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Abstract Adoptive T-cell immunotherapy holds great promise for the treatment of viral complications in immunocompromised patients resistant to standard anti-viral strategies. We present a retrospective analysis of 78 patients from 19 hospitals across Australia and New Zealand, treated over the last 15 years with “off-the-shelf” allogeneic T cells directed to a combination of Epstein–Barr virus (EBV), cytomegalovirus (CMV), BK polyomavirus (BKV), John Cunningham virus (JCV) and/or adenovirus (AdV) under the Australian Therapeutic Goods Administration’s Special Access Scheme. Most patients had severe post-transplant viral complications, including drug-resistant end-organ CMV disease, BKV-associated haemorrhagic cystitis and EBV-driven post-transplant lymphoproliferative disorder. Adoptive immunotherapy is well tolerated with few adverse effects. Importantly, 46/71 (65%) patients show definitive clinical improvement including reduction in viral load, clinical symptoms and complete resolution of end-organ disease. In addition, seven high-risk patients remain disease free. Based on this long-term encouraging clinical experience, we propose that a dedicated nationally funded centre for anti-viral cellular therapies should be considered to provide T cell therapies for critically ill patients for compassionate use.

Background: LGBTQ + individuals often face social stigma and workplace discrimination, negatively impacting their well-being. However, limited research exists on the factors and strategies that enhance their positive workplace experiences. This study was a sequential qualitative mixed-method design conducted in three phases. The study had the following objectives: identifying factors associated with workplace well-being, generating strategies for improving workplace well-being, and obtaining feedback on the identified strategies' acceptability. Methods: In Phase 1, in-depth interviews were conducted with 10 LGBTQ + who described factors that improved their satisfaction at work. In Phase 2, two focus group discussions were held with 13 participants, including LGBTQ + adults, scholars in positive psychology, human resource development, and civil rights advocates, to develop strategies for improving workplace well-being based on Phase 1 data. In Phase 3, a survey was sent to a subset of the focus group participants (N = 7) to ascertain the acceptability of the developed strategies. Data analysis was performed using deductive and inductive approaches. Results: The study's first phase identified the factors contributing to workplace well-being. These factors were categorized into intrapersonal, interpersonal, and social-ecological. In the second phase and third phase, 11 strategies were developed to improve workplace well-being. These strategies were divided into two sections. The first section includes strategies organizations and agencies can implement to promote employee well-being (such as emphasizing diversity and equity as core values). The second section outlines strategies for government and civil society sectors (such as establishing laws addressing LGBTQ + equal rights). The Index of Congruence (IOC) assessed the relationship between strategies and workplace well-being improvement. Results showed IOC values from 0.8 to 1 for 11 strategies, indicating high content validity. Conclusions: Strategies to enhance LGBTQ + workplace well-being were identified through community engagement, but further research is needed for implementation and evaluation.

The study aimed to explore prevalence, risk factors, and intervention approaches related to adolescent smoking in Pakistan. Databases included PubMed, Scopus, Embase, Google Scholar, and ProQuest. Studies were selected on Pakistani adolescents aged 10-21 years, original or secondary articles published in English, and the use of qualitative and quantitative methods. Out of 1300 articles, 300 duplicates were removed. After reviewing titles and abstracts, 980 records were excluded. The full text of the 18 remaining studies was reviewed based on inclusion criteria, with 13 eligible studies included. Data extraction included author, age, setting, design, sample, theory, prevalence, risk factors, findings, and appraisal. Ten eligible studies reported varying prevalence rates of adolescent smoking in Pakistan, ranging from 09% to 61.14%. Individual risk factors associated with smoking included disposition, mood, and substance abuse. Social risk factors included family and peer influences, including father's smoking status, family members' tobacco use, and peer pressure. Environmental risk factors, including attendance at a public school, school-related pressure, exposure to tobacco use on social media, and lower socioeconomic status, significantly increased the likelihood of smoking among adolescents. Three studies evaluating prevention and intervention approaches demonstrated positive outcomes, including increased awareness of smoking harms, attitude shifts, and increased intention to quit smoking. This scoping review identified the influence of individual, social, and environmental risk factors on adolescent smoking. Educational interventions showed positive results on knowledge and attitude; however, none specifically focused on smoking cessation. Future research should focus on addressing these risk factors and implementing theoryguided interventions.

To examine knowledge and attitudes about lung health promotion (smoking cessation and lung cancer screening) among Black male smokers in a large Midwestern city in the United States. Semi-structured, in-depth interviews were conducted with 25 study participants. Each interview lasted approximately 45 minutes. Participants also completed a brief (5–10 minutes) survey measuring demographic characteristics, smoking experiences and knowledge and attitudes about lung health promotion activities. Descriptive statistics were used for quantitative data, and deductive thematic analysis for qualitative data analysis. The mean age of study participants was 57.5 years. Eighty-four percent of participants were current smokers, with the majority being daily smokers. Perceived risk for lung cancer was mixed, with 56% of participants endorsing that they considered themselves to be at high or moderate risk and the remaining 44% at low or no risk for lung cancer. Forty percent of participants reported having had a test to check their lungs for cancer. Participants were aware of the health risks associated with smoking but reported limited assistance from providers regarding the receipt of smoking cessation treatments. Awareness of lung cancer screening was limited, but participants expressed openness to screening; however, barriers were anticipated, including costs, fear and a reduced willingness to be screened in the absence of symptoms. Study participants reported limited experiences with lung health promotion activities. Knowledge about the facilitators and barriers can be used to develop health promotion interventions targeting smoking cessation and lung cancer screening.

Abstract Background Sex workers, those who trade sex for monetary or nonmonetary items, experience high rates of HIV transmission but have not been adequately included in HIV prevention and Pre-Exposure Prophylaxis (PrEP) adherence program development research. Community-empowered (C.E.) approaches have been the most successful at reducing HIV transmission among sex workers. Centering Healthcare (Centering) is a C.E. model proven to improve health outcomes and reduce health disparities in other populations, such as pregnant women, people with diabetes, and sickle cell disease. However, no research exists to determine if Centering can be adapted to meet the unique HIV prevention needs of sex workers. Objective We aim to explain the process by which we collaboratively and iteratively adapted Centering to meet the HIV prevention and PrEP retention needs of sex workers. Methods We utilized the Assessment, Decision, Adaptation, Production, Topical Experts, Integration, Training, Testing (ADAPT-ITT) framework, a model for adapting evidence-based interventions. We applied phases one through six of the ADAPT-ITT framework (Assessment, Decision, Adaptation, Production, Topical Experts, Integration) to the design to address the distinct HIV prevention needs of sex workers in Chicago. Study outcomes corresponded to each phase of the ADAPT-ITT framework. Data used for adaptation emerged from collaborative stakeholder meetings, individual interviews (n = 36) and focus groups (n = 8) with current and former sex workers, and individual interviews with care providers (n = 8). In collaboration with our community advisory board, we used a collaborative and iterative analytical process to co-produce a culturally adapted 3-session facilitator's guide for the Centering Pre-exposure Prophylaxis (C-PrEP +) group healthcare model. Results The ADAPT-ITT framework offered structure and facilitated this community-empowered innovative adaptation of Centering Healthcare. This process culminated with a facilitator's guide and associated materials ready for pilot testing. Conclusions In direct alignment with community empowerment, we followed the ADAPT-ITT framework, phases 1–6, to iteratively adapt Centering Healthcare to suit the stated HIV Prevention and PrEP care needs of sex workers in Chicago. The study represents the first time Centering has been adapted to suit the HIV prevention and PrEP care needs of sex workers. Addressing a gap in HIV prevention care for sex workers, Centering PrEP harnesses the power of community as it is an iteratively adapted model that can be piloted and replicated regionally, nationally, and internationally.

This article describes using the Qualitative Pathway Project Mapping Tool (QL-PPMT) to guide the development of rigorous qualitative research proposals. The original PPMT was initially developed to assist nursing students in planning their quantitative research proposals and has been widely used by faculty to advise student research projects. In this paper, we have adapted the 26 sections of the PPMT to provide a comprehensive checklist and road map for qualitative proposal planning. Further, we describe each section of the QL-PPMT in detail with examples and suggest additional resources to guide the development of evidence-based qualitative research proposals for new investigators, students, and trainees.

Abstract Background Black girls are disproportionately impacted by HIV and sexually transmitted infections (STIs), underscoring the urgent need for innovative strategies to enhance the adoption and maintenance of HIV/STI prevention efforts. Historically, Black male caregivers have been left out of girls’ programming, and little guidance exists to inform intervention development for Black girls and their male caregivers. Engaging Black male caregivers in Black girls’ sexual and reproductive health may reduce sexual risk-taking and improve the sustainability of preventative behaviors. Objective This paper describes the formative phases, processes, and methods used to adapt an evidence-based mother-daughter sexual and reproductive health intervention for Black girls 9–18 years old and their male caregivers. Methods We used the ADAPT-ITT model to tailor IMARA for Black girls and their male caregivers. Diverse qualitative methods (interviews, focus groups, and theater testing) were used throughout the adaption process. Results Findings support using the ADAPT-ITT model to tailor an evidence-based HIV/STI intervention for Black girls and their Black male caregivers. Findings highlight the importance of community engagement and the use of qualitative methods to demonstrate the acceptability and feasibility of the adapted intervention. Key lessons learned are reviewed. Conclusions Adapting evidence-based interventions to incorporate Black girls and their Black male caregivers should be driven by a relevant theoretical framework that aligns with the target population(s). Adapting the intervention in partnership with the community has been shown to improve acceptability and feasibility as it is responsive to community needs. Using a systematic process like the ADAPT-ITT model will ensure that the new program is ready for efficacy trials.

Black/African American (BAA) men have the lowest life expectancy among other major demographic groups in the United States, with BAA male mortality rates 40% higher than their White male counterparts. Despite known benefits of preventive health care utilization, BAA men are 43% more likely to use the emergency department for usual care. Many intersecting factors like medical mistrust and religion have been identified as common barriers BAA men face in health care utilization with few studies exploring factors that impact their current preventive health care utilization. In addition, BAA men’s perceptions of health and ability to identify or seek help have always been disproportionately lower than other racial groups despite higher rates of preventable diseases. Using the tenets of the Andersen Healthcare Utilization Model, this cross-sectional study of 176 BAA men explores BAA men’s current preventive health care practices while examining the intersection of predisposing, enabling, and need factors on BAA men’s preventive health care utilization. While it is well known that higher income levels and higher education positively influence health care utilization, the intersection of religious affiliation and higher levels of medical mistrust was associated with BAA men’s decreased engagement with health care as religion posed as a buffer to health care utilization. This study demonstrated that BAA men’s perception of health differed by sexual orientation, educational status, and income. However, across all groups the participants’ perspective of their health was not in alignment with their current health outcomes. Future studies should evaluate the impact of masculine norms as potential enabling factors on BAA men’s preventive health care utilization.

The study's goal was to look at providers' knowledge, attitudes, and behaviors regarding lung cancer screening among Black male smokers served by a federally qualified healthcare center. Participants in the study were interviewed in depth. Participants completed a short (5-10 minute) survey that assessed demographics, training, and attitudes toward lung cancer screening. For quantitative data, descriptive statistics were used, and for qualitative data, deductive thematic analysis was used. This study included ten healthcare professionals, the majority of whom identified as Black (80%) and were trained as advanced practice providers (60%). The majority of providers (90%) have heard of LDCT lung cancer screening; however, participants reported only being “somewhat” familiar with the LDCT eligibility criteria (70%). Despite generally positive attitudes toward LDCT, patient referral rates for screening were low. Barriers included a lack of provider knowledge about screening eligibility, a lack of use of shared decision-making tools, and patient concerns about screening risks. The reasons for the low referral rates varied, but they included a preference to refer patients for smoking cessation rather than screening, low screening completion and follow-up rates among referred patients, and a lower likelihood that Black smokers will meet pack-year requirements for screening. Additionally, providers discussed patient-level factors such as a lack of information, mistrust, and transportation. The study findings add to the body of knowledge about lung cancer knowledge and screening practices among providers in FQHC settings. This data can be used to create health promotion interventions aimed at smoking cessation and lung cancer screening in Black males and other high-risk smokers.

Photovoltaic technologies provide significant capacity to electric grids, however, resource variability and production uncertainty complicate power balancing and reserve management. A crucial step in predicting solar generation is determining clear-sky irradiance. Clear-sky attenuation can be modeled using broadband atmospheric turbidity factors, but model accuracy is dependent on the measurements used to determine the current and future state of aerosol loading and water vapor content, which requires close proximity measurements, in time and space, to account for turbidity variability. Such measurements, though, are only available in near real-time at a limited, and decreasing, number of sites. This paper proposes a new method for estimating time-varying local turbidity conditions from more readily available pyranometer or PV output data. The method employs a long short-term memory recurrent neural network to distill the turbidity-driven signal from global irradiance (or global irradiance driven) observations, despite an inherent dampening issue. The method is developed to operate in near real-time for solar forecasting applications. Validation examines the ability of the method to (1) reproduce turbidity estimates derived from historical measurements of beam irradiance under clear-sky conditions; and (2) provide input for clear-sky models in the form of persistence forecasts generated from daily mean values.

Abstract Background Lesbian, gay, bisexual, and transgender (LGBT) individuals have documented disparities in mental health that are experienced across the life course. However, limited research has been conducted to identify the factors which contribute to evaluated risk for poor mental health among older Asian Americans who identify as LGBT. The purpose of this study was to determine the perspectives of leaders of community-based organizations about the mental health needs and concerns of their LGBT constituents from diverse Asian backgrounds. Methods Semi-structured qualitative interviews were conducted with leaders of community-based organizations serving the needs of LGBT individuals. A qualitative framework analysis approach was used to identify, analyze and report themes within the data. Results 11 members of community organizations located in California (54.5%), Chicago (27.2%), and New York (18.1%) were interviewed. Chronic stress was identified as negatively impacting constituents’ lives and was attributed to social determinants of health, including inadequate housing, financial insecurity, discrimination, barriers to adequate health care, and immigration status. Ageism, social isolation, language barriers, and limited connections to cultural, religious, or LGBT communities were identified as factors impacting middle-aged and older adults. Participants identified homelessness, violence, and lack of parental acceptance as contributing to distress among youth and younger adults. The most vulnerable community members were identified as gender minorities, undocumented individuals, and individuals with limited English proficiencies. Organizational leaders described strategies to address social determinants. Conclusions Asian Americans who are LGBT are confronted with substantial risks for poor mental health that are linked to modifiable social determinants of health. Organizations serving these populations play a vital role in meeting the needs of a highly underserved population.

Introduction: Cardiac resynchronisation therapy is ineffective in 30–40% of patients with heart failure with reduced ejection fraction. Targeting non-scarred myocardium by selecting the site of latest mechanical activation using echocardiography has been suggested to improve outcomes but at the cost of increased resource utilisation. The interval between the beginning of the QRS complex and the local LV lead electrogram (QLV) might represent an alternative electrical marker. Aims: To determine whether the site of latest myocardial electrical and mechanical activation are concordant. Methods: This was a single-centre, prospective pilot study, enrolling patients between March 2019 and June 2021. Patients underwent speckle-tracking echocardiography (STE) prior to CRT implantation. Intra-procedural QLV measurement and R-wave amplitude were performed in a blinded fashion at all accessible coronary sinus branches. Pearson’s correlation coefficient and Cohen’s Kappa coefficient were utilised for the comparison of electrical and echocardiographic parameters. Results: A total of 20 subjects had complete data sets. In 15, there was a concordance at the optimal site between the electrically targeted region and the mechanically targeted region; in four, the regions were adjacent (within one segment). There was discordance (≥2 segments away) in only one case between the two methods of targeting. There was a statistically significant increase in procedure time and fluoroscopy duration using the intraprocedural QLV strategy. There was no statistical correlation between the quantitative electrical and echocardiographic data. Conclusions: A QLV-guided approach to targeting LV lead placement appears to be a potential alternative to the established echocardiographic-guided technique. However, it is associated with prolonged fluoroscopy and overall procedure time.

HIV/AIDS disproportionately impacts Black cisgender female adolescents and emerging adults. Pre-Exposure Prophylaxis (PrEP) reduces the risk of HIV infection; however, structural barriers may exacerbate resistance to PrEP in this population. The purpose of this paper is to understand the characteristics of age, race, gender, history, and medical mistrust as barriers to PrEP uptake among Black female adolescents and emerging adults (N = 100 respondents) between the ages of 13–24 years in Chicago. Between January and June of 2019, participants completed the survey. We used directed content analysis to examine reported barriers to PrEP uptake. The most commonly identified barriers to PrEP uptake were side effects (N = 39), financial concerns (N = 15), and medical mistrust (N = 12). Less frequently reported barriers included lack of PrEP knowledge and misconceptions (N = 9), stigma (N = 2), privacy concerns (N = 4). We describe innovative multi-level strategies to provide culturally safe care to improve PrEP acceptability among Black female adolescents and emerging adults in Chicago. These recommendations may help mitigate the effect of medical mistrust, stigma, and misconceptions of PrEP within Black communities.

Background & Aim: Nurses play a vital role in discharge planning, especially for patients with colorectal cancer who require complex post-treatment care. However, there is a limited understanding of nurses’ discharge planning practice in oncology settings. This study aimed to examine current discharge planning practices for patients with colorectal cancer among oncology nurses in Thailand and associated factors. Methods & Materials: A cross-sectional survey study was conducted between October and November 2020. Oncology nurses involved in colorectal cancer care were recruited across Thailand via Facebook and the Line application. A convenience and snowball sample of 206 nurses completed the online survey. Descriptive statistics, t-test, and one-way ANOVA were used for data analysis. Results: The discharge planning activity with the lowest mean score was related to sharing discharge planning summaries and/or care plans with other healthcare facilities (M = 3.00, SD= 1.32), followed by providing information about returning to work (M= 3.06, SD= 1.28), financial resources (M= 3.12, SD= 1.26), and disease (M= 3.13, SD= 1.25). Factors significantly associated with discharge planning practice included nursing education levels, specialty training in cancer care, and experience in colorectal cancer care. Conclusion: Despite the availability of discharge planning guidelines, Thai oncology nurses did not perform the full scope of discharge planning activities required for patients with colorectal cancer. Additional strategies, resources, and support systems should be established to facilitate nurses’ performance of the full scope of their discharge planning practice in oncology settings. Moreover, our results suggest the need for additional education and training in the form of enhanced curriculums and continuing education seminars addressing cancer care to advance nurses’ discharge planning for patients with colorectal cancer.

Abstract Nasopharyngeal carcinoma (NPC) is an Epstein–Barr virus (EBV)-associated heterogeneous disease and is characterized by peritumoral immune infiltrate. Adoptive T-cell therapy (ACT) has emerged as a potential therapeutic strategy for NPC. However, the tumor microenvironment remains a major roadblock for the successful implementation of ACT in clinical settings. Expression of checkpoint molecules by malignant cells can inhibit the effector function of adoptively transferred EBV-specific T cells. Here we present a novel case report of a patient with metastatic NPC who was successfully treated with a combination of EBV-specific ACT and programmed cell death-1 blockade therapy. Following combination immunotherapy, the patient showed complete resolution of metastatic disease with no evidence of disease relapse for 22 months. Follow-up immunological analysis revealed dramatic restructuring of the global T-cell repertoire that was coincident with the clinical response. This case report provides an important platform for translating these findings to a larger cohort of NPC patients.

This article describes an educational program to engage African American men as citizen scientists (CSs) and future research partners in a lung cancer screening project. We provide an overview of the curriculum used, the structure and format of the educational sessions, and associated educational outcomes. Furthermore, we describe lessons learned in the engagement of African American men as CS in community-based lung-health equity research. The CS educational program included five group-based sessions delivered through zoom. The educational curriculum was adapted from the University of Florida Citizen Scientist program and tailored to address lung health and the contextual experiences of African American men. Each session lasted 90 minutes. Pre- and post-test measures were collected to examine changes in knowledge, comfort, health literacy, research interests, and medical mistrust. Eight African American men completed the CS educational program. Attendance rates were high for each session (100%). Seven participants completed additional human subject research certification. Improvements were observed from pre- to post-test in participants’ level of knowledge, comfort, and health literacy but not medical mistrust. CS reported the most interest in participating in research aimed to identify important community strengths and problems. Study findings suggest that it was feasible to deliver an online citizen scientist educational program designed to prepare participants to serve as partners in a lung cancer screening intervention for African American men. Results suggest the educational program has the potential to improve key outcomes including completion of regulatory training and increased research-related knowledge, comfort, and health literacy.

The National Center for Advancing Translational Sciences has called for more comprehensive research with priority populations to reduce disparities and for the development of additional resources to assist researchers in implementing these recommendations. Here we report the development and initial evaluation of five Priority Populations Toolkits, which are resources developed by the University of Illinois Center for Clinical and Translational Science to meet these goals. Three aims guide the content: increasing knowledge, facilitating communication, and improving research design. Materials were curated from scientific literature reviews and Internet searches and revised iteratively. Analytics and user surveys provide information about usage. In 22 months, 387 unique users accessed the toolkits. The top reason for usage was to improve research recruitment. Comprehensive toolkits for working with priority populations show promising potential for increasing knowledge and readiness to work with underrepresented populations. Further toolkit development and evaluation of effectiveness are warranted.

Abstract Background Effective mosquito control approaches incorporate both adult and larval stages. For the latter, physical, biological, and chemical control have been used with varying results. Successful control of larvae has been demonstrated using larvicides including insect growth regulators, e.g. the organophosphate temephos, as well as various entomopathogenic microbial species. However, a variety of health and environmental issues are associated with some of these. Laboratory trials of essential oils (EO) have established the larvicidal activity of these substances, but there are currently no commercially available EO-based larvicides. Here we report on the development of a new approach to mosquito larval control using a novel, yeast-based delivery system for EO. Methods Food-grade orange oil (OO) was encapsulated into yeast cells following an established protocol. To prevent environmental contamination, a proprietary washing strategy was developed to remove excess EO that is adsorbed to the cell exterior during the encapsulation process. The OO-loaded yeast particles were then characterized for OO loading, and tested for efficacy against Aedes aegypti larvae. Results The composition of encapsulated OO extracted from the yeast microparticles was demonstrated not to differ from that of un-encapsulated EO when analyzed by high performance liquid chromatography. After lyophilization, the oil in the larvicide comprised 26–30 percentage weight (wt%), and is consistent with the 60–65% reduction in weight observed after the drying process. Quantitative bioassays carried with Liverpool and Rockefeller Ae. aegypti strains in three different laboratories presented LD50 of 5.1 (95% CI: 4.6–5.6) to 27.6 (95% CI: 26.4–28.8) mg/l, for L1 and L3/L4 mosquito larvae, respectively. LD90 ranged between 18.9 (95% CI: 16.4–21.7) mg/l (L1 larvae) to 76.7 (95% CI: 69.7–84.3) mg/l (L3/L4 larvae). Conclusions The larvicide based on OO encapsulated in yeast was shown to be highly active (LD50

Adoptive T-cell immunotherapy has provided promising results in the treatment of viral complications in humans, particularly in the context of immunocompromised patients who have exhausted all other clinical options. The capacity to expand T cells from healthy immune individuals is providing a new approach to anti-viral immunotherapy, offering rapid off-the-shelf treatment with tailor-made human leukocyte antigen (HLA)-matched T cells. While most of this research has focused on the treatment of latent viral infections, emerging evidence that SARS-CoV-2-specific T cells play an important role in protection against COVID-19 suggests that the transfer of HLA-matched allogeneic off-the-shelf virus-specific T cells could provide a treatment option for patients with active COVID-19 or at risk of developing COVID-19. We initially screened 60 convalescent individuals and based on HLA typing and T-cell response profile, 12 individuals were selected for the development of a SARS-CoV-2-specific T-cell bank. We demonstrate that these T cells are specific for up to four SARS-CoV-2 antigens presented by a broad range of both HLA class I and class II alleles. These T cells show consistent functional and phenotypic properties, display cytotoxic potential against HLA-matched targets and can recognize HLA-matched cells infected with different SARS-CoV-2 variants. These observations demonstrate a robust approach for the production of SARS-CoV-2-specific T cells and provide the impetus for the development of a T-cell repository for clinical assessment.

Background: Smoking rates among low-income patients are double those of the general population. Access to health care is an essential social determinant of health. Federally qualified health care centers (FQHC) are government-supported and community-based centers to increase access to health care for non-insured and underinsured patients. However, barriers to implementation impact adherence and sustainability of evidence-based smoking cessation within FQHC settings. To address this implementation barrier, our multi-disciplinary team proposes Mi QUIT CARE (Mile Square QUITCommunity-Access-Referral-Expansion) to establish the acceptability, feasibility, and capacity of an FQHC system to deliver an evidence-based and multi-level intervention to increase patient engagement with a state tobacco quitline.Methods: A mixed-method approach, rooted in an implementation science framework of RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance), will be used in this hybrid effectiveness-implementation design. We aim to evaluate the efficacy of a novel delivery system (patient portal) for increasing access to smoking cessation treatment. In preparation for a future randomized clinical trial of Mi QUIT CARE, we will conduct the following developmental research: (1) Examine the burden of tobacco among patient populations served by our partner FQHC, (2) Evaluate among FQHC patients and health care providers, knowledge, attitudes, barriers, and facilitators related to smoking cessation and our intervention components, (3) Evaluate the use of tailored communication strategies and patient navigation to increase patient portal uptake among patients, and (4) To test the acceptability, feasibility, and capacity of the partner FQHC to deliver Mi QUIT CARE.Discussion: This study provides a model for developing and implementing smoking and other health promotion interventions for low-income patients delivered via patient health portals. If successful, the intervention has important implications for addressing a critical social determinant of cancer and other tobacco-related morbidities.Trial Registration: U.S. National Institutes of Health Clinical Trials, NCT04827420, https://clinicaltrials.gov/ct2/show/NCT04827420.

ABSTRACT Associated microorganisms (“microbiota”) play a central role in determining many animals’ survival and reproduction characteristics. The impact of these microbial influences on an animal’s fitness, or population growth, in a given environment has not been defined as clearly. We focused on microbiota-dependent host fitness by measuring life span and fecundity in Drosophila melanogaster fruit flies reared individually with 14 different bacterial species. Consistent with previous observations, the different bacteria significantly influenced the timing of fly life span and fecundity. Using Leslie matrices, we show that fly fitness was lowest when the microbes caused the flies to invest in life span over fecundity. Computational permutations showed that the positive fitness effect of investing in reproduction was reversed if fly survival over time was low, indicating that the observed fitness influences of the microbes could be context dependent. Finally, we showed that fly fitness is not influenced by bacterial genes that shape fly life span or fly triglyceride content, a trait that is related to fly survival and reproduction. Also, metagenome-wide association did not identify any microbial genes that were associated with variation in fly fitness. Therefore, the bacterial genetic basis for influencing fly fitness remains unknown. We conclude that bacteria influence a fly’s reproductive timing more than total reproductive output and that (e.g., environmental) conditions that influence fly survival likely determine which bacteria benefit fly fitness. IMPORTANCE The ability of associated microorganisms (“microbiota”) to influence animal life history traits has been recognized and investigated, especially in the past 2 decades. For many microbial communities, there is not always a clear definition of whether the microbiota or its members are beneficial, pathogenic, or relatively neutral to their hosts’ fitness. In this study, we report the influence of individual members of the microbiota on Drosophila melanogaster fitness using Leslie matrices that combine the microbial influences on fly survival and reproduction into a single fitness measure. Our results are consistent with a previous report that, in the laboratory, acetic acid bacteria are more beneficial to the flies than many strains of lactic acid bacteria. We add to the previous finding by showing that this benefit depends on fly survival rate. Together, our work helps to show how the microbiota of a fly influences its laboratory fitness and how these effects may translate to a wild setting.

Objective: The purpose of this study was to examine the influence of access to care on the uptake of low-dose computed tomography (LDCT) lung cancer screening among a diverse sample of screening-eligible patients.Methods: We utilized a cross-sectional study design. Our sample included patients evaluated for lung cancer screening at a large academic medical center (AMC) between 2015 and 2017 who met 2013 USPSTF guidelines for LDCT screening eligibility. The completion of LDCT screening (yes, no) was the primary dependent variable. The independent variable was access to care (insurance type, living within the AMC service area). We utilized binary logistic regression analyses to examine the influence of access to care on screening completion after adjusting for demographic factors (age, sex, race) and smoking history (current smoking status, smoking pack-year history).Results: A total of 1,355 individuals met LDCT eligibility criteria, and of those, 29.8% (n = 404) completed screening. Regression analysis results showed individuals with Medicaid insurance (OR, 1.51; 95% CI, 1.03-2.22), individuals living within the AMC service area (OR, 1.71; 95% CI, 1.21–2.40), and those aged 65–74 years (OR, 1.49; 95% CI, 1.12–1.98) had higher odds of receiving LDCT lung cancer screening. Lower odds of screening were associated with having Medicare insurance (OR, 0.30; 95% CI, 0.22–0.41) and out-of-pocket (OR, 0.27; 95% CI, 0.15–0.47).Conclusion: Access to care was independently associated with lowered screening rates. Study results are consistent with prior research identifying the importance of access factors on uptake of cancer early detection screening behaviors.

Increasing TCR cell surface expression can potentiate T cell responses to low-concentrations of antigen. Here the authors identify aminoacids in human TCR variable domains that impact its surface expression, and demonstrate how editing these residues can improve T cell activation and effector function without altering antigen specificity.

Representation of under-represented minority (URM) faculty in the health sciences disciplines is persistently low relative to both national and student population demographics. Although some progress has been made through nationally funded pipeline development programs, demographic disparities in the various health sciences disciplines remain. As such the development of innovative interventions to help URM faculty and students overcome barriers to advancement remains a national priority. To date, the majority of pipeline development programs have focused on academic readiness, mentorship, and professional development. However, insights from the social sciences literature related to “extra-academic” (e.g., racism) barriers to URM persistence in higher education suggest the limitations of efforts exclusively focused on cognitively mediated endpoints. The purpose of this article is to synthesize findings from the social sciences literature that can inform the enhancement of URM pipeline development programs. Specifically, we highlight research related to the social, emotional, and contextual correlates of URM success in higher education including reducing social isolation, increasing engagement with research, bolstering persistence, enhancing mentoring models, and creating institutional change. Supporting URM’s success in the health sciences has implications for the development of a workforce with the capacity to understand and intervene on the drivers of health inequalities.

When animal cells enter mitosis, they round up to become spherical. This shape change is accompanied by changes in mechanical properties. Multiple studies using different measurement methods have revealed that cell surface tension, intracellular pressure and cortical stiffness increase upon entry into mitosis. These cell-scale, biophysical changes are driven by alterations in the composition and architecture of the contractile acto-myosin cortex together with osmotic swelling and enable a mitotic cell to exert force against the environment. When the ability of cells to round is limited, for example by physical confinement, cells suffer severe defects in spindle assembly and cell division. The requirement to push against the environment to create space for spindle formation is especially important for cells dividing in tissues. Here we summarize the evidence and the tools used to show that cells exert rounding forces in mitosis in vitro and in vivo, review the molecular basis for this force generation and discuss its function for ensuring successful cell division in single cells and for cells dividing in normal or diseased tissues.

Abstract Objectives There is emerging evidence that SARS‐CoV‐2‐specific memory T‐cell responses are likely to provide critical long‐term protection against COVID‐19. Strategies to rapidly assess T‐cell responses are therefore likely to be important for assessing immunity in the global population. Methods Here, we have developed a rapid immune‐monitoring strategy to assess virus‐specific memory T‐cell responses in the peripheral blood of COVID‐19 convalescent individuals. We validated SARS‐CoV‐2‐specific memory T‐cell responses detected in whole blood using in vitro expansion with SARS‐CoV‐2 proteins. Results T‐cell immunity characterised by the production of IFN‐γ and IL‐2 could be consistently detected in the whole blood of recovered participants. T cells predominantly recognised structural SARS‐CoV‐2 proteins. In vitro expansion demonstrated that while CD8+ T cells recognised nucleocapsid protein, spike protein and ORF3a, CD4+ T cells more broadly targeted multiple SARS‐CoV‐2 proteins. Conclusion These observations provide a timely monitoring approach for identifying SARS‐CoV‐2 cellular immunity and may serve as a diagnostic for the stratification of risk in immunocompromised and other at‐risk individuals.

Despite the significant health disparities experienced by lesbian, gay, bisexual, and transgender (LGBT) populations, few investigators affiliated with the National Institutes of Health-funded Clinical and Translational Science Award Programs are conducting research related to this underserved population. We provide recommendations shared during a half-day workshop aimed at increasing researcher readiness to conduct LGBT research. This workshop was presented as part of a series on conducting research with underserved populations offered by the Recruitment, Retention, and Community Engagement Program of the Center for Clinical and Translational Science at the University of Illinois at Chicago. Six LGBT health research experts provided focused presentations. The workshop presentations included a summary of significant health inequality issues, theoretical models relevant to research on LGBT health, best practices in measuring sexual orientation and gender identity, recommendations for recruitment and retention, a discussion of community engagement, and ethical considerations in conducting LGBT research. We provide a summary of recommendations to guide future research, training, and public policy related to LGBT health. The information can increase capacity among Clinical and Translational Science Award affiliated researchers in conducting research in this special population.

Preparing investigators to competently conduct community-engaged research is critical to achieving Clinical and Translational Science Award (CTSA) program goals. The purpose of this study is to describe the perspectives of members of a long-standing community engagement advisory board (CEAB) on investigators’ readiness to engage communities and indicators of investigator competence in community-engaged research, in order to suggest core competencies to guide the development of CTSA-sponsored educational programs. Two 90-minute focus groups were conducted with a subset of members of a CEAB (n=19) affiliated with the Center for Clinical and Translational Science at the University of Illinois at Chicago. CEAB members identified a range of investigator skills and practices that demonstrate readiness to engage in community-engaged research. Eight competencies were identified that should be incorporated in providing education to enhance the readiness and competency of CTSA-affiliated researchers planning to engage communities in research. CEAB observations demonstrate the necessity of developing competency-based educational programs that prepare clinical and translational scientists at all levels for the important work of community-engaged research.

Rural populations have higher rates of late stage lung cancer incidence and mortality compared to urban populations, making them important target populations for low dose computed tomography (LDCT) screening. LDCT screening has been shown to reduce lung cancer mortality and is recommended by the United States Preventive Services Task Force for individuals who meet certain risk criteria. However, rural populations may experience greater system, provider, and individual-level barriers to screening and related health-seeking behavior (e.g. smoking cessation). LDCT screening was first tested in urban, academic centers, so it is still unknown how readily it may be implemented in rural areas. Additionally, rural populations have limited access to both primary care physicians who may refer to LDCT screening and specialty physicians who may perform the screening. Further, rural populations may be less likely to seek screening due to lack of awareness and understanding or other unknown knowledge or psychosocial barriers. There are several strategies that may address these rural specific challenges. First, further research is needed to better understand the individual-level barriers that rural patients experience. Second, to reduce system-level barriers, additional efforts should be made to increase rural access to screening through improved referral processes. Third, creation of decision support materials to equip rural providers to engage their patients in a shared decision making process regarding screening may help reduce physician level barriers. Fourth, development of a holistic approach to smoking cessation may help reduce lung cancer risk in conjunction with LDCT screening. Keywords: Rural cancer disparities, Lung cancer, Screening, Low dose computed tomography

PurposeCommunity engagement is deemed as critical to the success of the CTSA program. In 2009, to improve research engagement and build capacity for community-engaged research across the translational spectrum, the Center for Clinical and Translational Science at the University of Illinois at Chicago created a Community Engagement Advisory Board (CEAB). Here, we report results of our ongoing evaluation efforts.MethodsCEAB activities are evaluated using mixed methods. Annual CEAB evaluation surveys were completed from 2010 to 2016 (n=106 respondents). In 2014, two 90-minute focus groups were conducted with a subset of recent CEAB members (n=19).ResultsSurvey data suggest respondents perceive their consultations to be helpful in improving the capacity of researchers (90%) and the quality of research projects (80%). Further, CEAB members perceive themselves to have personally benefitted from their involvement including obtaining new knowledge (84%), expansion of their networks (76%), and forming new community linkages (51%). Results of the qualitative data were consistent with survey data.ConclusionsOur CEAB has improved research engagement and developed institutional capacity to conduct community-engaged research in several ways. Our findings can inform the establishment or enhancement of community engagement services for CTSA-affiliated researchers and community partners.

IntroductionThe purpose of this study was to obtain feedback from a diverse group of community advisory board members about different clinic or hospital-based approaches to increasing research participation.MethodsMembers of an established community engagement advisory board (n=16) provided qualitative and survey data regarding attitudes and preferences for 3 hospital and clinic system strategies to recruit patients into clinical research including universal consent for research, patient registries, and patient portals.ResultsOverall, there was moderate support for each of the 3 approaches discussed. Board members described advantages and disadvantages of each method. Based on the qualitative data, universal consent was viewed as the best strategy for consenting high volumes of patients for research. However, patient registries and portals were seen as more acceptable, less-intrusive and more likely to result in higher participation rates. Survey data were consistent with qualitative findings.ConclusionsInput from community stakeholders is needed to identify strategies to enhance participation and increase diversity in clinical research. Members of our CEAB identified patient registries and portals as feasible and nonintrusive approaches to increasing research participation. Additional research is needed to confirm these findings and to establish best practices for supporting patients in using registry approaches.

IntroductionThe purpose of this paper is to describe the formation, operation, and evaluation of a Community Engagement Advisory Board (CEAB) that serves as a resource of the University of Illinois at Chicago’s (UIC) Center for Clinical and Translational Sciences (CCTS).MethodsCurrent CEAB roles and functions, operating procedures for research consultations and program evaluation strategies were described. Investigators receiving a consultation from 2009 to 2017 (n=91, response rate 78%) were surveyed via an online survey immediately after the consultation and at 12-month follow-up.ResultsOverall, CEAB members were viewed as having sufficient information (92%) and expertise (79%) to provide consultation. Satisfaction levels with the specific consultation received and the overall consultation service were high. The majority of investigators indicated that they would come back to the CEAB for a future consultation, if needed, and would recommend a consultation to others (93% and 96%, respectively). At 12-months, 87% of respondents indicated they had implemented at least some of the recommendations received and 93% said that the consultation influenced their subsequent research.ConclusionsData from recent annual evaluations highlight the benefits of CEAB for consulting investigators. Our model can be used to inform the development of future CEAB boards.

Abstract Background Entry into mitosis triggers profound changes in cell shape and cytoskeletal organisation. Here, by studying microtubule remodelling in human flat mitotic cells, we identify a two-step process of interphase microtubule disassembly. Results First, a microtubule-stabilising protein, Ensconsin/MAP7, is inactivated in prophase as a consequence of its phosphorylation downstream of Cdk1/cyclin B. This leads to a reduction in interphase microtubule stability that may help to fuel the growth of centrosomally nucleated microtubules. The peripheral interphase microtubules that remain are then rapidly lost as the concentration of tubulin heterodimers falls following dissolution of the nuclear compartment boundary. Finally, we show that a failure to destabilise microtubules in prophase leads to the formation of microtubule clumps, which interfere with spindle assembly. Conclusions This analysis highlights the importance of the step-wise remodelling of the microtubule cytoskeleton and the significance of permeabilisation of the nuclear envelope in coordinating the changes in cellular organisation and biochemistry that accompany mitotic entry.

Abstract Objectives Clinical response to antibody‐based immunotherapies targeting checkpoint inhibitors is critically dependent on the tumor immune microenvironment (TIME). However, the precise impact of the TIME on adoptive cellular immunotherapy remains unexplored. Here we have conducted a long‐term follow‐up analysis of patients with recurrent glioblastoma multiforme (GBM) who were treated with autologous CMV‐specific T‐cell therapy to delineate the potential impact of the TIME on their clinical response. Methods Multiplexed immunohistochemical analysis of CD3, PD‐L1 and Sox‐2 in GBM tissue biopsies obtained before autologous T‐cell therapy was carried out and correlated with long‐term survival of GBM patients adoptively treated with T‐cell therapy. Results Tumor microenvironment analyses revealed that the pre‐treatment cellular composition of the tumor tissue may influence the subsequent response to adoptive T‐cell therapy. GBM patients who showed prolonged overall survival following T‐cell therapy had a significantly lower number of tumor‐infiltrating CD3+ T cells in recurrent tumors than that in patients with short‐term survival. Furthermore, long‐term surviving patients showed low or undetectable PD‐L1 expression in tumor cells in recurrent GBM biopsies. Conclusion We hypothesise that lack of PD‐L1‐mediated immunosuppression in the TIME may allow efficient immune control following adoptive T‐cell therapy. Future studies combining anti‐PD‐L1 or genetically modified T cells with PD‐1 receptor knockdown could be considered to improve clinical responses in patients who have high PD‐L1 expression in their tumors.

Objective: Andersen’s Behavioral Model of Health Services Utilization was used as a framework to examine the influence of acculturation and health literacy on cancer screening behaviors among older Chinese Americans living in the greater Chicago area. Method: Data were obtained from the Population Study of Chinese Elderly in Chicago ( N = 3,157; mean age = 72.8 years). Logistic regression analyses were conducted to examine the impact of acculturation and health literacy on lifetime cancer screening utilizations and adherence to cancer screening guideline established by American Cancer Society (ACS) after controlling for predisposing, enabling, and need factors of Andersen’s behavioral model. Results: Lifetime rates of ever had cancer screening were low among older Chinese Americans living in the greater Chicago area. The majority of study participants were not adherent to ACS early detection cancer screening guidelines. Results from multivariate analyses showed that higher health literacy (odds ratio range = 1.39-1.72) and acculturation (odds ratio range = 1.28-2.06) levels were associated with an increased likelihood of lifetime and current cancer screening among older Chinese Americans. Discussion: The findings of this study highlight the importance of working to improve health literacy and developing effective interventions to increase cancer screening among older Chinese Americans.

Exercising horses uniquely accommodate 7-8-fold increases in heart rate (HR). The present experiments for the first time analysed the related adaptations in action potential (AP) restitution properties recorded by in vivo telemetric electrocardiography from Thoroughbred horses. The horses were subjected to a period of acceleration from walk to canter. The QRS durations, and QT and TQ intervals yielded AP conduction velocities, AP durations (APDs) and diastolic intervals respectively. From these, indices of active, λ = QT/(QRS duration), and resting, λ0 = TQ/(QRS duration), AP wavelengths were calculated. Critical values of QT and TQ intervals, and of λ and λ0 at which plots of these respective pairs of functions showed unity slope, were obtained. These were reduced by 38.9±2.7% and 86.2±1.8%, and 34.1±3.3% and 85.9±1.2%, relative to their resting values respectively. The changes in λ were attributable to falls in QT interval rather than QRS duration. These findings both suggested large differences between the corresponding critical (129.1±10.8 or 117.4±5.6 bpm respectively) and baseline HRs (32.9±2.1 (n = 7) bpm). These restitution analyses thus separately identified concordant parameters whose adaptations ensure the wide range of HRs over which electrophysiological activation takes place in an absence of heart block or arrhythmias in equine hearts. Since the horse is amenable to this in vivo electrophysiological analysis and displays a unique wide range of heart rates, it could be a novel cardiac electrophysiology animal model for the study of sudden cardiac death in human athletes.