mRNA-based precision targeting of neoantigens and tumor-associated antigens in malignant brain tumors.

Background: Despite advancements in the successful use of immunotherapy in treating a variety of solid tumors, applications in treating brain tumors have lagged considerably. This is due, at least in part, to the lack of well-characterized antigens expressed within brain tumors that can mediate tumor rejection; the low mutational burden of these tumors that limits the abundance of targetable neoantigens; and the immunologically "cold" tumor microenvironment that hampers the generation of sustained and productive immunologic responses. The field of mRNA-based therapeutics has experienced a boon following the universal approval of COVID-19 mRNA vaccines.

Immunotherapy reverses glioma-driven dysfunction of immune system homeostasis.

Background: Glioma-induced immune dysregulation of the hematopoietic system has been described in a limited number of studies. In this study, our group further demonstrates that gliomas interrupt the cellular differentiation programming and outcomes of hematopoietic stem and progenitor cells (HSPCs) in the bone marrow. HSPCs from glioma-bearing mice are reprogrammed and driven towards expansion of myeloid lineage precursors and myeloid-derived suppressor cells (MDSCs) in secondary lymphoid organs.

Examining Research Domain Criteria (RDoC) constructs for anger expression and regulation in toddlers.

The present study is focused on anger expression and regulation within the National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC) construct of Frustrative Nonreward. Although previous studies have examined associations between child anger regulation and expression, these studies do not directly address the dynamic processes involved in Frustrative Nonreward using microlongitudinal methods. The current study used data from 561 adopted children, their adoptive parents, and birth parents and aimed to address gaps in the literature by examining: (a) temporal associations between anger expression during a frustrating situation, and behaviors thought to regulate emotions (e.

It Takes Two: An antenatal to postnatal RDoC framework for investigating the origins of maternal attachment and mother-infant social communication.

Transformation of the maternal-fetal relationship into the mother-infant relationship remains an enigmatic process. This progression is considered using an RDoC-informed approach centered on domains of Arousal/Regulation, Positive/Negative Valence, and Social Processes. 158 maternal-fetal dyads began participation during pregnancy, maternal-infant dyads were followed at 6-months postpartum.

Systematic review of the associations between prenatal sleep behaviours and components of energy balance for regulating weight gain.

This systematic review aimed to examine the magnitude and direction of the associations between prenatal sleep behaviours (i.e. nighttime sleep duration, sleep quality, night awakenings and daytime nap duration) and eating behaviours, physical activity and gestational weight gain.

Immune Escape After Adoptive T-cell Therapy for Malignant Gliomas.

Purpose: Immunotherapy has been demonstrably effective against multiple cancers, yet tumor escape is common. It remains unclear how brain tumors escape immunotherapy and how to overcome this immune escape.

Experimental Design: We studied KR158B-luc glioma-bearing mice during treatment with adoptive cellular therapy (ACT) with polyclonal tumor-specific T cells.

Associations between prenatal sleep and psychological health: a systematic review.

Study Objectives: This systematic review aimed to examine the: (1) strength of associations between prenatal sleep (ie, duration, quality, and insomnia) and psychological health (ie, depression, anxiety, and stress); and (2) moderating influence of sociodemographic characteristics (ie, maternal age, gestational age/trimester, parity, marital and socioeconomic status [SES]), body mass index (BMI), and meeting sleep recommendations.

Methods: A systematic search was conducted using PubMed, PsycINFO, Web of Science, and CINHAL to identify studies with at least one sleep measure and a psychological health outcome. Effect sizes (ES) were calculated by associations between individual components of sleep and psychological health (eg, sleep quality-depression).

Quantitative characterization of 3D bioprinted structural elements under cell generated forces.

With improving biofabrication technology, 3D bioprinted constructs increasingly resemble real tissues. However, the fundamental principles describing how cell-generated forces within these constructs drive deformations, mechanical instabilities, and structural failures have not been established, even for basic biofabricated building blocks. Here we investigate mechanical behaviours of 3D printed microbeams made from living cells and extracellular matrix, bioprinting these simple structural elements into a 3D culture medium made from packed microgels, creating a mechanically controlled environment that allows the beams to evolve under cell-generated forces.

In sync: Physiological correlates of behavioral synchrony in infants and mothers.

Infant-mother behavioral synchrony is thought to scaffold the development of self-regulation in the first years of life. During this time, infants' and mothers' physiological regulation may contribute to dyadic synchrony and, in infants, dyadic synchrony may support infants' physiological regulation. Because the sympathetic nervous system (SNS) and parasympathetic nervous system (PNS) serve different regulatory functions, the current study aimed to elucidate relations between infants' and mothers' SNS and PNS functioning and dyadic behavioral synchrony.

LinCCR2 hematopoietic stem and progenitor cells overcome resistance to PD-1 blockade.

Immune checkpoint blockade using anti-PD-1 monoclonal antibodies has shown considerable promise in the treatment of solid tumors, but brain tumors remain notoriously refractory to treatment. In CNS malignancies that are completely resistant to PD-1 blockade, we found that bone marrow-derived, lineage-negative hematopoietic stem and progenitor cells (HSCs) that express C-C chemokine receptor type 2 (CCR2) reverses treatment resistance and sensitizes mice to curative immunotherapy. HSC transfer with PD-1 blockade increases T-cell frequency and activation within tumors in preclinical models of glioblastoma and medulloblastoma.

Developmental patterns of anger from infancy to middle childhood predict problem behaviors at age 8.

Anger is a central characteristic of negative affect and is relatively stable from infancy onward. Absolute levels of anger typically peak in early childhood and diminish as children become socialized and better able to regulate emotions. From infancy to school age, however, there are also individual differences in rank-order levels of anger.

Personalized Tumor RNA Loaded Lipid-Nanoparticles Prime the Systemic and Intratumoral Milieu for Response to Cancer Immunotherapy.

Translation of nanoparticles (NPs) into human clinical trials for patients with refractory cancers has lagged due to unknown biologic reactivities of novel NP designs. To overcome these limitations, simple well-characterized mRNA lipid-NPs have been developed as cancer immunotherapeutic vaccines. While the preponderance of RNA lipid-NPs encoding for tumor-associated antigens or neoepitopes have been designed to target lymphoid organs, they remain encumbered by the profound intratumoral and systemic immunosuppression that may stymie an activated T cell response.

Postpartum Mothers' Leisure-Time Exercise Behavior is Linked to Positive Emotion During Partner Discussions.

Purpose: Marital dissatisfaction and conflict often increase for couples after the birth of a child and are evident in fewer positive family interactions and more negative family interactions. Because exercise is known to increase positive emotions and decrease negative emotions, the current study examined the extent to which higher levels of mothers' exercise during the postpartum period were related to more positive and fewer negative emotion-expressive behaviors with their infants' fathers.

Method: Mothers' (N = 46; M = 8 months postpartum) positive and negative expressive behaviors were coded during couples' discussions of current conflict and positive family experiences.

Mothers' Physiological and Affective Responding to Infant Distress: Unique Antecedents of Avoidant and Resistant Attachments.

In a sample of 127 mother-infant dyads, this study examined the predictive significance of mothers' physiological and observed emotional responding within distressing and nondistressing caregiving contexts at 6 months for infant attachment assessed with Fraley and Spieker's (2003) dimensional approach and the categorical approach at 12 months. Findings revealed that a lesser degree of maternal respiratory sinus arrhythmia withdrawal and higher levels of maternal neutral (vs. positive) affect within distressing (vs.

Opportunities and challenges in screening for childhood sexual abuse.

Retrospective studies suggest 1 in 4 girls and 1 in 6 boys will experience sexual abuse before 18 years of age, resulting in future morbidity. Successful interventions exist, however, victims are reluctant to disclose. Screening for childhood sexual abuse (CSA) may provide an opportunity to overcome this barrier, yet no current model for universal CSA screening exists.

Physiological functioning moderates infants' sensory sensitivity in higher conflict families.

Children exposed to parent conflict may be at risk for emotional and behavioral disorders by becoming sensitized to conflict cues in their environments. This study explored possible precursors to negative child outcomes associated with parent conflict by examining the relation between parent conflict and infants' (N = 36; 23-42 weeks; 44% female) behavioral sensitivity to general sensory stimuli (e.g.

The Interaction Between Child Respiratory Sinus Arrhythmia and Early Sensitive Parenting in the Prediction of Children's Executive Functions.

This study investigated the interaction between children's parasympathetic functioning and maternal sensitive parenting behaviors during infancy and toddlerhood in the prediction of children's executive functions (EF) at the age of 5 years. Participants included 137 children and their mothers who were followed from the age of 3 months to 5 years. Children's cardiac activity was recorded at rest at multiple times from ages 3 to 36 months, and estimates of respiratory sinus arrhythmia (RSA; a measure of parasympathetic functioning) were calculated.

Dyadic flexibility mediates the relation between parent conflict and infants' vagal reactivity during the Face-to-Face Still-Face.

Parent conflict is related to attenuated infant vagal reactivity, suggesting less effective regulation. Because infants' self-regulation develops in the context of coregulation, the current study examined a novel measure, flexibility, purported to reflect dyadic reorganization in response to contextual demands. Flexibility was expected to mediate the relation between greater conflict and lesser vagal reactivity during the reunion episode of the Face-to-Face Still-Face (FFSF).

Vagal Regulation in Breastfeeding Infants and Their Mothers.

Consistent with the gustatory-vagal hypothesis, vagal stimulation during breastfeeding may contribute to infants' physiological regulatory development independent of caregiving effects. This study examined whether breastfeeding predicted 6-month-old infants' (N = 151) and their mothers' vagal regulation during the face-to-face still-face (FFSF). Although breastfed and nonbreastfed infants showed expected vagal withdrawal during the Still-Face episode, only breastfed infants showed continued withdrawal during the reunion episode, suggesting greater physiological mobilization to repair the interaction.

Infant respiratory sinus arrhythmia and maternal depressive symptoms predict toddler sleep problems.

This study examined the direct and interactive effects of infants' respiratory sinus arrhythmia (RSA) and maternal depressive symptoms (MDS) during the first 6 months of life in the prediction of children's sleep problems at age 18 months. Participants included 156 children and their mothers who were followed from 3 to 18 months of age. At ages 3 and 6 months, infants' cardiac activity was recorded at rest and during the still-face paradigm, a mother-child social challenge task, and estimates of infant baseline RSA (RSAB) and RSA withdrawal (RSAW) were calculated.

Infant patterns of reactivity to tactile stimulation during parent-child interaction.

Touch is the primary modality infants use to engage with the world; atypical responses to tactile stimuli may indicate risk for disordered outcomes. The current study examined infants' responses to tactile stimulation within parent-child interaction, adding to prior knowledge based on parent report. Nine-month-old infants (N=497) were observed while parents painted and pressed infants' hands and feet to paper to make designs.

Associations between Infant Behaviors during the Face-To-Face Still-Face Paradigm and Oppositional Defiant and Callous-Unemotional Behaviors in Early Childhood.

Deficits in social orienting (i.e., gazing toward caregivers) during dyadic interactions and reactivity to stressful stimuli have been identified as behavioral correlates of oppositional defiant disorder (ODD) and callous-unemotional (CU) behaviors in older children.

A Simultaneous Genetic Screen for Zygotic and Sterile Mutants in a Hermaphroditic Vertebrate (Kryptolebias marmoratus).

The mangrove killifish, Kryptolebias marmoratus, is unique among vertebrates due to its self-fertilizing mode of reproduction involving an ovotestis. As a result, it constitutes a simplistic and desirable vertebrate model for developmental genetics as it is easily maintained, reaches sexual maturity in about 100 days, and provides a manageable number of relatively clear embryos. After the establishment and characterization of an initial mutagenesis pilot screen using N-ethyl-N-nitrosourea, a three-generation genetic screen was performed to confirm zygotic mutant allele heritability and simultaneously score for homozygous recessive mutant sterile F2 fish.

Don't worry, be (moderately) happy: Mothers' anxiety and positivity during pregnancy independently predict lower mother-infant synchrony.

Maternal positivity and mother-infant synchrony have been linked, independently, to beneficial infant outcomes; however, research that has examined relations between the two has found that higher positivity is associated with lower synchrony. Methodological issues may inform this counter-intuitive association and clinical theory supports its validity. This study examined the theory that heightened positivity associated with anxiety is a way of avoiding negative emotion and contributes to lower synchrony because it interferes with appropriate responding to infant cues.

INFANT AVOIDANCE DURING A TACTILE TASK PREDICTS AUTISM SPECTRUM BEHAVIORS IN TODDLERHOOD.

The experience of touch is critical for early communication and social interaction; infants who show aversion to touch may be at risk for atypical development and behavior problems. The current study aimed to clarify predictive associations between infant responses to tactile stimuli and toddler autism spectrum, internalizing, and externalizing behaviors. This study measured 9-month-old infants' (N = 561; 58% male) avoidance and negative affect during a novel tactile task in which parents painted infants' hands and feet and pressed them to paper to make a picture.