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Background: Student-run free clinics (SRFCs) can provide quality mental health care to low-income and uninsured populations who are at a greater risk of depression. Evidence demonstrates the association between social support and severity of depression, but this relationship has not been analyzed in an SRFC. Thus, we assessed the association between social support and depressive symptoms.Methods: We used electronic health records data for patients from 2013-2020 (n=2,501 patients). The dependent variable was severity of depression symptoms as determined by scores on the patient health questionnaire-4 (PHQ-4). Higher PHQ-4 scores correspond to increased severity of depression. The main predictor was the patient's social support, which was defined by their employment status, marital status, and the number of individuals in their household. We conducted a multinomial regression model to control for other patient-level factors (i.e. race, sex, and age).Results: When controlling for other factors, patients with higher social support scores had lower odds of scoring a 4 on the PHQ-4 (Odds ratio [OR]=0.838, 95% Confidence interval (CI)=0.770-0.912). When examining specific social support sources, when compared to patients who reported being not-married, those who were married had lower odds of scoring a 4 on the PHQ-4 (OR=0.578, 95% CI=0.401-0.833). Compared to patients who reported being employed, those who were unemployed had greater odds of scoring a 4 on the PHQ-4 (OR=2.323, 95% CI=1.766-3.055). We observed no significant differences in PHQ-4 by the number of people in the household.Conclusion: Patients with greater social support were associated with fewer depressive symptoms. Specifically, employment status and marital status may be larger contributors to a patient’s social support. Our results allow SRFCs to offer interventions such as investing in social work programs and community partnerships that offer professional development and employment opportunities to patients.

BACKGROUND: Lack of clinical trial awareness has been identified as a barrier to clinical trial recruitment. Identifying factors associated with clinical trial knowledge could inform ongoing efforts to improve diversity in clinical trials. METHODS: Using data from the Health Information National Trends Survey, 2020, we examined the knowledge of clinical trials, associated characteristics, sources of clinical trial information and motives to participate in clinical trials among the general population in the USA. RESULTS: Of 3,772 US adults, 41.3% reported not knowing about clinical trials. Prevalence of having no knowledge of clinical trials was higher among Hispanic adults (51.8%) and non-Hispanic Black adults (41.8%) compared with non-Hispanic White adults (37.4%; p=0.013). Other significant predictors of knowledge about clinical trials included higher education, online health information-seeking behaviour and patient portal access. Most respondents (73.2%) reported that healthcare providers were the most trusted source of information. Helping other people (71.6%) was the primary motivation for clinical trial participation, followed by financial compensation (12.5%) and receiving better treatment (5.1%). CONCLUSION: There is a gap in knowledge about clinical trials among the US population. Development of multimodal approaches, including online and offline information broadcasting, is needed to improve knowledge and clinical trial recruitment in diverse populations.

216 Background: Head and neck cancer (HNC) patients are at increased risk for suicide. Few studies have tested approaches to preventing suicide in this population, such as routine suicide risk screening. To address this issue, the current study pilots and assesses the feasibility and implementation of a suicide risk screening program for HNC patients at a National Cancer Institute (NCI)-designated Comprehensive Cancer Center. Methods: Routine screening was implemented at all in-person visits in the HNC clinic from February 1, 2021 – January 31, 2022 using the PHQ-9. Patients with passive suicidal ideation were consequently screened by social work for active suicidal ideation. Results: Most (92.6% or 1519/1641) HNC patients with a scheduled in-person visit completed at least one suicide risk screening; 9,968 screenings were completed (mean: 3.7; SD: 3.8 per patient) in total. Among patients who were screened, 3% (49/1519) of HNC patients reported passive suicidal ideation and 0.3% (5/1519) were identified as having active suicidal ideation. Patients with five or more visits were more likely to participate in screening compared with patients who only had one visit during the study period (100% vs. 82.7%; P

429 Background: Clinician burnout leads to increased job turnover and workforce shortages, and reduced patient satisfaction and quality of care. Despite its importance, there has been limited study of burnout among the cancer care workforce including sources of burnout. This information can be used to inform intervention design for use in the cancer care setting specifically. To address this gap, we analyzed open-ended responses to a well-being survey administered to clinicians (physicians and advanced practice providers) at a Cancer Center. Methods: In February 2022, we electronically administered the American Medical Association’s clinician well-being survey to all practicing clinicians at a National Cancer Institute-designated Comprehensive Cancer Center in Florida. Of 700 clinicians, 405 (58%) responded. Of the respondents, 259 (64.0%) answered the free-text question “Tell us more about your stressors and what we can do to minimize them.” We used in-vivo coding to develop qualitative themes across responses. If a given response incorporated multiple themes, we coded the response under all pertinent themes. Results: A majority (76/259) of respondents commented on staffing issues, such as their clinics being understaffed or the quality of current staff. Another frequent theme (64/259) was the electronic health records (EHR) system, such as lack of integration between modules, inbox fatigue, alert fatigue, and inefficient documentation review processes. Respondents also reported scheduling issues as a pain point (56/259), such as having schedules that do not reflect actual clinical practice, being overbooked, and scheduling errors. Documentation burden was also highlighted as an issue across respondents (34/259). Documentation was considered tedious and some respondents reported a mismatch between available documentation tools in the EHR and actual documentation needs. Less common themes reported across respondents included design issues of facility space (e.g., no dedicated workspace to complete work without interruptions) and insufficient time to complete administrative, research, and documentation requirements. Conclusions: Our findings suggest that interventions that optimize staffing models, EHR processes (e.g., documentation), and scheduling practices may reduce burnout for a considerable number of cancer care clinicians.

BACKGROUND Rapid implementation of telehealth for cancer care during COVID-19 required innovative and adaptive solutions among oncology health care providers and professionals (HPPs). OBJECTIVE The aim of this qualitative study was to explore oncology HPPs’ experiences with telehealth implementation during the COVID-19 pandemic. METHODS This study was conducted at Moffitt Cancer Center (Moffitt), an NCI (National Cancer Institute)-Designated Comprehensive Cancer Center. Prior to COVID-19, Moffitt piloted telehealth visits on a limited basis. After COVID-19, Moffitt rapidly expanded telehealth visits. Telehealth visits included real-time videoconferencing between HPPs and patients and virtual check-ins (ie, brief communication with an HPP by telephone only). We conducted semistructured interviews with 40 oncology HPPs who implemented telehealth during COVID-19. The interviews were recorded, transcribed verbatim, and analyzed for themes using Dedoose software (version 4.12). RESULTS Approximately half of the 40 participants were physicians (n=22, 55%), and one-quarter of the participants were advanced practice providers (n=10, 25%). Other participants included social workers (n=3, 8%), psychologists (n=2, 5%), dieticians (n=2, 5%), and a pharmacist (n=1, 3%). Five key themes were identified: (1) establishing and maintaining patient-HPP relationships, (2) coordinating care with other HPPs and informal caregivers, (3) adapting in-person assessments for telehealth, (4) developing workflows and allocating resources, and (5) future recommendations. Participants described innovative strategies for implementing telehealth, such as coordinating interdisciplinary visits with multiple HPPs and inviting informal caregivers (eg, spouse) to participate in telehealth visits. Health care workers discussed key challenges, such as workflow integration, lack of physical exam and biometric data, and overcoming the digital divide (eg, telehealth accessibility among patients with communication-related disabilities). Participants recommended policy advocacy to support telehealth (eg, medical licensure policies) and monitoring how telehealth affects patient outcomes and health care delivery. CONCLUSIONS To support telehealth growth, implementation strategies are needed to ensure that HPPs and patients have the tools necessary to effectively engage in telehealth. At the same time, cancer care organizations will need to engage in advocacy to ensure that policies are supportive of oncology telehealth and develop systems to monitor the impact of telehealth on patient outcomes, health care quality, costs, and equity.

Background Rapid implementation of telehealth for cancer care during COVID-19 required innovative and adaptive solutions among oncology health care providers and professionals (HPPs). Objective The aim of this qualitative study was to explore oncology HPPs’ experiences with telehealth implementation during the COVID-19 pandemic. Methods This study was conducted at Moffitt Cancer Center (Moffitt), an NCI (National Cancer Institute)-Designated Comprehensive Cancer Center. Prior to COVID-19, Moffitt piloted telehealth visits on a limited basis. After COVID-19, Moffitt rapidly expanded telehealth visits. Telehealth visits included real-time videoconferencing between HPPs and patients and virtual check-ins (ie, brief communication with an HPP by telephone only). We conducted semistructured interviews with 40 oncology HPPs who implemented telehealth during COVID-19. The interviews were recorded, transcribed verbatim, and analyzed for themes using Dedoose software (version 4.12). Results Approximately half of the 40 participants were physicians (n=22, 55%), and one-quarter of the participants were advanced practice providers (n=10, 25%). Other participants included social workers (n=3, 8%), psychologists (n=2, 5%), dieticians (n=2, 5%), and a pharmacist (n=1, 3%). Five key themes were identified: (1) establishing and maintaining patient-HPP relationships, (2) coordinating care with other HPPs and informal caregivers, (3) adapting in-person assessments for telehealth, (4) developing workflows and allocating resources, and (5) future recommendations. Participants described innovative strategies for implementing telehealth, such as coordinating interdisciplinary visits with multiple HPPs and inviting informal caregivers (eg, spouse) to participate in telehealth visits. Health care workers discussed key challenges, such as workflow integration, lack of physical exam and biometric data, and overcoming the digital divide (eg, telehealth accessibility among patients with communication-related disabilities). Participants recommended policy advocacy to support telehealth (eg, medical licensure policies) and monitoring how telehealth affects patient outcomes and health care delivery. Conclusions To support telehealth growth, implementation strategies are needed to ensure that HPPs and patients have the tools necessary to effectively engage in telehealth. At the same time, cancer care organizations will need to engage in advocacy to ensure that policies are supportive of oncology telehealth and develop systems to monitor the impact of telehealth on patient outcomes, health care quality, costs, and equity.

The preferential accumulation of vascular smooth muscle cells (vSMCs) on arteries versus veins during early development is a well-described phenomenon, but the molecular pathways underlying this polarization are not well understood. In zebrafish, the cxcr4a receptor (mammalian CXCR4) and its ligand cxcl12b (mammalian CXCL12) are both preferentially expressed on arteries at time points consistent with the arrival and differentiation of the first vSMCs during vascular development. We show that autocrine cxcl12b/cxcr4 activity leads to increased production of the vSMC chemoattractant ligand pdgfb by endothelial cells in vitro and increased expression of pdgfb by arteries of zebrafish and mice in vivo. Additionally, we demonstrate that expression of the blood flow-regulated transcription factor klf2a in primitive veins negatively regulates cxcr4/cxcl12 and pdgfb expression, restricting vSMC recruitment to the arterial vasculature. Together, this signalling axis leads to the differential acquisition of vSMCs at sites where klf2a expression is low and both cxcr4a and pdgfb are co-expressed, i.e. arteries during early development., Stratman et al. provide evidence linking the cxcl12b/cxcr4a signaling axis in endothelial cells to an increased release of platelet-derived growth factor b, leading to the recruitment of smooth muscle cells to developing arteries. This signalling axis is suppressed in the venous endothelium during early development by the high expression of blood flow-regulated transcription factor klf2a.

The preferential accumulation of vascular smooth muscle cells on arteries versus veins during early development is a well-described phenomenon, but the molecular pathways underlying this polarization are not well understood. During zebrafish embryogenesis thecxcr4areceptor (mammalian CXCR4) and its ligandcxcl12b(mammalian CXCL12) are both preferentially expressed on arteries at time points consistent with the arrival and differentiation of the first vascular smooth muscle cells (vSMCs). We show that autocrinecxcl12b/cxcr4activity leads to increased production of the vSMC chemoattractant ligandpdgfbby endothelial cellsin vitroand increased expression ofpdgfbby arteriesin vivo. Additionally, we demonstrate that expression of the well-characterized blood flow-regulated transcription factorklf2ain primitive veins negatively regulatescxcr4/cxcl12andpdgfbexpression, restricting vSMC recruitment to the arterial vasculature. Together, this signaling axis leads to the differential acquisition of smooth muscle cells at sites whereklf2aexpression is low and bothcxcr4aandpdgfbare co-expressed, i.e. arteries during early development.

Optimal scaffold characteristics are essential for the therapeutic application of engineered tissues. Hydraulic permeability ( k ) affects many properties of collagen gels, such as mechanical properties, cell–scaffold interactions within three dimensions (3D), oxygen flow and nutrient diffusion. However, the cellular response to 3D gel scaffolds of defined k values has not been investigated. In this study, unconfined plastic compression under increasing load was used to produce collagen gels with increasing solid volume fractions. The Happel model was used to calculate the resulting permeability values in order to study the interaction of k with gel mechanical properties and mesenchymal stem cell (MSC)-induced gel contraction, metabolism and differentiation in both non-osteogenic (basal medium) and osteogenic medium for up to 3 weeks. Collagen gels of fibrillar densities ranging from 0.3 to >4.1 wt.% gave corresponding k values that ranged from 1.00 to 0.03 μm 2 . Mechanical testing under compression showed that the collagen scaffold modulus increased with collagen fibrillar density and a decrease in k value. MSC-induced gel contraction decreased as a direct function of decreasing k value. Relative to osteogenic conditions, non-osteogenic MSC cultures exhibited a more than 2-fold increase in gel contraction. MSC metabolic activity increased similarly under both osteogenic and non-osteogenic culture conditions for all levels of plastic compression. Under osteogenic conditions MSC differentiation and mineralization, as indicated by alkaline phosphatase activity and von Kossa staining, respectively, increased in response to an elevation in collagen fibrillar density and decreased gel permeability. In this study, gel scaffolds with higher collagen fibrillar densities and corresponding lower k values provided a greater potential for MSC differentiation and appear most promising for bone grafting purposes. Thus, cell–scaffold interactions can be optimized by defining the 3D properties of collagen scaffolds through k adjustment.

Leishmania parasites have evolved sophisticated mechanisms to subvert macrophage immune responses by altering the host cell signal transduction machinery, including inhibition of JAK/STAT signalling and other transcription factors such as AP-1, CREB and NF-κB. AP-1 regulates pro-inflammatory cytokines, chemokines and nitric oxide production. Herein we show that upon Leishmania infection, AP-1 activity within host cells is abolished and correlates with lower expression of 5 of the 7 AP-1 subunits. Of interest, c-Jun, the central component of AP-1, is cleaved by Leishmania. Furthermore, the cleavage of c-Jun is dependent on the expression and activity of the major Leishmania surface protease GP63. Immunoprecipitation of c-Jun from nuclear extracts showed that GP63 interacts, and cleaves c-Jun at the perinuclear area shortly after infection. Phagocytosis inhibition by cytochalasin D did not block c-Jun down-regulation, suggesting that internalization of the parasite might not be necessary to deliver GP63 molecules inside the host cell. This observation was corroborated by the maintenance of c-Jun cleavage upon incubation with L. mexicana culture supernatant, suggesting that secreted, soluble GP63 could use a phagocytosis-independent mechanism to enter the host cell. In support of this, disruption of macrophage lipid raft microdomains by Methyl β-Cyclodextrin (MβCD) partially inhibits the degradation of full length c-Jun. Together our results indicate a novel role of the surface protease GP63 in the Leishmania-mediated subversion of host AP-1 activity., Author Summary Leishmaniasis is a tropical disease affecting more than 12 million people around the world. The disease is caused by the Leishmania parasites that are transmitted to the mammalian host by a sandfly vector when it takes a blood meal. The parasites are able to survive and multiply inside of cells that comprise the primary defence of the host, the macrophages. We have extensively studied the mechanism whereby Leishmania escapes from macrophage microbicidal functions. Herein we report that the parasite can inactivate these cells by decreasing the activity of transcription factors such as Activated Protein-1(AP-1) that are involved in transcription of genes coding for antimicrobial functions of macrophages. In this study, we showed that Leishmania parasites use their most abundant surface protein GP63 to inactivate the AP-1 transcription factor. Furthermore, we found that GP63 enter into the macrophages independently of parasite internalization using lipid rich microdomains localized in the cellular membrane. In addition, GP63 was observed to reach the nuclear compartment where it cleaves AP-1 subunit proteins. Collectively, our findings reveal a novel mechanism used by Leishmania to facilitate its survival and propagation within its mammalian host cells. Better knowledge concerning the mechanisms whereby this pathogen can escape the innate immune response may help to develop new anti-Leishmania therapy.