PIEZO1 regulates leader cell formation and cellular coordination during collective keratinocyte migration.

The collective migration of keratinocytes during wound healing requires both the generation and transmission of mechanical forces for individual cellular locomotion and the coordination of movement across cells. Leader cells along the wound edge transmit mechanical and biochemical cues to ensuing follower cells, ensuring their coordinated direction of migration across multiple cells. Despite the observed importance of mechanical cues in leader cell formation and in controlling coordinated directionality of cell migration, the underlying biophysical mechanisms remain elusive. The mechanically-activated ion channel PIEZO1 was recently identified to play an inhibitory role during the reepithelialization of wounds. Here, through an integrative experimental and mathematical modeling approach, we elucidate PIEZO1's contributions to collective migration. Time-lapse microscopy reveals that PIEZO1 activity inhibits leader cell formation at the wound edge. To probe the relationship between PIEZO1 activity, leader cell formation and inhibition of reepithelialization, we developed an integrative 2D continuum model of wound closure that links observations at the single cell and collective cell migration scales. Through numerical simulations and subsequent experimental validation, we found that coordinated directionality plays a key role during wound closure and is inhibited by upregulated PIEZO1 activity. We propose that PIEZO1-mediated retraction suppresses leader cell formation which inhibits coordinated directionality between cells during collective migration.

A phase 1/2 study of pepinemab in children, adolescents, or young adults with recurrent or refractory solid tumors: A children's oncology group consortium report (ADVL1614).

PURPOSE: Pepinemab, a humanized IgG4 monoclonal antibody, targets the SEMA4D (CD100) antigen to inhibit binding to its high-affinity receptors (plexin B1/PLXNB1, plexin B2/PLXNB2) and low-affinity receptor (CD72). SEMA4D blockade leads to increased cytotoxic T-cell infiltration, delayed tumor growth, and durable tumor rejection in murine tumor models. Pepinemab was well tolerated and improved T cell infiltration in clinical studies in adults with refractory tumors. SEMA4D was identified as a strong candidate proto-oncogene in a model of osteosarcoma. Based on these preclinical and clinical data, we conducted a phase 1/2 study to determine the recommended phase 2 dose (RP2D), pharmacokinetics, pharmacodynamics, and immunogenicity, of pepinemab in pediatric patients with recurrent/refractory solid tumors, and activity in osteosarcoma. EXPERIMENTAL DESIGN: Pepinemab was administered intravenously on Days 1 and 15 of a 28-day cycle at 20 mg/kg, the adult RP2D. Part A (phase 1) used a Rolling 6 design; Part B (phase 2) used a Simon 2-stage design in patients with osteosarcoma. Pharmacokinetics and target saturation were evaluated in peripheral blood. RESULTS: Pepinemab (20 mg/kg) was well tolerated and no dose-limiting toxicities were observed during Part A. There were no objective responses. Two patients with osteosarcoma achieved disease control and prolonged stable disease. Pepinemab pharmacokinetics were similar to adults. CONCLUSIONS: Pepinemab (20 mg/kg) is safe, well tolerated and resulted in adequate and sustained target saturation in pediatric patients. Encouraging disease control in two patients with osteosarcoma warrants further investigation with novel combination strategies to modulate the tumor microenvironment and antitumor immune response. CLINICAL TRIAL REGISTRY: This trial is registered as NCT03320330 at Clinicaltrials.gov. DISCLAIMER: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Exploring the association between social determinants and aphasia impairment: A retrospective data integration approach.

INTRODUCTION: Traditionally, the study of aphasia focused on brain trauma, clinical biomarkers, and cognitive processes, rarely considering the social determinants of health. This study evaluates the relationship between aphasia impairment and demographic, socioeconomic, and contextual determinants among people with aphasia (PWA). METHODS: PWA indexed within AphasiaBank-a database populated by multiple clinical aphasiology centers with standardized protocols characterizing language, neuropsychological functioning, and demographic information-were matched with respondents in the Medical Expenditure Panel Survey based on response year, age, sex, race, ethnicity, time post stroke, and mental health status. Generalized log-linear regression models with bootstrapped standard errors evaluated the association between scores on the Western Aphasia Battery-Revised Aphasia Quotient (WAB-R AQ) and demographic, economic, and contextual characteristics accounting for clustering of respondents and the stratification of data collection. Region, age, and income specific models tested the sensitivity of results. RESULTS: PWA over age 60 had 2.4% (SE = 0.020) lower WAB-R AQ scores compared with younger PWA. Compared to White PWA, Black and Hispanic PWA had 4.7% (SE = 0.03) and 0.81% (SE = 0.06) lower WAB-R AQ scores, respectively, as did those and living in the Southern US (-2.2%, SE = 0.03) even after controlling for age, family size, and aphasia type. Those living in larger families (ß = 0.005, SE = 0.008), with income over $30,000 (ß = 0.017, SE = 0.022), and a college degree (ß = 0.030, SE = 0.035) had higher WAB-R AQ relative to their counterparts. Region-specific models showed that racial differences were only significant in the South and Midwest, while ethnic differences are only significant in the West. Sex differences only appeared in age-specific models. Racial and ethnic differences were not significant in the high-income group regression. CONCLUSION: These findings support evidence that circumstances in which individuals live, work, and age are significantly associated with their health outcomes including aphasia impairment.

Prison Buprenorphine Implementation and Postrelease Opioid Use Disorder Outcomes.

Importance: Agonist medications for opioid use disorder (MOUD), buprenorphine and methadone, in carceral settings might reduce the risk of postrelease opioid overdose but are uncommonly offered. In April 2019, the Massachusetts Department of Correction (MADOC), the state prison system, provided buprenorphine for incarcerated individuals in addition to previously offered injectable naltrexone. Objective: To evaluate postrelease outcomes after buprenorphine implementation. Design, Setting, and Participants: This cohort study with interrupted time-series analysis used linked data across multiple statewide data sets in the Massachusetts Public Health Data Warehouse stratified by sex due to differences in carceral systems. Eligible participants were individuals sentenced and released from a MADOC facility to the community. The study period for the male sample was January 2014 to November 2020; for the female sample, January 2015 to October 2019. Data were analyzed between February 2022 and January 2024. Exposure: April 2019 implementation of buprenorphine during incarceration. Main Outcomes and Measures: Receipt of MOUD within 4 weeks after release, opioid overdose, and all-cause mortality within 8 weeks after release, each measured as a percentage of monthly releases who experienced the outcome. Segmented linear regression analyzed changes in outcome rates after implementation. Results: A total of 15 225 individuals were included. In the male sample there were 14 582 releases among 12 688 individuals (mean [SD] age, 35.0 [10.8] years; 133 Asian and Pacific Islander [0.9%], 4079 Black [28.0%], 4208 Hispanic [28.9%], 6117 White [41.9%]), a rate of 175.7 releases per month; the female sample included 3269 releases among 2537 individuals (mean [SD] age, 34.9 [9.8] years; 328 Black [10.0%], 225 Hispanic [6.9%], 2545 White [77.9%]), a rate of 56.4 releases per month. Among male participants at 20 months postimplementation, the monthly rate of postrelease buprenorphine receipt was higher than would have been expected under baseline trends (21.2% vs 10.6% of monthly releases; 18.6 additional releases per month). Naltrexone receipt was lower than expected (1.0% vs 6.0%; 8.8 fewer releases per month). Monthly rates of methadone receipt (1.4%) and opioid overdose (1.8%) were not significantly different than expected. All-cause mortality was lower than expected (1.9% vs 2.8%; 1.5 fewer deaths per month). Among female participants at 7 months postimplementation, buprenorphine receipt was higher than expected (31.6% vs 9.5%; 12.4 additional releases per month). Naltrexone receipt was lower than expected (3.4% vs 7.2%) but not statistically significantly different. Monthly rates of methadone receipt (1.1%), opioid overdose (4.8%), and all-cause mortality (1.6%) were not significantly different than expected. Conclusions and Relevance: In this cohort study of state prison releases, postrelease buprenorphine receipt increased and naltrexone receipt decreased after buprenorphine became available during incarceration.

Furthering Scientific Inquiry for Weight Loss Maintenance: Assessing the Psychological Processes Impacted by a Low intensity Technology-Assisted Intervention (NULevel Trial).

BACKGROUND: NULevel was a randomized control trial to evaluate a technology-assisted weight loss maintenance (WLM) program in the UK. The program included: (a) a face-to-face goal-setting session; (b) an internet platform, a pedometer, and wirelessly connected scales to monitor and report diet, physical activity, and weight, and; (c) regular automated feedback delivered by mobile phone, tailored to participants' progress. Components were designed to target psychological processes linked to weight-related behavior. Though intervention participants showed increased physical activity, there was no difference in WLM between the intervention and control groups after 12 months (Sniehotta FF, Evans EH, Sainsbury K, et al. Behavioural intervention for weight loss maintenance versus standard weight advice in adults with obesity: A randomized controlled trial in the UK (NULevel Trial). PLoS Med. 2019; 16(5):e1002793. doi:10.1371/journal.pmed.1002793). It is unclear whether the program failed to alter targeted psychological processes, or whether changes in these processes failed to influence WLM. PURPOSE: We evaluate whether the program influenced 16 prespecified psychological processes (e.g., self-efficacy and automaticity toward diet and physical activity), and whether these processes (at 6 months) were associated with successful WLM (at 12 months). METHODS: 288 adults who had previously lost weight were randomized to the intervention or control groups. The control group received wireless scales and standard advice via newsletters. Assessments occurred in person at 0, 6, and 12 months. RESULTS: The intervention significantly altered 10 of the 16 psychological processes, compared with the control group. However, few processes were associated with WLM, leading to no significant indirect effects of the intervention via the processes on WLM. CONCLUSIONS: Changes in targeted processes were insufficient to support WLM. Future efforts may more closely examine the sequence of effects between processes, behavior, and WLM.

Many tools exist to help people lose weight, but it is common for people to regain that weight over time. Thus, understanding how to support the maintenance of weight loss remains a priority. The NULevel program was a 12-month weight loss maintenance (WLM) intervention for individuals who had recently lost weight. It promoted psychological factors, shown to be tied to weight-related behaviors, using face-to-face and technology-based (e.g., mobile phone feedback) elements. For example, the program encouraged making plans to improve lifestyles (e.g., exercise, better diet) and promoted people's confidence in these behaviors. However, the program was not more successful than a control condition in maintaining weight loss. We sought to understand why this occurred. We found that the program was indeed successful in influencing most of the psychological factors it targeted. Instead, it was the psychological factors that failed to predict WLM. Were the psychological factors insufficient to impact behavior? Or did the promoted behaviors fail to aid WLM? Future research should focus on answering such questions. Doing so would inform whether interventions should target different psychological factors to change behaviors, or choose different sets of behaviors to support WLM.

Diffusion of medications for opioid use disorder treatment in jail settings: a convergent mixed methods study of jail staff perspectives.

BACKGROUND: Implementation of medications for opioid use disorder (MOUD) in jails varies by facility and across states. Organizational climate, including staff attitudes toward change and exposure to education, can influence perceptions of innovations like MOUD in jails. Using a mixed methods design, we aimed to understand the association between organizational climate and jail staff perceptions of MOUD. METHODS: Jail staff (n = 111) who operate MOUD programs in 6 Massachusetts jails completed surveys that included the Organizational Readiness for Implementing Change (ORIC) survey. Random effects logistic regression models assessed associations between organizational climate and several outcomes of perceived MOUD efficacy, acceptability, and knowledge, while controlling for covariates. Jail staff (N = 61) participated in qualitative interviews and focus groups focused on organizational climate and knowledge diffusion, which we analyzed using inductive and deductive methods. RESULTS: The results indicate that organizational change readiness on the ORIC was associated with positive perceptions of MOUD, and educational resources facilitated MOUD implementation. Greater ORIC was associated with higher perception of methadone as highly acceptable for jail populations (Odds ratio [OR] 2.3, 95% Confidence Interval [CI] 1.2 to 4.4), and high knowledge of methadone (OR 2.3, 95% CI 1.1 to 4.9), with similar magnitude of effects for buprenorphine. High levels of training for jail staff on methadone and buprenorphine were also associated with higher knowledge of these medications (Methadone: OR 7.2, 95% CI 2.2 to 23.2; Buprenorphine: OR 3.4, 95% CI 1.2 to 9.5). Qualitative results point towards the importance of organizational climate and elucidate educational strategies to improve staff perceptions of MOUD. CONCLUSION: Results underscore the importance of organizational climate for successful implementation of jail MOUD programs and provide support for medication-specific educational resources as a facilitator of successful MOUD implementation in jail settings. Findings highlight implementation strategies that may improve jail staff perceptions of MOUD.

Looking Upstream to Understand Race/Ethnicity as a Moderator for Poststroke Neuroinflammation and a Social Determinant for Poststroke Aphasia Outcomes.

INTRODUCTION: Over the past decade, the stroke literature has begun to acknowledge and explore explanations for longstanding racial/ethnic differences in stroke outcomes. Poststroke cognitive impairment (PSCI) and poststroke aphasia are two such negative poststroke outcomes where racial/ethnic differences exist. Physiological differences, such as stroke type and lesion size, have been used to partially explain the variation in PSCI and aphasia. However, there is some evidence, although limited, that suggests neuroinflammatory processes as part of allostatic load may be a key contributor to the observed disparities. METHOD: In this tutorial, we explore the influence of race differences in inflammation on poststroke cognitive outcomes. We suggest lifetime stress and other external determinants of health such as neighborhood environment and discriminatory practices through "weathering" explain differences in inflammation. While using an allostatic load framework, we explore the literature focusing specifically on the role of neuroinflammation on poststroke outcomes. CONCLUSIONS: Examination of the immune response poststroke provides a foundation for understanding the mechanisms of PSCI and poststroke aphasia and the potential contributions of neuroinflammatory processes on poststroke cognitive outcomes. Furthermore, understanding of racial differences in those processes may contribute to a better understanding of racial disparities in general stroke outcomes as well as poststroke aphasia.

Gender identity, stimulant drug use, and criminal justice history on internalized stigma among a nationally representative sample of adults who misuse opioids.

PURPOSE: The rise of fatal stimulant use among adults who use opioids is a public health problem. Internalized stigma is a barrier to substance use treatment, which is greater for women and populations with criminal justice involvement. METHODS: Using a nationally representative sample of adults in the United States from a probability-based survey on household opinions in 2021, we examined characteristics of women (n = 289) and men (n = 416) who misuse opioids. In gender-stratified multivariable linear regression, we investigated factors associated with internalized stigma, and tested for the interaction of stimulant use and criminal justice involvement. RESULTS: Compared to men, women reported greater mental health symptom severity (3.2 vs. 2.7 on a 1 to 6 scale, p < 0.001). Internalized stigma was similar between women (2.3 ± 1.1) and men (2.2 ± 0.1). Among women and not men, however, stimulant use was positively associated with internalized stigma (0.36, 95% CI [0.07, 0.65]; p = 0.02). Interaction between stimulant use and criminal justice involvement was negatively associated with internalized stigma among women (- 0.60, 95% CI [- 1.16, -0.04]; p = 0.04); among men, the interaction was not significant. Predictive margins illustrate among women, stimulant use eliminated the gap in internalized stigma such that women with no criminal justice involvement had a similar level of internalized stigma as women with criminal justice involvement. CONCLUSION: Internalized stigma between women and men who misuse opioids differed based on stimulant use and criminal justice involvement. Future research should assess whether internalized stigma influences treatment utilization among women with criminal justice involvement.

The Intersection of Social Determinants of Health and Post-stroke Aphasia Outcomes: A Need for Intersectional Analysis.

Aphasia is a disorder that results from damage to portions of the brain that are responsible for language and can vary significantly by type and severity. Differences in aphasia outcomes are influenced by the social determinants of health (SDOH). The SDOH are structural, environmental, and personal determinants that influence health outcomes. Intersectionality, or how one's social and political identities interact to influence individual life outcomes and/or advantage in our society, provides a way to examine the varying levels of the SDOH. However, intersectionality is complex, difficult to measure, and has not yet been explored in post-stroke aphasia outcomes. This article reviews the relationship of race and aphasia outcomes and the SDOH and aphasia outcomes. Additionally, we provide a novel current approach to examine the SDOH and aphasia outcomes. Lastly, we discuss the need for evaluation of intersectionality in aphasia and aim to provide a leveled social-ecological framework to examine aphasia-related outcomes. With notable individual differences among aphasia outcomes, we present a framework to support optimizing research and clinical aphasia care in speech-language pathology.

Lessons Learned from Implementation of a Post-opioid Overdose Outreach Program in a Rural Massachusetts Community.

Post-overdose outreach programs can play a key role in reducing opioid overdose deaths and increasing access to healthcare services. The design and implementation of these programs, especially in rural communities, remains a gap in knowledge. We aimed to understand the lessons learned from the implementation experiences of the Community, Opportunity, Network, Navigation, Exploration, and Connection Team (CONNECT), a post-overdose outreach program based in a rural community in Massachusetts. We conducted semi-structured focus groups and interviews with 21 community partners after the first year of implementation in 2022. Participants included behavioral health, medical, public health, and public safety personnel involved in the design and implementation of CONNECT. Using a combination of thematic and rapid qualitative analysis methods, we inductively coded transcripts for salient themes. Themes were mapped onto the Health Equity Implementation Framework to better understand implementation and health-equity factors. Facilitators to implementation of this innovation included efficient inter-partner data sharing and coordination, and ability to offer numerous health services to clients to meet their needs. Key partners identified that CONNECT serves clients who use opioids, have previous involvement with the legal system, and reside in low-income areas within this rural region. Unhoused individuals and individuals who do not call 9-11 after an overdose were identified as populations of need that CONNECT was missing due to structural barriers. Partners shared how the context of this rural community came with challenges related to limited access to health services and pervasive stigma towards substance use, while it was also perceived to foster a culture of collaboration and unity among multidisciplinary key partners. Post overdose outreach programs serve clients with complex health needs. The ability to access services for these health needs is shaped by the post overdose outreach program and its key partners, and by the broader community context. As post-overdose outreach programs continue to expand as a promising strategy to address the opioid overdose crisis, there exists a need to contextualize implementation strategies to inform adaptations and develop best-practices.

Validation of a Latin-American Spanish version of the Body Esteem Scale for Adolescents and Adults (BESAA-LA) in Colombian and Nicaraguan adults.

BACKGROUND: Body dissatisfaction (BD) is a growing concern in Latin America; reliable and culturally appropriate scales are necessary to support body image research in Spanish speaking Latin American countries. We sought to validate a Latin-American Spanish version of the Body Esteem Scale for Adolescents and Adults (BESAA; Mendelson et al. 2001). METHODS: The BESAA was translated, culturally adapted, and validated in a sample of adults in Colombia (N = 525, 65% women, Mage 24.4, SD = 9.28). We assessed factor structure (using confirmatory factor analysis (CFA), exploratory factor analysis (EFA) and exploratory structural equation model (ESEM)), internal reliability (using Cronbach's alpha and omega), validity (using the Body Appreciation Scale BAS and Sociocultural Attitudes Towards Appearance Questionnaire SATAQ), test-retest stability in a small subsample (N = 84, using Intraclass correlations ICC) and measurement invariance across gender. To evaluate the generalizability of the scale, we assessed reliability, validity, and factor structure in a second sample from rural Nicaragua (N = 102, 73% women, Mage 22.2, SD = 4.72), and assessed measurement invariance across Nicaraguan and Colombian participants. RESULTS: The scale showed good internal reliability and validity in both samples, and there was evidence of adequate test-retest stability in the Colombian sample. EFA showed a three-factor structure with subscales we labelled 'appearance-positive', 'appearance-negative' and 'weight', that was confirmed using CFA and ESEM in the Colombian sample. Measurement invariance was confirmed across the Colombian and Nicaraguan samples, and across gender within the Colombian sample. CONCLUSION: The Latin-American Spanish version of the BESAA (BESAA-LA) appears to be a psychometrically sound measure with good reliability, validity and invariance across gender and countries. These results support the use of this scale to measure body satisfaction/dissatisfaction in Latin American adult populations.

Diversion of medications to treat opioid use disorder: Qualitative findings from formerly incarcerated adults in Massachusetts.

BACKGROUND: Carceral officials often cite diversion of medication for opioid use disorder (MOUD) (e.g., buprenorphine) as a reason for not offering MOUD treatment in jails and prisons with little understanding of patient perspectives. We aimed to understand patient perceptions of medication diversion from jail-based MOUD programs and the factors that contribute to and reduce diversion. METHODS: We conducted thematic analyses of semi-structured interviews held in 2021-22 with 38 adults who received MOUD treatment and were released from eight Massachusetts jails that had implemented a MOUD program on or after September 2019. RESULTS: Consistent with prior reports from carceral staff, patients perceived MOUD diversion to happen less frequently than expected, which they attributed to dosing protocols that have effectively reduced it. Patients reported that MOUD availability reduced the contraband buprenorphine market, although other contraband substances have entered jails (fentanyl, oxycodone, K2). Patients perceived Subutex to have greater misuse potential and added diversion risks. Patients valued graduated consequences and other efforts to reduce MOUD diversion and contraband for making jails safer and for enabling patients to receive treatment. Nearly all participants reported having heard about, witnessed, or been involved in actual or attempted diversion, with variation in reports by jail. Patients suggested that dispensing MOUD to all who need it immediately upon intake would be the most effective way to reduce MOUD diversion and contraband. CONCLUSION: Formerly incarcerated patients perceived MOUD diversion within jail medication programs as occurring less often than expected and that it can be reduced with appropriate protocols. To help limit medication diversion, patients recommended provision of MOUD upon intake to all individuals with opioid use disorder who need it. Findings have implications for MOUD program adaptation, successful routinization, and diffusion in carceral settings.

Making clear and effective communication SOuND BETTeR for patients with communication barriers.

The consequences of ineffective communication between patients and clinicians in the ED range from frustration to significant adverse events. Unfortunately, scenarios where we are unable to understand what our patient is saying to us are common, due to a multitude of factors including acute illness, disability and patient diversity. Current communication aids can be difficult to access and use in the Emergency setting due to lack of physical resources, specific training and time. Our aim was to develop a communication tool which allowed for the rapid identification of urgent patient needs. In order to overcome current challenges, the tool had to be resource-light, quick to use and not reliant on additional staff training or patient education for its effective use. The SOuND BETTeR communication tool is a list of yes/no questions, formatted as a mnemonic, which aims to identify the most common and urgent needs of patients in the ED. As the list of potential needs is not exhaustive, the tool does not purport to replace formal communication aids in the medium and long term, but to bridge the gap often left in the ED where urgent needs must be met and more formal communication aids are not yet available. The tool can effectively and quickly identify important needs in patients with expressive communication barriers such as those with aphasia, facial trauma and on non-invasive ventilation. In addition, the tool can be modified for use in patients with non-English speaking backgrounds. At this stage the tool has not yet been prospectively validated.

Correlates and Patterns in Use of Medications to Treat Opioid Use Disorder in Jail.

OBJECTIVES: Little is known about the correlates of use of medications to treat opioid use disorder (MOUD, ie, buprenorphine, methadone, naltrexone) offered in jails. We evaluated the implementation and outcomes of a MOUD program offered by 2 of the first jails nationwide to provide access to such care. METHODS: We examined use of MOUD among adults with opioid use disorder (n = 347) incarcerated by 2 rural jails in Massachusetts (2018-2021). We examined MOUD transitions from intake to during incarceration. Using logistic regression, we examined factors associated with in-jail use of MOUD. RESULTS: At jail entry, 48.7% of individuals with opioid use disorder were being treated with MOUD. During incarceration, 65.1% received MOUD, attributable to a 9.2% increase in use of methadone (from 15.9% to 25.1%) and a 10.1% increase in use of buprenorphine (from 28.5% to 38.6%). During incarceration, 32.3% of individuals were continued on the same MOUD from the community, 25.4% were started, 8.9% stopped, and 7.5% switched type. A total of 25.9% entered jail not on any MOUD and were not started on it. Use of MOUD during incarceration was positively associated with having received MOUD in the community (odds ratio, 12.2; 95% confidence interval, 5.8-25.5) and incarceration at site 1 compared with site 2 (OR, 24.6; 95% CI, 10.9-54.4). CONCLUSIONS: Expanded access to MOUD in jails can engage an at-risk population with treatment. Understanding factors related to this population's use of MOUD may aid efforts to optimize care during incarceration and after community re-entry.

Evolutionary dynamics of genome size and content during the adaptive radiation of Heliconiini butterflies.

Heliconius butterflies, a speciose genus of Müllerian mimics, represent a classic example of an adaptive radiation that includes a range of derived dietary, life history, physiological and neural traits. However, key lineages within the genus, and across the broader Heliconiini tribe, lack genomic resources, limiting our understanding of how adaptive and neutral processes shaped genome evolution during their radiation. Here, we generate highly contiguous genome assemblies for nine Heliconiini, 29 additional reference-assembled genomes, and improve 10 existing assemblies. Altogether, we provide a dataset of annotated genomes for a total of 63 species, including 58 species within the Heliconiini tribe. We use this extensive dataset to generate a robust and dated heliconiine phylogeny, describe major patterns of introgression, explore the evolution of genome architecture, and the genomic basis of key innovations in this enigmatic group, including an assessment of the evolution of putative regulatory regions at the Heliconius stem. Our work illustrates how the increased resolution provided by such dense genomic sampling improves our power to generate and test gene-phenotype hypotheses, and precisely characterize how genomes evolve.

Nonestrogen Therapies for Treatment of Genitourinary Syndrome of Menopause: A Systematic Review.

OBJECTIVE: To systematically review the literature and provide clinical practice guidelines regarding various nonestrogen therapies for treatment of genitourinary syndrome of menopause (GSM). DATA SOURCES: MEDLINE, EMBASE, ClinicalTrials.gov , and Cochrane databases were searched from inception to July 2021. We included comparative and noncomparative studies. Interventions and comparators were limited to seven products that are commercially available and currently in use (vaginal dehydroepiandrosterone [DHEA], ospemifene, laser or energy-based therapies, polycarbophil-based vaginal moisturizer, Tibolone, vaginal hyaluronic acid, testosterone). Topical estrogen, placebo, other nonestrogen products, as well as no treatment were considered as comparators. METHODS OF STUDY SELECTION: We double-screened 9,131 abstracts and identified 136 studies that met our criteria. Studies were assessed for quality and strength of evidence by the systematic review group. TABULATION, INTEGRATION, AND RESULTS: Information regarding the participants, details on the intervention and comparator and outcomes were extracted from the eligible studies. Alternative therapies were similar or superior to estrogen or placebo with minimal increase in adverse events. Dose response was noted with vaginal DHEA and testosterone. Vaginal DHEA, ospemifene, erbium and fractional carbon dioxide (CO 2 ) laser, polycarbophil-based vaginal moisturizer, tibolone, hyaluronic acid, and testosterone all improved subjective and objective signs of atrophy. Vaginal DHEA, ospemifene, tibolone, fractional CO 2 laser, polycarbophil-based vaginal moisturizer, and testosterone improved sexual function. CONCLUSION: Most nonestrogen therapies are effective treatments for the various symptoms of GSM. There are insufficient data to compare nonestrogen options to each other.

Use of poxvirus display to select antibodies specific for complex membrane antigens.

Antibody discovery against complex antigens is limited by the availability of a reproducible pure source of concentrated properly folded antigen. We have developed a technology to enable direct incorporation of membrane proteins such as GPCRs and into the membrane of poxvirus. The protein of interest is correctly folded and expressed in the cell-derived viral membrane and does not require any detergents or refolding before downstream use. The poxvirus is selective in which proteins are incorporated into the viral membrane, making the antigen poxvirus an antigenically cleaner target for in vitro panning. Antigen-expressing virus can be readily purified at scale and used for antibody selection using any in vitro display platform.

A call to action: Contingency management to improve post-release treatment engagement among people with opioid use disorder who are incarcerated.

People with opioid use disorder (OUD) are overrepresented in US correctional facilities and experience disproportionately high risk for illicit opioid use and overdose after release. A growing number of correctional facilities offer medication for OUD (MOUD), which is effective in reducing these risks. However, a recent evaluation found that <50% of those prescribed MOUD during incarceration continued MOUD within 30 days after release, demonstrating a need to improve post-release continuity of care. We describe available evidence on contingency management (CM), an intervention wherein patients receive incentives contingent on behavior change, to achieve this goal. A prior systematic review reported strong evidence in support of CM for increasing treatment adherence in MOUD programs, but the trials reviewed did not include incarcerated participants. Research on CM to increase treatment adherence among participants in the criminal justice system is limited with mixed findings. However, in comparison to the trials that supported CM's efficacy in the community, CM trials in the criminal justice system provided smaller rewards with greater delays in the delivery of rewards to patients, which likely contributed to null findings. Indeed, a prior meta-analysis demonstrates a dose-response relationship between the magnitude and immediacy of reward and CM effectiveness. Thus, CM involving larger and more immediately delivered rewards are likely necessary to improve MOUD adherence during the critical period following release from incarceration. Future research on the effectiveness and implementation of CM to improve MOUD retention after release from incarceration is warranted.

Intersectional sociodemographic and neurological relationships in the naming ability of persons with post-stroke aphasia.

INTRODUCTION: Significant attention has been given to the role of brain function and disruption in determining performance on naming tasks among individuals with aphasia. However, scholarly pursuit of a neurological explanation has overlooked the fundamental cornerstone of individual health-the underlying social, economic, and environmental factors that shape how they live, work, and age, also known as the social determinants of health (SDOH). This study examines the correlation between naming performance and these underlying factors. METHODS: Individual level data from the 2010 Moss Aphasia Psycholinguistic Project Database (MAPPD) was matched with the 2009-2011 Medical Expenditure Panel Survey (MEPS) using a propensity score algorithm based on functional, health, and demographic characteristics. Multilevel, generalized, nonlinear regression models were applied to the resulting data set to assess the correlation between the Boston Naming Test (BNT) percentile score and age, income, sex, race, household size, marital status, aphasia type, and region of residence. Poisson regression models with bootstrapped standard errors were used to estimate these relationships RESULTS: Discrete dependent variable estimation with non-normal prior specification included individual level (age, marital status, years of education), socioeconomic (family income), health (aphasia type), household (family size), and environmental (region of residence) characteristics. Regression results indicated that, relative to individuals with Wernicke's, individuals with Anomic (0.74, SE = 0.0008) and Conduction (0.42, SE = 0.0009) aphasia performed better on the BNT. While age at the time of testing was not significantly correlated, higher income level (0.15, SE = 0.0003) and larger family size (0.002, SE = 0.002) was associated with higher BNT score percentiles. Finally, Black persons with aphasia (PWA) (-0.0124, SE = 0.0007) had lower average score percentiles when other factors were held constant. CONCLUSIONS: The findings reported here suggest higher income and larger family size are associated with better outcomes. As expected, aphasia type was significantly associated with naming outcomes. However, poorer performance by Black PWA and individuals with low income suggests that SDOH can play a critical role (positive and negative) in naming impairment in some populations with aphasia.

The impact of the implementation of medication for opioid use disorder and COVID-19 in a statewide correctional system on treatment engagement, postrelease continuation of care, and overdose.

BACKGROUND: People with opioid use disorder (OUD) are overrepresented in US correctional facilities and experience disproportionately high risk for overdose after release. Medications for OUD (MOUD) are highly efficacious but not available to most incarcerated individuals. In 2018, Vermont began providing MOUD for all incarcerated individuals with OUD statewide. In 2020, the COVID-19 state of emergency began. We assessed the impact of both events on MOUD utilization and treatment outcomes. METHODOLOGY: Analyses linked Vermont Department of Corrections administrative data and Medicaid claims data between 07/01/2017 and 03/31/2021. The study used logistic regression to analyze treatment engagement among all incarcerated individuals in Vermont. Multilevel modeling assessed change in clinical outcomes among release episodes that occurred among individuals with an OUD diagnosis Medicaid claim. RESULTS: Prescriptions for MOUD while incarcerated increased from 0.8% to 33.9% of the incarcerated population after MOUD implementation (OR = 67.4) and subsequently decreased with the onset of COVID-19 to 26.6% (OR = 0.7). After MOUD implementation, most prescriptions (63.1%) were to individuals who had not been receiving MOUD prior to incarceration, but this figure decreased to 53.9% with the onset of COVID-19 (OR = 0.7). Prescriptions for MOUD within 30 days after release increased from 33.9% of those with OUD before to 41.0% after MOUD implementation (OR = 1.4) but decreased to 35.6% with the onset of COVID-19 (OR = 0.8). Simultaneously, opioid-related nonfatal overdoses within 30 days after release decreased from 1.2% before to 0.8% after statewide MOUD implementation (OR = 0.3) but increased to 1.9% during COVID-19 (OR = 3.4). Fatal overdoses within 1 year after release decreased from 27 deaths before to ≤10 after statewide MOUD implementation and remained ≤10 during COVID-19. CONCLUSIONS: This longitudinal evaluation demonstrated increased treatment engagement and a decrease in opioid-related overdose following implementation of MOUD in a statewide correctional system. In contrast, these improvements were somewhat attenuated with the onset of COVID-19, which was associated with decreased treatment engagement and an increase in nonfatal overdoses. Considered together, these findings demonstrate the benefits of statewide MOUD for incarcerated individuals as well as the need to identify and address barriers to continuation of care following release from incarceration in the context of COVID-19.