambiguous social cues in 41 emerging adults (aged 18 to 19 years). Using representational similarity analysis, we assessed neural representations of ambiguous and threatening images within affective neural circuitry and tested whether similarity in these representations varied by ELA exposure. Greater exposure to ELA was associated with greater similarity in neural representations of ambiguous and threatening images. Moreover, individual differences in processing ambiguity related to global functioning, an association that varied as a function of ELA. By evidencing reduced neural differentiation between ambiguous and threatening cues in ELA-exposed emerging adults and linking behavioral responses to ambiguity to psychosocial wellbeing, these findings have important implications for future intervention work in at-risk, ELA-exposed populations.

2.
Emotion ; 24(5): 1125-1136, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38300553

ABSTRACT

Typologies serve to organize knowledge and advance theory for many scientific disciplines, including more recently in the social and behavioral sciences. To date, however, no typology exists to categorize an individual's use of emotion regulation strategies. This is surprising given that emotion regulation skills are used daily and that deficits in this area are robustly linked with mental health symptoms. Here, we attempted to identify and validate a working typology of emotion regulation across six samples (collectively comprised of 1,492 participants from multiple populations) by using a combination of computational techniques, psychometric models, and growth curve modeling. We uncovered evidence for three types of regulators: a type that infrequently uses emotion regulation strategies (Lo), a type that uses them frequently but indiscriminately (Hi), and a third type that selectively uses some (cognitive reappraisal and situation selection), but not other (expressive suppression), emotion regulation strategies frequently (Mix). Results showed that membership in the Hi and Mix types is associated with better mental health, with the Mix type being the most adaptive of the three. These differences were stable over time and across different samples. These results carry important implications for both our basic understanding of emotion regulation behavior and for informing future interventions aimed at improving mental health. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Subject(s)
Emotional Regulation , Humans , Emotional Regulation/physiology , Male , Female , Adult , Young Adult , Middle Aged , Adolescent , Psychometrics , Mental Health , Emotions/physiology
3.
Food Res Int ; 175: 113827, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38129014

ABSTRACT

Long-term space exploration endeavors, encompassing journeys from the Earth to the Moon by 2030 and subsequent voyages from the Moon to Mars by 2040, necessitate the utilization of plant-based materials not solely for sustenance and refreshments but also the production of pharmaceuticals and repair compounds, such as plastics, among others. Nevertheless, the vital aspects of research in this domain pertain to the nutritional value and sensory perception associated with plant-based food. Prior investigations have shown altered sensory perception in space, manifested as diminished olfactory sensations and heightened taste perception (saltiness and sweetness). Nonetheless, studies concerning changes in aroma, basic tastes, and mouthfeel have been limited due to the logistical challenges associated with conducting experiments in the unique environment of space. To address this limitation, the present study employed sensory trials and biometrics from video using simulated microgravity chairs to simulate alterations in sensory perception akin to those encountered in space conditions. The findings of this study align with previous reports of changes in aroma and taste perception and contribute to the understanding of changes in the mouthfeel, heart rate, blood pressure, and emotional response that could be experienced in space environments. These experimental endeavors are critical to facilitate the advancement and development of novel plants and food materials tailored to the requirements of long-term space exploration.


Subject(s)
Weightlessness , Sensation , Taste Perception , Emotions , Biometry
4.
Biol Psychol ; 182: 108624, 2023 09.
Article in English | MEDLINE | ID: mdl-37394090

ABSTRACT

The tendency to interpret ambiguous stimuli as threatening has been associated with a range of anxiety disorders. Responses to ambiguity may be particularly relevant to mental health during the transition from adolescence to adulthood ("emerging adulthood"), when individuals encounter unfamiliar challenges and navigate novel social situations. However, it remains unclear whether neural representations of ambiguity relate to risk for anxiety. The present study sought to examine whether multivariate representations of ambiguity - and their similarity to representations of threat - relate to appraisals of ambiguity or anxiety in a sample of emerging adults. Participants (N = 41) viewed threatening (angry), nonthreatening (happy), and ambiguous (surprised) facial stimuli while undergoing fMRI. Outside of the scanner, participants were presented with the same stimuli and categorized the ambiguous faces as positive or negative. Using representational similarity analyses (RSA), we investigated whether the degree of pattern similarity in responses to ambiguous, nonthreatening, and threatening faces within the amygdala related to appraisals of ambiguous stimuli and anxiety symptomatology. We found that individuals who evidenced greater similarity (i.e., less differentiation) in neural representations of ambiguous and nonthreatening faces within the left amygdala reported lower concurrent anxiety. Additionally, trial-level pattern similarity predicted subsequent appraisals of ambiguous stimuli. These findings provide insight into how neural representations of ambiguity relate to risk or resilience for the development of anxiety.


Subject(s)
Anxiety , Facial Expression , Adolescent , Adult , Humans , Anxiety/psychology , Anger/physiology , Happiness , Anxiety Disorders , Magnetic Resonance Imaging
5.
Affect Sci ; 4(2): 275-290, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37293683

ABSTRACT

Emotion regulation (ER) strategies and beliefs about emotions (implicit theories of emotions; ITE) may shape psychosocial outcomes during turbulent times, including the transition to adulthood and college while encountering stressors. The normative stressors associated with these transitions were compounded by the COVID-19 pandemic, providing a novel opportunity to examine how emerging adults (EAs) cope with sustained stressors. Stress exposures can heighten existing individual differences and serve as "turning points" that predict psychosocial trajectories. This pre-registered study (https://osf.io/k8mes) of 101 EAs (18-19 years old) examined whether ITE (believing emotions can change or not; incremental vs. entity beliefs) and ER strategy usage (cognitive reappraisal and expressive suppression usage) predicted changes in anxiety symptomatology and feelings of loneliness across five longitudinal assessments (across a 6-month period) before and during the initial months of the COVID-19 pandemic. On average, EAs' anxiety decreased after the pandemic outbreak but returned to baseline over time, while loneliness remained relatively unchanged across time. ITE explained variance in anxiety across time over and above reappraisal use. Conversely, reappraisal use explained variance in loneliness over and above ITE. For both anxiety and loneliness, suppression use resulted in maladaptive psychosocial outcomes across time. Thus, interventions that target ER strategies and ITE may ameliorate risk and promote resilience in EAs who experience increased instability. Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-023-00187-0.

6.
Dev Psychopathol ; 35(4): 1968-1981, 2023 Oct.
Article in English | MEDLINE | ID: mdl-36523255

ABSTRACT

Early caregiving adversity (ECA) is associated with elevated psychological symptomatology. While neurobehavioral ECA research has focused on socioemotional and cognitive development, ECA may also increase risk for "low-level" sensory processing challenges. However, no prior work has compared how diverse ECA exposures differentially relate to sensory processing, or, critically, how this might influence psychological outcomes. We examined sensory processing challenges in 183 8-17-year-old youth with and without histories of institutional (orphanage) or foster caregiving, with a particular focus on sensory over-responsivity (SOR), a pattern of intensified responses to sensory stimuli that may negatively impact mental health. We further tested whether sensory processing challenges are linked to elevated internalizing and externalizing symptoms common in ECA-exposed youth. Relative to nonadopted comparison youth, both groups of ECA-exposed youth had elevated sensory processing challenges, including SOR, and also had heightened internalizing and externalizing symptoms. Additionally, we found significant indirect effects of ECA on internalizing and externalizing symptoms through both general sensory processing challenges and SOR, covarying for age and sex assigned at birth. These findings suggest multiple forms of ECA confer risk for sensory processing challenges that may contribute to mental health outcomes, and motivate continuing examination of these symptoms, with possible long-term implications for screening and treatment following ECA.


Subject(s)
Cognition , Mental Health , Adolescent , Infant, Newborn , Humans , Perception
7.
Physiol Rev ; 103(1): 391-432, 2023 01 01.
Article in English | MEDLINE | ID: mdl-35953269

ABSTRACT

The heart is imbued with a vast lymphatic network that is responsible for fluid homeostasis and immune cell trafficking. Disturbances in the forces that regulate microvascular fluid movement can result in myocardial edema, which has profibrotic and proinflammatory consequences and contributes to cardiovascular dysfunction. This review explores the complex relationship between cardiac lymphatics, myocardial edema, and cardiac disease. It covers the revised paradigm of microvascular forces and fluid movement around the capillary as well as the arsenal of preclinical tools and animal models used to model myocardial edema and cardiac disease. Clinical studies of myocardial edema and their prognostic significance are examined in parallel to the recent elegant animal studies discerning the pathophysiological role and therapeutic potential of cardiac lymphatics in different cardiovascular disease models. This review highlights the outstanding questions of interest to both basic scientists and clinicians regarding the roles of cardiac lymphatics in health and disease.


Subject(s)
Edema, Cardiac , Heart Diseases , Lymphatic Vessels , Animals , Disease Models, Animal , Edema, Cardiac/physiopathology , Heart Diseases/physiopathology , Lymphatic Vessels/physiopathology
8.
Curr Epidemiol Rep ; 10(4): 240-251, 2023 Dec.
Article in English | MEDLINE | ID: mdl-39055963

ABSTRACT

Purpose of Review: Preparing for pandemics requires a degree of interdisciplinary work that is challenging under the current paradigm. This review summarizes the challenges faced by the field of pandemic science and proposes how to address them. Recent Findings: The structure of current siloed systems of research organizations hinders effective interdisciplinary pandemic research. Moreover, effective pandemic preparedness requires stakeholders in public policy and health to interact and integrate new findings rapidly, relying on a robust, responsive, and productive research domain. Neither of these requirements are well supported under the current system. Summary: We propose a new paradigm for pandemic preparedness wherein interdisciplinary research and close collaboration with public policy and health practitioners can improve our ability to prevent, detect, and treat pandemics through tighter integration among domains, rapid and accurate integration, and translation of science to public policy, outreach and education, and improved venues and incentives for sustainable and robust interdisciplinary work.

9.
Dev Cogn Neurosci ; 58: 101172, 2022 12.
Article in English | MEDLINE | ID: mdl-36368089

ABSTRACT

Early pubertal timing has been linked to increased risk for internalizing psychopathology in adolescents. Work in older adolescents and adults suggests that heightened reward sensitivity may buffer risk for internalizing symptoms. However, few studies have investigated these associations during the early transition to puberty, a window of vulnerability to mental health risk. In this preregistered study, we investigated the associations among pubertal timing, internalizing symptoms, and reward sensitivity in a large, population-based sample of 11,224 9-10 year-olds from the ABCD Study®. Using split-half analysis, we tested for within-sample replications of hypothesized effects across two age- and sex-matched subsets of the sample. Early pubertal timing was associated with higher internalizing symptoms in female and male participants across samples, with 9-10 year-olds in the mid-pubertal stage at the highest risk for internalizing symptoms. Additionally, early pubertal timing was robustly associated with greater self-reported reward sensitivity in both female and male participants. We observed inconsistent evidence for a moderating role of reward sensitivity across measurement domains (self-report, behavioral, and fMRI data), several of which differed by sex, but none of these interactions replicated across samples. Together, these findings provide unique insights into early indicators of risk for internalizing psychopathology during the transition to puberty in a large, population-based, demographically diverse sample of youth.


Subject(s)
Puberty , Reward , Adolescent , Adult , Humans , Male , Female , Magnetic Resonance Imaging
10.
Psychol Sci ; 33(10): 1664-1679, 2022 10.
Article in English | MEDLINE | ID: mdl-36219573

ABSTRACT

Cross-species research suggests that exploratory behaviors increase during adolescence and relate to the social, affective, and risky behaviors characteristic of this developmental stage. However, how these typical adolescent behaviors manifest and relate in real-world settings remains unclear. Using geolocation tracking to quantify exploration-variability in daily movement patterns-over a 3-month period in 58 adolescents and adults (ages 13-27) in New York City, we investigated whether daily exploration varied with age and whether exploration related to social connectivity, risk taking, and momentary positive affect. In our cross-sectional sample, we found an association between daily exploration and age, with individuals near the transition to legal adulthood exhibiting the highest exploration levels. Days of higher exploration were associated with greater positive affect irrespective of age. Higher mean exploration was associated with greater social connectivity in all participants but was linked to higher risk taking selectively among adolescents. Our results highlight the interplay of exploration and socioemotional behaviors across development and suggest that societal norms may modulate their expression in naturalistic contexts.


Subject(s)
Adolescent Behavior , Risk-Taking , Adolescent , Adolescent Behavior/psychology , Adult , Cross-Sectional Studies , Humans , New York City , Social Norms , Young Adult
11.
Article in English | MEDLINE | ID: mdl-36152130

ABSTRACT

Beginning college involves changes that can increase one's vulnerability to loneliness and associated negative outcomes. Parent and friend relationships are potential protective factors against loneliness given their positive association with adjustment. The present longitudinal study, with data collection at baseline, 1 month, and 2 months later, assessed the comparative effects of self-reported parent and friend relationship quality on loneliness in first-year college students (N = 101; 80 female, Mage = 18.36). At baseline, parent and friend relationship quality were negatively associated with loneliness. Longitudinal data revealed that friend relationship quality interacted with time, such that its effects on loneliness attenuated over the course of 2 months. By contrast, parent relationship quality continued to predict lower loneliness 2 months post-baseline. These results highlight the importance of close relationships and suggest that targeting relationship quality could be effective in helping youth transition to college.

12.
Hum Brain Mapp ; 43(15): 4750-4790, 2022 10 15.
Article in English | MEDLINE | ID: mdl-35860954

ABSTRACT

The model-free algorithms of "reinforcement learning" (RL) have gained clout across disciplines, but so too have model-based alternatives. The present study emphasizes other dimensions of this model space in consideration of associative or discriminative generalization across states and actions. This "generalized reinforcement learning" (GRL) model, a frugal extension of RL, parsimoniously retains the single reward-prediction error (RPE), but the scope of learning goes beyond the experienced state and action. Instead, the generalized RPE is efficiently relayed for bidirectional counterfactual updating of value estimates for other representations. Aided by structural information but as an implicit rather than explicit cognitive map, GRL provided the most precise account of human behavior and individual differences in a reversal-learning task with hierarchical structure that encouraged inverse generalization across both states and actions. Reflecting inference that could be true, false (i.e., overgeneralization), or absent (i.e., undergeneralization), state generalization distinguished those who learned well more so than action generalization. With high-resolution high-field fMRI targeting the dopaminergic midbrain, the GRL model's RPE signals (alongside value and decision signals) were localized within not only the striatum but also the substantia nigra and the ventral tegmental area, including specific effects of generalization that also extend to the hippocampus. Factoring in generalization as a multidimensional process in value-based learning, these findings shed light on complexities that, while challenging classic RL, can still be resolved within the bounds of its core computations.


Subject(s)
Magnetic Resonance Imaging , Reinforcement, Psychology , Generalization, Psychological , Humans , Learning , Magnetic Resonance Imaging/methods , Reward
13.
ACS ES T Water ; 2(5): 863-872, 2022 May 13.
Article in English | MEDLINE | ID: mdl-35822195

ABSTRACT

Challenges associated with water separation technologies for per- and polyfluoroalkyl substances (PFASs) require efficient and sustainable processes supported by a proper understanding of the separation mechanisms. The solute rejections by nanofiltration (NF) at pH values near the membrane isoelectric point were compared to the size- and mass-transfer-dependent modeled rejection rates of these compounds in an ionized state. We find that the low pK a value of perfluorooctanoic acid (PFOA) relates to enhanced solute exclusions by minimizing the presence and partitioning of the protonated organic compound into the membrane domain. The effects of Donnan exclusion are moderate, and co-ion transport also contributes to the PFAS rejection rates. An additional support barrier with thermo-responsive (quantified by water permeance variation) adsorption/desorption properties allows for enhanced separations of PFAS. This was possible by successfully synthesizing an NF layer on top of a poly-N-isopropylacrylamide (PNIPAm) pore-functionalized microfiltration support structure. The support layer adsorbs organics (178 mg PFOA adsorbed/m2 membrane at an equilibrium concentration of 70 mg/L), and the simultaneous exclusion from the NF layer allows separations of PFOA and the smaller sized heptafluorobutyric acid from solutions containing 70 µg/L of these compounds at a high water flux of 100 L/m2-h at 7 bar.

14.
J Exp Biol ; 225(13)2022 07 01.
Article in English | MEDLINE | ID: mdl-35694960

ABSTRACT

Mitochondrial function is fundamental to organismal performance, health and fitness - especially during energetically challenging events, such as migration. With this investigation, we evaluated mitochondrial sensitivity to ecologically relevant stressors. We focused on an iconic migrant, the North American monarch butterfly (Danaus plexippus), and examined the effects of two stressors: 7 days of food deprivation and infection by the protozoan parasite Ophryocystis elektroscirrha (known to reduce survival and flight performance). We measured whole-animal resting metabolic rate (RMR) and peak flight metabolic rate, and mitochondrial respiration of isolated mitochondria from the flight muscles. Food deprivation reduced mass-independent RMR and peak flight metabolic rate, whereas infection did not. Fed monarchs used mainly lipids in flight (respiratory quotient 0.73), but the respiratory quotient dropped in food-deprived individuals, possibly indicating switching to alternative energy sources, such as ketone bodies. Food deprivation decreased mitochondrial maximum oxygen consumption but not basal respiration, resulting in lower respiratory control ratio (RCR). Furthermore, food deprivation decreased mitochondrial complex III activity, but increased complex IV activity. Infection did not result in any changes in these mitochondrial variables. Mitochondrial maximum respiration rate correlated positively with mass-independent RMR and flight metabolic rate, suggesting a link between mitochondria and whole-animal performance. In conclusion, low food availability negatively affects mitochondrial function and flight performance, with potential implications for migration, fitness and population dynamics. Although previous studies have reported poor flight performance in infected monarchs, we found no differences in physiological performance, suggesting that reduced flight capacity may be due to structural differences or low energy stores.


Subject(s)
Apicomplexa , Butterflies , Parasites , Animals , Apicomplexa/physiology , Butterflies/physiology , Host-Parasite Interactions , Mitochondria
15.
J Exp Psychol Gen ; 151(12): 3249-3267, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35679187

ABSTRACT

Cognitive systems that track, update, and utilize information about reward (consequences) and risk (uncertainty) are critical for adaptive decision-making as well as everyday functioning and well-being. However, it remains unclear how individual differences in reward and risk sensitivity are independently shaped by environmental influences and give rise to decision-making. Here, we investigated the impact of early life experience-a potent sculptor of development-on behavioral sensitivity to reward and risk. We administered a widely used decision-making paradigm to 55 adolescents and young adults who were exposed to early deprivation in the form of early institutional (orphanage) care (a type of early life adversity) and 81 comparison individuals who were reared by their biological parents and did not experience institutional care. Leveraging random coefficient regression and computational models, we observed that previously institutionalized individuals displayed general reward hyposensitivity, contributing to a decreased propensity to make decisions that stood to earn relatively large rewards relative to comparison individuals. By contrast, group differences in risk sensitivity were selectively observed on loss, but not gain, trials. These results are the first to independently and explicitly link early experiences to reward and risk sensitivity during decision-making. As such, they lay the groundwork for therapeutic efforts to identify and treat adversity-exposed individuals at risk for psychiatric disorders characterized by aberrant decision-making processes. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Subject(s)
Decision Making , Reward , Adolescent , Young Adult , Humans , Risk-Taking , Uncertainty , Individuality
16.
Dev Cogn Neurosci ; 55: 101115, 2022 06.
Article in English | MEDLINE | ID: mdl-35636343

ABSTRACT

As the largest longitudinal study of adolescent brain development and behavior to date, the Adolescent Brain Cognitive Development (ABCD) Study® has provided immense opportunities for researchers across disciplines since its first data release in 2018. The size and scope of the study also present a number of hurdles, which range from becoming familiar with the study design and data structure to employing rigorous and reproducible analyses. The current paper is intended as a guide for researchers and reviewers working with ABCD data, highlighting the features of the data (and the strengths and limitations therein) as well as relevant analytical and methodological considerations. Additionally, we explore justice, equity, diversity, and inclusion efforts as they pertain to the ABCD Study and other large-scale datasets. In doing so, we hope to increase both accessibility of the ABCD Study and transparency within the field of developmental cognitive neuroscience.


Subject(s)
Cognition , Cognitive Neuroscience , Adolescent , Adolescent Development , Brain , Humans , Longitudinal Studies
17.
Support Care Cancer ; 30(2): 1655-1662, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34554280

ABSTRACT

BACKGROUND: The COVID-19 pandemic has fundamentally impacted the delivery of healthcare services globally. In line with UK government guidelines on social distancing, the use of telemedicine was implemented to facilitate the ongoing provision of cancer rehabilitation. PURPOSE: We sought to evaluate and co-design telemedicine services to meet the complex needs of our patients and carers at a tertiary cancer centre. METHODS: Experience-based co-design methodology was adapted to include virtual methods. Staff members (n = 12) and patients (n = 11) who had delivered or received therapies services at our UK cancer centre since March 2020 were recruited to take part in one-to-one virtual interviews. Patient interviews were video recorded, analysed and edited to a 30-min "trigger film". Patient and staff virtual events were undertaken thereafter. A joint virtual patient and staff event occurred. Staff and patients watched the trigger film and as partners, agreed areas for change and developed groups for service co-design. RESULTS: Positive aspects regarding telemedicine provision were highlighted including reduced financial and time burden on patients, and increased flexibility for both staff and patients. The key concerns included digital exclusion, safety, communication and patient choice. Four co-design groups have been established to enact changes in these priority areas. CONCLUSION: Using a participatory design approach, we have worked in partnership with patients and staff to ensure the safe, acceptable and effective delivery of rehabilitation services with integrated telemedicine.


Subject(s)
COVID-19 , Telemedicine , Humans , Medical Oncology , Pandemics , SARS-CoV-2
18.
Circ Res ; 130(1): 5-23, 2022 01 07.
Article in English | MEDLINE | ID: mdl-34789016

ABSTRACT

BACKGROUND: The adherens protein VE-cadherin (vascular endothelial cadherin) has diverse roles in organ-specific lymphatic vessels. However, its physiological role in cardiac lymphatics and its interaction with lymphangiogenic factors has not been fully explored. We sought to determine the spatiotemporal functions of VE-cadherin in cardiac lymphatics and mechanistically elucidate how VE-cadherin loss influences prolymphangiogenic signaling pathways, such as adrenomedullin and VEGF (vascular endothelial growth factor)-C/VEGFR3 (vascular endothelial growth factor receptor 3) signaling. METHODS: Cdh5flox/flox;Prox1CreERT2 mice were used to delete VE-cadherin in lymphatic endothelial cells across life stages, including embryonic, postnatal, and adult. Lymphatic architecture and function was characterized using immunostaining and functional lymphangiography. To evaluate the impact of temporal and functional regression of cardiac lymphatics in Cdh5flox/flox;Prox1CreERT2 mice, left anterior descending artery ligation was performed and cardiac function and repair after myocardial infarction was evaluated by echocardiography and histology. Cellular effects of VE-cadherin deletion on lymphatic signaling pathways were assessed by knockdown of VE-cadherin in cultured lymphatic endothelial cells. RESULTS: Embryonic deletion of VE-cadherin produced edematous embryos with dilated cardiac lymphatics with significantly altered vessel tip morphology. Postnatal deletion of VE-cadherin caused complete disassembly of cardiac lymphatics. Adult deletion caused a temporal regression of the quiescent epicardial lymphatic network which correlated with significant dermal and cardiac lymphatic dysfunction, as measured by fluorescent and quantum dot lymphangiography, respectively. Surprisingly, despite regression of cardiac lymphatics, Cdh5flox/flox;Prox1CreERT2 mice exhibited preserved cardiac function, both at baseline and following myocardial infarction, compared with control mice. Mechanistically, loss of VE-cadherin leads to aberrant cellular internalization of VEGFR3, precluding the ability of VEGFR3 to be either canonically activated by VEGF-C or noncanonically transactivated by adrenomedullin signaling, impairing downstream processes such as cellular proliferation. CONCLUSIONS: VE-cadherin is an essential scaffolding protein to maintain prolymphangiogenic signaling nodes at the plasma membrane, which are required for the development and adult maintenance of cardiac lymphatics, but not for cardiac function basally or after injury.


Subject(s)
Antigens, CD/metabolism , Cadherins/metabolism , Lymphatic Vessels/metabolism , Pericardium/metabolism , Signal Transduction , Animals , Antigens, CD/genetics , Cadherins/genetics , Cells, Cultured , Female , Humans , Lymphatic Vessels/physiology , Male , Mice , Mice, Inbred C57BL , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor Receptor-3/metabolism
19.
J Am Med Inform Assoc ; 28(9): 1936-1946, 2021 08 13.
Article in English | MEDLINE | ID: mdl-34151965

ABSTRACT

OBJECTIVE: Multitask learning (MTL) using electronic health records allows concurrent prediction of multiple endpoints. MTL has shown promise in improving model performance and training efficiency; however, it often suffers from negative transfer - impaired learning if tasks are not appropriately selected. We introduce a sequential subnetwork routing (SeqSNR) architecture that uses soft parameter sharing to find related tasks and encourage cross-learning between them. MATERIALS AND METHODS: Using the MIMIC-III (Medical Information Mart for Intensive Care-III) dataset, we train deep neural network models to predict the onset of 6 endpoints including specific organ dysfunctions and general clinical outcomes: acute kidney injury, continuous renal replacement therapy, mechanical ventilation, vasoactive medications, mortality, and length of stay. We compare single-task (ST) models with naive multitask and SeqSNR in terms of discriminative performance and label efficiency. RESULTS: SeqSNR showed a modest yet statistically significant performance boost across 4 of 6 tasks compared with ST and naive multitasking. When the size of the training dataset was reduced for a given task (label efficiency), SeqSNR outperformed ST for all cases showing an average area under the precision-recall curve boost of 2.1%, 2.9%, and 2.1% for tasks using 1%, 5%, and 10% of labels, respectively. CONCLUSIONS: The SeqSNR architecture shows superior label efficiency compared with ST and naive multitasking, suggesting utility in scenarios in which endpoint labels are difficult to ascertain.


Subject(s)
Machine Learning , Multiple Organ Failure , Electronic Health Records , Humans , Intensive Care Units , Neural Networks, Computer
20.
J Neurosci ; 2021 May 24.
Article in English | MEDLINE | ID: mdl-34039658

ABSTRACT

Understanding adolescent decision-making is significant for informing basic models of neurodevelopment as well as for the domains of public health and criminal justice. System-based theories posit that adolescent decision-making is guided by activity amongst reward and control processes. While successful at explaining behavior, system-based theories have received inconsistent support at the neural level, perhaps because of methodological limitations. Here, we used two complementary approaches to overcome said limitations and rigorously evaluate system-based models. Using decision-level modeling of fMRI data from a risk-taking task in a sample of 2000+ decisions across 51 human adolescents (25 females, mean age = 15.00 years), we find support for system-based theories of decision-making. Neural activity in lateral prefrontal cortex and a multivariate pattern of cognitive control both predicted a reduced likelihood of risk-taking, whereas increased activity in the nucleus accumbens predicted a greater likelihood of risk-taking. Interactions between decision-level brain activity and age were not observed. These results garner support for system-based accounts of adolescent decision-making behavior.SIGNIFICANCE STATEMENT:Adolescent decision-making behavior is of great import for basic science, and carries equally consequential implications for public health and criminal justice. While dominant psychological theories seeking to explain adolescent decision-making have found empirical support, their neuroscientific implementations have received inconsistent support. This may be partly due to statistical approaches employed by prior neuroimaging studies of system-based theories. We used brain modeling-an approach that predicts behavior from brain activity-of univariate and multivariate neural activity metrics to better understand how neural components of psychological systems guide decision behavior in adolescents. We found broad support for system-based theories such that neural systems involved in cognitive control predicted a reduced likelihood to make risky decisions, whereas value-based systems predicted greater risk-taking propensity.

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