Advancing Cancer Workforce Capacity for American Indians and Alaska Natives: The Development of a Validated System to Optimize Trainee Participation and Outcome Tracking.

Although American Indian and Alaska Native (AIAN) students are the most underrepresented group in the U.S. in biomedical and health sciences relative to population size, little is known about long-term research education programs and outcome tracking. For over 20 years, the Partnership for Native American Cancer Prevention (NACP) has been supported under the National Cancer Institute's (NCI)-funded Comprehensive Partnerships to Advance Cancer Health Equity (CPACHE) program. Programming included hands-on mentored research and an array of development opportunities. A validated tracking system combining participation records, institutional records, and enrollment/degree attainment from the National Student Clearinghouse documents outcomes. Collectively (2002-2022) NACP engaged 367 AIAN trainees, of whom 237 individuals earned 220 bachelors, 87 masters, and 34 doctoral/professional degrees. Approximately 45% of AIAN doctoral recipients are currently engaged in academic or clinical work, and 10% in industry or tribal leadership. A total of 238 AIAN students participated in mentored research, with 85% demonstrating strong outcomes; 51% attained a degree, and 34% are currently enrolled. Implementation of a robust tracking system documented acceleration in degree attainment over time. Next steps will evaluate the most impactful training activities on student outcomes.

Snuffbox distal transradial access (dTRA) for arteriovenous fistuloplasty in Singapore: Going distal is safe.

AIM: Arteriovenous fistula (AVF) dysfunction resulting from stenosis or occlusion, is a prevalent issue in end-stage renal failure patients reliant on autogenous AVFs for dialysis. Recently, a distal transradial approach (dTRA) has emerged, offering advantages such as diminished access site complications, better patient comfort and reduced risk of radial artery occlusion. Our study seeks to assess the effectiveness, outcomes and complication rates of employing dTRA for arteriovenous fistuloplasty in Singaporean patients. METHODS: A retrospective review of all dTRA fistuloplasties performed on dysfunctional or slow to mature AVFs from 2017 to 2023 in our institution was performed. Patients with a distal radial artery measuring 2 mm or more with no evidence of occlusion or thrombosis were included. Patients who required central venoplasty or cutting balloon angioplasty were excluded. Outcome measures included technical success, mean procedure duration, complications and post-intervention primary patency at 1, 3 and 6 months. Patients were followed up for 12 months post-intervention. RESULTS: A total of 37 patients were included. 97.3% of patients undergoing dTRA fistuloplasty had radiocephalic fistulas while 2.7% had brachiobasilic fistulas. There was 100% technical success (defined as success in radial artery cannulation, sheath insertion and crossing of stenotic lesions) in our study as all patients successfully underwent fistuloplasty via dTRA approach. One-month patency rate was 97.4%, 3-month patency rate was 92.1% and 6-month patency rate was 86.8%. There were no immediate complications (haematoma, infection, bleeding, pseudoaneurysm, occlusion) of the radial artery post-intervention. CONCLUSION: Our paper illustrates the safety and efficacy of utilising dTRA for arteriovenous fistuloplasty. This approach offers distinct benefits in addressing non-mature or dysfunctional distal forearm arteriovenous fistulas and should be taken into account in anatomically suitable cases.

A bacteriophage virus-like particle vaccine against oxycodone elicits high-titer and long-lasting antibodies that sequester drug in the blood.

Opioid use disorder (OUD) and opioid overdoses are public health emergencies. In 2021, 80,000 opioid overdose associated deaths were reported in the United States. Despite the availability of treatment strategies, including medications for opioid use disorder (MOUD) and naloxone, opioid overdoses continue to increase at an alarming rate. Opioid vaccines are a novel approach to combat the growing crisis with several candidates recently entering human clinical trials. In this study, we investigated Qß bacteriophage virus-like particles (VLPs) as a vaccine platform for immunogenic display of oxycodone. A derivative of oxycodone was conjugated to pre-formed Qß VLPs using a sulfhydryl-amine reactive heterobifunctional crosslinker with high loading of oxycodone. In mice, intramuscular immunization with Qß-oxycodone elicited high-titer, high-avidity and long-lasting antibody responses. Qß-oxycodone was also immunogenic after storage at ambient room temperature for over two weeks, demonstrating that the vaccine is highly thermostable. In mice, immunization with Qß-oxycodone elicited antibodies that sequester oxycodone in the serum, an important mechanism for preventing the adverse effects of opioid activity. Finally, Qß-oxycodone is immunogenic in nonhuman primates, eliciting serum oxycodone antibodies after intramuscular immunization of rhesus macaques. These data establish Qß-oxycodone as a promising opioid vaccine candidate.

Accentuate the positive: Evidence that context dependent self-reference drives self-bias.

There is abundant evidence of a self-bias in cognition, with prioritised processing of information that is self-relevant. There is also abundant evidence of a positivity-bias in cognition, with prioritised processing of information that is positively valenced (e.g., positive emotional expressions, rewards). While the effects of self-bias and positivity-bias have been well documented in isolation, they have seldom been examined in parallel, so it is unclear whether one or other of these stimulus classes is prioritised or whether they interact. Addressing this gap, the current research aimed to establish the relative primacy of self-bias and positivity-bias using a classification task that paired self-relevant information with emotional expressions (i.e., Expt. 1) or reward information (i.e., Expt. 2). When the self was paired with relatively more positive information (i.e., smiling faces or high reward) we found evidence of a self-bias but no evidence of a positivity-bias. Whereas when the self was paired with relatively less positive information (i.e., neutral faces or low reward) we found evidence of a positivity-bias but no evidence of a self-bias. These results suggest the relative primacy of prioritised processing is flexible, context dependent and might be caused by a drive towards self-enhancement and the self-positivity bias.

The Many Hosts of Mycobacteria 9 (MHM9): A conference report.

The Many Hosts of Mycobacteria (MHM) meeting series brings together basic scientists, clinicians and veterinarians to promote robust discussion and dissemination of recent advances in our knowledge of numerous mycobacterial diseases, including human and bovine tuberculosis (TB), nontuberculous mycobacteria (NTM) infection, Hansen's disease (leprosy), Buruli ulcer and Johne's disease. The 9th MHM conference (MHM9) was held in July 2022 at The Ohio State University (OSU) and centered around the theme of "Confounders of Mycobacterial Disease." Confounders can and often do drive the transmission of mycobacterial diseases, as well as impact surveillance and treatment outcomes. Various confounders were presented and discussed at MHM9 including those that originate from the host (comorbidities and coinfections) as well as those arising from the environment (e.g., zoonotic exposures), economic inequality (e.g. healthcare disparities), stigma (a confounder of leprosy and TB for millennia), and historical neglect (a confounder in Native American Nations). This conference report summarizes select talks given at MHM9 highlighting recent research advances, as well as talks regarding the historic and ongoing impact of TB and other infectious diseases on Native American Nations, including those in Southwestern Alaska where the regional TB incidence rate is among the highest in the Western hemisphere.

Infectious diseases in Indigenous populations in North America: learning from the past to create a more equitable future.

The COVID-19 pandemic, although a profound reminder of endured injustices by and the disparate impact of infectious diseases on Indigenous populations, has also served as an example of Indigenous strength and the ability to thrive anew. Many infectious diseases share common risk factors that are directly tied to the ongoing effects of colonisation. We provide historical context and case studies that illustrate both challenges and successes related to infectious disease mitigation in Indigenous populations in the USA and Canada. Infectious disease disparities, driven by persistent inequities in socioeconomic determinants of health, underscore the urgent need for action. We call on governments, public health leaders, industry representatives, and researchers to reject harmful research practices and to adopt a framework for achieving sustainable improvements in the health of Indigenous people that is both adequately resourced and grounded in respect for tribal sovereignty and Indigenous knowledge.

Combating the Dust Devil: Utilizing Naturally Occurring Soil Microbes in Arizona to Inhibit the Growth of Coccidioides spp., the Causative Agent of Valley Fever.

The fungal disease Valley fever causes a significant medical and financial burden for affected people in the endemic region, and this burden is on the rise. Despite the medical importance of this disease, little is known about ecological factors that influence the geographic point sources of high abundance of the pathogens Coccidioides posadasii and C. immitis, such as competition with co-occurring soil microbes. These "hot spots", for instance, those in southern Arizona, are areas in which humans are at greater risk of being infected with the fungus due to consistent exposure. The aim of this study was to isolate native microbes from soils collected from Tucson, Arizona (endemic area for C. posadasii) and characterize their relationship (antagonistic, synergistic, or neutral) to the fungal pathogen with in vitro challenge assays. Secreted metabolites from the microbes were extracted and described using analytical techniques including high-performance liquid chromatography (HPLC) and mass spectrometry. Bacteria belonging to the genus Bacillus and fungi in the Fennellomyces and Ovatospora genera were shown to significantly decrease the growth of Coccidioides spp. In vitro. In contrast, other bacteria in the Brevibacillus genus, as well as one species of Bacillus bacteria, were shown to promote growth of Coccidioides when directly challenged. The metabolites secreted from the antagonistic bacteria were described using HPLC and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The microbes identified in this study as antagonists to Coccidioides and/or the metabolites they secrete have the potential to be used as natural biocontrol agents to limit the amount of fungal burden at geographic point sources, and therefore limit the potential for human infection.

Community Health Representatives as Trusted Sources for Increasing Representation of American Indian Communities in Clinical Research.

Indigenous and American Indian Alaskan Native (AI/AN) community members are systematically underrepresented in clinical trial research. This paper focuses on exploratory steps to partner with Native Nations of Arizona to engage Community Health Representatives (CHR) as a trusted source for building COVID-19 clinical trial research, including vaccine trials awareness. CHRs are frontline public health workers who apply a unique understanding of the experience, language, and culture of the population served. This workforce has entered the spotlight as essential to the prevention and control of COVID-19. METHODS: Three Tribal CHR programs were engaged to develop and refine culturally centered educational materials and a pre-post survey using a consensus-based decision-making approach. CHRs used these materials in brief education sessions during regular client home visits and community events. RESULTS: At 30 days post CHR intervention, participants (N = 165) demonstrated significantly increased awareness about and ability to enroll in COVID-19 treatment and vaccine trials. Participants also described a significant increase in trust in researchers, decreased perceived barriers related to cost for participation in a clinical trial, and improved belief that participation in a COVID-19 clinical trial for treatment was considered a benefit to American Indian and Alaskan Native people. CONCLUSION: CHRs as trusted sources of information, coupled with culturally centered education materials designed by CHRs for CHR clients, demonstrated a promising approach to improved awareness of clinical trial research generally and COVID-19 trials specifically among Indigenous and American Indian community members of Arizona.

Community Engagement Alliance (CEAL) Against COVID-19 Disparities: Academic-community partnership to support workforce capacity building among Arizona community health workers.

The COVID-19 pandemic has both highlighted and worsened existing health inequities among communities of color and structurally vulnerable populations. Community Health Workers, inclusive of Community Health Representatives (CHW/Rs) have entered the spotlight as essential to COVID-19 prevention and control. To learn about community experiences and perspectives related to COVID-19 and inform CHW/R workforce capacity building efforts, a series of focus groups were conducted with CHW/Rs throughout Arizona at two time points in 2021. Throughout the data collection and analysis process, researchers and community partners engaged in ongoing and open dialogue about what CHW/Rs on the ground were reporting as priority community concerns, needs, and challenges. Thus, CHW/Rs informed the development of culturally and linguistically relevant health education messages, materials, and training for CHW/Rs. In this community case study, we detail the efforts of partnership between a statewide CHW professional association and an academic research team that facilitated rapid decision-making and knowledge sharing to create community-grounded tools and resources supportive of CHW/R workforce capacity building in the context of the COVID-19 pandemic.

Novel Vaccine Strategies and Factors to Consider in Addressing Health Disparities of HPV Infection and Cervical Cancer Development among Native American Women.

Cervical cancer is the 4th most common type of cancer in women world-wide. Many factors play a role in cervical cancer development/progression that include genetics, social behaviors, social determinants of health, and even the microbiome. The prevalence of HPV infections and cervical cancer is high and often understudied among Native American communities. While effective HPV vaccines exist, less than 60% of 13- to 17-year-olds in the general population are up to date on their HPV vaccination as of 2020. Vaccination rates are higher among Native American adolescents, approximately 85% for females and 60% for males in the same age group. Unfortunately, the burden of cervical cancer remains high in many Native American populations. In this paper, we will discuss HPV infection, vaccination and the cervicovaginal microbiome with a Native American perspective. We will also provide insight into new strategies for developing novel methods and therapeutics to prevent HPV infections and limit HPV persistence and progression to cervical cancer in all populations.

Depression screening using a non-verbal self-association task: A machine-learning based pilot study.

BACKGROUND: Effective screening is important to combat the raising burden of depression and opens a critical time window for early intervention. Clinical use of non-verbal depression screening is nascent, yet a promising and viable candidate to supplement verbal screening. Differential self- and emotion-processing in depression patients were previously reported by non-verbal behavioural assessments, corroborated by neuroimaging findings of distinct neuroanatomical markers. Thus non-verbal validated brain-behaviour based self-emotion-related assessment data reflect physiological differences and may support individual level screening of depression. METHODS: In this pilot study (n = 84) we collected two longitudinal sessions of behavioural assessment data in a laboratory setting. Depression was assessed using Beck Depression Inventory II (BDI-II), to explore optimal screening methods with machine-learning, and to establish the validity of adapting a novel behavioural assessment focusing on self and emotions for depression screening. RESULTS: The best machine-learning model achieved high performance in depression screening, 10-Fold cross-validation (CV) Area Under the receiver operating characteristic Curve (AUC) of 0.90 and balanced accuracy of 0.81, using a Gradient Boosting algorithm. Prospective prediction using a model trained with session 1 data to predict session 2 depression status achieved a 10-Fold CV AUC of 0.77 and balanced accuracy of 0.66. We also identified interpretable behavioural signatures for depression patients based on the best model. CONCLUSION: The study supports the utility of using behavioural data as a viable and cost-effective solution for depression screening, with a potential wide range of applications in clinical settings.

Cultural identity central to Native American persistence in science.

Native Americans are the least represented population in science fields. In recent years, undergraduate and graduate level summer research programs that aimed to increase the number of Native Americans in science have made some progress. As new programs are designed, key characteristics that address science self-efficacy and science identity and provide supports for Native American students' commitment to a scientific career should be considered. In this study, we used sequential mixed methods to investigate the potential of culturally tailored internship programs on Native American persistence in science. We analyzed surveys (n = 47) and interviews (n = 4) with Native American students to understand their perceptions of themselves in relation to science research and how summer research experiences might develop science identities. Based on regression modeling, science identity, but not science self-efficacy, predicted intent to persist in science. In turn, science self-efficacy and Native American identity predicted science identity, and this suggests cultural identity is central to Native American persistence in science. In interviews, students' comments reinforced these findings and shed light on students' reasoning about the kinds of science experiences they sought; specifically, they chose to participate in culturally tailored internships because these programs provided a sense of belonging to the scientific community that did not conflict with their cultural identities. Based on our analysis, we propose an Indigenous science internship model and recommend that agencies target funding for culturally tailored programs from high school through early-investigator levels as well as provide inclusive programmatic and mentoring guidelines.

Building Trust and Awareness to Increase AZ Native Nation Participation in COVID-19 Vaccines.

The goal of this study was to establish effective, culturally appropriate strategies to enhance participation of American Indian/Alaska Native (AI/AN) communities in prevention and treatment of COVID-19, including vaccine uptake. Thirteen Community Health Representatives (CHRs) from three Arizona Native nations tailored education materials to each community. CHRs delivered the intervention to over 160 community members and administered a pre-posttest to assess trusted sources of information, knowledge, and self-efficacy and intention regarding COVID-19 vaccines. Based on pre-posttest results, doctors/healthcare providers and CHRs were the most trusted health messengers for COVID-19 information; contacts on social media, the state and federal governments, and mainstream news were among the least trusted. Almost two-thirds of respondents felt the education session was relevant to their community and culture, and more than half reported using the education materials to talk to a family member or friend about getting vaccinated. About 67% trusted the COVID-19 information provided and 74% trusted the CHR providing the information. Culturally and locally relevant COVID-19 vaccine information was welcomed and used by community members to advocate for vaccination. The materials and education provided by CHRs were viewed as helpful and emphasized the trust and influence CHRs have in their communities.

Perceiving the Self and Emotions with an Anxious Mind: Evidence from an Implicit Perceptual Task.

Anxiety disorders cause mental distress and low wellbeing in many people worldwide. Theories of anxiety describe negative worldviews and self-views as maintaining factors of the disorders. Recent research in social cognition has found a link between depression and altered perceptual biases to emotions, but the same research on anxiety is still missing. In this study, we measured perceptual biases to emotional and self-related stimuli in sub-clinically anxious participants and healthy controls using a self-emotional shape-label matching task. Results demonstrate that anxious participants had a diminished perceptual self-bias compared with healthy controls. Furthermore, the severity of anxiety was related to an emotional bias towards valanced other-related stimuli. The findings confirm the hypothesis that anxious individuals display an altered self-prioritisation effect in comparison with healthy individuals and that anxiety severity is linked to altered responses to emotionally valanced others. These findings have potential implications for early diagnosis and treatment of anxiety disorders.

Designing Inclusive HPV Cancer Vaccines and Increasing Uptake among Native Americans-A Cultural Perspective Review.

Despite a global and nationwide decrease, Native Americans continue to experience high rates of cancer morbidity and mortality. Vaccination is one approach to decrease cancer incidence such as the case of cervical cancer. However, the availability of vaccines does not guarantee uptake, as evident in the Coronavirus 2019 pandemic. Therefore, as we consider current and future cancer vaccines, there are certain considerations to be mindful of to increase uptake among Native Americans such as the incidence of disease, social determinants of health, vaccine hesitancy, and historical exclusion in clinical trials. This paper primarily focuses on human papillomavirus (HPV) and potential vaccines for Native Americans. However, we also aim to inform researchers on factors that influence Native American choices surrounding vaccination and interventions including cancer therapies. We begin by providing an overview of the historical distrust and trauma Native Americans experience, both past and present. In addition, we offer guidance and considerations when engaging with sovereign Tribal Nations in vaccine development and clinical trials in order to increase trust and encourage vaccine uptake.

Placebo comparator group selection and use in surgical trials: the ASPIRE project including expert workshop.

BACKGROUND: The use of placebo comparisons for randomised trials assessing the efficacy of surgical interventions is increasingly being considered. However, a placebo control is a complex type of comparison group in the surgical setting and, although powerful, presents many challenges. OBJECTIVES: To provide a summary of knowledge on placebo controls in surgical trials and to summarise any recommendations for designers, evaluators and funders of placebo-controlled surgical trials. DESIGN: To carry out a state-of-the-art workshop and produce a corresponding report involving key stakeholders throughout. SETTING: A workshop to discuss and summarise the existing knowledge and to develop the new guidelines. RESULTS: To assess what a placebo control entails and to assess the understanding of this tool in the context of surgery is considered, along with when placebo controls in surgery are acceptable (and when they are desirable). We have considered ethics arguments and regulatory requirements, how a placebo control should be designed, how to identify and mitigate risk for participants in these trials, and how such trials should be carried out and interpreted. The use of placebo controls is justified in randomised controlled trials of surgical interventions provided that there is a strong scientific and ethics rationale. Surgical placebos might be most appropriate when there is poor evidence for the efficacy of the procedure and a justified concern that results of a trial would be associated with a high risk of bias, particularly because of the placebo effect. CONCLUSIONS: The use of placebo controls is justified in randomised controlled trials of surgical interventions provided that there is a strong scientific and ethics rationale. Feasibility work is recommended to optimise the design and implementation of randomised controlled trials. An outline for best practice was produced in the form of the Applying Surgical Placebo in Randomised Evaluations (ASPIRE) guidelines for those considering the use of a placebo control in a surgical randomised controlled trial. LIMITATIONS: Although the workshop participants involved international members, the majority of participants were from the UK. Therefore, although every attempt was made to make the recommendations applicable to all health systems, the guidelines may, unconsciously, be particularly applicable to clinical practice in the UK NHS. FUTURE WORK: Future work should evaluate the use of the ASPIRE guidelines in making decisions about the use of a placebo-controlled surgical trial. In addition, further work is required on the appropriate nomenclature to adopt in this space. FUNDING: Funded by the Medical Research Council UK and the National Institute for Health Research as part of the Medical Research Council-National Institute for Health Research Methodology Research programme.

WHAT WAS THE RESEARCH ABOUT?: One of the best ways to prove that a new medicine really works is to use a scientific test called a 'placebo-controlled trial'. In this type of test, half of the participants are given a new pill and the other half are given a 'placebo', which is a dummy pill (usually a sugar pill) that is made to taste and look the same as the active pill, but has no active ingredients. The results are then compared. Just like medicines, new surgical procedures need to be tested to show that they are safe and benefit patients. Ideally, they would also be tested using the 'placebo-controlled trial' approach, but asking patients to have 'dummy' surgery is not the same as asking people to take a dummy pill. Placebo surgery raises lots of ethics questions and is controversial. As it is controversial, guidelines are needed to recommend when placebo surgery studies can be used (if at all) and what special considerations need to be taken into account. Our research team was commissioned to develop these guidelines. WHAT DID WE DO?: We summarised, to the best of our knowledge, all previous research that had used placebo surgery and reviewed all the ethics literature on this topic. We also looked at the latest scientific understanding of how placebos work. We then held a workshop to discuss and summarise the existing knowledge and to develop the new guidelines. This involved an international team of patients, surgeons, researchers, ethicists, psychologists, physiologists and funders. We published the guidelines [i.e. the ASPIRE (Applying Surgical Placebo in Randomised Evaluations) guidelines] in an influential medical journal and also wrote several other publications. This report provides a slightly more detailed version of our findings and recommendations. WHO WILL THIS HELP?: The guidelines will help researchers and doctors know when, and how, to best design placebo surgery studies in the future.

A comprehensive tool box for large animal studies of intervertebral disc degeneration.

Preclinical studies involving large animal models aim to recapitulate the clinical situation as much as possible and bridge the gap from benchtop to bedside. To date, studies investigating intervertebral disc (IVD) degeneration and regeneration in large animal models have utilized a wide spectrum of methodologies for outcome evaluation. This paper aims to consolidate available knowledge, expertise, and experience in large animal preclinical models of IVD degeneration to create a comprehensive tool box of anatomical and functional outcomes. Herein, we present a Large Animal IVD Scoring Algorithm based on three scales: macroscopic (gross morphology, imaging, and biomechanics), microscopic (histological, biochemical, and biomolecular analyses), and clinical (neurologic state, mobility, and pain). The proposed algorithm encompasses a stepwise evaluation on all three scales, including spinal pain assessment, and relevant structural and functional components of IVD health and disease. This comprehensive tool box was designed for four commonly used preclinical large animal models (dog, pig, goat, and sheep) in order to facilitate standardization and applicability. Furthermore, it is intended to facilitate comparison across studies while discerning relevant differences between species within the context of outcomes with the goal to enhance veterinary clinical relevance as well. Current major challenges in pre-clinical large animal models for IVD regeneration are highlighted and insights into future directions that may improve the understanding of the underlying pathologies are discussed. As such, the IVD research community can deepen its exploration of the molecular, cellular, structural, and biomechanical changes that occur with IVD degeneration and regeneration, paving the path for clinically relevant therapeutic strategies.