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BackgroundIntimate partner violence (IPV) disproportionately affects married women living with HIV (MWLHIV), resulting in undesirable human rights, socio-economic, mental, maternal, and child health consequences. Community Support systems against Violence (CoSaV) are widely available and promising public and voluntary resources for the prevention and mitigation of IPV but are poorly investigated. We set out to identify the predictors for the utilization of the CoSaV among the MWLHIV.MethodsThis was a quantitative cross-sectional study conducted among 424 consecutively sampled MWLHIV attending the Antiretroviral Therapy (ART) clinic at Kabale Regional Referral Hospital in southwestern Uganda in April 2021. Using an interviewer-administered questionnaire, data were collected on the participant's socio-demographic characteristics, exposure to IPV, awareness about the CoSaV, perceptions about the quality, accessibility and challenges in accessing the CoSaV and the utilization. Modified Poisson regression model was used to identify the predictors for the utilization of CoSaV using the Statistical Package for Social Sciences (SPSS) version 23.0.ResultsThe mean age of the 424 participants in the study was 39.5 ± 10.2 years. More than half of the participants 51.9% (220/424) reported exposure to any IPV. Utilization of any CoSaV was found to be above average at 58.3% among the participants. The formal support (police, local government leaders, health workers and counselors) were more frequently utilized compared to the informal support (family, relatives and friends). Utilization of any CoSaV was higher among the women who were aware of the CoSaV and also those who were exposed to violence. Accessibility was identified as an independent predictor for utilization of any CoSaV.ConclusionsIntimate partner violence (IPV) was prevalent among MWLHIV in southwestern Uganda. However, the utilization of any CoSaV was suboptimal. The formal CoSaV were more frequently utilized than the informal support systems. Accessibility was an independent predictor for utilization of any CoSaV. There is need to improve access in order to increase the utilization of the CoSaV and contribute to the attainment of sustainable development goal 5.2.1 and end violence against women.

Objective: Identify barriers to the adoption of the Ohio State University Traumatic Brain Injury Identification Method (OSU TBI-ID) in behavioral healthcare organizations and match these barriers to implementation strategies to inform future implementation efforts., Participants: Twenty behavioral health providers., Design: Qualitative study involving individual, semi-structured interviews regarding barriers to adopting the OSU TBI-ID. Data were thematically analyzed around constructs from the Consolidated Framework for Implementation Research (CFIR). Results were matched to strategies using the Expert Recommendations for Implementing Change (CFIR/ERIC) matching tool., Results: Ten barriers were identified across 4 CFIR domains. Inner-Setting barriers were inadequate leadership engagement, priorities, resources, and organizational incentives. Individual-Characteristics barriers were insufficient knowledge about the connection between TBI and behavioral health and how to conduct the OSU TBI-ID with fidelity, low self-efficacy to conduct screening, and inadequate motivation and buy-in to conduct screening. Outer-Setting barriers were lack of state-level mandates and inadequate incentives to conduct screenings. The Process domain barrier was an insufficient engagement of key personnel. Strategy recommendations include: identify and prepare champions; alter incentive and allowance structures; inform local opinion leaders; build a coalition; access new funding; conduct local consensus discussions; involve executive boards; capture/share local knowledge; conduct educational meetings; assess for readiness and identify determinants; identify early adopters; fund and contract for the clinical innovation; create a learning collaborative; and conduct a local needs assessment., Conclusions: This is the first study to examine barriers to adopting the OSU TBI-ID in real-world practice settings. Our results suggest that multilevel implementation strategies addressing mechanisms of change are necessary at the provider, organizational, and systems levels to overcome the complex barriers affecting TBI screening adoption and implementation. Future research is needed to test these strategies and their mechanisms of action on the adoption, implementation, and sustainment of TBI screening, as well as their effect on client-level outcomes., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc.)

Prior studies have suggested that immune thrombotic thrombocytopenic purpura (iTTP) may display seasonal variation; however, methodologic limitations and sample sizes have diminished the ability to perform a rigorous assessment. This 5-year retrospective study assessed the epidemiology of iTTP and determined whether it displays a seasonal pattern. Patients with both initial and relapsed iTTP (defined as a disintegrin and metalloprotease with thrombospondin type motifs 13 activity <10%) from 24 tertiary centers in Australia, Canada, France, Greece, Italy, Spain, and the US were included. Seasons were defined as: Northern Hemisphere-winter (December-February); spring (March-May); summer (June-August); autumn (September-November) and Southern Hemisphere-winter (June-August); spring (September-November); summer (December-February); autumn (March-May). Additional outcomes included the mean temperature in months with and without an iTTP episode at each site. A total of 583 patients experienced 719 iTTP episodes. The observed proportion of iTTP episodes during the winter was significantly greater than expected if equally distributed across seasons (28.5%, 205/719, 25.3%-31.9%; p = .03). Distance from the equator and mean temperature deviation both positively correlated with the proportion of iTTP episodes during winter. Acute iTTP episodes were associated with the winter season and colder temperatures, with a second peak during summer. Occurrence during winter was most pronounced at sites further from the equator and/or with greater annual temperature deviations. Understanding the etiologies underlying seasonal patterns of disease may assist in discovery and development of future preventative therapies and inform models for resource utilization., (© 2024 The Author(s). American Journal of Hematology published by Wiley Periodicals LLC.)

The conservation status of monarch butterflies in North America is a topic of intense scrutiny and debate. It is clear that winter colonies in Mexico are declining, yet some recent studies suggest that summer breeding populations are relatively stable and similar to historical abundances. One possible explanation for these discordant patterns is that fall migration success has been recently disrupted. Here, we use a relatively unexplored citizen-scientist dataset on the size of monarch "roosts," which are resting aggregations on vegetation, to infer changes in monarch abundance along the fall migration route over the last 17 y. We found that the timing of migration remained relatively unchanged while the flyway has generally become warmer and greener. Warmer and greener conditions were associated with larger roosts, yet we found steady, dramatic declines in roost sizes through time that were independent of climate and landscape factors. Roost sizes have declined as much as 80%, with losses increasing from north to south along the migration route. These findings suggest that failure during the fall migration could explain the apparent drop in monarch numbers from summer breeding to overwintering populations. This in turn suggests that conservation efforts that support fall migration success are most needed, such as providing high quality nectar plants along the migration route or limiting the planting of nonnative milkweeds that enhance monarch parasite loads. Overall, it appears the fall migration of monarch butterflies is under imminent threat, even if the species' overall survival is not., Competing Interests: Competing interests statement:The authors declare no competing interest.

There is an urgent need to develop better treatments for mental health conditions that affect one in every eight people in the world. To combat this concern, psychedelic drugs have been combined with psychotherapy and studied in clinical trials in the United States and Europe. Psychedelics are hallucinogenic drugs that alter brain activity and facilitate altered states of consciousness. The proposed benefits of psychedelic-assisted therapy (PAT) include relatively short treatment times and stronger effects compared to other treatments. Although results of trials using MDMA for trauma or psilocybin for depression are promising, PAT is controversial because many questions about its safety and effectiveness are unanswered. This is evident in the recent ruling by the US Food and Drug Administration against the approval of MDMA therapy for post-traumatic stress disorder and the retraction of several papers about MDMA trials owing to unethical conduct by study therapists and data integrity, among other concerns. This field is at a crossroads, and the research community must address several obstacles to transition from exploratory trials to established, evidence-based treatments while avoiding pitfalls that can hinder advancement.

While the critical role of NKX2-1 and its transcriptional targets in lung morphogenesis and pulmonary epithelial cell differentiation is increasingly known, mechanisms by which chromatin accessibility alters the epigenetic landscape and how NKX2-1 interacts with other co-activators required for alveolar epithelial cell differentiation and function are not well understood. Combined deletion of the histone methyl transferases Prdm3 and Prdm16 in early lung endoderm causes perinatal lethality due to respiratory failure from loss of AT2 cells and the accumulation of partially differentiated AT1 cells. Combination of single-cell RNA-seq, bulk ATAC-seq, and CUT&RUN data demonstrate that PRDM3 and PRDM16 regulate chromatin accessibility at NKX2-1 transcriptional targets critical for perinatal AT2 cell differentiation and surfactant homeostasis. Lineage specific deletion of PRDM3/16 in AT2 cells leads to lineage infidelity, with PRDM3/16 null cells acquiring partial AT1 fate. Together, these data demonstrate that NKX2-1-dependent regulation of alveolar epithelial cell differentiation is mediated by epigenomic modulation via PRDM3/16., (© 2024. The Author(s).)

We sought to identify patterns of psychedelic use among United States military veterans, compare demographic variables and perspectives of those who did and did not report use, and characterize benefits and adverse outcomes associated with use. Respondents ( N  = 426) were recruited to complete an online cross-sectional survey. Approximately one-half (51%) reported using psychedelics. Most did so for healing/treatment (70%) and/or spiritual purposes (48%), and most (85%) reported benefiting from use. Those who used psychedelics reported they would be more likely to use VA services ( p  < .001, d = 0.64) and to return to the VA for care ( p  < .001, d = 0.79) if psychedelic therapy was offered. Almost two-thirds (59%) reported adverse outcomes associated with use. Equivalent proportions rated their psychedelic experiences as beneficial among those who did (89%) and did not (81%) report adverse outcomes. Fewer adverse outcomes were associated with being older, using psilocybin, feeling prepared and confident in the reasons for use, being in a comfortable setting, and being able to "trust, let go, and be open" (R c  = 0.77; p  < .001). Psychedelics may offer benefits but may also lead to adverse outcomes without proper preparation and support. Future research should examine the utility of psychedelic-based approaches for veteran mental health care.

This study translated and tested the psychometric properties of acute psychedelic effects measures among Spanish-speaking people. The Psychological Insight Questionnaire (PIQ), Challenging Experiences Questionnaire (CEQ), and Mystical Experiences Questionnaire (MEQ) were translated before being incorporated into a web-based survey. We recruited native Spanish-speakers ( N  = 442; M age  = 30.8, SD = 10.9; Latino/Latina = 62%; Hispanic = 91.4%; male = 71.5%) to assess their previous experience with one of two psychedelics (LSD = 58.4%; Psilocybin = 41.6%) and their acute and enduring effects. Confirmatory factor analysis (confirming factor structure based on the English version) revealed a good fit for the MEQ, PIQ and the CEQ. Repeating our analysis in each drug subsample revealed consistency in factor structure for each assessment tool. Construct validity was supported by significant positive associations between the PIQ and MEQ, and between the PIQ and MEQ and changes in cognitive fusion and negative associations between changes in prosocial behaviors. As a signal of predictive validity, persisting effects (PEQ) were strongly related to scores on the MEQ and PIQ. Findings demonstrate that the Spanish versions of these measures can be reliably employed in studies of psychedelic use or administration in Spanish-speaking populations.

When animals perceive an acute stressor like a predator, they typically undergo a suite of physiological changes that function to improve survival during the encounter, such as elevation in cardiac output, to supply more energy to muscles. If bodily energy is limited, such as by parasites or infections, these functions could become less efficient and lessen host survival. In the aquatic world of microorganisms, individuals can become colonized by other organisms on their surface (epibionts), which could sap energy from their host from their weight, or even compete with the host for food. Here, we tested if one epibiont (a ciliated protozoan, Vorticella spp.) affects its hosts' ability to mount a physiological stress reaction. We collected wild daphnia ( Daphnia ambigua ) that had varying burdens of these on their bodies and exposed them to a simulated stressor (crushed daphnia, to simulate nearby predation) under a microscope while monitoring for changes in their heart rates in real time. Out of 121 daphnia, those with no Vorticella epibionts showed no meaningful changes in their heart rate after exposure, but those with light or heavy burdens showed immediate elevations (within 5 min). Moreover, the heart rates of heavily burdened daphnia continued to rise for 1.5 h thereafter, to as much as 17% higher than at baseline. These patterns were unexpected, as they suggest that the ciliated epibionts act to elevate their hosts' physiological reaction, rather than dampen it, perhaps by churning the water column around the host, thereby enhancing the chemical alarm cue. The procedures used in this study may be useful for future investigations into the acute stress reactions of daphnia or other microorganisms.

An invasive spider from East Asia has established in the U.S. southeast (the "jorō spider," Trichonephila clavata ) and is rapidly expanding its range. Studies assessing the impact of this species are needed, including how expansive its diet is. An open question is whether monarch butterflies, Danaus plexippus , are a potential prey item for this spider, given that jorō spiders do not coexist with monarchs in their native range. Since monarch larvae feed on milkweed, they sequester cardiac glycosides into their adult tissues, rendering them unpalatable to many predators. At sites within northeast Georgia, we staged a series of trials (n = 61) where we tossed monarchs into jorō spider webs and, for comparison, performed similar trials with another aposematic species, gulf fritillary ( Agraulis vanilla ), and a palatable species, tiger swallowtail ( Papilio glaucus ). We recorded the outcome of the trials, which included whether the spider attacked or did not attack the prey. We also conducted a visual survey during the same fall season to look for evidence of jorō spiders consuming monarchs naturally. Our findings revealed that jorō spiders avoided eating monarchs; spiders only attacked monarchs 20% of the time, which was significantly less than the attack rates of similarly sized or larger butterflies: 86% for gulf fritillaries and 58% for tiger swallowtails. Some jorō spiders even removed monarchs from their webs. From our visual surveys of the surrounding area, we found no evidence of natural monarch consumption and, in general, butterflies made up only a fraction of the jorō spider diet. We conclude that jorō spiders appear to recognize monarch butterflies as being unpalatable, even without having a prior history with the species. This invokes questions about how these spiders can immediately recognize their unpalatability without touching the butterflies.

We examined if the therapeutic alliance between study participants and intervention facilitators in a psilocybin-assisted therapy (PAT) trial changed over time and whether there were relationships between alliance, acute psilocybin experiences, and depression outcomes. In a randomized, waiting list-controlled clinical trial for major depressive disorder in adults (N = 24), participants were randomized to an immediate (N = 13) or delayed (N = 11) condition with two oral doses of psilocybin (20mg/70kg and 30mg/70kg). Ratings of therapeutic alliance significantly increased from the final preparation session to one-week post-intervention (p = .03, d = .43). A stronger total alliance at the final preparation session predicted depression scores at 4 weeks (r = -.65, p = .002), 6 months (r = -.47, p = .036), and 12 months (r = -.54, p = .014) post-intervention. A stronger total alliance in the final preparation session was correlated with higher peak ratings of mystical experiences (r = .49, p = .027) and psychological insight (r = .52, p = .040), and peak ratings of mystical experience and psychological insight were correlated with depression scores at 4 weeks (r = -.45, p = .030 for mystical; r = -.75, p < .001 for insight). Stronger total alliance one week after the final psilocybin session predicted depression scores at 4 weeks (r = -.85, p < .001), 3 months (r = -.52, p = .010), 6 months (r = -.77, p < .001), and 12 months (r = -.61, p = .001) post-intervention. These findings highlight the importance of the therapeutic relationship in PAT. Future research should explore therapist and participant characteristics which maximize the therapeutic alliance and evaluate its relationship to treatment outcomes. Trial registration: Registration: Clinicaltrials.gov NCT03181529. https://classic.clinicaltrials.gov/ct2/show/NCT03181529., Competing Interests: AKD and RL are on the board of Source Research Foundation. RRG is on the board of the Heffter Research Institute. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Levin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study evaluated prospective associations of ibogaine and 5-MeO-DMT treatment for risky alcohol use and post-traumatic stress disorder (PTSD) symptoms among United States (US) Special Operations Forces Veterans (SOFV). Data were collected during standard clinical operations at pre-treatment and 1-month (1 m), 3-months (3 m), and 6-months (6 m) post-treatment in an ibogaine and 5-MeO-DMT treatment program in Mexico. Of the 86 SOFV that completed treatment, 45 met criteria for risky alcohol use at pre-treatment (mean age = 44; male = 100%; White = 91%). There was a significant reduction in alcohol use from pre-treatment (M = 7.2, SD = 2.3) to 1 m (M = 3.6; SD = 3.5) post-treatment, which remained reduced through 6 m (M = 4.0; SD = 2.9; p < .001, partial eta squared = .617). At 1 m, 24% were abstinent, 33% were non-risky drinking, and 42% were risky drinkers. At 6 m, 16% were abstinent, 31% were non-risky drinking, and 53% were risky drinkers. There were no differences between responders (abstinent/non-risky drinkers) and non-responders (risky drinkers) in demographics/clinical characteristics. However, there were significant and very large differences between responders and non-responders in PTSD symptom (p < .01, d = -3.26) and cognitive functioning change (p < .01, d = -0.99). Given these findings, future clinical trials should determine whether psychedelic-assisted therapy holds promise for individuals with complex trauma and alcohol misuse who have not been successfully treated with traditional interventions.

Qualitative studies and anecdotal reports suggest that experiences with ayahuasca, a psychedelic brew found in Central and South America, may be followed by individuals enduringly feeling more grateful and connected to nature. Yet, to date, these changes have been understudied. Here, participants ( N  = 54) completed validated surveys related to gratitude, nature relatedness, and nature appreciation one-week before, one-week after, and one-month after attending an ayahuasca retreat center. Compared to baseline, there was a significant increase in gratitude, nature relatedness, and nature appreciation at the one-week and one-month follow-ups. Ratings of mystical-type experiences and awe, but not ego dissolution, during participants' ayahuasca sessions were weakly-to-moderately correlated with these increases. The number of ayahuasca ceremonies attended at the retreat was not related to change in outcomes, underscoring the importance of the quality rather than the quantity of the experiences in post-acute change. Lastly, participant age was negatively related to the occurrence of mystical-type experiences and awe, supporting literature indicating blunted psychedelic effects with increased age. In the context of study limitations, the results suggest that mystical-type experiences and awe occasioned by ayahuasca may be linked to prosocial changes in gratitude and relationships with nature that may be beneficial to mental health.

Amphibian declines are a global phenomenon but responses of populations to specific threats are often context dependent and mediated by individual physiological condition. Habitat degradation due to reduced riparian forest cover and parasitism are two threats facing the hellbender salamander ( Cryptobranchus alleganiensis ), but their potential to interact in nature remains largely unexplored. We investigated associations between forest cover, parasitic infection and physiology of hellbenders to test the hypotheses that physiological condition responds to infection and/or habitat degradation. We sampled 17 stream reaches in southwest Virginia, USA, on a year-round basis from 2013 to 2016 and recorded 841 captures of 405 unique hellbenders. At each capture we documented prevalence of two blood-associated parasites (a leech and trypanosome) and quantified up to three physiological condition indices (body condition, hematocrit, white blood cell [WBC] differentials). We used generalized linear mixed models to describe spatiotemporal variation in parasitic infection and each condition index. In general, living in the most heavily forested stream reaches, where hellbender density was highest, was associated with the greatest risk of parasitism, elevated neutrophil-to-lymphocyte (N:L) ratios and eosinophils, slightly lower hematocrit and lower mean body condition in hellbenders. All condition indices fluctuated temporally in a manner consistent with seasonal variation in hellbender metabolic demands and breeding phenology and were associated with land use during at least part of the year. Paradoxically, relatively low levels of forest cover appeared to confer a potential advantage to individuals in the form of release from parasites and improved body condition. Despite improved body condition, individuals from less forested areas failed to exhibit fluctuating body condition in response to spawning, which was typical in hellbenders from more forested habitats. We postulate this lack of fluctuation could be due to reduced conspecific competition or reproductive investment and/or high rates of filial cannibalism in response to declining forest cover., (© The Author(s) 2024. Published by Oxford University Press and the Society for Experimental Biology.)

Introduction: We examined whether the Dualistic Model of Passion (DMP; i.e., obsessive passion [OP] and harmonious passion [HP]) for cannabis use was prospectively associated with cannabis use and use-related outcomes, and with academic performance, relationship attachment style, and social connectedness among college students. We also explored whether the DMP was associated with outcomes when included in a model using established constructs (e.g., coping motives, refusal self-efficacy, cannabis use disorder [CUD] symptoms) as predictors of cannabis use and outcomes., Methods: Using a longitudinal cohort design (baseline, 5-month, 10-month [timepoints chosen to better correspond to 9-month academic year]), 513 undergraduate students from two universities who reported using cannabis at least four times in the past month completed a baseline survey (308 meeting criteria for CUD). We used Generalized Estimating Equations to assess longitudinal associations between OP/HP and cannabis use and academic/social outcomes at 5-month and 10-month., Results: At baseline, participants were young adults (Mean age = 20.57, SD = 2.51), 78.8% non-Hispanic, 83.8% White, 55.0% female, and 72.3% heterosexual. Greater HP was not associated with greater past month cannabis use or cannabis-related problems. Greater OP was associated with greater past month cannabis use and more cannabis-related problems. There were no significant passion by time interactions. Greater HP was associated with more anxious attachment. OP was associated with less social connection., Conclusion: This research suggests that the DMP provides novel information about factors associated with cannabis use and use-related consequences, which can aid in our understanding of cannabis use, misuse, and CUD among college students., (© 2023 Authors et al.)

mTOR, as a serine/threonine kinase, is a widely pursued anticancer target. Multiple clinical trials of mTOR kinase inhibitors are ongoing, but their specificity and safety features remain lacking. Here, we have employed an inducible kinase-inactive D2338A mTOR knock-in mouse model (mTOR -/KI ) together with a mTOR conditional knockout model (mTOR -/- ) to assess the kinase-dependent/-independent function of mTOR in hematopoiesis and the on-/off-target effects of mTOR kinase inhibitor AZD2014. Despite exhibiting many similar phenotypes to mTOR -/- mice in hematopoiesis, the mTOR -/KI mice survived longer and showed differences in hematopoietic progenitor cells compared to mTOR -/- mice, suggesting a kinase-independent function of mTOR in hematopoiesis. Gene expression signatures in hematopoietic stem cells (HSCs) further revealed both kinase-dependent and independent effects of mTOR. AZD2014, a lead mTOR kinase inhibitor, appeared to work mostly on-target in suppressing mTOR kinase activity, mimicking that of mTOR -/KI HSCs in transcriptome analysis, but it also induced a small set of off-target responses in mTOR -/KI HSCs. In murine and human myeloid leukemia, besides kinase-inhibitory on-target effects, AZD2014 displayed similar off-target and growth-inhibitory cytostatic effects. These studies provide new insights into kinase-dependent/-independent effects of mTOR in hematopoiesis and present a genetic means for precisely assessing the specificity of mTOR kinase inhibitors., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Research in psychedelic medicine has focused primarily on civilian populations. Further study is needed to understand whether these treatments are effective for Veteran populations. Objectives: Here, we examine the effectiveness of psychedelic-assisted therapy among trauma-exposed Special Operations Forces Veterans (SOFV) seeking treatment for cognitive and mental health problems in Mexico. Methods: Data were collected from an ibogaine and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) clinical treatment program for SOFV with a history of trauma exposure. This clinical program collects prospective clinical program evaluation data, such as background characteristics, symptom severity, functioning (e.g., satisfaction with life, posttraumatic stress disorder symptoms, depression symptoms, anxiety symptoms, sleep disturbance, psychological flexibility, disability in functioning, cognitive functioning, neurobehavioral symptoms, anger, suicidal ideation), and substance persisting/enduring effects through online surveys at four timepoints (baseline/pre-treatment, one-, three-, and six-months after treatment). Results: The majority of the sample ( n  = 86; Mean Age = 42.88, SD = 7.88) were Caucasian (87.2%), non-Hispanic (89.5%), and males (100%). There were significant and large improvements in self-reported PTSD symptoms ( p  < .001, d = .414), depression ( p  < .001, d = .275), anxiety ( p  < .001, d = .276), insomnia severity ( p  < .001, d = .351), and post-concussive symptoms ( p  < .001, d = .389) as well as self-reported satisfaction with life ( p  < .001, d = .371), psychological flexibility ( p  < .001, d = .313) and cognitive functioning ( p  < .001, d = .265) from baseline to one-month follow-up. Conclusions: Data suggest combined ibogaine and 5-MeO-DMT assisted therapy has potential to provide rapid and robust changes in mental health functioning with a signal of durable therapeutic effects up to 6-months. Future research in controlled settings is warranted.

We conducted a meta-analysis using individual participant data from three, two-dose psilocybin trials for depression (N = 102) with the aim of assessing the risk of symptom worsening. Clinically significant symptom worsening occurred for a minority of participants in the psilocybin and escitalopram conditions (∼10%) and for a majority of participants in the waitlist condition (63.6%). Using data from the two trials with control arms, the psilocybin arm showed a lower likelihood of symptom worsening versus waitlist, and no difference in the likelihood of symptom worsening versus escitalopram. The limitation of a relatively small sample size should be addressed in future studies., Competing Interests: Declaration of Competing Interest The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: OS was a co-founder of Eudelics AB. RCH is a scientific advisor to Synthesis Institute, Osmind, Journey Colab, Maya Health, Mydecine, Beckley Psytech and Mindstate. AKD is a board member of Source Research Foundation and Lead Training at Fluence. DJN is a scientific advisor to COMPASS Pathways who have an interest in psilocybin therapy for depression. He is also chair or PAREA (Psychedelic access and research European alliance) and a member of the UK Drug Science charity's Medical Psychedelic Working Group. DE is a scientific advisor to Clerkenwell Health, Aya Biosciences, Field Trip Health, Mindstate, Pangea Botanica, and Smallpharma LTD. RRG is on the Board of Directors of the Heffter Research Institute. All other authors declare that there is no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Traumatic brain injury (TBI) is a complex condition common among individuals treated in behavioral healthcare, but TBI screening has not been adopted in these settings which can affect optimal clinical decision-making. Integrating evidence-based practices that address complex health comorbidities into behavioral healthcare settings remains understudied in implementation science, limited by few studies using theory-driven hypotheses to disentangle relationships between proximal and medial indicators on distal implementation outcomes. Grounded in the Theory of Planned Behavior, we examined providers' attitudes, perceived behavioral control (PBC), subjective norms, and intentions to adopt The Ohio State University TBI Identification Method (OSU TBI-ID) in behavioral healthcare settings., Methods: We used an explanatory sequential mixed-methods design. In Phase I, 215 providers from 25 organizations in the USA completed training introducing the OSU TBI-ID, followed by a survey assessing attitudes, PBC, norms, and intentions to screen for TBI. After 1 month, providers completed another survey assessing the number of TBI screens conducted. Data were analyzed using structural equation modeling (SEM) with logistic regressions. In Phase II, 20 providers were purposively selected for semi-structured interviews to expand on SEM results. Qualitative data were analyzed using thematic analysis, integrated with quantitative results, and combined into joint displays., Results: Only 25% (55/215) of providers adopted TBI screening, which was driven by motivations to trial the intervention. Providers who reported more favorable attitudes (OR: 0.67, p < .001) and greater subjective norms (OR: 0.12, p < .001) toward TBI screening demonstrated increased odds of intention to screen, which resulted in greater TBI screening adoption (OR: 0.30; p < .01). PBC did not affect intentions or adoption. Providers explained that although TBI screening can improve diagnostic and clinical decision-making, they discussed that additional training, leadership engagement, and state-level mandates are needed to increase the widespread, systematic uptake of TBI screening., Conclusions: This study advances implementation science by using theory-driven hypothesis testing to disentangle proximal and medial indicators at the provider level on TBI screening adoption. Our mixed-methods approach added in-depth contextualization and illuminated additional multilevel determinants affecting intervention adoption, which guides a more precise selection of implementation strategies., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: Campus sexual assault (SA) prevention programs are widely implemented, despite few having strong empirical support. To inform the development and refinement of prevention programs, we collected pilot qualitative data to capture undergraduates' perspectives regarding desirable program characteristics., Participants: Undergraduates completed an audio-taped interview (n = 19) or a focus group (n = 16) in June - November 2016., Methods: We double-coded transcripts for a priori and emerging themes using NVivo 11. A third coder resolved disagreements; we assessed intercoder reliability using Cohen's Kappa., Results: Participants preferred SA prevention programming to be delivered in-person to small, coed groups of unfamiliar students. Students preferred programming with peer-facilitated, candid conversation about SA outcomes and prevention strategies. Participants also preferred for the tone of these training sessions to match the serious subject matter., Conclusions: Students' perceptions of desirable program characteristics differ somewhat from current evidence-based programs in several ways, highlighting important future directions for SA prevention research.

Elucidating the adaptations that promote flight in animals can aid the understanding of evolution and species divergence, and/or provide inspiration for aerospace engineering and the design of better aerial vehicles. The famed long-distance migration of monarch butterflies in North America still holds many questions and opportunities for inspiration. For example, there is little research on whether the monarch's primary wing colors themselves (black, orange, or white) have any aerodynamic or migration function. Dark colors on wings of other animals have recently been shown to aid flight by enhancing solar absorption, which reduces drag forces. However, too much black surface could be problematic for monarchs, which are exposed to increasing amounts of solar energy along their flightpath. This paper describes the results of two related investigations that attempt to elucidate the importance of wing color to the monarch migration. By measuring the color proportions of nearly 400 monarch wings collected at different stages of their journey, we found, surprisingly, that successful migrants tended to have less black on their wings (about 3% less), but also more white pigment (about 3% more); monarchs have a band of light-colored marginal wing spots. Second, image analysis of museum specimens revealed migratory monarchs had significantly larger white spots, proportional to the wing area, than most non-migratory, New World Danaid butterflies, which argues spot size has evolved along with migratory behavior. Combined, these findings strongly suggest that the long-distance migration itself selects for larger white spots every fall, so that only those individuals with large spots will survive to pass on their genes. Further experimental work is needed to elucidate how the spots aid the migration, but it is possible that they enhance aerodynamic efficiency; other work by the authors demonstrates how alternating white and black pigment on wings can reduce drag. These results will serve as a useful starting point for such endeavors, which should improve understanding of one of the world's most fascinating animal migrations, and also provide practical knowledge for the field of aerospace engineering., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Davis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

As a transcription factor in the RUNT domain core-binding factor family, RUNX1 is crucial in multiple stages of hematopoiesis, and its mutation can cause familial platelet disorder with a predisposition to acute myeloid leukemia. Previous work has established that RUNX1 is involved in the maturation of megakaryocytes (MKs) and the production of platelets. Recent studies have shown that there exists a subpopulation of hematopoietic stem cells (HSCs) with relatively high expression of von Willebrand factor and CD41 at the apex of the HSC hierarchy, termed MK-HSCs, which can give rise to MKs without going through the traditional differentiation trajectory from HSC via MPP (multipotent progenitors) and MEP (megakaryocyte-erythroid progenitor). Here, by using Runx1F/FMx1-Cre mouse model, we discovered that the MK-HSC to MK direct differentiation can occur within 1 cell division, and RUNX1 is an important regulator in the process. Runx1 knockout results in a drastic decrease in platelet counts and a severe defect in the differentiation from MK-HSCs to MKs. Single cell RNA sequencing (RNAseq) analysis shows that MK-HSCs have a distinct gene expression signature compared with non-MK-HSCs, and Runx1 deletion alters the platelet and MK-related gene expression in MK-HSCs. Furthermore, bulk RNAseq and Cut&Run analyses show that RUNX1 binds to multiple essential MK or platelet developmental genes, such as Spi1, Selp, and Itga2b and regulates their expressions in MK-HSCs. Thus, by modulating the expression of MK-related genes, RUNX1 governs the direct differentiation from MK-HSCs to MKs and platelets., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Introduction: Evidence suggests that psychedelics may serve as a therapeutic approach to reduce substance use; however, people with racial and ethnic minoritized (REM) identities are often excluded from this research. We investigated whether psychedelic use affects other substance use among REM people and whether perceived changes in psychological flexibility and racial trauma mediates this association., Methods: REM people in the United States and Canada (N = 211; 32 % Black, 29 % Asian, 18 % American Indian/Indigenous Canadian, 21 % Native Hawaiian/Pacific Islander; 57 % female; mean age = 33.1, SD = 11.2) completed an online survey retrospectively reporting their substance use, psychological flexibility, and racial trauma symptoms 30 days before and after their most memorable psychedelic experience., Results: Analyses showed a significant perceived reduction in alcohol (p < .0001, d = 0.54) and drug use (p = .0001, d = 0.23) from before to after the psychedelic experience. Preliminary associations found perceived reductions in racial trauma symptoms were associated with perceived reductions in alcohol use and this association varied by race, dose, ethnic identity, and change in depressive symptoms. Specifically, Indigenous participants experienced greater perceived reductions in alcohol use relative to participants who identified as Asian, Black, or other. Those who took a high dose of psychedelics experienced greater perceived reductions in alcohol use relative to those who took a low dose. Participants with a stronger ethnic identity and those with a perceived reduction in depressive symptoms experienced a perceived reduction in alcohol use. Serial mediation indicated a perceived increase in psychological flexibility and reduction in racial trauma symptoms mediated the association between acute psychedelic effects and perceived reductions in alcohol and drug use., Conclusion: These findings suggest that psychedelic experiences may contribute to an increase in psychological flexibility and reduction in racial trauma symptoms and alcohol and drug use among REM people. REM people have been largely excluded from psychedelic treatment research even though psychedelic use is considered a traditional healing practice in many communities of color. Longitudinal studies of REM people should replicate our findings., Competing Interests: Declaration of competing interest MW and AKD are on the board of directors at Source Research Foundation. AKD is a lead trainer at Fluence. Neither organization was financially involved in this study., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Paroxysmal nocturnal haemoglobinura is an acquired life-threatening haemolytic condition, which is generally well controlled with terminal complement blockade with eculizumab. Whilst almost all patients treated with terminal complement inhibitors develop extravascular haemolysis, only a small proportion of these results in symptomatic anaemia limiting their activities and requiring red cell transfusion. This case highlights the potential role for the C3 inhibitor, pegcetacoplan, in controlling both intravascular and extravascular haemolysis, and is the first case to report on the use of additional doses of pegcetacoplan to control breakthrough haemolysis., Competing Interests: AKD: advisory board membership for Sobi. JS: consultancies, advisory board membership and speaker for Alexion, Apellis, Sobi, Novartis, Takeda, Pfizer. NB has nothing to declare., (© 2023 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Introduction: Psilocybin-assisted therapy has shown significant promise in treating the cluster of mood and anxiety symptoms that comprise post-traumatic stress disorder (PTSD) but has yet to be tested specifically in this condition. Furthermore, current pharmacological and psychotherapeutic treatments for PTSD are difficult to tolerate and limited in efficacy, especially in the US Military Veteran (USMV) population. This open-label pilot study will examine the safety and efficacy of two psilocybin administration sessions (15 mg and 25 mg), combined with psychotherapy, among USMVs with severe, treatment resistant PTSD., Methods and Analysis: We will recruit 15 USMVs with severe, treatment resistant PTSD. Participants will receive one low dose (15 mg) and one moderate/high dose (25 mg) of psilocybin in conjunction with preparatory and post-psilocybin therapy sessions. The primary safety outcome will be the type, severity and frequency of adverse events and suicidal ideation/behaviour, as measured by the Columbia Suicide Severity Rating Scale. The primary outcome measure for PTSD will be the Clinician Administered PTSD Scale-5. The primary endpoint will be 1 month following the second psilocybin administration session, and the total follow-up time will be 6 months., Ethics and Dissemination: All participants will be required to provide written informed consent. The trial has been authorised by the Ohio State University Institutional Review Board (study number: 2022H0280). Dissemination of results will occur via a peer-reviewed publication and other relevant media., Trial Registration Number: NCT05554094., Competing Interests: Competing interests: AKD and RLL are board members of Source Research Foundation. This organisation was not involved in the design/execution of this study or the interpretation or communication of findings. AKD is a lead trainer at Fluence., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Some animals react to predation threats or other stressors by adopting a freezing posture in an attempt to avoid detection, and the duration of this behavior usually corresponds with individual personality, such that timid individuals freeze longer. Despite decades of research on this or related behaviors (thanatosis), never has the impact of parasitism been considered. Parasites could prolong the duration, if hosts are less motivated to move (i.e. lethargic), or they could reduce it, if hosts are motivated to forage more to compensate for energy drain. We examined this behavior within a natural beetle-nematode system, where hosts (horned passalus beetles, Odontotaenius disjunctus) are parasitized by a nematode, Chondronema passali. We exposed beetles (n = 238) to four stressors in our lab, including noise, vibration, light and inversion, and recorded how long they adopt a frozen stance. Afterward, we determined nematode burdens, which can range from dozens to hundreds of worms. Beetles tended to freeze for 20 seconds on average, with some variation between stressors. We detected no effect of beetle mass on the duration of freezing, and this behavior did not differ in beetles collected during the breeding or non-breeding season. There was a surprising sex-based difference in the impact of nematodes; unparasitized females remained frozen twice as long as unparasitized males, but for beetles with heavy nematode burdens, the opposite was true. From this we infer that heavily parasitized females are more bold, while males with heavy burdens would be more timid. The explanation for this finding remains elusive, though we can rule out many possibilities based on prior work on this host-parasite system., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Davis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Subjective experiences seem to play an important role in the enduring effects of psychedelic experiences. Although the importance of the subjective experience on the impact of psychedelics is frequently discussed, a more detailed understanding of the subtypes of psychedelic experiences and their associated impacts on mental health has not been well documented., Methods: In the current study, machine learning cluster analysis was used to derive three subtypes of psychedelic experience in a large (n = 985) cross sectional sample., Results: These subtypes are not only associated with reductions in anxiety and depression symptoms and other markers of psychological wellbeing, but the structure of these subtypes and their subsequent impact on mental health are highly reproducible across multiple psychedelic substances., Limitations: Data were obtained via retrospective self-report, which does not allow for definitive conclusions about the direction of causation between baseline characteristics of respondents, qualities of subjective experience, and outcomes., Conclusions: The present analysis suggests that psychedelic experiences, in particular those that are associated with enduring improvements in mental health, may be characterized by reproducible and predictable subtypes of the subjective psychedelic effects. These subtypes appear to be significantly different with respect to the baseline demographic characteristics, baseline measures of mental health, and drug type and dose. These findings also suggest that efforts to increase psychedelic associated personal and mystical insight experiences may be key to maximizing beneficial impact of clinical approaches using this treatment in their patients., Competing Interests: Conflict of interest AKD and RL are board members at Source Research Foundation. AKD is a lead trainer at Fluence. RRG is a board member at Heffter Research Institute., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Assessing numbers of leukocytes in salamanders and other amphibians can be useful metrics for understanding health or stress levels of individuals in a population. In this chapter we describe the procedures for obtaining blood samples from amphibians, preparing blood films for microscopy, counting, and identifying cells. We also provide reference values for amphibian leukocytes for use in interpreting leukocyte data. From our assessment of the published and unpublished literature, "non-stressed" salamanders would have a leukocyte profile where 60-70% of cells are lymphocytes, 17-30% are neutrophils, 1-4% are eosinophils, 4-12% are basophils, and 2-6% are monocytes. In Ambystoma spp., the eosinophil abundance can be notably higher (30% of all white blood cells), for reasons unknown. Finally, the neutrophil-lymphocyte ratio of most non-stressed salamanders tends to be between 0.3 and 0.4 (sometimes less), while the ratios of stressed salamanders tend to be over 1.0., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Fibromyalgia (FM) is a difficult to treat chronic pain condition for which there is strong interest in alternative treatments. There is growing interest in the potential of psychedelic substances (e.g., psilocybin) in conjunction with psychotherapy to treat chronic pain. Via a cross-sectional, anonymous, online survey, we aimed to characterize knowledge, perceptions, and past use of serotonergic ("classic") and non-serotonergic psychedelics among a population of individuals with FM, and to investigate interest in psychedelic-based FM treatments. Among a North American population of 354 participants with FM, 29.9% reported past use of a psychedelic, with lysergic acid diethylamide (LSD) and psilocybin mushrooms being most commonly used. Perceptions of benefit from psychedelic use were generally neutral (59.4%) or positive (36.8%), with <3% reporting negative impacts on overall health or pain symptoms. Among 12 participants who used psychedelics with intentions of treating chronic pain, 11 reported improved symptoms. Regardless of past use, the majority of participants believed that psychedelics have potential for chronic pain treatments and would be willing to participate in a psychedelic-based clinical trial for their pain. These findings support the need for additional studies to understand the potential and effectiveness of psychedelic substances in managing FM symptoms.

There is a need to understand ways in which Asians in North America attempt to heal from racial trauma, given their well-documented high risk of exposure and associated adverse mental health outcomes. We conducted a secondary analysis of Asians from a survey of people of color in North America who have consumed psychedelics in response to racial discrimination. Ninety-two Asian participants ( M age  = 30.25, SD  = 6.83) completed online questions assessing demographics, racial discrimination frequency, characteristics and acute effects of their most meaningful psychedelic experience, change in racial trauma symptoms 30 days before and after their psychedelic experience, and current ethnic identity. Participants reported improvements in racial trauma symptoms ( d = 0.52). Bootstrapped mediation analyses controlling for racial discrimination frequency and psychedelic dose and duration indicated complete mediation of the link between higher intensity of insightful experiences and stronger ethnic identity, via improvements in racial trauma symptoms (indirect effect = .08, 95% CI = [.004, .19]). There was partial mediation for the independent variable of lower intensity of challenging experiences (indirect effect = -.08, 95% CI = [-.18, -.005]). This study highlights the central role of higher-intensity insightful experiences and both higher- and lower-intensity challenging experiences in alleviating racial trauma symptoms and promoting ethnic identity among Asians in North America who have experienced racial discrimination. Future research should attune to culturally relevant outcomes of psychedelic use in response to racial discrimination among Asians.

Problematic substance use (SU) is a significant issue among LGBTQ+ individuals, but rates of treatment/help-seeking in this population remain low. This review aimed to investigate literature about intersectional stigma of SU and LGBTQ+ identity and its impact on SU help-seeking behaviours in the U.S. Eligible studies from eight-database were included if peer-reviewed, in English, from the U.S., published between 2000 and 2022, focused on SU, stigma, SU help-seeking behaviours, among LGBTQ+ adults. Of 458 search results, 50 underwent full-text review, 12 were included in the final sample. Minority Stress Theory emerged as a relevant theoretical framework. Findings revealed that increased SU as a coping strategy was associated with minority stress. Intersectional stigma negatively impacted SU treatment experience among LGBTQ+ individuals, leading to avoidance of help-seeking or poor treatment outcomes. Patterns of SU and impact of stigma among LGBTQ+ individuals differ, wherein bisexual and transgender individuals reported significantly more treatment barriers and unique stressors. LGBTQ+ individuals reported earlier age of SU onset and were more likely to encounter opportunities for SU. This review highlights the impact of intersectional stigma on SU help-seeking behaviour among LGBTQ+ individuals in the U.S. Recommendations are provided for future clinical practice, research, and policy to better support LGBTQ+ individuals.

The alleged prevalence of anti-gay bias among Black communities in the United States has received ample popular and academic attention in recent decades. But just how consistent is the purported relationship between race and homophobia? In this paper, we use the American National Election Studies and the General Social Survey to show that public claims about "Black homophobia" have been dangerously overstated. Moreover, where racial differences in attitudes toward same-gender sexuality do occur, we find that the two most prevalent scholarly explanations for such gaps-religious institutions and gender ideologies-do not predict anti-gay bias for Black survey respondents. We thus derive an alternative explanation from scholarship on group threat: that perceived competition for political resources is what motivates racial differences in antagonism toward same-gender sexuality. Our results support that alternative and, in so doing, evince the importance of a relational approach to homophobia in academic and activist spheres alike.

Monarch butterflies in North America have an exceptionally large breeding distribution, occupying regions west of the Rocky Mountains and throughout the eastern seaboard. An experimental study conducted 17 years ago and published in this journal appeared to show that western monarch larvae tend to have smaller black stripes than those from eastern parents, which at the time was thought to be an adaptation to higher solar exposure in California. Here, we revisit this question by measuring melanism of eastern and western larvae from online photographs submitted to iNaturalist by members of the public. We downloaded over 500 photos of larvae from 10 different states (4 in the west, 6 in the east) and used image analysis to quantify the size of each larva's black stripes (% of surface covered by black). We compared average melanism level between east and west, while also accounting for temperature (at the photo location), seasonal effects, and latitude. Results showed larvae tended to be darker with lower development temperatures, and later in the season, though there was no significant difference between eastern and western larvae in their degree of melanism. It is not yet clear why findings here were different from the prior experimental study. Also, the wild larvae appeared to be notably lighter in color than the captive-reared larvae of the original study, suggesting that the captive environment does not truly replicate the developmental experience of wild larvae, at least in terms of cuticular development. Thus, if there truly are innate tendencies for western larvae to differ (morphologically) from eastern, they are not observable in nature., Competing Interests: Declaration of competing interest The authors declare there are no competing interests., (Copyright © 2022. Published by Elsevier Ltd.)

Background: The psychedelic 5-MeO-DMT has shown clinical potential due to its short duration and ability to induce mystical experiences. However, a phenomenon known as "reactivations" (similar to "flashbacks") is a poorly understood and frequently reported phenomenon which appears associated with 5-MeO-DMT use and warranted further investigation., Aims: This study examined whether differences in age, gender, education, lifetime use, use location, and preparation strategies predict reactivations (primary outcome). Additionally, we explored how reactivations were perceived by survey respondents and whether demographic data predicted emotional valence (secondary outcome) of reported reactivations., Materials and Methods: This study used secondary quantitative data from a survey assessing epidemiological and behavioral associations of 5-MeO-DMT use in non-clinical settings ( N = 513). Descriptive statistics, chi-square tests, t -tests, and logistic regressions were utilized to explore aims., Results: Being female, older at the time of first 5-MeO-DMT dose, having higher educational attainment, and dosing in a structured group setting were associated with increased odds of reporting a reactivation event. Higher mystical experience scores, greater personal wellbeing and having had a non-dual awareness experience that was not substance-induced were associated with higher likelihood of reporting a neutral or positive emotional valence of a reactivation event., Conclusion: These findings suggest that reactivation phenomena, in this particular sample may most often represent a neutral or positive byproduct of the acute 5-MeO-DMT experience. More information is needed to best identify individuals most likely to experience a reactivation as a negative event to prevent such potential challenging outcomes., Competing Interests: Author CLR serves as a consultant for Usona Institute, Emory Healthcare, Alfasigma, and Novartis. Authors AKD and RLL were board members at Source Research Foundation and AKD was a lead trainer at Fluence. These organizations were not involved in the design/execution of this study or the interpretation or communication of findings. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ortiz Bernal, Raison, Lancelotta and Davis.)

An invasive spider ( Trichonephila clavata [L. Koch 1878], or jorō spider) is rapidly expanding throughout the southeast of the United States, engendering many questions about how native fauna will be affected. Here, we describe an observation of a northern cardinal ( Cardinalis cardinalis , L.) consuming prey items from a jorō web, which serves as an example of a native species deriving a (small) benefit from this new invader. Moreover, the manner of the kleptoparasitism is also noteworthy; the cardinal perched directly on the web, which supported its weight (which is 42-48 g in this species). This appears to be the first documented case of a spider web supporting a perching bird. We also include measurements of other jorō webs, where web strength had been assessed using a force gauge, which revealed that typical webs can support masses up to 70 g before collapsing. Collectively, this information adds to the small but growing body of knowledge about the biology of this non-native spider.

Background: Cancer immunotherapy has taken center stage in cancer treatment. However, the current immunotherapies only benefit a small proportion of patients with cancer, necessitating better understanding of the mechanisms of tumor immune evasion and improved cancer immunotherapy strategies. Regulatory T (Treg) cells play an important role in maintaining immune tolerance through inhibiting effector T-cell function. In the tumor microenvironment, Treg cells are used by tumor cells to counteract effector T cell-mediated tumor suppression. Targeting Treg cells may thus unleash the antitumor activity of effector T cells. While systemic depletion of Treg cells can cause excessive effector T-cell responses and subsequent autoimmune diseases, controlled targeting of Treg cells may benefit patients with cancer., Methods: Treg cells from Treg cell-specific heterozygous Cdc42 knockout mice, C57BL/6 mice treated with a Cdc42 inhibitor CASIN, and control mice were examined for their homeostasis and stability by flow cytometry. The autoimmune responses in Treg cell-specific heterozygous Cdc42 knockout mice, CASIN-treated C57BL/6 mice, and control mice were assessed by H&E staining and ELISA. Antitumor T-cell immunity in Treg cell-specific heterozygous Cdc42 knockout mice, CASIN-treated C57BL/6 mice, humanized NSGS mice, and control mice was assessed by challenging the mice with MC38 mouse colon cancer cells, KPC mouse pancreatic cancer cells, or HCT116 human colon cancer cells., Results: Treg cell-specific heterozygous deletion or pharmacological targeting of Cdc42 with CASIN does not affect Treg cell numbers but induces Treg cell instability, leading to antitumor T-cell immunity without detectable autoimmune reactions. Cdc42 targeting causes an additive effect on immune checkpoint inhibitor anti-programmed cell death protein-1 antibody-induced T-cell response against mouse and human tumors. Mechanistically, Cdc42 targeting induces Treg cell instability and unleashes antitumor T-cell immunity through carbonic anhydrase I-mediated pH changes., Conclusions: Rational targeting of Cdc42 in Treg cells holds therapeutic promises in cancer immunotherapy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Evidence points to an incongruence between international drug policy and expert opinion about safety, abuse potential, and therapeutic potential of specific drugs. However, no prior studies have directly explored psychiatrists' attitudes about the current drug schedule. Therefore, we examined whether American psychiatrists' perceptions of four psychoactive drugs differed from those indicated by their schedules., Methods: A quasi-experimental online survey of a convenience sample of psychiatrists in the United States (N=181; Mean age=48.7; Female=35%). Participants were randomized to receive 1-of-4 vignettes, each depicting a depressed patient reporting relief from symptoms after non-prescribed psychoactive drug use (i.e., psilocybin [Schedule I], methamphetamine [SchedII], ketamine [SchedIII], or alprazolam [SchedIV]). Participants responded to questions related to this clinical scenario and then rated the safety, therapeutic, and abuse potentials of these four drugs and alcohol., Results: There were significant differences by vignette condition in mean likelihood ratings of: warning against engaging in drug use again (p<.01), being concerned about developing a new psychiatric problem (p<.001), being concerned about increased suicide risk (p<.01) and being supportive of further use of this drug as part of the treatment plan (p<.001). Overall, non-prescribed use of methamphetamine and alprazolam was rated more concerning and less acceptable than non-prescribed use of psilocybin and ketamine. Compared to psilocybin and ketamine, participants rated methamphetamine and alprazolam as less safe (p<.001), having less therapeutic potential (p<.001), and having more abuse potential (p<.001). Mean ratings of safety and abuse/therapeutic potential of alprazolam and methamphetamine were equivalent to that of alcohol, and all three were rated more harmful than psilocybin and ketamine., Conclusion: American psychiatrists' perceptions about safety and abuse/therapeutic potentials associated with certain psychoactive drugs were inconsistent with those indicated by their placement in drug schedules. These findings add to a growing consensus amongst experts that the current drug policy is not scientifically coherent., Competing Interests: Declarations of Interest AKD is a board member of Source Research Foundation. This organization was not involved in the design/execution of this study or the interpretation or communication of findings., (Copyright © 2022. Published by Elsevier B.V.)

Psychologists are a vital component of mental health treatment and their perceptions of psychedelic-assisted therapy are critical for future implementation. This cross-sectional quasi-experimental electronic survey study explored the attitudes about psychedelics used in treatment among 366 clinical psychologists in the United States. Participants expressed cautiously favorable attitudes toward therapeutic psychedelic experiences but indicated concern about possible psychiatric and neurocognitive risks. Most participants indicated that they lack an understanding of the full range of effects of psychedelics, would need to seek out additional consultation, and endorsed positive beliefs in the potential of psychedelic treatment and the need for further research. Overall, this research identified the need to increase education and training about psychedelics for psychologists in order to help increase knowledge and reduce stigma about psychedelic therapies.

Background and Aims: There is growing evidence that psilocybin, a serotonergic psychedelic substance, may be useful in the treatment of substance use disorders. However, there is a lack of data on the beliefs and attitudes towards psilocybin amongst Black individuals diagnosed with Opioid Use Disorder (OUD). This study characterized psilocybin use patterns and perception of risk amongst a cohort of Black individuals diagnosed with OUD., Methods: Using a convenience sampling approach, patients were recruited from an urban methadone treatment program and paid five dollars to complete an anonymous phone-based survey., Results: Twenty-eight patients participated (mean age 53.8; N = 28; 35.7% female). Most ( N = 23; 82.1%) had "heard of" psilocybin mushrooms before taking the survey, but only five ( N = 5; 17.8%) had ever used them. More than 80% perceived a risk or were "unsure" of the risk for sixteen of the seventeen items queried about psilocybin. Approximately half ( N = 15; 53.6%) were willing to try therapy incorporating psilocybin and half ( N = 14; 50%) said they would be more likely to try if it were FDA approved for OUD. Most ( N = 18; 64.3%) preferred to stay on methadone treatment alone, 32.1% ( N = 9) wanted to try treatment with both psilocybin and methadone, and only one participant opted for psilocybin treatment without methadone., Conclusion: Many Black individuals with Opioid Use Disorder perceive psilocybin as dangerous and may be hesitant to try psilocybin treatment. Culturally informed treatment models, educational interventions and community outreach programs should be developed to increase racial/ethnic minority representation in psilocybin research and treatment., Competing Interests: Disclosure of interest: AKD is a board member of Source Research Foundation. This organization was not involved in the design/execution of this study or the interpretation or communication of findings. AKD is also a member of the editorial board at the Journal. Peer review has been handled without his involvement, hence, he does not have a conflict with the review process.

Many insects are in clear decline, with monarch butterflies (Danaus plexippus) drawing particular attention as a flagship species. It is well documented that, among migratory populations, numbers of overwintering monarchs have been falling across several decades, but trends among breeding monarchs are less clear. Here, we compile >135,000 monarch observations between 1993 and 2018 from the North American Butterfly Association's annual butterfly count to examine spatiotemporal patterns and potential drivers of adult monarch relative abundance trends across the entire breeding range in eastern and western North America. While the data revealed declines at some sites, particularly the US Northeast and parts of the Midwest, numbers in other areas, notably the US Southeast and Northwest, were unchanged or increasing, yielding a slightly positive overall trend across the species range. Negative impacts of agricultural glyphosate use appeared to be counterbalanced by positive effects of annual temperature, particularly in the US Midwest. Overall, our results suggest that population growth in summer is compensating for losses during the winter and that changing environmental variables have offsetting effects on mortality and/or reproduction. We suggest that density-dependent reproductive compensation when lower numbers arrive each spring is currently able to maintain relatively stable breeding monarch numbers. However, we caution against complacency since accelerating climate change may bring growing threats. In addition, increases of summer monarchs in some regions, especially in California and in the south, may reflect replacement of migratory with resident populations. Nonetheless, it is perhaps reassuring that ubiquitous downward trends in summer monarch abundance are not evident., (© 2022 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

Purpose: Alcohol use among adolescents and emerging adults is an important public health issue requiring prevention approaches. Herein, we describe outcomes from a randomized controlled trial testing the efficacy of group-based social media interventions targeting risky drinking among youth., Procedures: Using social media advertisements to screen potential participants, we recruited 955 youth (ages 16-24) reporting recent risky drinking. After completing a baseline assessment, participants were randomized to 8-week secret Facebook group conditions: Social Media Intervention + Incentives for engagement, Social Media Intervention only, and attention-placebo control. Electronic coaches trained in motivational interviewing facilitated interaction in intervention groups. Primary outcomes include past 3-month alcohol use and consequences over 3-, 6-, and 12-month follow-ups. Secondary outcomes include other drug use, consequences, and impaired driving. We also measured intervention engagement and acceptability., Results: The interventions were well-received, with significantly greater acceptability ratings and engagement in the SMI+I condition relative to other groups. In adjusted analyses, there were no significant differences between interventions and control on alcohol-related outcomes, with all groups showing reductions. Regarding secondary outcomes (70.4% used other drugs), compared to control, the incentivized group reduced other drug use, consequences, and cannabis-impaired driving; the non-incentivized group did not significantly differ from the control condition., Conclusions: Among this predominantly poly-substance using sample, findings were mixed, with significant effects of the incentivized social media intervention on drug (but not alcohol) outcomes. Future studies are needed to further refine social media-delivered interventions to reduce alcohol and other drug use., Trial Registration: ClinicalTrials.gov NCT02809586; University of Michigan HUM#00102242., (Copyright © 2022 Elsevier B.V. All rights reserved.)

CHD8 is an ATP-dependent chromatin-remodeling factor whose monoallelic mutation defines a subtype of autism spectrum disorders (ASDs). Previous work found that CHD8 is required for the maintenance of hematopoiesis by integrating ATM-P53-mediated survival of hematopoietic stem/progenitor cells (HSPCs). Here, by using Chd8 F/F Mx1-Cre combined with a Trp53 F/F mouse model that suppresses apoptosis of Chd8 -/- HSPCs, we identify CHD8 as an essential regulator of erythroid differentiation. Chd8 -/- P53 -/- mice exhibited severe anemia conforming to congenital dyserythropoietic anemia (CDA) phenotypes. Loss of CHD8 leads to drastically decreased numbers of orthochromatic erythroblasts and increased binucleated and multinucleated basophilic erythroblasts with a cytokinesis failure in erythroblasts. CHD8 binds directly to the gene bodies of multiple Rho GTPase signaling genes in erythroblasts, and loss of CHD8 results in their dysregulated expression, leading to decreased RhoA and increased Rac1 and Cdc42 activities. Our study shows that autism-associated CHD8 is essential for erythroblast cytokinesis., Competing Interests: Declaration of interests The authors declare no competing financial interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)