B7-H3 Inhibitors in Oncology Clinical Trials: A Review.

B7-H3 is a transmembrane receptor highly prevalent on malignant cells and plays an important role in adaptive immunity that is not fully elucidated. Targeted B7-H3 inhibitors, including antibody-drug conjugates, radioimmunotherapy, and monoclonal antibodies, are a new class of antineoplastic agents showing promising preliminary clinical efficacy, observed with several of these agents against multiple tumor types. Particularly promising treatments are enoblituzumab for prostate cancer, 131I-omburtamab for central nervous system malignancies, and HS-20093 for small-cell lung cancer but further studies are warranted. There are clinical trials on the horizon that have not yet enrolled patients examining chimeric antigen receptor T-cell therapies, bi- and tri-specific killer engagers, and dual-affinity retargeting proteins. These data will be telling of the efficacy of B7-H3 inhibitors in both hematologic and solid malignancies. This study aimed to compile available results of B7-H3 inhibitors in oncology clinical trials.

Potential mechanisms for osteopathic manipulative treatment to alleviate migraine-like pain in female rats.

Introduction: Migraines are the leading cause of disability in the United States, and the use of non-pharmaceutical treatments like osteopathic manipulative treatment (OMT) has shown promise. Despite its potential, the lack of mechanistic understanding has hindered widespread adoption. This study aims to investigate the efficacy of OMT in treating acute migraines and unravel its underlying mechanisms of action. Methods: Female rats were subjected to a "two-hit" approach to induce migraine-like pain. This involved bilateral injections of Complete Freund's Adjuvant (CFA) into the trapezius muscle (1st hit) followed by exposure to Umbellulone, a human migraine trigger, on Day 6 post-CFA (2nd hit). Soft tissue and articulatory techniques were applied to the cervical region for acute abortive or repeated prophylactic treatment. Cutaneous allodynia and trigeminal system activation were assessed through behavioral tests and immunohistochemical staining. Results: Following Umbellulone inhalation, CFA-primed rats exhibited periorbital and hind paw allodynia. Immediate application of OMT after Umbellulone inhalation as an abortive treatment partially alleviated cutaneous allodynia. With OMT applied thrice as a prophylactic measure, complete suppression of tactile hypersensitivity was observed. Prophylactic OMT also prevented the increase of c-fos signals in the trigeminal nucleus caudalis and the elevation of calcitonin gene-related peptide expression in trigeminal ganglia induced by CFA and Umbellulone exposure at 2 h post-inhalation. Discussion: These findings provide mechanistic insights into OMT's migraine-relief potential and underscore its viability as a non-pharmacological avenue for managing migraines.

Specifying cross-system collaboration strategies for implementation: a multi-site qualitative study with child welfare and behavioral health organizations.

BACKGROUND: Cross-system interventions that integrate health, behavioral health, and social services can improve client outcomes and expand community impact. Successful implementation of these interventions depends on the extent to which service partners can align frontline services and organizational operations. However, collaboration strategies linking multiple implementation contexts have received limited empirical attention. This study identifies, describes, and specifies multi-level collaboration strategies used during the implementation of Ohio Sobriety Treatment and Reducing Trauma (Ohio START), a cross-system intervention that integrates services across two systems (child welfare and evidence-based behavioral health services) for families that are affected by co-occurring child maltreatment and parental substance use disorders. METHODS: In phase 1, we used a multi-site qualitative design with 17 counties that implemented Ohio START. Qualitative data were gathered from 104 staff from child welfare agencies, behavioral health treatment organizations, and regional behavioral health boards involved in implementation via 48 small group interviews about collaborative approaches to implementation. To examine cross-system collaboration strategies, qualitative data were analyzed using an iterative template approach and content analysis. In phase 2, a 16-member expert panel met to validate and specify the cross-system collaboration strategies identified in the interviews. The panel was comprised of key child welfare and behavioral health partners and scholars. RESULTS: In phase 1, we identified seven cross-system collaboration strategies used for implementation. Three strategies were used to staff the program: (1) contract for expertise, (2) provide joint supervision, and (3) co-locate staff. Two strategies were used to promote service access: (4) referral protocols and (5) expedited access agreements. Two strategies were used to align case plans: (6) shared decision-making meetings, and (7) sharing data. In phase 2, expert panelists specified operational details of the cross-system collaboration strategies, and explained the processes by which strategies were perceived to improve implementation and service system outcomes. CONCLUSIONS: We identified a range of cross-system collaboration strategies that show promise for improving staffing, service access, and case planning. Leaders, supervisors, and frontline staff used these strategies during all phases of implementation. These findings lay the foundation for future experimental and quasi-experimental studies that test the effectiveness of cross-system collaboration strategies.

Lessons learned from housing first, rapid rehousing trials with youth experiencing homelessness.

BACKGROUND: Youth, 18 to 24 years, experiencing homelessness (YEH) are recognized as having developmental challenges dissimilar to older adults. Yet, research on efforts to end homelessness and prevent or intervene in drug use and mental health problems among youth have lagged behind that of adults. The Housing First (HF) Model which underlies Permanent Supportive Housing (PSH) and Rapid Re-Housing (RRH) has become preferred over treatment-first models. METHODS AND RESULTS: We provide an overview of PSH and RRH studies to date and summarize our current understanding of their utility for use with YEH. Finally, we review our team's current and past randomized trials testing RRH with YEH, providing lessons learned and recommendations. CONCLUSION: Current research efforts to guide best practices are hampered by a lack of fidelity to HF principles, lack of randomized design, and lack of focus on youth. Lessons learned and recommendations from our work are offered to facilitate the future work of those who seek to end homelessness and address drug use and mental health problems among youth.

Ten years of implementation outcomes research: a scoping review.

BACKGROUND: Proctor and colleagues' 2011 paper proposed a taxonomy of eight implementation outcomes and challenged the field to address a research agenda focused on conceptualization, measurement, and theory building. Ten years later, this paper maps the field's progress in implementation outcomes research. This scoping review describes how each implementation outcome has been studied, research designs and methods used, and the contexts and settings represented in the current literature. We also describe the role of implementation outcomes in relation to implementation strategies and other outcomes. METHODS: Arksey and O'Malley's framework for conducting scoping reviews guided our methods. Using forward citation tracing, we identified all literature citing the 2011 paper. We conducted our search in the Web of Science (WOS) database and added citation alerts sent to the first author from the publisher for a 6-month period coinciding with the WOS citation search. This produced 1346 titles and abstracts. Initial abstract screening yielded 480 manuscripts, and full-text review yielded 400 manuscripts that met inclusion criteria (empirical assessment of at least one implementation outcome). RESULTS: Slightly more than half (52.1%) of included manuscripts examined acceptability. Fidelity (39.3%), feasibility (38.6%), adoption (26.5%), and appropriateness (21.8%) were also commonly examined. Penetration (16.0%), sustainability (15.8%), and cost (7.8%) were less frequently examined. Thirty-two manuscripts examined implementation outcomes not included in the original taxonomy. Most studies took place in healthcare (45.8%) or behavioral health (22.5%) organizations. Two-thirds used observational designs. We found little evidence of progress in testing the relationships between implementation strategies and implementation outcomes, leaving us ill-prepared to know how to achieve implementation success. Moreover, few studies tested the impact of implementation outcomes on other important outcome types, such as service systems and improved individual or population health. CONCLUSIONS: Our review presents a comprehensive snapshot of the research questions being addressed by existing implementation outcomes literature and reveals the need for rigorous, analytic research and tests of strategies for attaining implementation outcomes in the next 10 years of outcomes research.

Housing and supportive services for substance use and self-efficacy among young mothers experiencing homelessness: A randomized controlled trial.

AIMS: Homeless mothers with young children in their care contend with high rates of substance use and low self-efficacy. However, a limited number of studies have examined these outcomes associated with housing and supportive services. DESIGN: Participants were randomly assigned to: (1) housing + support services (n = 80), (2) housing-only (n = 80), or (3) services as usual (SAU) (n = 80) and were re-assessed at 3-, 6-, 9- and 12-months postbaseline. SETTINGS: The study recruited a community-based sample from homeless service agencies and advertisements in a large Midwestern city. PARTICIPANTS: The study recruited two hundred forty (N = 240) women between the ages of 18 to 24 years, experiencing homelessness and with a substance use disorder (SUD) who also had a biological child under the age of 6 years in their care. MEASUREMENTS: We measured frequency of alcohol and drug use using the Form 90 semi-structured interview, and self-efficacy using Pearlin and Schooler's (1978) 7-item Mastery Scale. FINDINGS: Overall, mothers showed significant improvement in substance use and self-efficacy over time in each condition. However, as expected, patterns of change differentiated intervention groups with more mothers showing better substance use and self-efficacy outcomes in housing + supportive services than in SAU. Unexpectedly, more mothers in SAU showed better outcomes than those in housing-only. CONCLUSIONS: Substance use decreased and self-efficacy increased over time, but patterns of change characterized the intervention groups. In particular, findings suggest that when providing housing to this population, supportive services should also be offered.

Personality Across World Regions Predicts Variability in the Structure of Face Impressions.

Research on face impressions has often focused on a fixed, universal architecture, treating regional variability as noise. Here, we demonstrated a crucial yet neglected role of cultural learning processes in forming face impressions. In Study 1, we found that variability in the structure of adult perceivers' face impressions across 42 world regions (N = 287,178) could be explained by variability in the actual personality structure of people living in those regions. In Study 2, data from 232 world regions (N = 307,136) revealed that adult perceivers use the actual personality structure learned from their local environment to form lay beliefs about personality, and these beliefs in turn support the structure of perceivers' face impressions. Together, these results suggest that people form face impressions on the basis of a conceptual understanding of personality structure that they have come to learn from their regional environment. The findings suggest a need for greater attention to the regional and cultural specificity of face impressions.

Delineation of blacktip shark (Carcharhinus limbatus) nursery habitats in the north-western Gulf of Mexico.

Coevolution with predators leads to the use of low-risk habitats by many prey species, which promotes survival during early developmental phases. These nurseries are valued by conservation and management agencies because of their contributions to adult populations. However, the physical and geographic characteristics, like shallow depths and isolation from other marine habitats, that restrict access to predators and thereby reduce risk to juvenile animals can also limit scientific research. Consequently, many nursery habitats are still unidentified and understudied. Here we used gillnet monitoring from 1982 to 2018 to delineate blacktip shark (Carcharhinus limbatus) nurseries in the north-western Gulf of Mexico and elucidated their physical, environmental and biological characteristics. Nursery habitats within estuaries (<2% of spatial area) were proximate to the Gulf of Mexico and exhibited significantly lower variability in salinity than non-nurseries. However, relative abundances of predators and prey were not significant delineators of nursery habitats. As such, food and risk may not influence juvenile blacktip habitat use as expected. Alternatively, reduced osmoregulatory stress attributed to predictable environments likely provides advantageous conditions for blacktips to develop foraging and antipredator tactics, which is vital prior to the winter migration of juvenile sharks into the Gulf of Mexico.

Brain-wide mapping reveals that engrams for a single memory are distributed across multiple brain regions.

Neuronal ensembles that hold specific memory (memory engrams) have been identified in the hippocampus, amygdala, or cortex. However, it has been hypothesized that engrams of a specific memory are distributed among multiple brain regions that are functionally connected, referred to as a unified engram complex. Here, we report a partial map of the engram complex for contextual fear conditioning memory by characterizing encoding activated neuronal ensembles in 247 regions using tissue phenotyping in mice. The mapping was aided by an engram index, which identified 117 cFos+ brain regions holding engrams with high probability, and brain-wide reactivation of these neuronal ensembles by recall. Optogenetic manipulation experiments revealed engram ensembles, many of which were functionally connected to hippocampal or amygdala engrams. Simultaneous chemogenetic reactivation of multiple engram ensembles conferred a greater level of memory recall than reactivation of a single engram ensemble, reflecting the natural memory recall process. Overall, our study supports the unified engram complex hypothesis for memory storage.

Six practical recommendations for improved implementation outcomes reporting.

BACKGROUND: Implementation outcomes research spans an exciting mix of fields, disciplines, and geographical space. Although the number of studies that cite the 2011 taxonomy has expanded considerably, the problem of harmony in describing outcomes persists. This paper revisits that problem by focusing on the clarity of reporting outcomes in studies that examine them. Published recommendations for improved reporting and specification have proven to be an important step in enhancing the rigor of implementation research. We articulate reporting problems in the current implementation outcomes literature and describe six practical recommendations that address them. RECOMMENDATIONS: Our first recommendation is to clearly state each implementation outcome and provide a definition that the study will consistently use. This includes providing an explanation if using the taxonomy in a new way or merging terms. Our second recommendation is to specify how each implementation outcome will be analyzed relative to other constructs. Our third recommendation is to specify "the thing" that each implementation outcome will be measured in relation to. This is especially important if you are concurrently studying interventions and strategies, or if you are studying interventions and strategies that have multiple components. Our fourth recommendation is to report who will provide data and the level at which data will be collected for each implementation outcome, and to report what kind of data will be collected and used to assess each implementation outcome. Our fifth recommendation is to state the number of time points and frequency at which each outcome will be measured. Our sixth recommendation is to state the unit of observation and the level of analysis for each implementation outcome. CONCLUSION: This paper advances implementation outcomes research in two ways. First, we illustrate elements of the 2011 research agenda with concrete examples drawn from a wide swath of current literature. Second, we provide six pragmatic recommendations for improved reporting. These recommendations are accompanied by an audit worksheet and a list of exemplar articles that researchers can use when designing, conducting, and assessing implementation outcomes studies.

Valuation of emotion underlies cultural variation in cardiovascular stress responses.

Cultural context shapes individuals' valuation of emotions. Although studies have documented cultural differences in beliefs about the utility of negative emotions, little is known about how such cultural valuation is associated with physiological stress responses. In the present work, we examined whether East Asians and European Americans differ in how they value nervousness in a demanding situation and whether such valuation predicts acute cardiovascular responses. We found that East Asians were more likely than European Americans to believe feeling nervous in a demanding situation was useful. Furthermore, greater valuation of negative emotion predicted attenuated cardiovascular responses to a laboratory mental stressor and partially mediated the relationship between culture and cardiovascular stress responses. The present results highlight the importance of valuation of emotions as a psychological mechanism underlying cultural as well as individual differences in stress-evoked cardiovascular responses. We discuss one implication for this line of research, unpacking how cross-cultural differences in valuation of negative emotions may lead to cultural variation in physiological patterns related to health outcomes. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Emojis as social information in digital communication.

Facial expressions of emotion are nonverbal cues that evoke affective, inferential, and social responses during face-to-face communication. Given that communication is moving more and more from face-to-face to digital contexts, the present research tested the functional equivalence of their digital counterparts-emojis. Eleven high-powered experiments tested the general effectiveness of emojis to convey emotionality and to disambiguate discourse during digital communication, as well as predictions about their social-emotional properties derived from the Emotion as Social Information (EASI) model. Compared to messages without emojis, those including emojis were perceived as emotionally more intense and as of more extreme valence. Furthermore, the effects of emojis on perceived valence were mediated via perceived emotional intensity. This suggests that emojis are effective quasi-nonverbal cues for digital communication. Furthermore, in line with predictions of the EASI model, emojis produced patterns similar to what has been observed for facial expressions of emotion in face-to-face communication, supporting their functional equivalence. Specifically, they instigated affective (emotion contagion) and inferential (understanding) processes, which subsequently resulted in behavioral intentions (empathic concern). In terms of the predicted mediating processes, we found differences between emojis and offline facial expressions of emotion. These deviations from our predictions are attributed to inherent differences between digital and face-to-face communication and limitations in the employed methodology. In light of the present findings, we discuss a theoretical synthesis of emojis in digital communication with the EASI model and propose a research agenda to connect emotion research with predominant forms of modern communication. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Living in ancestrally diverse states of the United States is associated with greater vagal tone.

Historically, exposure to dissimilar others ("strangers") was a physiologically arousing event-resulting in avoidance, distrust, and even conflict. Despite this, contemporary migration patterns are increasing intergroup contact. What gives rise to an individual's ability to regulate their arousal such that social engagement with outgroup members is possible? We propose that cultural practices that evolve in ancestrally diverse, compared to ancestrally homogeneous, societies provide more opportunities for society members to engage in emotion regulation. This regulatory exercise, in turn, promotes higher vagal tone-a physiological indicator of one's ability to effectively manage arousal in social interaction. In a secondary analysis of data from the MIDUS 2 Biomarker Project, we find that the ancestral diversity of the states of the United States significantly predicts the average vagal tone of the state's citizens. The findings suggest that social context is associated with predictable and significant adaptations of human physiology over individual lifetimes.

Evidence for Distinct Facial Signals of Reward, Affiliation, and Dominance from Both Perception and Production Tasks.

Smiles are nonverbal signals that convey social information and influence the social behavior of recipients, but the precise form and social function of a smile can be variable. In previous work, we have proposed that there are at least three physically distinct types of smiles associated with specific social functions: reward smiles signal positive affect and reinforce desired behavior; affiliation smiles signal non-threat and promote peaceful social interactions; dominance smiles signal feelings of superiority and are used to negotiate status hierarchies. The present work advances the science of the smile by addressing a number of questions that directly arise from this smile typology. What do perceivers think when they see each type of smile (Study 1)? How do perceivers behave in response to each type of smile (Study 2)? Do people produce three physically distinct smiles in response to contexts related to each of the three social functions of smiles (Study 3)? We then use an online machine learning platform to uncover the labels that lay people use to conceptualize the smile of affiliation, which is a smile that serves its social function but lacks a corresponding lay concept. Taken together, the present findings support the conclusion that reward, affiliation, and dominance smiles are distinct signals with specific social functions. These findings challenge the traditional assumption that smiles merely convey whether and to what extent a smiler is happy and demonstrate the utility of a social-functional approach to the study of facial expression.

Dominance, reward, and affiliation smiles modulate the meaning of uncooperative or untrustworthy behaviour.

We investigated the effects of different types of smiles on the perception of uncooperative or untrustworthy behaviour. In five studies, participants assigned to one group played an economic game with a representative of another group. In an initial round, the representative acted uncooperatively by favouring their group and then displayed a dominance, reward, or affiliation smile. Participants rated the motives of the representative and played a second round of the game with a different member of the same outgroup. Following uncooperative or untrustworthy behaviour, affiliation smiles communicated less positivity and superiority, and a greater desire to both repair the relationship between groups and change the uncooperative decision than reward or dominance smiles. Perceptions of a desire to repair the relationship and to change the decision were associated with trust and cooperation in a subsequent round of the game. Together, these findings show that smiles that are subtly different in their morphology can convey different messages and highlight the importance of these expressions in influencing the perceptions of others' intentions.

Housing First Combined with Suicide Treatment Education and Prevention (HOME + STEP): study protocol for a randomized controlled trial.

BACKGROUND: Youth experiencing homelessness are at high risk for suicide, yet few studies have evaluated risk reduction interventions targeting suicidal ideation in this vulnerable population. A comprehensive approach to risk-reduction is needed that addresses basic needs and provides targeted interventions for those at highest risk. The protocol described builds on the design of the first randomized trial of Housing First (HF) for homeless youth. The primary objective is to determine whether housing combined with supportive services that include suicide screening and targeted psychotherapy (Cognitive Therapy for Suicide Prevention) is effective for reducing suicidal ideation and other secondary outcomes (depression and suicide attempts). Additionally, we will explore mediators of the treatment effect (housing stability and substance use) and determinants of implementation. METHODS: Youth recruited to the HF trial will be randomized to HF + supportive services (n = 120), or supportive services alone (n = 120). The "Suicide Treatment Education and Prevention" (STEP) protocol will additionally screen youth in both arms at baseline and 3 months for suicidal ideation (SSI-W). Those who screen as moderate risk for suicide (SSI-W ≥ 10) will be offered CTSP, which includes up to 9 sessions over the first 6 months following enrollment. CTSP will be delivered in one-on-one sessions by a trained advocate. Research assessments will be collected to assess outcomes (including suicidal ideation) at baseline, 3, 6, 9 and 12 months. Qualitative interviews with subjects receiving CTSP and other stakeholders will explore implementation determinants. DISCUSSION: The study will fill an important gap in the literature about the added benefit of HF combined with supportive services including suicide screening and treatment for reducing suicidal ideation in homeless youth. With the urgent need to address both homelessness and suicide risk, evidence is needed about services that can be integrated into delivery settings for youth experiencing homelessness. TRIAL REGISTRATION: NCT04135703 . Date of registration: October 23, 2019.

Housing, opportunities, motivation and engagement (HOME) for homeless youth at-risk for opioid use disorder: study protocol for a randomized controlled trial.

BACKGROUND: Homeless youth experience high rates of substance use disorders, exposures to violence, mental and physical health conditions, and mortality. They have been particularly affected by the opioid crisis. However, no study to date has used a randomized controlled design to test preventive interventions of opioid and other drug use among this vulnerable population. Resolution of youth homelessness through housing and supportive services including prevention services, often referred to as "Housing First," has great potential to reduce the likelihood for the development of an opioid use disorder as well as other problem behaviors associated with living on the streets. Housing First has been tested through randomized trials among homeless adults with mental health and substance use disorders, but has not been empirically tested for opioid prevention among homeless youth. METHODS: Homeless youth will be recruited from a drop-in shelter site frequented by disconnected youth; they will be screened for eligibility, including current homelessness, age 18-24 years, and not currently meeting criteria for opioid use disorder (OUD). In a controlled trial, 240 youth will then be randomized to one of two conditions, (1) housing + opioid and related risk prevention services, or (2) opioid and related risk prevention services alone. This project utilizes existing efficacious models of prevention to address opioid-related risks, including motivational interviewing, strengths-based outreach and advocacy, and an HIV risk preventive intervention. Follow-up will be conducted at 3, 6, 9 and 12-months post-baseline. The economic cost of each intervention will be determined to support implementation decisions with other providers and their funders. DISCUSSION: This study will provide essential information for researchers and providers on the efficacy of housing + opioid and related risk prevention services in an RCT for effects on opioid use and mechanisms underlying change. Because youth experiencing homelessness are at increased risk for a variety of adverse outcomes, the proposed intervention may produce substantial health care benefits to the youths and society at large. Trial registration ClinicalTrials.gov, NCT04135703, Registered October 13, 2019, https://clinicaltrials.gov/ct2/show/NCT04135703?term=NCT04135703&draw=2&rank=1#contacts.