Teaching Systems-Thinking Concepts with Hypothetical Case Scenarios: An Exploration in Food-Systems Science Education.

BACKGROUND: The ability to solve complex challenges facing the food system is an increasingly important skill for undergraduate students entering into the global workforce. However, the curriculum tools to enhance systems thinking in the undergraduate agricultural and natural resource classroom are limited, specifically related to food systems education. METHODS: The current study explored the use of hypothetical case scenarios in a teaching curriculum related to the seafood industry, in order to determine the use of these tools as a mechanism for increasing undergraduate students' systems-thinking capacity. The mixed-method study used a survey and focus groups. Results indicated that participants' understanding of, and capacity for, using systems thinking to reason through complex scenarios increased during the mixed-method educational intervention. Participants stated the experience helped them learn more about their own patterns of thinking, created transformational learning moments through dissonance, helped them learn about the unintended consequences of decision-making, and increased their understanding of system complexity. CONCLUSIONS: The implications of using hypothetical case scenarios in the food system education classroom are explored.

Friends Not Foes: Optimizing Collaboration with Subspecialists.

Pediatric orthopedic patients can be complex to manage. As orthopedists plan for possible surgical interventions, consultation with pediatric subspecialists will be necessary. This article discusses the considerations an orthopedist should make when deciding on the timing and the appropriateness of consultation-both preoperatively and perioperatively. Consultation before surgical intervention will especially be useful if the subspecialist will be collaborating in the management of the condition postoperatively (whether inpatient or outpatient). Clear and early consultation in both written and verbal format will facilitate quality and expedite the patient's care.

The Influence of Sustainability on Identities and Seafood Consumption: Implications for Food Systems Education for Generation Z.

Seafood is a vital source of nutrition yet many consumers in the United States have been exposed to competing discourse about the industry's environmental impacts, influencing consumption habits. Generation Z, a generational cohort whose members value the sustainability of their purchasing decisions, may have unique opinions regarding sustainable seafood given their sustainability values. This qualitative study explored Generation Z undergraduate students' experiences with seafood and how they perceive the role of seafood in feeding people while sustaining the future natural environment. Data were collected using 11 focus groups in undergraduate classrooms. Researchers conducted an emergent thematic analysis and sufficient interrater reliability was established. Themes identified based on participants' experience with seafood included geographic location, experience fishing or with fishermen, and seafood and family, implying place attachment and family identity were intertwined with consumption behaviors. Themes identified based on participants' perception of seafood's role in feeding people included sustainability, regulations, limited seafood consumption, and limited knowledge, implying Generation Z's emerging status as the sustainability generation. Results indicate educators should focus on how sustainability can be emphasized in the classroom with clear actions undergraduate Generation Z students can take to improve sustainability.

A Needs Assessment to Inform Research and Outreach Efforts for Sustainable Agricultural Practices and Food Production in the Western United States.

Increasing the adoption of sustainable agricultural practices can help maintain sufficient food production while reducing its environmental impact. To ensure this adoption, it is important to assess the research and training needs of those helping farmers and producers adopt sustainable agricultural practices. However, there is a gap in the literature related to the training needs of producers in the Western United States for sustainable agriculture. Needs assessments help organizations, such as the Western Sustainable Agriculture Research and Education (SARE) program and Cooperative Extension, to address the demonstrated needs of intended audiences. This study presents the results of a needs assessment with the objective of examining training needs and barriers to adoption to help direct extension programming for sustainable agricultural practices in the western region of the United States, to identify gaps, and to inform sustainable agriculture outreach programs. Using a modified Borich method with an inferential statistical method, the discrepancies between the level at which sustainable agricultural practice training competencies "should be addressed" and the level at which they were "currently being addressed" were examined. Competencies with the largest gaps included financial disparity, food waste, and policy/communicating with decision makers. The top three barriers to adopting sustainable agricultural practices included the potential for financial loss, perceived risk of adoption, and time investment associated with adoption. Results indicated that training needs varied and that these were not all on-farm training needs. The results imply that future funding from Western SARE and other groups looking to support sustainable agricultural food system efforts, may wish to focus on requesting proposals for programs that address these competency gaps and barriers in novel and supplementary ways in combination with existing programmatic efforts.

Examining the Relationship Between Existing Community Resources and Community Leaders' Perceptions of Resilience and Rural Health During COVID-19.

This study explored the relationship between existing community resources and community leaders' perceptions of resilience and rural health during COVID-19. Observational data of material capitals (e.g., grocery stores and physical activity resources) present in five rural communities involved in a health promotion project were collected and compared with key informant interviews of perceived community health and resilience during the COVID-19 pandemic. The analysis compares the differences in community leaders' perceptions of resilience during the pandemic to the actual material capitals of the community. While these rural counties were average in terms of available physical activity and nutritional resources, the onset of the pandemic led to varying degrees of disruption in access due to structural closures of mainstay resources, as well as residents perceiving that they cannot or should not access available resources. In addition, county coalition progress was stalled as individuals and groups could not gather together to complete projects, such as building playground equipment. This study demonstrates that existing quantitative instruments, such as NEMS and PARA, fail to take into account perceived access and utility of resources. Therefore, practitioners should consider multiple ways to evaluate resources, capacity, and progress on a health intervention or program and consider community voice to ensure feasibility, relevance, and sustainability-especially when faced with a public health emergency like COVID-19.

Community Gardens: A Catalyst for Community Change.

Community gardens are increasing in popularity and are associated with extensive physical and mental health benefits, increased access to fresh produce, and increased social connections. However, evidence is primarily from research in urban and school settings, and little is known about the role of community gardens in rural settings as part of policy, systems, and environmental (PSE) changes to promote health. This study explores the implementation of community gardens as part of an obesity prevention project, titled Healthier Together (HT), in five rural Georgia counties with limited food access and high obesity prevalence (>40%) using a mixed-methods research design that included data from project records, a community survey, interviews, and focus groups with county coalition members. Nineteen community gardens were implemented across five counties, 89% distributed produce direct to consumers, and 50% were integrated into the food system. Few (8.3%) of the survey respondents (n = 265) identified gardens as a food source, but 21.9% reported using an HT garden in the past year. Themes emerging from interviews (n = 39) and five focus groups suggested community gardens were a catalyst for broader community health change by increasing awareness of the value and absence of healthy food and generating excitement for future PSE initiatives to more comprehensively address food and physical activity access. Practitioners should consider placement of rural community gardens to optimize access to and distribution of produce as well as communication and marketing strategies to increase engagement and leverage gardens as gateways for PSE approaches to improve rural health.

Qualitative Exploration of Cultural Influence on a Rural Health-Promotion Initiative.

OBJECTIVE: To develop a conceptualization of cultural influence on perceptions of a rural food and physical activity policy, systems, and environmental (PSE) change project to inform public health research and practice. DESIGN: Basic qualitative research design, semistructured phone interviews with community health coalition members. SETTING: Five rural Southern counties (obesity prevalence > 40%). PARTICIPANTS: Thirty-nine community coalition members. INTERVENTION: The Centers for Disease Control and Prevention High Obesity Program. PSE initiatives to increase access to healthy food and physical activity opportunities through a community coalition model. PHENOMENON OF INTEREST: Social norms and cultural influences surrounding community members' food preferences, physical activity behavior, and future hopes for community development. ANALYSIS: Abductive content analysis. RESULTS: Major categories on food social norms (subcategories: physical health, eating habits, and food preference), race relations, generational factors, physical activity social norms, and hopes for the community (subcategories: increased engagement, health, awareness, cohesion, and inspiration) were discussed in relation to the progress of PSE initiatives. CONCLUSIONS AND IMPLICATIONS: Because of community member perceptions, PSE initiatives became associated with factors beyond food and fitness, such as race relations, generational differences, and community cohesion. A focus on increased youth and church involvement, community values, relationship building, and input from diverse voices can be foundational to culturally-appropriate PSE efforts in rural settings.

"We Shall Tell them with Love, Inform them what we have Learnt and then Allow them to go" - Men's Perspectives of Self-Collected Cervical Cancer Screening in Rural Uganda: A Qualitative Inquiry.

Uganda has high incidence rates of cervical cancer (47.5/100,000/year) due to limited screening access. In settings where men hold most of the decision-making power, they play an important role in women's uptake of cervical cancer screening. We aimed to capture men's knowledge, beliefs and perspectives about cervical cancer, community-based screening and health system barriers. Focus group discussions were conducted with men in rural Uganda. Data were verbatim translated and transcribed into English. Transcripts were analysed in ATLAS.ti using a deductive approach of thematic content analysis and applied to an implementation research framework. Twenty-three men participated in focus groups. Men held poor knowledge of cervical cancer, its causes and treatment. Men felt screening would be acceptable by women if men and women were educated. Men highlighted health system barriers to accessing screening including: 1) poor-quality health services, 2) large distances to facilities/lack of affordable transportation and 3) lack of health workers/mistreatment by health workers. Men described supporting women through assisting with transportation, psychosocial support and sharing information. They requested services for men to be decentralized alongside community outreaches for cervical cancer screening. Engaging men in the implementation, education and planning of community-based cervical cancer screening programs is critical. Not engaging men is a missed opportunity to provide them with services and education. Concerted efforts must be made in educating men and reducing health system barriers to ensure rural women receive cervical cancer screening and follow-up care in low-income settings. Clinicaltrials.gov, NCT04000503; Registered 27 June 2019.

Anti-spike T-cell and Antibody Responses to SARS-CoV-2 mRNA Vaccines in Patients with Hematologic Malignancies.

The anti-spike T-cell and antibody responses to SARS-CoV-2 mRNA vaccines in patients with B-cell malignancies were examined in a real-world setting. A next-generation sequencing (NGS)-based molecular assay was used to assess SARS-CoV-2-specific T-cell responses. After the second dose, 58% (166/284) of seropositive and 45% (99/221) of seronegative patients display anti-spike T cells. The percentage of patients who displayed T-cell response was higher among patients receiving mRNA-1273 vaccines compared with those receiving BNT162b2 vaccines. After the third vaccination, 40% (137/342) of patients seroconverted, although only 22% displayed sufficient antibody levels associated with the production of neutralizing antibodies. 97% (717/738) of patients who were seropositive before the third dose had markedly elevated anti-spike antibody levels. Anti-spike antibody levels, but not T-cell responses, were depressed by B cell-directed therapies. Vaccinated patients with B-cell malignancies with a poor response to SARS-CoV-2 vaccines may remain vulnerable to COVID-19 infections. SIGNIFICANCE: This study represents the first investigation of SARS-CoV-2-specific immune responses to vaccination in a patient registry using an NGS-based method for T-cell receptor repertoire-based analysis combined with anti-spike antibody assessments. Vaccinated patients with B cell-derived hematologic malignancies are likely at higher risk of infection or severe COVID-19. This article is highlighted in the In This Issue feature, p. 476.

An Allogeneic Multiple Myeloma GM-CSF-Secreting Vaccine with Lenalidomide Induces Long-term Immunity and Durable Clinical Responses in Patients in Near Complete Remission.

PURPOSE: This proof-of-principle clinical trial evaluated whether an allogeneic multiple myeloma GM-CSF-secreting vaccine (MM-GVAX) in combination with lenalidomide could deepen the clinical response in patients with multiple myeloma in sustained near complete remission (nCR). PATIENTS AND METHODS: Fifteen patients on lenalidomide were treated with MM-GVAX and pneumococcal conjugate vaccine (PCV; Prevnar) at 1, 2, 3, and 6 months. RESULTS: Eight patients (53.3%) achieved a true CR. With a median follow-up of 5 years, the median progression-free survival had not been reached, and the median overall survival was 7.8 years from enrollment. MM-GVAX induced clonal T-cell expansion and measurable cytokine responses that persisted up to 7 years in all patients. At baseline, a higher minimal residual disease was predictive of early relapse. After vaccination, a lack of both CD27-DNAM1-CD8+ T cells and antigen-presenting cells was associated with disease progression. CONCLUSIONS: MM-GVAX, along with lenalidomide, effectively primed durable immunity and resulted in long-term disease control, as suggested by the reappearance of a detectable, fluctuating M-spike without meeting the criteria for clinical relapse. For patients in a nCR, MM-GVAX administration was safe and resulted in prolonged clinical responses.

Acceptability and preferences for self-collected screening for cervical cancer within health systems in rural Uganda: A mixed-methods approach.

OBJECTIVE: To understand the knowledge, preferences, and barriers for self-collected cervical cancer screening (SC-CCS) and follow-up care at the individual and health system level to inform the implementation of community-based SC-CCS. METHODS: Surveys and focus group discussions (FGDs) with women and FGDs with healthcare providers were conducted in Uganda. Survey data were analyzed using frequencies and FGD data were analyzed using thematic content analysis. Data were triangulated between methods. RESULTS: Sixty-four women were surveyed and 58 participated in FGDs. Facilitators to screening access included decentralization, convenience, privacy, confidentiality, knowledge, and education. Barriers to accessing screening included lack of transportation and knowledge, long wait times, difficulty accessing health care, and lack of trust in the health system. Additional implementation challenges included insufficiently trained human resources and lack of infrastructure. CONCLUSION: Integrating SC-CCS within rural health systems in low-resource settings has been under-evaluated. Community-based SC-CSS could prevent high cervical cancer-related mortalities while working within the human and financial resource limitations of rural health systems. SC-CCS is acceptable to women and healthcare providers. By addressing rural women's preferences and barriers to care, decision-makers can build health systems that provide community-centered care close to women's homes across the care continuum.

Publisher Correction: Exuberant fibroblast activity compromises lung function via ADAMTS4.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Exuberant fibroblast activity compromises lung function via ADAMTS4.

Severe respiratory infections can result in acute respiratory distress syndrome (ARDS)1. There are no effective pharmacological therapies that have been shown to improve outcomes for patients with ARDS. Although the host inflammatory response limits spread of and eventually clears the pathogen, immunopathology is a major contributor to tissue damage and ARDS1,2. Here we demonstrate that respiratory viral infection induces distinct fibroblast activation states, which we term extracellular matrix (ECM)-synthesizing, damage-responsive and interferon-responsive states. We provide evidence that excess activity of damage-responsive lung fibroblasts drives lethal immunopathology during severe influenza virus infection. By producing ECM-remodelling enzymes-in particular the ECM protease ADAMTS4-and inflammatory cytokines, damage-responsive fibroblasts modify the lung microenvironment to promote robust immune cell infiltration at the expense of lung function. In three cohorts of human participants, the levels of ADAMTS4 in the lower respiratory tract were associated with the severity of infection with seasonal or avian influenza virus. A therapeutic agent that targets the ECM protease activity of damage-responsive lung fibroblasts could provide a promising approach to preserving lung function and improving clinical outcomes following severe respiratory infections.

T Cell Clonal Dynamics Determined by High-Resolution TCR-ß Sequencing in Recipients after Allogeneic Hematopoietic Cell Transplantation.

Delayed reconstitution of the immune system is a long-recognized complication after allogeneic hematopoietic cell transplantation (HCT). Specifically, loss of T cell diversity has been thought to contribute to infectious complications, graft-versus-host disease (GVHD), and disease relapse. We performed serial high-resolution next-generation sequencing of T cell receptor (TCR)-ß in 99 related or unrelated donor (57 unrelated, 42 related) allogeneic HCT recipients (55 with reduced-intensity conditioning, 44 with myeloablative conditioning) during the first 3 months after HCT using the immunoSEQ Assay. We measured T cell fraction, clonality (1- Peilou's evenness) and Daley-Smith richness from recipient samples at multiple time points. In agreement with previous studies, we found that although absolute T cell numbers recover relatively quickly after HCT, T cell repertoire diversity remains diminished. Restricted diversity was associated with conditioning intensity, use of antithymocyte globulin, and donor type. Increased number of expanded clones compared to donor T cell clones at day +30 was associated with the incidence of acute GVHD (hazard ratio [HR], 1.11; P = .00005). Even after exclusion of the 12 patients who developed acute GVHD before day +30, the association between acute GVHD and increased clonal expansion at day +30 remained (HR, 1.098; P = .041), indicating that increased clonal T cell expansion preceded the development of acute GVHD. Our results highlight T cell clonal expansion as a potential novel biomarker for acute GVHD that warrants further study.

A National Behavioral and Clinical Surveillance System of Adults With Diagnosed HIV (The Medical Monitoring Project): Protocol for an Annual Cross-Sectional Interview and Medical Record Abstraction Survey.

BACKGROUND: The Medical Monitoring Project (MMP) is a national population-based behavioral and clinical surveillance system of adults with diagnosed HIV in the United States, and it is sponsored by the Centers for Disease Control and Prevention (CDC). Its purpose is to provide locally and nationally representative estimates of factors affecting HIV transmission risk and clinical outcomes. OBJECTIVE: This study aimed to describe the rationale for and methodology of the MMP, in addition to its contribution to evaluating and monitoring HIV prevention, care, and treatment efforts in the United States. METHODS: MMP employs a stratified 2-stage sample design to select annual samples of persons living with diagnosed HIV from the National HIV Surveillance System and conducts interviews and medical record abstractions with participating persons. RESULTS: MMP data are published routinely via annual reports, conference presentations, and scientific publications. Data may be accessed upon request from the CDC, contingent on the guidelines established for the security and confidentiality of HIV surveillance data. CONCLUSIONS: MMP is the only source of annual population-based data on the behaviors and clinical care of persons with diagnosed HIV in the United States. It provides essential information for monitoring progress toward national treatment and prevention goals and guiding efforts to improve the health of persons with diagnosed HIV and prevent HIV transmission. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/15453.

T Cell Repertoire Dynamics during Pregnancy in Multiple Sclerosis.

Identifying T cell clones associated with human autoimmunity has remained challenging. Intriguingly, many autoimmune diseases, including multiple sclerosis (MS), show strongly diminished activity during pregnancy, providing a unique research paradigm to explore dynamics of immune repertoire changes during active and inactive disease. Here, we characterize immunomodulation at the single-clone level by sequencing the T cell repertoire in healthy women and female MS patients over the course of pregnancy. Clonality is significantly reduced from the first to third trimester in MS patients, indicating that the T cell repertoire becomes less dominated by expanded clones. However, only a few T cell clones are substantially modulated during pregnancy in each patient. Moreover, relapse-associated T cell clones identified in an individual patient contract during pregnancy and expand during a postpartum relapse. Our data provide evidence that profiling the T cell repertoire during pregnancy could serve as a tool to discover and track "private" T cell clones associated with disease activity in autoimmunity.

Informing Data to Care: Contacting Persons Sampled for the Medical Monitoring Project.

BACKGROUND: Data to care (D2C) is a public health strategy that uses HIV surveillance and other data to identify persons in need of HIV medical care. The Medical Monitoring Project (MMP), which uses similar methods to contact and recruit HIV-positive persons, may inform predictors of successful contact for D2C programs. SETTING: MMP is a Centers for Disease Control and Prevention-funded surveillance system that collects nationally representative data on adults with diagnosed HIV in the United States and Puerto Rico. METHODS: Using MMP's 2016 data collection cycle, we present contact rates (ie, proportion of HIV-positive persons successfully contacted for MMP) by the age of contact information and age of laboratory test results available from HIV surveillance data. RESULTS: Nationally, 27.6% of eligible persons did not have a recorded laboratory test performed within the past year (project area range: 10.8%-54.6%). The national contact rate among persons with laboratory tests older than 1 year was 37.0% (project area range: 16.5%-67.1%). Higher contact rates were found among persons with more recent laboratory tests. Similar results were found by the age of contact information. Nationally, the most common reason for MMP ineligibility was that the person was deceased; the most common reason for not being contacted was lack of correct contact information. CONCLUSIONS: MMP findings suggest that D2C programs would benefit from efforts to improve the quality of HIV surveillance data and local surveillance practices-in particular, death ascertainment, the completeness of laboratory reporting, and the routine updating of contact information. Strengthening collaboration and integration with existing MMP programs may be beneficial.

The Combined Effect of FGFR Inhibition and PD-1 Blockade Promotes Tumor-Intrinsic Induction of Antitumor Immunity.

The success of targeted or immune therapies is often hampered by the emergence of resistance and/or clinical benefit in only a subset of patients. We hypothesized that combining targeted therapy with immune modulation would show enhanced antitumor responses. Here, we explored the combination potential of erdafitinib, a fibroblast growth factor receptor (FGFR) inhibitor under clinical development, with PD-1 blockade in an autochthonous FGFR2K660N/p53mut lung cancer mouse model. Erdafitinib monotherapy treatment resulted in substantial tumor control but no significant survival benefit. Although anti-PD-1 alone was ineffective, the erdafitinib and anti-PD-1 combination induced significant tumor regression and improved survival. For both erdafitinib monotherapy and combination treatments, tumor control was accompanied by tumor-intrinsic, FGFR pathway inhibition, increased T-cell infiltration, decreased regulatory T cells, and downregulation of PD-L1 expression on tumor cells. These effects were not observed in a KRASG12C-mutant genetically engineered mouse model, which is insensitive to FGFR inhibition, indicating that the immune changes mediated by erdafitinib may be initiated as a consequence of tumor cell killing. A decreased fraction of tumor-associated macrophages also occurred but only in combination-treated tumors. Treatment with erdafitinib decreased T-cell receptor (TCR) clonality, reflecting a broadening of the TCR repertoire induced by tumor cell death, whereas combination with anti-PD-1 led to increased TCR clonality, suggesting a more focused antitumor T-cell response. Our results showed that the combination of erdafitinib and anti-PD-1 drives expansion of T-cell clones and immunologic changes in the tumor microenvironment to support enhanced antitumor immunity and survival.

Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma.

Glioblastoma is the most common primary malignant brain tumor in adults and is associated with poor survival. The Ivy Foundation Early Phase Clinical Trials Consortium conducted a randomized, multi-institution clinical trial to evaluate immune responses and survival following neoadjuvant and/or adjuvant therapy with pembrolizumab in 35 patients with recurrent, surgically resectable glioblastoma. Patients who were randomized to receive neoadjuvant pembrolizumab, with continued adjuvant therapy following surgery, had significantly extended overall survival compared to patients that were randomized to receive adjuvant, post-surgical programmed cell death protein 1 (PD-1) blockade alone. Neoadjuvant PD-1 blockade was associated with upregulation of T cell- and interferon-γ-related gene expression, but downregulation of cell-cycle-related gene expression within the tumor, which was not seen in patients that received adjuvant therapy alone. Focal induction of programmed death-ligand 1 in the tumor microenvironment, enhanced clonal expansion of T cells, decreased PD-1 expression on peripheral blood T cells and a decreasing monocytic population was observed more frequently in the neoadjuvant group than in patients treated only in the adjuvant setting. These findings suggest that the neoadjuvant administration of PD-1 blockade enhances both the local and systemic antitumor immune response and may represent a more efficacious approach to the treatment of this uniformly lethal brain tumor.