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The tropism of adenoviruses (Ads) is significantly influenced by the binding of various blood factors. To investigate differences in their binding, we conducted cryo-EM analysis on complexes of several human adenoviruses with human platelet factor-4 (PF4), coagulation factors FII (Prothrombin), and FX. While we observed EM densities for FII and FX bound to all the species-C adenoviruses examined, no densities were seen for PF4, even though PF4 can co-pellet with various Ads. Similar to FX, the γ-carboxyglutamic acid (Gla) domain of FII binds within the surface cavity of hexon trimers. While FII binds equally to species-C Ads: Ad5, Ad6, and Ad657, FX exhibits significantly better binding to Ad5 and Ad657 compared to Ad6. Although only the FX-Gla domain is observed at high-resolution (3.7 Å), the entire FX is visible at low-resolution bound to Ad5 in three equivalent binding modes consistent with the 3-fold symmetric hexon. Only the Gla and kringle-1 domains of FII are visible on all the species-C adenoviruses, where the rigid FII binds in an upright fashion, in contrast to the flexible and bent FX. These data suggest that differential binding of FII and FX may shield certain species-C adenoviruses differently against immune molecules, thereby modulating their tropism. The tropism of adenoviruses is influenced by the binding of host blood factors. Here, the authors show the N-terminal non-polar residues of γ-carboxyglutamic acid domains of vitamin K-dependent blood clotting factors interact with the hexon cavities on the surface of species-C adenoviruses. [ABSTRACT FROM AUTHOR]

Plasma RNAemia, delayed antibody responses and inflammation predict COVID-19 outcomes, but the mechanisms underlying these immunovirological patterns are poorly understood. We profile 782 longitudinal plasma samples from 318 hospitalized patients with COVID-19. Integrated analysis using k-means reveals four patient clusters in a discovery cohort: mechanically ventilated critically-ill cases are subdivided into good prognosis and high-fatality clusters (reproduced in a validation cohort), while non-critical survivors segregate into high and low early antibody responders. Only the high-fatality cluster is enriched for transcriptomic signatures associated with COVID-19 severity, and each cluster has distinct RBD-specific antibody elicitation kinetics. Both critical and non-critical clusters with delayed antibody responses exhibit sustained IFN signatures, which negatively correlate with contemporaneous RBD-specific IgG levels and absolute SARS-CoV-2-specific B and CD4+ T cell frequencies. These data suggest that the "Interferon paradox" previously described in murine LCMV models is operative in COVID-19, with excessive IFN signaling delaying development of adaptive virus-specific immunity. The role of IFN signaling in SARS-CoV-2 infection and outcome is still debated. Here, the authors longitudinally profiled plasma samples from hospitalized patients and show that a persistent inflammatory response is linked to delayed generation of adaptive immunity and increased risk of death when coupled with severe infection. [ABSTRACT FROM AUTHOR]

Safety behaviors attenuate the effects of exposure therapy. Less is known about how safety behaviors interact with parenting behaviors in relation to anxious children's fear responses. We examined if child safety behaviors interact with maternal punitive responses to explain unique variance in children's fear downregulation—defined as self-reported reduction of anxious arousal—during an anxiety-provoking task. Anxious children ages 8–12 (N = 105; 57.1% female; 61.9% racial minority) completed a diagnostic interview and structured speech task. Mothers reported how often they responded punitively to children's negative emotions. Independent observers coded child safety behaviors used during the speech, and a fear downregulation score was computed per child by subtracting post-speech fear scores from pre-speech fear scores. The interaction between child safety behaviors and maternal punitive responses predicted unique variance in subjective fear downregulation, such that increased use of safety behaviors during the speech task was associated with more difficulties downregulating subjective fear only among children whose mothers reported moderate and high use of punitive responses. Maternal punitive responses to children's negative emotions may promote child safety behavior use to avoid anxiety, resulting in greater difficulties downregulating fear. Our findings provide preliminary evidence for targeting child safety behaviors and parenting behaviors during child anxiety treatment. Highlights: Higher child safety behaviors were associated with more difficulty downregulating fear. Higher maternal punitive responses were associated with more difficulty downregulating fear. Maternal punitive responses interacted with safety behaviors to predict fear downregulation. Parental emotion socialization practices may be important treatment targets. [ABSTRACT FROM AUTHOR]

Musical interactions are a common and multimodal part of an infant’s daily experiences. Infants hear their parents sing while watching their lips move and see their older siblings dance along to music playing over the radio. Here, we explore whether 8- to 12-month-old infants associate musical rhythms they hear with synchronous visual displays by tracking their dynamic visual attention to matched and mismatched displays. Visual attention was measured using eye-tracking while they attended to a screen displaying two videos of a finger tapping at different speeds. These videos were presented side by side while infants listened to an auditory rhythm (high or low pitch) synchronized with one of the two videos. Infants attended more to the low-pitch trials than to the highpitch trials but did not display a preference for attending to the synchronous hand over the asynchronous hand within trials. Exploratory evidence, however, suggests that tempo, pitch, and rhythmic complexity interactively engage infants’ visual attention to a tapping hand, especially when that hand is aligned with the auditory stimulus. For example, when the rhythm was complex and the auditory stimulus was low in pitch, infants attended to the fast hand more when it aligned with the auditory stream than to misaligned trials. These results suggest that the audiovisual integration in rhythmic non-speech contexts is influenced by stimulus properties. [ABSTRACT FROM AUTHOR]

In multilevel models, disaggregating predictors into level-specific parts (typically accomplished via centering) benefits parameter estimates and their interpretations. However, the importance of level-specificity has been sparsely addressed in multilevel literature concerning collinearity. In this study, we develop novel insights into the interactivity of centering and collinearity in multilevel models. After integrating the broad literatures on centering and collinearity, we review level-specific and conflated correlations in multilevel data. Next, by deriving formal relationships between predictor collinearity and multilevel model estimates, we demonstrate how the consequences of collinearity change across different centering specifications and identify data characteristics that may exacerbate or mitigate those consequences. We show that when all or some level-1 predictors are uncentered, slope estimates can be greatly biased by collinearity. Disaggregation of all predictors eliminates the possibility that fixed effect estimates will be biased due to collinearity alone; however, under some data conditions, collinearity is associated with biased standard errors and random effect (co)variance estimates. Finally, we illustrate the importance of disaggregation for diagnosing collinearity in multilevel data and provide recommendations for the use of level-specific collinearity diagnostics. Overall, the necessity of disaggregation for identifying and managing collinearity's consequences in multilevel models is clarified in novel ways. [ABSTRACT FROM AUTHOR]

Objective: To determine the chronic effects of oral cannabidiol (CBD) use on tear production, intraocular pressure (IOP), and concentration of CBD in tears of healthy dogs. Animals Studied: Eighteen healthy research Beagles. Procedures: This was a masked, placebo‐controlled, randomized prospective study. Eighteen dogs were randomly assigned to three groups (six dogs per group) based on daily dosage of oral MCT oil (placebo), CBD 5 mg/kg, and CBD 10 mg/kg. Schirmer tear test (STT‐1) and IOP were measured twice daily (7 am and 7 pm) every 4 weeks for 36 weeks. Week 36 tears were collected and analyzed for CBD concentrations (ng/mL) using liquid chromatography/mass spectrometry. A mixed linear model was used as the statistical method and p‐value <.05 was considered significant. Results: No significant differences were found between placebo vs. 5 mg/kg vs. 10 mg/kg for STT‐1 or IOP (AM and PM). CBD was detected in 10 out of 11 (91%) viable tear samples receiving 5 mg/kg or 10 mg/kg dosages. One sample in the 5 mg/kg group had inadequate tear volume for analysis. The CBD concentration in tears was at or below the lower limit of quantification in placebo group, 4.12–11.2 ng/mL for the 5 mg/kg group, and 6.22–152 ng/mL for the 10 mg/kg group. Conclusions: Long‐term administration of oral CBD in healthy research beagles demonstrates a favorable safety profile regarding ocular tolerability. Oral CBD administration does not appear to affect tear production or IOP over a 36‐week period. This is the first canine study positively identifying concentrations of CBD in tears following oral administration. [ABSTRACT FROM AUTHOR]

Most people have been harmed by another at some point in their lives. Many of these hurts linger in the lives of those who were hurt, through anger, fear, and rumination. Forgiving others, when it is safe and prudent to do so, can be one route toward healing these past hurts. Group therapy has specific strengths that might help people to effectively forgive others. One of those strengths is the creation of therapeutic factors. In the current paper we discuss how group forgiveness interventions and the development of three specific therapeutic factors (universality, cohesion, and altruism) can help to promote forgiveness. We review prior work on forgiveness interventions in group therapy, focused on effectiveness generally. We then provide an applied case study of a specific group that used Worthington's REACH Forgiveness model. In this case study we highlight the themes of universality, cohesion, and altruism to illustrate the benefit of forgiveness interventions in group therapy. [ABSTRACT FROM AUTHOR]

Plasma RNAemia, delayed antibody responses and inflammation predict COVID-19 outcomes, but the mechanisms underlying these immunovirological patterns are poorly understood. We profile 782 longitudinal plasma samples from 318 hospitalized patients with COVID-19. Integrated analysis using k-means reveals four patient clusters in a discovery cohort: mechanically ventilated critically-ill cases are subdivided into good prognosis and high-fatality clusters (reproduced in a validation cohort), while non-critical survivors segregate into high and low early antibody responders. Only the high-fatality cluster is enriched for transcriptomic signatures associated with COVID-19 severity, and each cluster has distinct RBD-specific antibody elicitation kinetics. Both critical and non-critical clusters with delayed antibody responses exhibit sustained IFN signatures, which negatively correlate with contemporaneous RBD-specific IgG levels and absolute SARS-CoV-2-specific B and CD4+ T cell frequencies. These data suggest that the "Interferon paradox" previously described in murine LCMV models is operative in COVID-19, with excessive IFN signaling delaying development of adaptive virus-specific immunity. The role of IFN signaling in SARS-CoV-2 infection and outcome is still debated. Here, the authors longitudinally profiled plasma samples from hospitalized patients and show that a persistent inflammatory response is linked to delayed generation of adaptive immunity and increased risk of death when coupled with severe infection. [ABSTRACT FROM AUTHOR]

Summary: Humans exhibit considerable variability in their immune responses to the same immune challenges. Such variation is widespread and affects individual and population‐level susceptibility to infectious diseases and immune disorders. Although the factors influencing immune response diversity are partially understood, what mechanisms lead to the wide range of immune traits in healthy individuals remain largely unexplained. Here, we discuss the role that natural selection has played in driving phenotypic differences in immune responses across populations and present‐day susceptibility to immune‐related disorders. Further, we touch on future directions in the field of immunogenomics, highlighting the value of expanding this work to human populations globally, the utility of modeling the immune response as a dynamic process, and the importance of considering the potential polygenic nature of natural selection. Identifying loci acted upon by evolution may further pinpoint variants critically involved in disease etiology, and designing studies to capture these effects will enrich our understanding of the genetic contributions to immunity and immune dysregulation. [ABSTRACT FROM AUTHOR]

Introductions are a critical tool in the recovery of many imperiled species, yet adequate evaluation and development of best practices has lagged. Importantly, long‐term post‐introduction data are typically lacking, as well as suitable comparisons to wild populations to provide a baseline against which to assess performance. Here, we report on three experimental introductions of Crotalaria avonensis (Fabaceae), a federally endangered perennial herb that is narrowly endemic to scrub of the Lake Wales Ridge in peninsular Florida, U.S.A. We synthesize 10 years of post‐introduction monitoring at both the introduced and a nearby, protected wild population to (1) develop best practices for conservation, and (2) evaluate the success of the introduction. First, our study identified best practices that included using transplants propagated from stem cuttings, as well as several factors that may increase seed germination such as habitat choice, seed burial, and litter addition. Second, during the 10 years following the introduction, population density in the introduced population was higher than in a nearby protected, wild population, and a comparison of vital rates revealed that this result was due to relatively high clonal and seedling recruitment rates in the introduced population. Furthermore, the source population, which occurred on unprotected lands, precipitously declined during this time period, further highlighting the importance of safeguarding plants from that population. We report that a new, growing population of C. avonensis has been established to date, with important implications for the species' conservation as well as how introductions are evaluated. [ABSTRACT FROM AUTHOR]

Variability in treatment effects is common in intervention studies using cluster randomized controlled trial (C-RCT) designs. Such variability is often examined in multilevel modeling (MLM) to understand how treatment effects (TRT) differ based on the level of a covariate (COV), called TRT × COV. In detecting TRT × COV effects using MLM, relationships between covariates and outcomes are assumed to vary across clusters linearly. However, this linearity assumption may not hold in all applications and an incorrect assumption may lead to biased statistical inference about TRT × COV effects. In this study, we present generalized additive mixed model (GAMM) specifications in which cluster-specific functional relationships between covariates and outcomes can be modeled using by-variable smooth functions. In addition, the implementation for GAMM specifications is explained using the mgcv R package (Wood, 2021). The usefulness of the GAMM specifications is illustrated using intervention data from a C-RCT. Results of simulation studies showed that parameters and by-variable smooth functions were recovered well in various multilevel designs and the misspecification of the relationship between covariates and outcomes led to biased estimates of TRT × COV effects. Furthermore, this study evaluated the extent to which the GAMM can be treated as an alternative model to MLM in the presence of a linear relationship. [ABSTRACT FROM AUTHOR]

Engagement in citizen science can result in participant outcomes including increased science and environmental literacy and civic action. One factor which may increase the likelihood of these outcomes is facilitation by groups such as employers, schools, or other organizations. We examined how a partnership between SciStarter and Girl Scouts of the USA facilitated participation in citizen science to shape participants' learning and civic engagement. Between July 2017 and February 2020, participants from over 200 Girl Scout troops completed the Think Like a Citizen Scientist Journey, consisting of science learning activities, participation in an environmental citizen science project on SciStarter, and a Take Action Project (TAP). Troop leaders provided open-ended descriptions of TAPs which we analyzed qualitatively. Responses provided evidence of learning outcomes spanning informal science learning goals, Girl Scout Leadership Experience outcomes, and Girl Scout STEM outcomes. Participants' TAPs overwhelmingly related to science and environmental topics (81%) and the majority sought to educate and inspire others (66%), reaching audiences of peers, adults, the general public, and civic leaders. This program demonstrates the potential for facilitator organizations to leverage existing citizen science projects to promote learning outcomes, civic science education, and community action with participants as young as 4–5 years old. [ABSTRACT FROM AUTHOR]

Background: With recent changes in tobacco and marijuana use patterns, it becomes crucial to understand how the prenatal co‐use of these substances impacts birth outcomes. The goal of this study was to examine the risk of adverse birth outcomes among infants born to women who used tobacco and marijuana concurrently throughout pregnancy compared to infants of women who used tobacco alone. Methods: This study involved a retrospective chart review of pregnant women identified via self‐report or biochemical testing who used tobacco products alone (N = 71) or tobacco and marijuana simultaneously (N = 127) at any point throughout pregnancy. Differences in birth outcomes between these groups, including APGAR (appearance, pulse, grimace, activity, and respiration) scores, respiratory distress, neonatal intensive care unit admission, intrauterine growth restriction, birth weight, birth length, head circumference, gestational age, and length of hospital stay, were analyzed using linear regression and odds ratio analysis. Results: There were no significant differences in outcomes for infants of women who used tobacco and marijuana compared to infants of women who used tobacco alone during pregnancy. Rates of adverse birth outcomes were high among women who used tobacco compared to what would be expected in unexposed pregnancies. Conclusions: Tobacco and marijuana co‐use during pregnancy was not associated with an additional risk of adverse birth outcomes compared to tobacco use alone. Women should be educated on potential risks of marijuana, and especially, tobacco use during pregnancy. These results will inform clinical recommendations for pregnant women using tobacco and marijuana, aiming to decrease preventable adverse outcomes for patients and infants. [ABSTRACT FROM AUTHOR]

Few studies have described changes in SARS-CoV-2 antibody levels in response to infection and vaccination at frequent intervals and over extended follow-up periods. The purpose of this study was to assess changes in SARS-CoV-2–specific antibody responses among a prospective cohort of health care personnel over 18 months with up to 22 samples per person. Antibody levels and live virus neutralization were measured before and after mRNA-based vaccination with results stratified by (1) SARS-CoV-2 infection status prior to initial vaccination and (2) SARS-CoV-2 infection at any point during follow-up. We found that the antibody response to the first dose was almost 2-fold higher in individuals who were seropositive prior to vaccination, although neutralization titers were more variable. The antibody response induced by vaccination appeared to wane over time but generally persisted for 8 to 9 months, and those who were infected at any point during the study had slightly higher antibody levels over time vs those who remained uninfected. These findings underscore the need to account for SARS-CoV-2 natural infection as a modifier of vaccine responses, and they highlight the importance of frequent testing of longitudinal antibody titers over time. Together, our results provide a clearer understanding of the trajectories of antibody response among vaccinated individuals with and without prior SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Objective: To understand how parents of young children coped with stress during the first year of the COVID‐19 pandemic. Background: Families with young children faced substantial stress during the COVID‐19 pandemic. Yet, relatively few studies have examined parents' mental health during the pandemic and the behaviors parents have used to cope with their stress. Method: The current study surveyed 199 parents (76% women, Mage = 33 years) of children aged 2 to 4 years from across the United States between September and December 2020 about their COVID‐related stress and coping behaviors since stay‐at‐home orders began in March 2020. Results: The coping behavior that parents most commonly endorsed was spending time with their children, a strategy that frequently made parents feel better. Successful coping (engaging in behaviors that made parents feel better) was positively associated with better mental health, regardless of parents' COVID‐related stress. Distraction and unsuccessful coping were not significantly associated with parents' mental health as a main effect. However, parents who engaged in more unsuccessful coping under conditions of high COVID‐related stress reported greater symptoms of anxiety and depression. Conclusion: Although the COVID‐19 pandemic presented novel stressors for parents, it also presented new opportunities to spend time with family, which may have helped parents cope with the stress of the pandemic. Implications: Young children may be considered an asset in the family system that prompts parents to engage in activities that make them feel better. [ABSTRACT FROM AUTHOR]

Social support is associated with positive physical and psychological health outcomes for youth. We took a qualitative approach to examine the sources, forms, and functions of social support youth receive from natural mentoring relationships in their lives. Based on in‐depth interviews with 40 adolescents participating in a study of youth–adult relationships and natural mentoring processes, we found that (1) different types of adults had the capacity to provide different types of support and were likely to provide overlapping supports; (2) emotional, informational, and instrumental support qualitatively differed depending on the adult's role (e.g., teacher), while companionship and validation were consistent across adults; and (3) youth were able to identify benefits attached to the social support received from adults. Our findings contribute to a more nuanced understanding of aspects and characteristics of effective youth–adult mentoring processes and call for fuller assessments of social support in youths' lives so we may better meet their developmental needs. [ABSTRACT FROM AUTHOR]

Forested land is increasingly owned in small parcels by family forest owners who are becoming less likely to conduct the management which supports ecosystems, economies, and communities. One way to encourage private land management is through group cooperatives. Characteristics of collective action that support group cooperative participation are well understood but how they relate to management implementation is not. Examining Wisconsin's Deer Management Assistance Program as a case, we sought to understand how characteristics associated with collective action relate to cooperative cross-boundary management implementation. Through a member survey, we found elements of trust, social capital, information sharing, and goal alignment to be associated with management action implementation. Significant characteristics and their relationship to implementation varied across land, habitat, and forest management actions. Our results emphasize the need to customize professional assistance to complement the group cooperative's landowner demographics and management goals. [ABSTRACT FROM AUTHOR]

A fundamental goal of developmental biology is to understand how cell and tissue fates are specified. The imaginal discs of Drosophila are excellent model systems for addressing this paradigm as their fate can be redirected when discs regenerate after injury or when key selector genes are misregulated. Here, we show that when Polycomb expression is reduced, the wing selector gene vestigial is ectopically activated. This leads to the inappropriate formation of the Vestigial-Scalloped complex, which forces the eye to transform into a wing. We further demonstrate that disrupting this complex does not simply block wing formation or restore eye development. Instead, immunohistochemistry and high-throughput genomic analysis show that the eye-antennal disc unexpectedly undergoes hyperplastic growth with multiple domains being organized into other imaginal discs and tissues. These findings provide insight into the complex developmental landscape that tissues must navigate before adopting their final fate. [ABSTRACT FROM AUTHOR]

Background: Although childhood exposure to parental threatening behaviors is associated with elevated anxiety in emerging adulthood, the underlying mechanisms remain unexplored. Perceived stress—a subjective experience comprised of feelings of helplessness (being unable to cope or exert control) and poor self‐efficacy (confidence in one's ability to manage stressors)—is one candidate mechanism. The present investigation examined the underlying role of perceived stress in the association between childhood exposure to parental threatening behaviors and anxiety symptom severity in a sample of emerging adults. Methods: Participants (N = 855; Mage = 18.75 years, SD = 1.05, range 18−24; 70.8% female) were recruited from a large state university and administered a battery of self‐report questionnaires assessing constructs of interest. Results: Structural equation modeling (SEM) analyses indicated that only greater childhood exposure to maternal threatening behaviors was directly associated with greater feelings of helplessness and lower self‐efficacy. Furthermore, only childhood exposure to maternal threatening behaviors was indirectly associated with anxiety severity through greater feelings of helplessness and lower self‐efficacy. In contrast, childhood exposure to paternal threatening behaviors was neither directly nor indirectly associated with anxiety severity. Limitations: Limitations include a cross‐sectional design, use of self‐report measures, and a nonclinical sample. Replicating these findings in a clinical sample and testing the hypothesized model in a longitudinal design is necessary. Conclusions: Findings underscore the need for intervention efforts that screen for and target perceived stress in emerging adults exposed to negative maternal parenting behaviors. [ABSTRACT FROM AUTHOR]

A fearful temperament in childhood is associated with child internalizing symptoms. However, the cognitive mechanisms explaining this association are poorly understood. We examined the effects of child fearful temperament on child internalizing symptoms and the underlying role of catastrophizing cognitions among clinically anxious youth. Children (N = 105; M age = 10.09 years, SD = 1.22; 56.7% female; 62% ethnic minority) completed a diagnostic interview; self-report measures of temperament, catastrophizing, and internalizing symptoms; and behaviorally-indexed measures of catastrophizing and anxiety. Indirect effects were found for child fearful temperament on child self-reported internalizing symptoms by way of self-reported (but not behaviorally-indexed) catastrophizing cognitions. Models predicting behaviorally-indexed child anxiety were not significant. Our findings suggest that targeting fearful temperament during childhood before catastrophizing cognitions develop may have clinical utility. Likewise, among children temperamentally at-risk, addressing catastrophic cognitions may prevent later internalizing psychopathology. [ABSTRACT FROM AUTHOR]

The management of shoulder instability in children and adolescents continues to evolve. The purpose of this study was to evaluate the epidemiology of shoulder stabilization procedures in a large, nationally representative pediatric population. The Pediatric Health Information System (PHIS) database was queried for patients 18 years and younger undergoing surgical shoulder stabilization between 2008 and 2017. Patients undergoing arthroscopic surgery were compared with patients undergoing complex (open or bony augment stabilization) procedures. Annual trends were calculated using linear regression. A total of 3925 procedures were performed, of which 92.9% were arthroscopic Bankart repairs. There was a significant increase in overall pediatric shoulder stabilizations and arthroscopic repairs between 2008 and 2017. Complex procedures were performed most often in the Northeast, but the annual frequency did not increase nationally. [Orthopedics. 2023;46(3):e167–e172.] [ABSTRACT FROM AUTHOR]

Although a ubiquitous social behavior, little is known about bullshitting (i.e., communicating with no regard for truth and/or evidence) and its effects on social perception and influence. Although bullshit and lies are viewed as undesirable, the distinction may have important implications for social influence. Frankfurt's (1986) insidious bullshit hypothesis (i.e., bullshitting is evaluated less negatively, but more insidious, than lying) is examined in light of social perception (i.e., evaluation and perceived motives; Experiment 1) and social influence (Experiment 2). Results suggest bullshitting is evaluated less negatively than lying and identifies ignorance, dishonesty, and opinion expression as mediators of a bullshit/lie-evaluation link. Furthermore, relative to lies, bullshit appears to have a more potent impact on that which is perceived to be true as well as attitudes formed for novel attitude objects. [ABSTRACT FROM AUTHOR]

Purpose: Companies are beginning to rely more on customer participation (CP). As a result, consumers are expected to expend more resources throughout the service exchange. Through three studies, this study aims to examine the effect of CP on customers' evaluations of these exchanges. Study 1 examines the interaction between two levels of CP (low versus high) and shopping experience type (hedonic versus utilitarian). In Study 2, the focus shifts to understanding the negative consequences of high CP. In Study 3, the authors explore how the negative effects of high CP can be mitigated. Design/methodology/approach: Scenario-based experiments were implemented across three studies. This study used multivariate analysis of variance (Study 1) and PROCESS (Hayes, 2018; Studies 2 and 3) to uncover how consumers respond to CP. Findings: Results of Study 1 indicate that the CP level negatively impacts satisfaction and positive word-of mouth (PWOM) in a utilitarian context but has no effect in a hedonic context. Study 2 finds that the negative effects of high CP on satisfaction and PWOM are mediated by fairness and frustration. Study 3 suggests that these negative results can be mitigated by offering a financial incentive. Originality/value: This study's two primary objectives address specific calls in the CP literature. First, this study examines the effects of increased CP during hedonic and utilitarian shopping experiences. Second, this study investigates mediators and moderators associated with the negative effects of increased CP, shedding light on how the consumer processes high CP service encounters. [ABSTRACT FROM AUTHOR]

Many of our most powerful musical experiences are shared with others, and researchers have increasingly investigated responses to music in group contexts. Though musical performances for infants are growing in popularity, most research on infants' responses to live music has focused on solitary caregiver‐infant pairs. Here, we report infants' attentional, affective, and motor responses to live music as audience members. Two groups of caregiver‐infant (6–18 months) pairs (50 total) watched a short musical performance with two song styles – lullaby and playsong. Caregivers were instructed to watch passively or interactively. The playsong captured more infant attention and, especially in the interactive condition, elicited more infant smiles. Notably, infant attention was more coordinated with their own caregiver than a random caregiver, and infants with no experience attending group musical events in the past were especially attentive to the performance. Infants were more likely to generate movements when parents remained still. Overall, infants' responses to live musical performance in an audience were influenced by song style, caregiver behavior, and their own musical histories. A video abstract of this article can be viewed at https://www.youtube.com/watch?v=q61qnDMW8dU. Research Highlights: Infants' responses to live musical performances are shaped by the music, by their caregivers, and by their own musical historiesDuring a concert for babies, a playsong more effectively elicited infant attention and smiles than a lullaby, especially when caregivers were interactiveInfant attention was more coordinated with their own caregiver than with other caregivers watching the same show [ABSTRACT FROM AUTHOR]

The letter responds to a paper that claims there was a risk of selection bias in the NINDS rt-PA for Acute Ischemic Stroke Study. The authors of the letter argue that the paper contains factual errors and misconceptions about the study. They clarify that there were errors in the randomization process, but these errors did not contribute to bias in the treatment effect. The authors also explain the difference between concealment and blinding in clinical trials and refute the suggestion that treatment assignment was manipulated. They emphasize the benefits of thrombolytic therapy for acute ischemic stroke and urge readers to review the literature on the topic. [Extracted from the article]

The present study investigated the interactive effect of reactive (negative emotionality) and regulatory (effortful control) aspects of temperament in the prediction of child anxiety and depressive symptoms. Clinically anxious children and their mothers completed a battery of questionnaires that included self- and mother-ratings of child effortful control, negative emotionality, anxiety, and depressive symptoms. Multiple regression analyses were conducted to examine the moderating effect of effortful control on the relation between negative emotionality and child anxiety and depressive symptom severity. The interaction between negative emotionality and effortful control was statistically significant and simple slopes revealed that as effortful control increased, the relationship between negative emotionality and anxiety and depressive symptoms weakened. Among anxious children high in negative emotionality, greater effortful control was related to less severe anxiety and depressive symptoms. Future work should evaluate whether targeting effortful control leads to reductions in internalizing symptoms among clinically anxious youth. [ABSTRACT FROM AUTHOR]

Studies indicate antenatal opioid use is associated with birth size deficits, as evidenced by reductions in birth weight and head circumference. However, there remains a limited understanding of how early this growth restriction occurs, and what specific parameters are affected. This novel study evaluated global and specific growth deficits associated with prenatal opioid exposure between 18–22 weeks' gestation as assessed during anatomy ultrasounds. Pregnant women who completed an anatomy ultrasound were identified via electronic medical records from a large academic obstetric practice. The study group used opioids, with tobacco and/or marijuana use permitted (n = 41). The control group could have used tobacco and/or marijuana, but not opioids (n = 308). Neither group had alcohol or other drug exposure. Records were reviewed for medical history and ultrasound size parameters, coded as percentiles for gestational age. Demographics and medical histories were compared with several significant differences noted. After controlling for these differences, significant (p < 0.05) growth deficits were identified in opioid-exposed fetuses. Specifically, reductions >10 percentile points were observed in head circumference, biparietal diameter, and humerus length for opioid-exposed fetuses compared to controls. Additionally, intrauterine growth restriction (IUGR) was diagnosed five times more often. Femur length was significantly reduced in opioid-exposed fetuses prior to adjustment for confounding (p =.016), but this reduction was not significant (p =.072) after controlling for background differences. Estimated fetal weight (p =.274) and abdominal circumference (p =.633) were not significantly different between exposure groups. Fetal opioid exposure predicted various bone growth deficits during routine anatomy ultrasound, indicating the effects of opioid exposure on size deficits may be evident as early as 18–22 weeks' gestation. These findings may also suggest that in utero opioid exposure negatively impacts bone growth specifically rather than weight or fat/muscle mass. Additional studies with larger sample sizes may also reveal significantly reduced femur length, further supporting a negative impact on bone growth. Future studies evaluating bone health and immune function in children after antenatal opioid exposure may help clarify this specific effect of opioids on bone development. [ABSTRACT FROM AUTHOR]

Objective. We evaluated eight recruitment methods (Craigslist, Facebook ads, Google AdWords, in-person, newspaper, parenting magazines, ResearchMatch, and direct mailing) in terms of their ability to accrue fathers of 3- to 7-year-old children into a laboratory-based behavioral trial for parents. The trial was related to child obesity risk and parental health behaviors.Design. Each recruitment method was implemented such that half its occurrences advertised for fathers only, and half advertised for mothers and fathers. Methods were evaluated in terms of number of fathers recruited, cost- and time-efficiency, response rates, and demographic characteristics of individuals recruited. We also assessed fathers' and mothers' motivations for participating in the study. 101 fathers and 260 mothers were recruited.Results. Father-targeted ads were essential for father recruitment; 79% of accruals from father-targeted ads were male, whereas only 14% of accruals from parent-targeted ads were male. Craigslist, ResearchMatch, and Facebook ads were the most cost-efficient for accruing fathers. A greater proportion of fathers was motivated by increasing fathers' representation in research (16%) compared to mothers who wished to increase mothers' representation in research (5.4%). Similar proportions of fathers and mothers were motivated by improving their parenting knowledge and improving their child's health.Conclusions. Future researchers should employ father-targeted recruitment materials (rather than parent-targeted) that capitalize on fathers' unique motivations for participating in research. [ABSTRACT FROM AUTHOR]

In this paper, we report the structural analysis of dihydroorotase (DHOase) from the hyperthermophilic and barophilic archaeon Methanococcus jannaschii. DHOase catalyzes the reversible cyclization of N‐carbamoyl‐l‐aspartate to l‐dihydroorotate in the third step of de novo pyrimidine biosynthesis. DHOases form a very diverse family of enzymes and have been classified into types and subtypes with structural similarities and differences among them. This is the first archaeal DHOase studied by x‐ray diffraction. Its structure and comparison with known representatives of the other subtypes help define the structural features of the archaeal subtype. The M. jannaschii DHOase is found here to have traits from all subtypes. Contrary to expectations, it has a carboxylated lysine bridging the two Zn ions in the active site, and a long catalytic loop. It is a monomeric protein with a large β sandwich domain adjacent to the TIM barrel. Loop 5 is similar to bacterial type III and the C‐terminal extension is long. [ABSTRACT FROM AUTHOR]

The hippocampus participates in spatial navigation and behavioral processes, displays molecular plasticity in response to environmental challenges, and can play a role in neuropsychiatric diseases. The combined effects of inflammatory prenatal and postnatal challenges can disrupt the hippocampal gene networks and regulatory mechanisms. Using a proven pig model of viral maternal immune activation (MIA) matched to controls and an RNA-sequencing approach, the hippocampal transcriptome was profiled on two-month-old female and male offspring assigned to fasting, mimetic viral, or saline treatments. More than 2600 genes presented single or combined effects (FDR-adjusted p-value < 0.05) of MIA, postnatal stress, or sex. Biological processes and pathways encompassing messenger cyclic adenosine 3′,5′-monophosphate (cAMP) signaling were enriched with genes including gastric inhibitory polypeptide receptor (GIPR) predominantly over-expressed in the MIA-exposed fasting males relative to groups that differed in sex, prenatal or postnatal challenge. While this pattern was amplified in fasting offspring, the postnatal inflammatory challenge appeared to cancel out the effects of the prenatal challenge. The transcription factors C-terminal binding protein 2 (CTBP2), RE1 silencing transcription factor (REST), signal transducer and activator of transcription 1 (STAT1), and SUZ12 polycomb repressive complex 2 subunit were over-represented among the genes impacted by the prenatal and postnatal factors studied. Our results indicate that one environmental challenge can influence the effect of another challenge on the hippocampal transcriptome. These findings can assist in the identification of molecular targets to ameliorate the effects of pre-and post-natal stressors on hippocampal-associated physiology and behavior. [ABSTRACT FROM AUTHOR]

An experiment was conducted to determine the effect of substituting modified corn distillers grains with solubles (DGS) or crude soy glycerin (CG) for steam–flaked corn (SFC) in finishing diets on growth performance and carcass characteristics. Treatments were arranged as a 2 × 2 factorial with DGS (0% or 40%) and CG (0% or 10%) replacing dietary SFC in a basal diet. Growth performance and carcass traits were measured on 48 individually fed crossbred yearling cattle (21 steers and 27 heifers; 380 ± 37 kg). Cattle were randomly allotted to 48 Calan gate bunks. After the first 28 days, nine animals were removed from the study for health reasons or observed confirmation of consumption of feed from unassigned Calan gate bunk (n = 39). After the feeding period, cattle were harvested in two groups on day-124 and day-173. No DGS × CG interactions were observed (P > 0.10) for any dependent growth performance or carcass characteristic variable tested. Cattle-fed DGS as 40% of diet dry matter (DM) had greater (P < 0.01) dry matter intake (DMI), while CG inclusion at 10% of diet DM did not affect DMI (P = 0.16). Carcass–adjusted average daily gain (ADG) was not affected by DGS (P = 0.73) or CG (P = 0.28). Decreased (P = 0.03) carcass–adjusted gain-to-feed (G:F) was observed as the main effect of DGS. Greater DMI resulting from feeding DGS as 40% of diet DM appears to have driven the tendency for reduced G:F. Hot carcass weight, longissimus muscle area, 12th rib fat depth, yield grade, and marbling score were not (P > 0.10) influenced by DGS or CG. However, kidney, pelvic, fat (KPH) was increased (P = 0.01) when cattle were fed DGS as 40% of diet DM. Based on the findings presented, it is concluded that CG can substitute up to 10% of SFC in the diet without negatively affecting cattle growth performance or carcass characteristics, regardless of DGS inclusion as 40% of the diet DM. [ABSTRACT FROM AUTHOR]

An experiment was conducted to evaluate the impact of feeding bio-fuel co-products on ruminal fermentation characteristics and composition of omasal digesta flow. Four ruminally cannulated Holstein steers (371 ± 5 kg) were used in a 4 × 4 Latin Square design. Omasal sample collection and triple marker technique was used to quantify fatty acid omasal flow. Treatments were applied as a 2 × 2 factorial where a steam flaked corn (SFC) basal diet (DGS-N CG-N) was replaced with 40% of diet DM as corn distillers grains (DGS; DGS-Y CG-N) or 10% of diet DM as crude glycerin (DGS-N CG-Y) or 40% of diet DM distillers grains and 10% of diet DM as crude glycerin (DGS-Y CG-Y). No effects were observed for the interaction of DGS and glycerin on measured rumen characteristics. Dietary inclusion of glycerin decreased (P = 0.05) ruminal content 4-h post feeding on a DM basis but did not influence DMI (P = 0.64). Feeding DGS had no effect (P = 0.34) on particulate passage to the omasum (kg/d) in spite of greater (P = 0.04) DMI. Feeding DGS reduced flow rate (% of rumen volume/h) (P = 0.05) but did not affect total VFA concentration (P = 0.46) or average ruminal pH (P = 0.72). No differences (P > 0.05) were observed in ruminal parameters when feeding glycerin, besides ruminal particulate content (kg) on DM basis (P = 0.05). An interaction of DGS and glycerin affected intake of stearic (P < 0.01), linoleic (P < 0.01), and linolenic acid (P < 0.01). An interaction of DGS and glycerin did not affect individual fatty acid flow with respect to intake for stearic (P = 0.17), linoleic (P = 0.18), or linolenic acid (P = 0.66). Dietary inclusion of glycerin had no impact on g of linolenic (P = 0.16) or linoleic (P = 0.32) acid transformed. A trend was identified for cattle fed diets with glycerin to have increased (P = 0.07) grams of conjugated linoleic acid (CLA; C18:2 cis -9, trans -11) per gram of linoleic acid intake, with no impact on the percent of saturated fat (P = 0.44) or unsaturated fat (P = 0.43) in omasal flow. For cattle fed diets with DGS, fewer grams of linoleic (P < 0.01) and linolenic (P < 0.01) were present in digesta flow per gram of intake. Inclusion of DGS in the treatment diets also increased (P < 0.01) stearic acid flow (g) and CLA flow (g) per gram of stearic and linoleic acid intake, respectively. Observed differences in CLA proportion post fermentation may indicate interrupted biohydrogenation when glycerin is fed. [ABSTRACT FROM AUTHOR]

The drive to move to music is evident across a variety of contexts, from the simple urge to tap our toe to a song on the radio, to massive crowds dancing in time at a rock concert. Though seemingly effortless, beat synchronization is difficult to master and children are often poor beat synchronizers. Nevertheless, auditory‐motor integration is fundamental for many daily processes, such as speech. A topic that has been relatively understudied concerns how stimulus properties affect young children's movement in responses to auditory stimuli. In the present study, we examined how musical groove (adult‐rated desire to move) affected 3.0‐ to 6.9‐year‐old children's free dancing in the comfort of their home (n = 78). In the high groove conditions, children danced more and with more energy compared to the low groove conditions. Moreover, in the high groove condition, children's movement tempos corresponded better with the tempos of the music. Results point to early childhood sensitivity to the musical features that motivate adults to move to music. High groove music may therefore prove especially effective at facilitating early auditory‐motor integration. A video abstract of this article can be viewed at https://youtu.be/vli0‐6N12Ts. [ABSTRACT FROM AUTHOR]

DNA methylation is an epigenetic modification with wide-ranging consequences across the life of an organism. This modification can be stable, persisting through development despite changing environmental conditions. However, in other contexts, DNA methylation can also be flexible, underlying organismal phenotypic plasticity. One underappreciated aspect of DNA methylation is that it is a potent mutagen; methylated cytosines mutate at a much faster rate than other genetic motifs. This mutagenic property of DNA methylation has been largely ignored in eco-evolutionary literature, despite its prevalence. Here, we explore how DNA methylation induced by environmental and other factors could promote mutation and lead to evolutionary change at a more rapid rate and in a more directed manner than through stochastic genetic mutations alone. We argue for future research on the evolutionary implications of DNA methylation driven mutations both within the lifetime of organisms, as well as across timescales. [ABSTRACT FROM AUTHOR]

While industry and academia serve different roles when it comes to propelling the animal science industry forward, there is a need to more formally bridge efforts between industry and academia when developing employees, both future and current. Commencement speeches typically include reflections on the great accomplishments students will achieve as they begin their industry careers. But how do animal science educators ensure programming is designed to fill the learner’s metaphoric toolbox with the right skills to tackle the complicated, and ever-evolving challenges of the animal science industry? Design of academic programming needs to be strategic and interdisciplinary in order to equip graduates with the skills needed to solve the wicked problems present in animal science. Often the design process begins with an identified need or gap in knowledge that industry has observed or anticipates based on strategic initiatives. Once a connection is made between a segment of the industry and an academic institution with the willingness to fill the education gap surrounding the identified industry problem, a pipeline of employees educated in that area of need can be established. There are three key characteristics often observed when evaluating successful academic talent pipelines. First, industry must be integrated into all aspects of the process: development, launch, and delivery. Involving subject matter experience from industry allows for real-world experience-based learning in a variety of forms. This could be on-site tours/ training, connecting students with industry mentors, or bringing industry-based guest lecturers and panels into the classroom for students to network with. Industry has specific views on how they want to be involved with academia, listening to that feedback ensures respectful use of professional’s time, and effective education for future employees helping with job placement. Secondly, successful academic talent pipeline programs are able to embrace interdisciplinary skill development, while not losing sight of students’ areas of interest. It is crucial that as students are recruited to industry need-based programs, students see clear connections between skills learned and real-world application. Thirdly, successful programs meet students where they are. There is a growing population of students pursuing non-traditional education pathways to meet their career goals. Academic programs need to be prepared to train both the next generation as well as the current generation of employees in the animal science industry. While the diversity in student background experience escalates dramatically when you blend traditional and non-traditional students in the classroom, the enriching insight and discussion that follows a well-designed program highlights the importance of leveraging experience-based learning and fostering an inclusive environment for all types of learners. [ABSTRACT FROM AUTHOR]

A cluster randomized controlled trial (C‐RCT) is common in educational intervention studies. Multilevel modelling (MLM) is a dominant analytic method to evaluate treatment effects in a C‐RCT. In most MLM applications intended to detect an interaction effect, a single interaction effect (called a conflated effect) is considered instead of level‐specific interaction effects in a multilevel design (called unconflated multilevel interaction effects), and the linear interaction effect is modelled. In this paper we present a generalized additive mixed model (GAMM) that allows an unconflated multilevel interaction to be estimated without assuming a prespecified form of the interaction. R code is provided to estimate the model parameters using maximum likelihood estimation and to visualize the nonlinear treatment‐by‐covariate interaction. The usefulness of the model is illustrated using instructional intervention data from a C‐RCT. Results of simulation studies showed that the GAMM outperformed an alternative approach to recover an unconflated logistic multilevel interaction. In addition, the parameter recovery of the GAMM was relatively satisfactory in multilevel designs found in educational intervention studies, except when the number of clusters, cluster sizes, and intraclass correlations were small. When modelling a linear multilevel treatment‐by‐covariate interaction in the presence of a nonlinear effect, biased estimates (such as overestimated standard errors and overestimated random effect variances) and incorrect predictions of the unconflated multilevel interaction were found. [ABSTRACT FROM AUTHOR]

Plants harbor a variety of fungal symbionts both above- and belowground, yet little is known about how these fungi interact within hosts, especially in a world where resource availability is changing due to human activities. Systemic vertically transmitted endophytes such as Epichloë spp. may have particularly strong effects on the diversity and composition of later-colonizing symbionts such as root fungal endophytes, especially in primary successional systems. We made use of a long-term field experiment in Great Lakes sand dunes to test whether Epichloë colonization of the dune-building grass, Ammophila breviligulata, could alter fungal root endophyte species richness or community composition in host plants. We also tested whether nitrogen addition intensified the effects of Epichlöe on the root endophyte community. We found that Epichloë increased richness of root endophytes in Ammophila by 17% overall, but only shifted community composition of root endophytes under nitrogen-enriched conditions. These results indicate that Epichlöe acts as a key species within Ammophila, changing richness and composition of the root mycobiome and integrating above- and belowground mycobiome interactions. Further, effects of Epichloë on root endophyte communities were enhanced by N addition, indicating that this fungal species may become even more important in future environments. [ABSTRACT FROM AUTHOR]

During range expansions, organisms can use epigenetic mechanisms to adjust to conditions in novel areas by altering gene expression and enabling phenotypic plasticity. Here, we predicted that the number of CpG sites within the genome, one form of epigenetic potential, would be important for successful range expansions because DNA methylation can modulate gene expression and, consequently, plasticity. We asked how the number of CpG sites and DNA methylation varied across five locations in the ∼70-year-old Kenyan house sparrow (Passer domesticus) range expansion. We found that the number of CpG sites was highest toward the vanguard of the invasion and decreased toward the range core. Analysis suggests that this pattern may have been driven by selection, favoring birds with more CpG sites at the range edge. However, we cannot rule out other processes, including nonrandom gene flow. Additionally, DNA methylation did not change across the range expansion, nor was it more variable. We hypothesize that as new areas are colonized, epigenetic potential may be selectively advantageous early but eventually be replaced by less plastic and perhaps genetically canalized traits as populations adapt to local conditions. Although further work is needed on epigenetic potential, this form (CpG number) appears to be a promising mechanism to investigate as a driver of expansions via capacitated phenotypic plasticity in other natural and anthropogenic range expansions. [ABSTRACT FROM AUTHOR]

This review article addresses the frequently noted comorbidity between obsessive-compulsive disorder (OCD) and obsessive-compulsive personality disorder (OCPD). We begin by reviewing the recent empirical literature on the co-occurrence of these two conditions and the functional consequences of comorbid OCPD on OCD. We describe theoretical conceptualizations of the links between these disorders, including shared mechanisms that may drive the association between these two distinct conditions. We then provide an overview of diagnostic measures for OCPD and differential diagnosis. We also review data on the impact of comorbid OCPD on cognitive-behavioral treatment for OCD, including how to address potential treatment barriers through which OCPD may complicate OCD treatment. Lastly, we conclude with directions for future research. [ABSTRACT FROM AUTHOR]

We recently published a preliminary assessment of the activity of a poly (ADP-ribose) polymerase (PARP) inhibitor, stenoparib, also known as 2X-121, which inhibits viral replication by affecting pathways of the host. Here we show that stenoparib effectively inhibits a SARS-CoV-2 wild type (BavPat1/2020) strain and four additional variant strains; alpha (B.1.1.7), beta (B.1.351), delta (B.1.617.2) and gamma (P.1) in vitro, with 50% effective concentration (EC50) estimates of 4.1 μM, 8.5 μM, 24.1 μM, 8.2 μM and 13.6 μM, respectively. A separate experiment focusing on a combination of 10 μM stenoparib and 0.5 μM remdesivir, an antiviral drug, resulted in over 80% inhibition of the alpha variant, which is substantially greater than the effect achieved with either drug alone, suggesting at least additive effects from combining the different mechanisms of activity of stenoparib and remdesivir. [ABSTRACT FROM AUTHOR]