Prothrombotic autoantibodies targeting platelet factor 4/polyanion are associated with pediatric cerebral malaria.

BACKGROUNDFeatures of consumptive coagulopathy and thromboinflammation are prominent in cerebral malaria (CM). We hypothesized that thrombogenic autoantibodies contribute to a procoagulant state in CM.METHODSPlasma from children with uncomplicated malaria (UM) (n = 124) and CM (n = 136) was analyzed by ELISA for a panel of 8 autoantibodies including anti-platelet factor 4/polyanion (anti-PF4/P), anti-phospholipid, anti-phosphatidylserine, anti-myeloperoxidase, anti-proteinase 3, anti-dsDNA, anti-ß-2-glycoprotein I, and anti-cardiolipin. Plasma samples from individuals with nonmalarial coma (NMC) (n = 49) and healthy controls (HCs) (n = 56) were assayed for comparison. Associations with clinical and immune biomarkers were determined using univariate and logistic regression analyses.RESULTSMedian anti-PF4/P and anti-PS IgG levels were elevated in individuals with malaria infection relative to levels in HCs (P < 0.001) and patients with NMC (PF4/P: P < 0.001). Anti-PF4/P IgG levels were elevated in children with CM (median = 0.27, IQR: 0.19-0.41) compared with those with UM (median = 0.19, IQR: 0.14-0.22, P < 0.0001). Anti-PS IgG levels did not differ between patients with UM and those with CM (P = 0.39). When patients with CM were stratified by malaria retinopathy (Ret) status, the levels of anti-PF4/P IgG correlated negatively with the peripheral platelet count in patients with Ret+ CM (Spearman's rho [Rs] = 0.201, P = 0.04) and associated positively with mortality (OR = 15.2, 95% CI: 1.02-275, P = 0.048). Plasma from patients with CM induced greater platelet activation in an ex vivo assay relative to plasma from patients with UM (P = 0.02), and the observed platelet activation was associated with anti-PF4/P IgG levels (Rs= 0.293, P = 0.035).CONCLUSIONSThrombosis mediated by elevated anti-PF4/P autoantibodies may be one mechanism contributing to the clinical complications of CM.

How undergraduates historically underrepresented in biomedical sciences value multiple components of a research training program.

To promote diversity in the STEM workforce, undergraduate research training programs incorporating a variety of intervention strategies have been developed to support students from historically underrepresented backgrounds in overcoming numerous systemic barriers to pursuing careers in science. However, relatively little research has focused on how students experience and value these interventions and the ways in which the interventions support student success. The current study analyzed qualitative interviews from participants (n=15) in a comprehensive research training program for undergraduates historically underrepresented in biomedical research to investigate the student perspective on how specific program components address barriers and support their research training, academic progress, and career preparation. Findings indicated that students benefit from authentic research experiences, mentoring, supplemental curriculum, financial assistance, and a supportive program environment. Participants described how the program helped them address financial concerns, navigate academic and career choices, build science identity and efficacy, and feel a sense of belonging within a caring community. The study highlights how multi-faceted research training programs offering a variety of supports can contribute to student retention and development according to the needs and circumstances of individual students.

Community-based participatory research to improve alumni transition from an intensive research training program for historically underrepresented undergraduates.

Various initiatives for undergraduates from historically underrepresented backgrounds attempt to address disparities in the completion of science, technology, engineering, mathematics (STEM) degrees and the pursuit of careers in scientific research. Intensive research training programs for historically underrepresented undergraduates may include multiple components, such as authentic research experiences, advising and mentoring, supplemental curriculum, and financial assistance. Following comprehensive support during program participation, the post-program transition may present a vulnerable period in students' career trajectories. This study used a community-based participatory research (CBPR) approach to investigate the experiences of students completing an intensive research training program to understand and develop recommendations for the post-program transition process. As a team of program alumni, academic researchers, and program staff, we developed, conducted, and analyzed semi-structured, open-ended interviews of recent program alumni and students approaching program completion (n=11; 55% female, 55% non-White). Applying thematic analysis at semantic and latent levels through a critical paradigm revealed the transition as a bittersweet experience, with feelings of pride and accomplishment mixed with sadness and anxiety. Findings also suggested the transition is described as a narrative influenced by preceding program experiences and adaptations. Financial concerns were prominent, and specific barriers and facilitators of successful transition included: aligned mentoring, negotiation of continued research employment, consideration of culture, planning for next steps, and engagement with the scholar community. Collaboratively, we developed recommendations for program improvements potentially relevant to similarly intensive STEM diversity programs. We also highlight the value of a CBPR approach that includes students equitably as co-researchers in program research and evaluation.

Identifying predictors of psychological well-being among volunteer mentors in Big Brothers Big Sisters.

Big Brothers Big Sisters (BBBS) facilitates mentoring relationships between youth and volunteer mentors. Although research has examined outcomes for youth in BBBS, relatively less investigation has been undertaken for volunteer outcomes. This study explored factors associated with changes in psychological well-being among BBBS volunteer mentors. Participants included 593 mentors (Mage = 31) surveyed at study baseline and 15-month follow-up. A classification and regression decision tree approach was used to predict residualized change in psychological well-being from study baseline with match length included as the first split variable, and demographic, individual, and relationship variables included as candidate predictors. Analyses indicated that mentors with longer relationships (>4.5 months) reported more positive change in psychological well-being compared with mentors with shorter relationships. Perceived quality of program supervision was a further predictor within both groups of volunteers. Findings suggest that longer relationships and greater program support may contribute to mentor well-being.

Do program practices matter for mentors?: How implementation of empirically supported program practices is associated with youth mentoring relationship quality.

This study investigates how the implementation of program-level practices by formal youth mentoring programs is associated with the quality of youth mentoring relationships as contexts for youth development and also examines whether this connection is mediated by the mentor-staff working alliance. Using data from mentors (n = 542) participating in multiple programs (n = 55), multilevel path models examined hypothesized direct and mediated effects. Parallel analyses were conducted with assessments of program practices from staff (n = 219). Greater exposure to program practices was associated with higher ratings of mentoring relationship satisfaction, commitment, and security and lower mentor-youth relationship negativity. The mentor-staff working alliance either partially or fully mediated these associations. Staff-reported practices predicted mentoring relationship satisfaction and commitment without mediation by the working alliance. This study suggests program practices contribute to stronger youth mentoring relationships. The findings also highlight the mentor-staff working alliance in supporting the development of positive mentoring relationships.

Formal youth mentoring relationships in the context of risk: What is the role of caregiver-mentor collaboration?

Most research on youth mentoring relationships has focused on the mentor-mentee dyad, yet caregivers play an important role in supporting these relationships. Drawing on a large, multisite sample of youth in formal mentoring programs (N = 2165), this study investigated associations between caregiver-mentor collaboration and mentoring relationship outcomes in the context of environmental and individual youth risk factors. Analysis of novel quantitative measures assessing caregivers' experiences of the mentoring relationships revealed two factors reflecting caregivers' collaboration with mentors (caregiver involvement and mentor backing), and three factors reflecting caregivers' perceptions of mentor effectiveness (meeting youth needs, advocating for youth, and supporting youth behavior). Results indicated that greater caregiver involvement was associated with higher-quality and longer-lasting mentoring relationships. Few associations between risk and mentoring relationships were observed; however, indirect effects indicated that youth environmental risk was positively associated with caregiver involvement, which, in turn, was positively associated with mentoring relationship outcomes.

Mentoring and depressive symptoms of youth: Examining prospective and interactive associations with mentoring relationship quality.

A significant body of research has demonstrated that mentoring relationships support positive youth development. The quality of the mentoring relationship has been identified as a predictor of positive youth outcomes. However, limited research has examined how engagement in a mentoring program may be related to youth depressive symptoms specifically. The current study utilized a sample of 2003 youth participating in mentoring programs across the country (Mage = 12.32, SD = 1.42, 55.1% female) from diverse racial and ethnic backgrounds (39.1% Black, 23.6% White, 22.1% Hispanic, 3.3% Native American or Alaskan Native, .4% Asian or Pacific Islander, 1.8% other, and 9.7% Multi-Ethnic) to investigate associations between youth depressive symptoms and mentoring relationship quality. Results revealed that: (1) mean depressive symptoms decreased after participation in a mentoring program; (2) several, but not all, relationship quality indicators predicted change in depressive symptoms; (3) baseline levels of depressive symptoms negatively predicted indicators of relationship quality; and (4) associations between several relationship quality indicators and follow-up depressive symptoms differed by baseline levels of depressive symptoms. These findings highlight the potential benefits of mentoring programs to youth and the need to provide mentors with support around building relationships with youth, especially those experiencing depressive symptoms.

(Not) minding the gap: A qualitative interview study of how social class bias can influence youth mentoring relationships.

This study sought to examine how social class bias may be enacted by mentors and mentoring program staff within community-based youth mentoring relationships and how these biases may influence the mentoring relationship. A narrative thematic analysis was conducted with interviews from mentors, mentees' parents/caregivers, and mentoring program staff representing 36 matches participating in a larger, prospective, mixed-methods study examining factors associated with early match closures. Findings indicate that although some mentors were able to partner with the youth and family to effectively navigate challenges related to the family's economic circumstances, other mentors and some mentoring program staff held deficit views of the youth and their family that appeared to be at least partially rooted in negative social class-based assumptions about attitudes and behaviors. Specifically, we observed tendencies on the part of some mentors and program staff toward (a) deficit-based views of families and youth, (b) individual-level attributions for the family's economic circumstances and blaming of caregivers, and (c) perceiving mentors as being underappreciated by the youth's caregiver. These deficit perspectives contributed to the minimization of parent/caregiver voice in the mentoring process and negative interpretations of parent/caregiver and, in some cases, youth attitudes and behaviors.

Supporting Biomedical Research Training for Historically Underrepresented Undergraduates Using Interprofessional, Nonformal Education Structures.

Research experience provides critical training for new biomedical research scientists. Students from underrepresented populations studying science, technology, engineering, and mathematics (STEM) are increasingly recruited into research pathways to diversify STEM fields. However, support structures outside of research settings designed to help these students navigate biomedical research pathways are not always available; nor are program support components outside the context of laboratory technical skills training and formal mentorship well understood. This study leveraged a multi-institutional research training program, Enhancing Cross-Disciplinary Infrastructure and Training at Oregon (EXITO), to explore how nine institutions designed a new curricular structure (Enrichment) to meet a common goal of enhancing undergraduate research training and student success. EXITO undergraduates participated in a comprehensive, 3-year research training program with the Enrichment component offered across nine sites: three universities and six community colleges, highly diverse in size, demographics, and location. Sites' approaches to supporting students in the training program were studied over a 30-month period. All sites independently created their own nonformal curricular structures, implemented interprofessionally via facilitated peer groups. Site data describing design and implementation were thematically coded to identify essential programmatic components across sites, with student feedback used to triangulate findings. Enrichment offered students time to critically reflect on their interests, experiences, and identities in research; network with peers and professionals; and support negotiation of hidden and implicit curricula. Students reported the low-pressure setting and student-centered curriculum balanced the high demands associated with academics and research. Core curricular themes described Enrichment as fostering a sense of community among students, exposing students to career paths and skills, and supporting development of students' professional identities. The non-formal, interprofessional curricula enabled students to model diverse biomedical identities and pathways for each other while informing institutional structures to improve diverse undergraduate students' success in academia and research.

How youth mentoring relationships end and why it matters: a mixed-methods, multi-informant study.

Scant empirical attention has been devoted to understanding endings in youth mentoring relationships, despite the frequency with which they occur. This study examined data from a mixed-methods study of mentoring relationship endings in which youth mentees, the youth's parents or guardians, mentors, and program staff were surveyed about the closure process, and a subsample of program staff, mentors, and parents or guardians also participated in in-depth qualitative interviews. Findings from a descriptive analysis detailing the perceptions of multiple stakeholders in the closure process as reported in surveys are presented along with case studies derived from a case-based analysis of in-depth qualitative interview data. Most relationship endings were initiated by the mentors, and although some matches engaged in an intentional and direct closure process, more often the endings were unclear or even confusing to program participants. Implications for practice are discussed, including recommendations for more training and greater involvement of program staff in the closure process, as are implications for future research.

Influence of program staff on quality of relationships in a community-based youth mentoring program.

In many mentoring programs, mentor-youth pairs have the latitude to engage in a wide range of activities together across varying community settings. Within this context, program staff are tasked with supporting development of high-quality relationships between mentors and youth. To date, however, this role of program staff has been largely overlooked in research. The current study investigates potential contributions of program staff to mentoring relationships in the Big Brothers Big Sisters community-based mentoring program over their first 15 months of relationship development with a sample of 450 mentor-youth pairs that were supported by 76 program staff across 10 agencies. Two-level analyses (mentoring relationships nested within program staff) examined characteristics and approaches of program staff as prospective predictors of several facets of mentoring relationship quality as reported by youth: closeness, help with coping, youth-centeredness, growth orientation, and attachment. Staff-reported work engagement and emphasis on adherence to program guidelines as well as supervisor-rated staff competence predicted more favorable mentoring relationship quality. By contrast, a nondirective approach to supporting mentors, as reported by staff, predicted lower relationship quality. These findings suggest that further investigation of program staff influences on mentoring relationship development could be fruitful and ultimately provide a basis for enhancing program effectiveness.

Connecting Youth: The Role of Mentoring Approach.

While formal youth mentoring can positively influence youth connectedness, little research has studied the specific approaches mentors engage in that support mentee social development. This study examines how mentors' specific approaches are uniquely associated with youth connection outcomes in formal community-based mentoring. Participants were 766 youth, ranging in age from 11 to 14 (M = 12.29), 56.7% female, and racially/ethnically diverse (41.0% Black/African American, 21.4% Hispanic/Latinx, 20.0% White, 10.2% Multiracial/Multiethnic, 5.9% Native American, 1.2% other race, and 0.4% Asian/Pacific Islander). Person-centered analyses revealed three mentoring profiles which were differentially associated with youth outcomes: "Status Quo Mentors," who reported low-to-moderate levels of closeness within the mentor-mentee dyad, low levels of connecting their mentees with programs and people in their community, and low levels of mediating for their mentees; "Close Connectors," who reported moderate-to-high levels of closeness, moderate-to-high levels of connecting, and low levels of mediating; and "Connector-Mediators," who reported moderate levels of closeness, connecting, and mediating. Youth mentored by "Close Connectors" demonstrated the greatest benefit, with significant improvements in parent-child relationship quality, extracurricular activity involvement, and help-seeking. Results suggest that community-based mentoring programs that emphasize connecting youth within their communities may be more effective in enhancing youth support networks.

Investigating mentor commitment in youth mentoring relationships: The role of perceived program practices.

Highly committed mentors may be less likely to end their mentoring relationships with their mentees. Theory suggests commitment is predicted by relationship satisfaction, investment, and perceptions of available alternatives. Mentoring program practices may influence commitment, but little research has investigated potential mechanisms. Using data from 537 mentors representing 55 mentoring programs, this study examined a theoretical path model in which mentor perceptions of program practices, specifically setting expectations, prematch mentor training, and matching based on mentor preferences, predict mentor satisfaction, investment, perceptions of available alternatives, and ultimately, relationship commitment. As expected, commitment was associated positively with satisfaction and investment and negatively with available alternatives. Perceptions of the program setting clear expectations, the amount of prematch training, and matching by preferences predicted mentor commitment. These associations were mediated by relationship satisfaction, investment, and available alternatives, respectively. These findings identify program practices that can support mentor commitment.

Investigating a multiple mentor model in research training for undergraduates traditionally underrepresented in biomedical sciences.

Models of persistence and success in undergraduate research training emphasize the importance of engagement and integration across social, educational, research, and career settings. Students are likely to benefit from multiple sources of mentoring to meet their multi-dimensional needs for support across these domains. As part of a comprehensive training initiative for traditionally underrepresented students aspiring to careers in biomedical research, BUILD EXITO implemented a multiple mentoring model matching each undergraduate scholar with a research mentor, a faculty mentor, and a peer mentor. By design, each mentor has a different functional role. The current study investigates whether the nature of support scholars actually receive differs by type of mentor. The data are activity records (n=11,756) generated from monthly logs on which scholars (n=223) indicated the form of support received from each mentor by selecting from several items (e.g. personal support, making connections, career advising). Analyses with repeated-measures ANOVA indicate that peer mentors are more likely to address scholars' personal lives, academic skills, and connections to campus programs and services. Career mentors focus on advising related to academics, academic progress, and careers. Research mentors, although also providing career advising and addressing personal life, primarily engage scholars in research-related training activities. The findings confirm that each type of mentor provides a distinctive pattern of support for undergraduate scholars, suggesting that students in comprehensive programs emphasizing academic success, research training, and career development may benefit from multiple sources of mentoring.

Contributions Made by Undergraduates to Research Projects: Using the CREDIT Taxonomy to Assess Undergraduate Research Experiences.

The authors developed a novel tool, the CREDIT URE, to define and measure roles performed by undergraduate students working in research placements. Derived from an open-source taxonomy for determining authorship credit, the CREDIT URE defines 14 possible roles, allowing students and their research mentors to rate the degree to which students participate in each role. The tool was administered longitudinally across three cohorts of undergraduate student-mentor pairs involved in a biomedical research training program for students from diverse backgrounds. Students engaged most frequently in roles involving data curation, investigation, and writing. Less frequently, students engaged in roles related to software development, supervision, and funding acquisition. Students' roles changed over time as they gained experience. Agreement between students and mentors about responsibility for roles was high.

Iron Hack - A symposium/hackathon focused on porphyrias, Friedreich's ataxia, and other rare iron-related diseases.

Background: Basic and clinical scientific research at the University of South Florida (USF) have intersected to support a multi-faceted approach around a common focus on rare iron-related diseases. We proposed a modified version of the National Center for Biotechnology Information's (NCBI) Hackathon-model to take full advantage of local expertise in building "Iron Hack", a rare disease-focused hackathon. As the collaborative, problem-solving nature of hackathons tends to attract participants of highly-diverse backgrounds, organizers facilitated a symposium on rare iron-related diseases, specifically porphyrias and Friedreich's ataxia, pitched at general audiences. Methods: The hackathon was structured to begin each day with presentations by expert clinicians, genetic counselors, researchers focused on molecular and cellular biology, public health/global health, genetics/genomics, computational biology, bioinformatics, biomolecular science, bioengineering, and computer science, as well as guest speakers from the American Porphyria Foundation (APF) and Friedreich's Ataxia Research Alliance (FARA) to inform participants as to the human impact of these diseases. Results: As a result of this hackathon, we developed resources that are relevant not only to these specific disease-models, but also to other rare diseases and general bioinformatics problems. Within two and a half days, "Iron Hack" participants successfully built collaborative projects to visualize data, build databases, improve rare disease diagnosis, and study rare-disease inheritance. Conclusions: The purpose of this manuscript is to demonstrate the utility of a hackathon model to generate prototypes of generalizable tools for a given disease and train clinicians and data scientists to interact more effectively.

"I really wanted her to have a Big Sister": Caregiver perspectives on mentoring for early adolescent girls.

Formal youth mentoring programs tend to focus on the mentor-mentee dyad as the primary relationship cultivated and supported. The interests and preferences of the parent or caregiver in the mentoring relationship may receive little attention. In this study, semi-structured qualitative interviews were conducted with primary caregivers (N=20) of early adolescent girls participating in a Big Brothers Big Sisters community-based mentoring program to explore reasons why they wanted mentors for their daughters. Thematic analysis revealed that caregivers expected mentors to support their daughters as trusted companions, confidants, and conduits to opportunities and services. In addition, caregivers noted ways in which mentoring offered them respite and reinforced their parenting. The findings highlight the potential value of assessing caregiver perspectives and priorities so that program staff and mentors can partner more effectively with youth and families for successful mentoring experiences.

Enhancing Institutional Research Capacity: Results and Lessons from a Pilot Project Program.

The National Institutes of Health (NIH) established the Building University Infrastructure Leading to Diversity (BUILD) initiative to increase engagement and retention of undergraduates from diverse backgrounds in biomedical research. Portland State University, in partnership with ten other academic institutions, received a BUILD award and developed the BUILD EXITO (Enhancing Cross-Disciplinary Infrastructure and Training at Oregon) project. The EXITO program offers a three-year research and mentorship experience for undergraduates in biomedical, behavioral, social science, clinical, and bioengineering disciplines. The BUILD initiative also emphasizes enhancing research capacity and infrastructure through institutional change and faculty development. A key piece of EXITO's program to enhance research capacity is offering faculty an opportunity to apply for up to $50,000 of funding to carry out a one-year pilot study. We conducted two separate RFAs for this purpose, closely modeled on NIH's Small Grant Program (R03), over two years. Principal Investigators of pilot projects were encouraged to include EXITO students, or other undergraduate students, on their research teams. Students then worked on these research projects as part of EXITO's intensive mentored research program. This paper reports on methods to conduct and implement a pilot project program intended to train primarily junior faculty members to write and submit an NIH proposal and fund successful applicants to gather pilot project data to aid in applying for future proposals. We provided a step-by-step rigorous submission and review process. We provided proposal writing and revising workshops, technical support, and helped pilot project Principal Investigators (PIs) with biosketches, IRB applications, IUCUC documents, budgets, and other proposal sections. We secured at least three external (not at any BUILD EXITO institution) reviewers for each proposal. PIs revised proposals before resubmitting and receiving their final scores. Across two RFAs, we provided funds twenty PIs to conduct pilot projects; these projects included at least 21 students working on them who received mentoring in research methods and in disseminating results. This paper describes important lessons learned, including the importance of: allotting sufficient time to recruit reviewers; recruiting reviewers through a variety of sources and methods; and assisting PIs in engaging with research administration staff at Portland State University and partner institutions. Challenges included: finding an optimal timeline that was neither too compressed nor too stretched out; encouraging applicants from distant partner institutions to apply and keeping them engaged and retained through the entire process; and assisting PIs from partner institutions to efficiently utilize Portland State University's sponsored projects department if similar resources were not available at their home institutions. Our goal is to provide guidance and insights to faculty and research-administration staff at other institutions interested in replicating or adapting EXITO's program to enhance institutional research capacity.

Assessing Support Network Stability With Transition-Age Foster Youth: Measuring Change Over Time.

OBJECTIVE: This study uses the Support Network Assessment for Practice (SNAP) approach to measure the support provided to young people transitioning from foster care. METHODS: The SNAP was administered on two occasions, approximately 7 months apart, to a cohort of transition-age foster youth (n = 27). Analyses investigated measurement reliability and sensitivity to change for network-level characteristics as well as baseline factors associated with relationship stability. RESULTS: Most network-level indicators had strong test-retest correlations, and differences in mean scores over time also were detected, suggesting measurement sensitivity to change. Respondents were able to explain most observed changes in their networks, further suggesting reliable measurement. Stable relationships were those reported as stronger and providing more multifaceted support and those with family members and/or parent figures. DISCUSSION: The SNAP approach could be used to facilitate planning around support needs for youth transitioning out of foster care and to evaluate efforts to enhance support networks.

Investigation of the Integration of Supports for Youth Thriving Into a Community-Based Mentoring Program.

A randomized control trial involving 806 youth (ages 10-16; 85.4% low-income households) served in U.S. Big Brothers Big Sisters affiliates investigated effects of incorporating activities to promote youth thriving into mentoring relationships over a 15-month period. Outcomes included support for thriving in youths' relationships with adults, youths' personal resources for thriving, and levels of problem behavior. Intent-to-treat analyses revealed no differences in outcomes based on assignment to thriving promotion or standard services. There was substantial variability in youth exposure to thriving promotion activities, primarily in association with premature endings of mentoring relationships. In path analyses, positive engagement with the activities predicted enhanced support for thriving from adults and, via this support, increased personal resources for thriving and reduced problem behavior.