Experiences of Leaders in Diversity, Equity, and Inclusion in US Academic Health Centers.

Importance: The murder of George Floyd in 2020 spurred an outpouring of calls for racial justice in the United States, including within academic medicine. In response, academic health centers announced new antiracism initiatives and expanded their administrative positions related to diversity, equity, and/or inclusion (DEI). Objective: To understand the experiences of DEI leaders at US allopathic medical schools and academic health centers, ie, the structure of their role, official and unofficial responsibilities, access to resources, institutional support, and challenges. Design, Setting, and Participants: This qualitative study used key informant interviews with participants who held formal DEI positions in their school of medicine, health system, or department. Interviews were conducted from December 2020 to September 2021. Transcripts were coded using a phenomenographic approach, with iterative concurrent analysis to identify thematic categories across participants. Data were analyzed from January to December 2021. Exposure: Formal DEI role. Main Outcomes and Measures: Questions elicited reflection on the responsibilities of the role and the strengths and challenges of the unit or office. Results: A total of 32 participants (18 of 30 [56%] cisgender women; 16 [50%] Black or African American, 6 [19%] Latinx or Hispanic, and 8 [25%] White) from 27 institutions with a mean (range) of 14 (3-43) years of experience in medical education were interviewed. More than half held a dean position (17 [53%]), and multiple participants held 2 or more titled DEI roles (4 [13%]). Two-thirds self-identified as underrepresented in medicine (20 [63%]) and one-third as first generation to attend college (11 [34%]). Key themes reflected ongoing challenges for DEI leaders, including (1) variability in roles, responsibilities, and access to resources, both across participants and institutions as well as within the same position over time; (2) mismatch between institutional investments and directives, including insufficient authority, support staff, and/or funding, and reduced efficacy due to lack of integration with other units within the school or health system; (3) lack of evidence-based practices, theories of change, or standards to guide their work; and (4) work experiences that drive and exhaust leaders. Multiple participants described burnout due to increasing demands that are not met with equivalent increase in institutional support. Conclusions and Relevance: In this qualitative study, DEI leaders described multiple institutional challenges to their work. To effectively address stated goals of DEI, medical schools and academic centers need to provide leaders with concomitant resources and authority that facilitate change. Institutions need to acknowledge and implement strategies that integrate across units, beyond one leader and office. Policymakers, including professional organizations and accrediting bodies, should provide guidance, accountability mechanisms, and support for research to identify and disseminate evidence for best practices. Creating statements and positions, without mechanisms for change, perpetuates stagnation and injustice.

The health implications of neighborhood networks based on daily mobility in US cities.

A large body of research has been dedicated to understanding the neighborhood conditions that impact health, which outcomes are affected, and how these associations vary by demographic and socioeconomic neighborhood and individual characteristics. This literature has focused mostly on the neighborhoods in which individuals reside, thus failing to recognize that residents across race/ethnicity and class spend a non-trivial amount of their time in neighborhoods far from their residential settings. To address this gap, we use mobile phone data from the company SafeGraph to compare racial inequality in neighborhood socioeconomic advantage exposure across three scales: the neighborhoods that residents live in, their adjacent neighborhoods, and the neighborhoods that they regularly visit. We found that the socioeconomic advantage levels in neighborhood networks differ from the levels at the residential and adjacent scales across all ethnoracial neighborhoods. Furthermore, socioeconomic advantage at the network level is associated with diabetes and hypertension prevalence above and beyond its impact at the residential and adjacent levels. We also find ethnoracial differences in these associations, with greater beneficial consequences of network socioeconomic advantage exposure on hypertension and diabetes for white neighborhoods. Future social determinants of health research needs to reconceptualize exposure to include the larger neighborhood network that a community is embedded in based on where their residents travel to and from.

Psychological Outcomes in Families of PICU Survivors: A Meta-Analysis.

BACKGROUND: Pediatric critical illness exposes family members to stressful experiences that may lead to subsequent psychological repercussions. OBJECTIVE: To systematically review psychological outcomes among PICU survivors' family members. DATA SOURCES: Four medical databases (PubMed, Embase, CINAHL and PsycInfo) were searched from inception till October 2023. STUDY SELECTION: Studies reporting psychological disorders in family members of PICU patients with at least 3 months follow-up were included. Family members of nonsurvivors and palliative care patients were excluded. DATA EXTRACTION: Screening and data extraction was performed according to PRISMA guidelines. Data were pooled using a random-effects model. RESULTS: Of 5360 articles identified, 4 randomized controlled trials, 16 cohort studies, and 2 cross-sectional studies were included (total patients = 55 597; total family members = 97 506). Psychological distress was reported in 35.2% to 64.3% and 40.9% to 53% of family members 3 to 6 months and 1 year after their child's PICU admission, respectively. Post-traumatic stress disorder was diagnosed in 10% to 48% of parents 3 to 9 months later. Parents that experienced moderate to severe anxiety and depression 3 to 6 months later was 20.9% to 42% and 6.1% to 42.6%, respectively. Uptake of mental counseling among parents was disproportionately low at 0.7% to 29%. Risk factors for psychiatric morbidity include mothers, parents of younger children, and longer duration of PICU stay. LIMITATIONS: The majority of studies were on parents with limited data on siblings and second degree relatives. CONCLUSIONS: There is a high burden of psychological sequelae in family members of PICU survivors. Risk stratification to identify high-risk groups and early interventions are needed.

Race, community disadvantage, and cognitive decline: Findings from KHANDLE and STAR.

INTRODUCTION: Community disadvantage is associated with late-life cognition. Few studies examine its contribution to racial disparities in cognition/cognitive change. METHODS: Inverse probability weighted models estimated expected mean differences in cognition/cognitive change attributed to residing in less advantaged communities, defined as cohort top quintile of Area Deprivation Indices (ADI): childhood 66-100; adulthood ADI 5-99). Interactions by race tested. RESULTS: More Black participants resided in less advantaged communities. Semantic memory would be lower if all participants had resided in less advantaged childhood (b = -0.16, 95% confidence interval [CI] = -0.30, -0.03) or adulthood (b = -0.14, 95% CI = -0.22, -0.04) communities. Race interactions indicated that, among Black participants, less advantaged childhood communities were associated with higher verbal episodic memory (interaction p-value = 0.007) and less advantaged adulthood communities were associated with lower semantic memory (interaction p-value = 0.002). DISCUSSION: Examining racial differences in levels of community advantage and late-life cognitive decline is a critical step toward unpacking community effects on cognitive disparities.

Experiences of low-income college students in selection of health insurance, access, and quality of care.

OBJECTIVE: To understand the experiences and perspectives of low-income University of California undergraduates related to their health insurance options, access to and quality of care. PARTICIPANTS: 14 undergraduate students across five UC campuses who identified as socioeconomically disadvantaged or low-income. METHODS: We conducted 4 focus groups organized by type of insurance coverage in April 2022. RESULTS: (1) the insurance selection process for low-income students is complicated by multiple, sometimes competing factors; (2) the lack of clear information confuses students' selection of insurance and health care options; and (3) students experiences challenges in access and quality of care, irrespective of insurance type. CONCLUSIONS: Ensuring access to high quality care, information and coverage is critical to the university mission to support a diverse, equitable and inclusive environment, for a student body that reflects the needs of the population of California.

A 19-Year-Old With Hemoptysis and Shortness of Breath.

CASE PRESENTATION: A 19-year-old woman with no medical history who did not use tobacco presented to the hospital with post-COVID-19 cough for 2 months and new onset of shortness of breath and blood-tinged sputum. She was initially treated empirically for community-acquired pneumonia because her chest radiograph showed a right upper lobe infiltrate. Further CT scan imaging revealed a right hilar lymph node conglomerate and extensive lymphadenopathy. The patient left to pursue care at a facility that accepted her insurance. Two weeks later, the patient presented for severe left-sided lower back pain, and she was found to have new complete left lower lobe collapse, likely because of extrinsic compression of the left lower lobe bronchus. She was treated for pain, and she left for insurance reasons. Two months later, the patient presented with progressive shortness of breath and hemoptysis and a 23-kg weight loss over the past 4 months. Because of the patient's increasing medical needs, she was transferred to our institution, where she was admitted to the medical ICU.

Lifestyle Interventions to Prevent Type 2 Diabetes in Women with a History of Gestational Diabetes: A Systematic Review and Meta-Analysis through the Lens of Health Equity.

BACKGROUND: Type 2 diabetes mellites is one of the health problems disproportionally affecting people with low socioeconomic statuses. Gestational diabetes mellites increases the risk of type 2 diabetes by up to ten-fold for women. Lifestyle interventions prevent type 2 diabetes in women with prior gestational diabetes. However, it is unknown if similar effectiveness can be expected for all population subgroups. OBJECTIVE: This study aims to assess the prevention of type 2 diabetes in women with prior gestational diabetes using population characteristics according to the PROGRESS (place of residence, race/ethnicity/culture/language, occupation, gender/sex, religion, education, socioeconomic status, and social capital) criteria. METHODS: MEDLINE, CINAHL, EMBASE, PubMed, PsycINFO, Web of Science, and EBM Reviews databases were searched for interventional studies of diet, physical activity, or behavioural interventions published up to 21 February 2023. Random effects subgroup meta-analysis was conducted to evaluate the association of population characteristics and intervention effects. RESULTS: All studies were conducted in high-income countries or middle-income countries. Two-thirds of the studies reported on race/ethnicity and education level. Less than one-third reported on place (urban/rural), occupation, and socioeconomic status. None reported on religion or social capital. Studies from high-income countries (MD = -1.46; 95% CI: -2.27, -0.66, I2 = 70.46, p < 0.001) showed a greater reduction in bodyweight compared with the studies conducted in middle-income countries (MD = -0.11; 95% CI: -1.12, 0.89, I2 = 69.31, p < 0.001) (p for subgroup difference = 0.04). CONCLUSION: There are significant equity gaps in the evidence for the prevention of type 2 diabetes in women with prior gestational diabetes due to reports on population characteristics being poor. Interventions may be less effective in reducing bodyweight in women from middle-income countries compared to high-income countries. Collecting and analysing data related to equity is needed to understand the effect of lifestyle interventions on type 2 diabetes for different population subgroups.

A real-life comparison of hypoglycaemia symptomatology between insulin-treated type 2 diabetes participants with and without impaired awareness of hypoglycaemia.

AIMS: We aim to compare and correlate Gold and Clarke questionnaire scores with hypoglycaemic symptomatic responses between insulin-treated type 2 diabetes participants with and without IAH in a real-life study. METHODS: Insulin-treated type 2 diabetes participants attending an outpatient diabetes clinic in Singapore were asked to complete the Gold and Clarke questionnaires, record capillary blood glucose (CBG) and hypoglycaemic symptoms for 4 weeks. RESULTS: Data were collected from 153 participants (M:F = 98:55) with mean age 61.0 ± 9.4 years, duration of diabetes 19.5 ± 8.8 years and HbA1c 68 ± 17 mmol/mol (8.4 ± 1.5%). Gold and Clarke methods classified 19.6% and 26.8% of participants with IAH, respectively. Using CBG threshold of <3 mmol/L, significantly greater proportion of participants with intact awareness were experiencing autonomic symptoms than those with IAH with either method (Gold: 69% vs. 18%, p = 0.006; Clarke: 85% vs. 46%, p = 0.010). Significantly greater proportion of participants with IAH experienced no hypoglycaemia symptoms than those with intact awareness (Gold: 3.4% vs. 36%, p = 0.015; Clarke: 3.7% vs. 31%, p = 0.031). Participants with IAH had significantly higher rates of severe hypoglycaemia in the preceding year compared to those without (Gold: 17% vs. 3.3%; Clarke: 15% vs. 2.7%, p = 0.012). CONCLUSIONS: Gold and Clarke questionnaires are appropriate tools in ascertaining IAH status in insulin-treated type 2 diabetes participants. This is the first time whereby the hypoglycaemia symptomology has robustly validated the Gold and Clarke questionnaire in insulin-treated type 2 diabetes participants.

Structural Factors and Racial/Ethnic Inequities in Travel Times to Acute Care Hospitals in the Rural US South, 2007-2018.

Policy Points Policymakers should invest in programs to support rural health systems, with a more targeted focus on spatial accessibility and racial and ethnic equity, not only total supply or nearest facility measures. Health plan network adequacy standards should address spatial access to nearest and second nearest hospital care and incorporate equity standards for Black and Latinx rural communities. Black and Latinx rural residents contend with inequities in spatial access to hospital care, which arise from fundamental structural inequities in spatial allocation of economic opportunity in rural communities of color. Long-term policy solutions including reparations are needed to address these underlying processes. CONTEXT: The growing rate of rural hospital closures elicits concerns about declining access to hospital-based care. Our research objectives were as follows: 1) characterize the change in rural hospital supply in the US South between 2007 and 2018, accounting for health system closures, mergers, and conversions; 2) quantify spatial accessibility (in 2018) for populations most at risk for adverse outcomes following hospital closure-Black and Latinx rural communities; and 3) use multilevel modeling to examine relationships between structural factors and disparities in spatial access to care. METHODS: To calculate spatial access, we estimated the network travel distance and time between the census tract-level population-weighted centroids to the nearest and second nearest operating hospital in the years 2007 and 2018. Thereafter, to describe the demographic and health system characteristics of places in relation to spatial accessibility to hospital-based care in 2018, we estimated three-level (tract, county, state-level) generalized linear models. FINDINGS: We found that 72 (10%) rural counties in the South had ≥1 hospital closure between 2007 and 2018, and nearly half of closure counties (33) lost their last remaining hospital to closure. Net of closures, mergers, and conversions meant hospital supply declined from 783 to 653. Overall, 49.1% of rural tracts experienced worsened spatial access to their nearest hospital, whereas smaller proportions experienced improved (32.4%) or unchanged (18.5%) access between 2007 and 2018. Tracts located within closure counties had longer travel times to the nearest acute care hospital compared with tracts in nonclosure counties. Moreover, rural tracts within Southern states with more concentrated commercial health insurance markets had shorter travel times to access the second nearest hospital. CONCLUSIONS: Rural places affected by rural hospital closures have greater travel burdens for acute care. Across the rural South, racial/ethnic inequities in spatial access to acute care are most pronounced when travel times to the second nearest open acute care hospital are accounted for.

Comparing the pooled cohort equations and coronary artery calcium scores in a symptomatic mixed Asian cohort.

Background: The value of pooled cohort equations (PCE) as a predictor of major adverse cardiovascular events (MACE) is poorly established among symptomatic patients. Coronary artery calcium (CAC) assessment further improves risk prediction, but non-Western studies are lacking. This study aims to compare PCE and CAC scores within a symptomatic mixed Asian cohort, and to evaluate the incremental value of CAC in predicting MACE, as well as in subgroups based on statin use. Methods: Consecutive patients with stable chest pain who underwent cardiac computed tomography were recruited. Logistic regression was performed to determine the association between risk factors and MACE. Cohort and statin-use subgroup comparisons were done for PCE against Agatston score in predicting MACE. Results: Of 501 patients included, mean (SD) age was 53.7 (10.8) years, mean follow-up period was 4.64 (0.66) years, 43.5% were female, 48.3% used statins, and 50.0% had no CAC. MI occurred in 8 subjects while 9 subjects underwent revascularization. In the general cohort, age, presence of CAC, and ln(Volume) (OR = 1.05, 7.95, and 1.44, respectively) as well as age and PCE score for the CAC = 0 subgroup (OR = 1.16 and 2.24, respectively), were significantly associated with MACE. None of the risk factors were significantly associated with MACE in the CAC > 0 subgroup. Overall, the PCE, Agatston, and their combination obtained an area under the receiver operating characteristic curve (AUC) of 0.501, 0.662, and 0.661, respectively. Separately, the AUC of PCE, Agatston, and their combination for statin non-users were 0.679, 0.753, and 0.734, while that for statin-users were 0.585, 0.615, and 0.631, respectively. Only the performance of PCE alone was statistically significant (p = 0.025) when compared between statin-users (0.507) and non-users (0.783). Conclusion: In a symptomatic mixed Asian cohort, age, presence of CAC, and ln(Volume) were independently associated with MACE for the overall subgroup, age and PCE score for the CAC = 0 subgroup, and no risk factor for the CAC > 0 subgroup. Whilst the PCE performance deteriorated in statin versus non-statin users, the Agatston score performed consistently in both groups.

Rural residence across the life course and late-life cognitive decline in KHANDLE: A causal inference study.

Background: Modifiable risks for dementia are more prevalent in rural populations, yet there is a dearth of research examining life course rural residence on late-life cognitive decline. Methods: The association of rural residence and socioeconomic status (SES) in childhood and adulthood with late-life cognitive domains (verbal episodic memory, executive function, and semantic memory) and cognitive decline in the Kaiser Healthy Aging and Diverse Life Experiences cohort was estimated using marginal structural models with stabilized inverse probability weights. Results: After adjusting for time-varying SES, the estimated marginal effect of rural residence in childhood was harmful for both executive function (ß = -0.19, 95% confidence interval [CI] = -0.32, -0.06) and verbal episodic memory (ß = -0.22, 95% CI = -0.35, -0.08). Effects of adult rural residence were imprecisely estimated with beneficial point estimates for both executive function (ß = 0.19; 95% CI = -0.07, 0.44) and verbal episodic memory (ß = 0.24, 95% CI = -0.07, 0.55). Conclusions: Childhood rurality is associated with poorer late-life cognition independent of SES.

US Medical School Admissions Leaders' Experiences With Barriers to and Advancements in Diversity, Equity, and Inclusion.

Importance: Despite decades-long calls for increasing racial and ethnic diversity, the medical profession continues to exclude members of Black or African American, Hispanic or Latinx, and Indigenous groups. Objective: To describe US medical school admissions leaders' experiences with barriers to and advances in diversity, equity, and inclusion. Design, Setting, and Participants: This qualitative study involved key-informant interviews of 39 deans and directors of admission from 37 US allopathic medical schools across the range of student body racial and ethnic composition. Interviews were conducted in person and online from October 16, 2019, to March 27, 2020, and analyzed from October 2019 to March 2021. Main Outcomes and Measures: Participant experiences with barriers to and advances in diversity, equity, and inclusion. Results: Among 39 participants from 37 medical schools, admissions experience ranged from 1 to 40 years. Overall, 56.4% of participants identified as women, 10.3% as Asian American, 25.6% as Black or African American, 5.1% as Hispanic or Latinx, and 61.5% as White (participants could report >1 race and/or ethnicity). Participants characterized diversity broadly, with limited attention to racial injustice. Barriers to advancing racial and ethnic diversity included lack of leadership commitment; pressure from faculty and administrators to overemphasize academic scores and school rankings; and political and social influences, such as donors and alumni. Accreditation requirements, holistic review initiatives, and local policy motivated reforms but may also have inadvertently lowered expectations and accountability. Strategies to overcome challenges included narrative change and revision of school leadership structure, admissions goals, practices, and committee membership. Conclusions and Relevance: In this qualitative study, admissions leaders characterized the ways in which entrenched beliefs, practices, and power structures in medical schools may perpetuate institutional racism, with far-reaching implications for health equity. Participants offered insights on how to remove inequitable structures and implement process changes. Without such action, calls for racial justice will likely remain performative, and racism across health care institutions will continue.

Generation and age of immigration on later life cognitive performance in KHANDLE.

OBJECTIVES: We examined the association of generational status and age at immigration with later life cognitive outcomes in a diverse sample of Latinos and Asian Americans. DESIGN: Baseline data were obtained from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study, and a prospective cohort is initiated in 2017. SETTING: Older adults in Northern California. PARTICIPANTS: Our cohort consisted of Asians (n = 411) and Latinos (n = 340) who were on average 76 years old (SD = 6.8). MEASUREMENTS: We used multivariable linear regression models to estimate associations between generational status and age at immigration (collapsed into one five-level variable) with measures of verbal episodic memory, semantic memory, and executive function, adjusting for age, gender, race and ethnicity, and own- and parental education. RESULTS: Generational status and age at immigration were associated with cognitive outcomes in a graded manner. Compared to third-generation or higher immigrants, first-generation immigration in adulthood was associated with lower semantic memory (ß = -0.96; 95% CI: -1.12, -0.81) than immigration in adolescence (ß = -0.68; 95% CI: -0.96, -0.41) or childhood (ß = -0.28; 95% CI: -0.49, -0.06). Moreover, immigration in adulthood was associated with lower executive function (ß = -0.63; 95% CI: -0.78, -0.48) than immigration in adolescence (ß = -0.49; 95% CI: -0.75, -0.23). Similarly, compared to third-generation individuals, first-generation immigrants had lower executive functioning scores. CONCLUSIONS: Our study supports the notion that sociocontextual influences in early life impact later life cognitive scores. Longitudinal studies are needed to further clarify how immigration characteristics affect cognitive decline.

Perceptions of workplace climate and diversity, equity, and inclusion within health services and policy research.

OBJECTIVE: To describe the perception of professional climate in health services and policy research (HSPR) and efforts to advance diversity, equity, and inclusion (DEI) in the HSPR workforce and workplaces. DATA SOURCE: We administered the HSPR Workplace Culture Survey online to health services and policy researchers. STUDY DESIGN: Our survey examined participants' sociodemographic, educational, and professional backgrounds, their perception on DEI in HSPR, experience with DEI initiatives, feeling of inclusion, and direct and witnessed experiences of discrimination at their institutions/organizations. We calculated sample proportions of responses by gender identity, sexual orientation, race/ethnicity, and disability status and compared them with Fisher's exact test. DATA COLLECTION: We administered the survey online from July 28 to September 4, 2020. HSPR professionals and trainees aged 18 and older were eligible to participate. Analyses used complete cases only (n = 906; 70.6% completion rate). PRINCIPAL FINDINGS: 53.4% of the participants did not believe that the current workforce reflects the diversity of communities impacted by HSPR. Although most participants have witnessed various DEI initiatives at their institutions/organizations, nearly 40% characterized these initiatives as "tokenistic." Larger proportions of participants who identified as female, LGBQI+, underrepresented racial/ethnic groups, and those with a disability held this perception than their male, heterosexual, White, and non-disabled counterparts. Current DEI initiatives focused on "planning" activities (e.g., convening task forces) rather than "implementation" activities (e.g., establishing mentoring or network programs). 43.7% of the participants felt supported on their career development, while female, Black, Hispanic/Latino, LGBQI+ participants and those with a disability experienced discrimination at their workplace. CONCLUSIONS: Despite an increasing commitment to increasing the diversity of the HSPR workforce and improving equity and inclusion in the HSPR workplace, our results suggest that there is more work to be done to achieve such goals.

Perceptions of School Climate Shape Adolescent Health Behavior: A Longitudinal Multischool Study.

BACKGROUND: Adolescent behaviors and academic outcomes are thought to be shaped by school climate. We sought to identify longitudinal associations between school climate measures and downstream health and academic outcomes. METHODS: Data from a longitudinal survey of public high school students in Los Angeles were analyzed. Eleventh-grade health and academic outcomes (dependent variables, eg, substance use, delinquency, risky sex, bullying, standardized exams, college matriculation), were modeled as a function of 10th-grade school climate measures (independent variables: institutional environment, student-teacher relationships, disciplinary style), controlling for baseline outcome measures and student/parental covariates. RESULTS: The 1114 student respondents (87.8% retention), were 46% male, 90% Latinx, 87% born in the United States, and 40% native English speakers. Greater school order and teacher respect for students were associated with lower odds of multiple high risk behaviors including 30-day alcohol use (odds ratio [OR] 0.81; 95% confidence interval [CI] [0.72, 0.92] and OR 0.73; [0.62, 0.85]) and 30-day cannabis use (OR 0.74; [0.59, 0.91] and OR 0.76; [0.63, 0.92]). Neglectful disciplinary style was associated with multiple poor health and academic outcomes while permissive disciplinary style was associated with favorable academic outcomes. IMPLICATIONS FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY: School health practitioners may prospectively leverage school environment, teacher-student relationships, and disciplinary style to promote health and learning. CONCLUSIONS: Our findings identify specific modifiable aspects of the school environment with critical implications for life course health.

Potent GCN2 Inhibitor Capable of Reversing MDSC-Driven T Cell Suppression Demonstrates In Vivo Efficacy as a Single Agent and in Combination with Anti-Angiogenesis Therapy.

General control nonderepressible 2 (GCN2) protein kinase is a cellular stress sensor within the tumor microenvironment (TME), whose signaling cascade has been proposed to contribute to immune escape in tumors. Herein, we report the discovery of cell-potent GCN2 inhibitors with excellent selectivity against its closely related Integrated Stress Response (ISR) family members heme-regulated inhibitor kinase (HRI), protein kinase R (PKR), and (PKR)-like endoplasmic reticulum kinase (PERK), as well as good kinome-wide selectivity and favorable PK. In mice, compound 39 engages GCN2 at levels ≥80% with an oral dose of 15 mg/kg BID. We also demonstrate the ability of compound 39 to alleviate MDSC-related T cell suppression and restore T cell proliferation, similar to the effect seen in MDSCs from GCN2 knockout mice. In the LL2 syngeneic mouse model, compound 39 demonstrates significant tumor growth inhibition (TGI) as a single agent. Furthermore, TGI mediated by anti-VEGFR was enhanced by treatment with compound 39 demonstrating the complementarity of these two mechanisms.

Doing the Work-or Not: The Promise and Limitations of Diversity, Equity, and Inclusion in US Medical Schools and Academic Medical Centers.

While the number of positions, committees, and projects described as "Diversity, Equity, and Inclusion (DEI)" work has grown rapidly in recent years, there has been little attention to the theory, praxis, or lived experience of this work. In this perspective, we briefly summarize the research and concepts put forth by DEI leaders in higher education more broadly, followed by an analysis of the literature's application to academic medicine. We then discuss the ways in which language obscures the nature of DEI and the necessity of scholarship to evaluate the extensive range of practices, policies, statements, and programs the label is given to.

An innate IL-25-ILC2-MDSC axis creates a cancer-permissive microenvironment for Apc mutation-driven intestinal tumorigenesis.

Interleukin-25 (IL-25) and group 2 innate lymphoid cells (ILC2s) defend the host against intestinal helminth infection and are associated with inappropriate allergic reactions. IL-33-activated ILC2s were previously found to augment protective tissue-specific pancreatic cancer immunity. Here, we showed that intestinal IL-25-activated ILC2s created an innate cancer-permissive microenvironment. Colorectal cancer (CRC) patients with higher tumor IL25 expression had reduced survival and increased IL-25R-expressing tumor-resident ILC2s and myeloid-derived suppressor cells (MDSCs) associated with impaired antitumor responses. Ablation of IL-25 signaling reduced tumors, virtually doubling life expectancy in an Apc mutation-driven model of spontaneous intestinal tumorigenesis. Mechanistically, IL-25 promoted intratumoral ILC2s, which sustained tumor-infiltrating MDSCs to suppress antitumor immunity. Therapeutic antibody-mediated blockade of IL-25 signaling decreased intratumoral ILC2s, MDSCs, and adenoma/adenocarcinoma while increasing antitumor adaptive T cell and interferon-γ (IFN-γ)-mediated immunity. Thus, the roles of innate epithelium-derived cytokines IL-25 and IL-33 as well as ILC2s in cancer cannot be generalized. The protumoral nature of the IL-25-ILC2 axis in CRC highlights this pathway as a potential therapeutic target against CRC.