Evaluating the immunologically "cold" tumor microenvironment after treatment with immune checkpoint inhibitors utilizing PET imaging of CD4 + and CD8 + T cells in breast cancer mouse models.

BACKGROUND: Immune-positron emission tomography (PET) imaging with tracers that target CD8 and granzyme B has shown promise in predicting the therapeutic response following immune checkpoint blockade (ICB) in immunologically "hot" tumors. However, immune dynamics in the low T-cell infiltrating "cold" tumor immune microenvironment during ICB remain poorly understood. This study uses molecular imaging to evaluate changes in CD4 + T cells and CD8 + T cells during ICB in breast cancer models and examines biomarkers of response. METHODS: [89Zr]Zr-DFO-CD4 and [89Zr]Zr-DFO-CD8 radiotracers were used to quantify changes in intratumoral and splenic CD4 T cells and CD8 T cells in response to ICB treatment in 4T1 and MMTV-HER2 mouse models, which represent immunologically "cold" tumors. A correlation between PET quantification metrics and long-term anti-tumor response was observed. Further biological validation was obtained by autoradiography and immunofluorescence. RESULTS: Following ICB treatment, an increase in the CD8-specific PET signal was observed within 6 days, and an increase in the CD4-specific PET signal was observed within 2 days in tumors that eventually responded to immunotherapy, while no significant differences in CD4 or CD8 were found at the baseline of treatment that differentiated responders from nonresponders. Furthermore, mice whose tumors responded to ICB had a lower CD8 PET signal in the spleen and a higher CD4 PET signal in the spleen compared to non-responders. Intratumoral spatial heterogeneity of the CD8 and CD4-specific PET signals was lower in responders compared to non-responders. Finally, PET imaging, autoradiography, and immunofluorescence signals were correlated when comparing in vivo imaging to ex vivo validations. CONCLUSIONS: CD4- and CD8-specific immuno-PET imaging can be used to characterize the in vivo distribution of CD4 + and CD8 + T cells in response to immune checkpoint blockade. Imaging metrics that describe the overall levels and distribution of CD8 + T cells and CD4 + T cells can provide insight into immunological alterations, predict biomarkers of response to immunotherapy, and guide clinical decision-making in those tumors where the kinetics of the response differ.

Trauma History Questionnaire: validation with novel samples of incarcerated women and perinatal women.

Trauma exposure is associated with numerous negative outcomes, many of which are amplified within at-risk populations. Two under-researched and at-risk populations, incarcerated women and perinatal women, both report high rates of trauma, psychopathology, and PTSD compared to the general population. One common measure of trauma exposure in various populations, including incarcerated women and perinatal women, is the Trauma History Questionnaire (THQ). However, no known studies have validated the THQ within these two unique, understudied populations. Using data from two studies of incarcerated women and one study of perinatal women, researchers explored indices of THQ construct, predictive, and convergent validity. The study also included between-sample comparisons, highlighting differences in trauma incidence between the included samples. Analyses supported statistically significant relations between THQ scores and Severity of Violence Against Women Scale (SVAWS), depressive symptoms, PTSD, and psychological distress. Prenatal women's THQ scores were also predictive of later postpartum depressive symptoms. Significantly higher THQ scores were found within the incarcerated samples compared to the perinatal sample. The study results provide further information about trauma within incarcerated and perinatal populations, as well as increase understanding of the utility of trauma assessments within these vulnerable groups.

Sleepless behind bars: the connection between mental health, environment, and sleep among women in jail.

Study Objectives: Given the barriers to good sleep in corrections facilities and the lack of research in this area, the current study aimed to characterize sleep quality and insomnia incidence in women in jail. Furthermore, we aimed to investigate the relation of sleep to depression, posttraumatic stress disorder (PTSD), and trauma exposure in incarcerated women. Lastly, we examined self-reports of environmental and individual factors that impaired sleeping in this population. Methods: Participants included 176 women incarcerated in two jails in southeast Idaho. Participants were randomly selected to complete several self-report questionnaires, including the Pittsburgh Sleep Quality Index and the Insomnia Severity Index, verbally administered by interviewers. Results: A majority of participants endorsed poor sleep quality (76%) and subthreshold or higher levels of insomnia (70%). Multiple regression analyses found that depressive symptoms and PTSD symptoms were both significantly related to insomnia and poor sleep quality. Excessive noise, poor bedding, and mental health were commonly cited factors that disrupted sleep. Conclusions: These results are consistent with previous literature that has examined these outcomes in prison populations and incarcerated populations in other countries. Correctional facilities can consider altering environmental factors that impair sleep to not only promote better overall health but also as a way to address common manifestations of poor mental health in their inmate populations. Screening for and treating mental health problems, namely depression and PTSD, is another way these facilities can improve inmate health and promote better sleep.

A Novel Approach for Conducting a Catchment Area Analysis of Breast Cancer by Age and Stage for a Community Cancer Center.

BACKGROUND: The U.S. Preventive Services Task Force recently issued an updated draft recommendation statement to initiate breast cancer screening at age 40, reflecting well-documented disparities in breast cancer-related mortality that disproportionately impact younger Black women. This study applied a novel approach to identify hotspots of breast cancer diagnosed before age 50 and/or at an advanced stage to improve breast cancer detection within these communities. METHODS: Cancer registry data for 3,497 women with invasive breast cancer diagnosed or treated between 2012 and 2020 at the Helen F. Graham Cancer Center and Research Institute (HFGCCRI) and who resided in the HFGCCRI catchment area, defined as New Castle County, Delaware, were geocoded and analyzed with spatial intensity. Standardized incidence ratios stratified by age and race were calculated for each hotspot. RESULTS: Four hotspots were identified, two for breast cancer diagnosed before age 50, one for advanced breast cancer, and one for advanced breast cancer diagnosed before age 50. Younger Black women were overrepresented in these hotspots relative to the full-catchment area. CONCLUSIONS: The novel use of spatial methods to analyze a community cancer center catchment area identified geographic areas with higher rates of breast cancer with poor prognostic factors and evidence that these areas made an outsized contribution to racial disparities in breast cancer. IMPACT: Identifying and prioritizing hotspot breast cancer communities for community outreach and engagement activities designed to improve breast cancer detection have the potential to reduce the overall burden of breast cancer and narrow racial disparities in breast cancer.

Factors Associated With Racial and Ethnic Disparities in Locally Advanced Rectal Cancer Outcomes.

Importance: Hispanic and non-Hispanic Black patients receiving neoadjuvant therapy and surgery for locally advanced rectal cancer (LARC) achieve less favorable clinical outcomes than non-Hispanic White patients, but the source of this disparity is incompletely understood. Objective: To assess whether racial and ethnic disparities in treatment outcomes among patients with LARC could be accounted for by social determinants of health and demographic, clinical, and pathologic factors known to be associated with treatment response. Design, Setting, and Participants: The National Cancer Database was interrogated to identify patients with T3 to T4 or N1 to N2 LARC treated with neoadjuvant therapy and surgery. Patients were diagnosed between January 1, 2004, and December 31, 2017. Data were culled from the National Cancer Database from July 1, 2022, through December 31, 2023. Exposure: Neoadjuvant therapy for rectal cancer followed by surgical resection. Main Outcomes and Measures: The primary outcome was the rate of pathologic complete response (pCR) following neoadjuvant therapy. Secondary outcomes were rate of tumor downstaging and achievement of pN0 status. Results: A total of 34 500 patient records were reviewed; 21 679 of the patients (62.8%) were men and 12 821 (37.2%) were women. The mean (SD) age at diagnosis was 59.7 (12.0) years. In terms of race and ethnicity, 2217 patients (6.4%) were Hispanic, 2843 (8.2%) were non-Hispanic Black, and 29 440 (85.3%) were non-Hispanic White. Hispanic patients achieved tumor downstaging (48.9% vs 51.8%; P = .01) and pN0 status (66.8% vs 68.8%; P = .02) less often than non-Hispanic White patients. Non-Hispanic Black race, but not Hispanic ethnicity, was associated with less tumor downstaging (odds ratio [OR], 0.86 [95% CI, 0.78-0.94]), less frequent pN0 status (OR, 0.91 [95% CI, 0.83-0.99]), and less frequent pCR (OR, 0.81 [95% CI, 0.72-0.92]). Other factors associated with reduced rate of pCR included rural location (OR, 0.80 [95% CI, 0.69-0.93]), lack of or inadequate insurance (OR for Medicaid, 0.86 [95% CI, 0.76-0.98]; OR for no insurance, 0.65 [95% CI, 0.54-0.78]), and treatment in a low-volume center (OR for first quartile, 0.73 [95% CI, 0.62-0.87]; OR for second quartile, 0.79 [95% CI, 0.70-0.90]; OR for third quartile, 0.86 [95% CI, 0.78-0.94]). Clinical and pathologic variables associated with a decreased pCR included higher tumor grade (OR, 0.58 [95% CI, 0.49-0.70]), advanced tumor stage (OR for T3, 0.56 [95% CI, 0.42-0.76]; OR for T4, 0.30 [95% CI, 0.22-0.42]), and lymph node-positive disease (OR for N1, 0.83 [95% CI, 0.77-0.89]; OR for N2, 0.73 [95% CI, 0.65-0.82]). Conclusions and Relevance: The findings of this cohort study suggest that disparate treatment outcomes for Hispanic and non-Hispanic Black patients are likely multifactorial in origin. Future investigation into additional social determinants of health and biological variables is warranted.

Dual anti-HER2/EGFR inhibition synergistically increases therapeutic effects and alters tumor oxygenation in HNSCC.

Epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and hypoxia are associated with radioresistance. The goal of this study is to study the synergy of anti-HER2, trastuzumab, and anti-EGFR, cetuximab, and characterize the tumor microenvironment components that may lead to increased radiation sensitivity with dual anti-HER2/EGFR therapy in head and neck squamous cell carcinoma (HNSCC). Positron emission tomography (PET) imaging ([89Zr]-panitumumab and [89Zr]-pertuzumab) was used to characterize EGFR and HER2 in HNSCC cell line tumors. HNSCC cells were treated with trastuzumab, cetuximab, or combination followed by radiation to assess for viability and radiosensitivity (colony forming assay, immunofluorescence, and flow cytometry). In vivo, [18F]-FMISO-PET imaging was used to quantify changes in oxygenation during treatment. Bliss Test of Synergy was used to identify combination treatment synergy. Quantifying EGFR and HER2 receptor expression revealed a 50% increase in heterogeneity of HER2 relative to EGFR. In vitro, dual trastuzumab-cetuximab therapy shows significant decreases in DNA damage response and increased response to radiation therapy (p < 0.05). In vivo, tumors treated with dual anti-HER2/EGFR demonstrated decreased tumor hypoxia, when compared to single agent therapies. Dual trastuzumab-cetuximab demonstrates synergy and can affect tumor oxygenation in HNSCC. Combination trastuzumab-cetuximab modulates the tumor microenvironment through reductions in tumor hypoxia and induces sustained treatment synergy.

[89Zr]-CD8 ImmunoPET imaging of glioblastoma multiforme response to combination oncolytic viral and checkpoint inhibitor immunotherapy reveals CD8 infiltration differential changes in preclinical models.

Rationale: Novel immune-activating therapeutics for the treatment of glioblastoma multiforme (GBM) have shown potential for tumor regression and increased survival over standard therapies. However, immunotherapy efficacy remains inconsistent with response assessment being complicated by early treatment-induced apparent radiological tumor progression and slow downstream effects. This inability to determine early immunotherapeutic benefit results in a drastically decreased window for alternative, and potentially more effective, treatment options. The objective of this study is to evaluate the effects of combination immunotherapy on early CD8+ cell infiltration and its association with long term response in orthotopic syngeneic glioblastoma models. Methods: Luciferase positive GBM orthotopic mouse models (GSC005-luc) were imaged via [89Zr]-CD8 positron emission tomography (PET) one week following treatment with saline, anti-PD1, M002 oncolytic herpes simplex virus (oHSV) or combination immunotherapy. Subsequently, brains were excised, imaged via [89Zr]-CD8 ImmunoPET and evaluated though autoradiography and histology for H&E and CD8 immunohistochemistry. Longitudinal immunotherapeutic effects were evaluated through [89Zr]-CD8 PET imaging one- and three-weeks following treatment, with changes in tumor volume monitored on a three-day basis via bioluminescence imaging (BLI). Response classification was then performed based on long-term BLI signal changes. Statistical analysis was performed between groups using one-way ANOVA and two-sided unpaired T-test, with p < 0.05 considered significant. Correlations between imaging and biological validation were assessed via Pearson's correlation test. Results: [89Zr]-CD8 PET standardized uptake value (SUV) quantification was correlated with ex vivo SUV quantification (r = 0.61, p < 0.01), autoradiography (r = 0.46, p < 0.01), and IHC tumor CD8+ cell density (r = 0.55, p < 0.01). Classification of therapeutic responders, via bioluminescence signal, revealed a more homogeneous CD8+ immune cell distribution in responders (p < 0.05) one-week following immunotherapy. Conclusions: Assessment of early CD8+ cell infiltration and distribution in the tumor microenvironment provides potential imaging metrics for the characterization of oHSV and checkpoint blockade immunotherapy response in GBM. The combination therapies showed enhanced efficacy compared to single agent immunotherapies. Further development of immune-focused imaging methods can provide clinically relevant metrics associated with immune cell localization that can inform immunotherapeutic efficacy and subsequent treatment response in GBM patients.

Effect of neighborhood and individual-level socioeconomic factors on breast cancer screening adherence in a multi-ethnic study.

BACKGROUND: Although mammography can significantly reduce breast cancer mortality, many women do not receive their annual breast cancer screening. Differences in screening adherence exist by race/ethnicity, socioeconomic status (SES), and insurance status. However, more detailed investigations into the impact of neighborhood disadvantage and access to resources on screening adherence are lacking. METHODS: We comprehensively examined the effect of individual social, economic, and demographic factors (n = 34 variables), as well as neighborhood level SES (nSES) indicators (n = 10 variables) on breast cancer screening adherence across a multi-ethnic population (n = 472). In this cross-sectional study, participants were surveyed from 2017 to 2018. The data was analyzed using univariate regression and LASSO for variable reduction. Significant predictors were carried forward into final multivariable mixed-effect logistic regression models where odds ratios (OR), 95% confidence intervals and p-values were reported. RESULTS: Nineteen percent of participants were non-adherent to breast screening guidelines. Race/ethnicity was not associated with adherence; however, increasing age (OR = 0.97, 95%CI = 0.95-0.99, p = 0.01), renting a home (OR = 0.53, 95%CI = 0.30-0.94, p = 0.04), food insecurity (OR 0.46, 95%CI = 0.22-0.94, p = 0.01), and overcrowding (OR = 0.58, 95% CI = 0.32-0.94, p = 0.01) were significantly associated with lower breast cancer screening adherence. CONCLUSION: Socioeconomic indicators at the individual and neighborhood levels impact low breast cancer screening adherence and may help to inform future screening interventions.

Disparities in care of older adults of color with cancer: A narrative review.

This review describes the barriers and challenges faced by older adults of color with cancer and highlights methods to improve their overall care. In the next decade, cancer incidence rates are expected to increase in the United States for people aged ≥65 years. A large proportion will be older adults of color who often have worse outcomes than older White patients. Many issues contribute to racial disparities in older adults, including biological factors and social determinants of health (SDOH) related to healthcare access, socioeconomic concerns, systemic racism, mistrust, and the neighborhood where a person lives. These disparities are exacerbated by age-related challenges often experienced by older adults, such as decreased functional status, impaired cognition, high rates of comorbidities and polypharmacy, poor nutrition, and limited social support. Additionally, underrepresentation of both patients of color and older adults in cancer clinical research results in a lack of adequate data to guide the management of these patients. Use of geriatric assessments (GA) can aid providers in uncovering age-related concerns and personalizing interventions for older patients. Research demonstrates the ability of GA-directed care to result in fewer treatment-related toxicities and improved quality of life, thus supporting the routine incorporation of validated GA into these patients' care. GA can be enhanced by including evaluation of SDOH, which can help healthcare providers understand and address the needs of older adults of color with cancer who face disparities related to their age and race.

"Cancer's a demon": a qualitative study of fear and multilevel factors contributing to cancer treatment delays.

PURPOSE: Delays initiating cancer therapy are increasingly common, impact outcomes, and have implications for health equity. However, it remains unclear (1) whether patients' beliefs regarding acceptable diagnostic to treatment intervals align with current guidelines, and (2) to what degree psychological factors contribute to longer intervals. We conducted a qualitative study with patients and cancer care team members ("providers"). METHODS: We interviewed patients with several common solid tumors as well as providers. Interviews were analyzed using an interpretive approach, guided by modified grounded theory. RESULTS: Twenty-two patients and 12 providers participated. Half of patients had breast cancer; 27% waited >60 days between diagnosis and treatment. Several themes emerged. (1) Patients felt treatment should begin immediately following diagnosis, while providers' opinion on the goal timeframe to start treatment varied. (2) Patients experienced psychological distress while waiting for treatment. (3) Participants identified logistical, social, and psychological sources of delay. Fear related to multiple aspects of cancer care was common. Emotion-driven barriers could manifest as not taking steps to move ahead, or as actions that delayed care. (4) Besides addressing logistical challenges, patients believed that education and anticipatory guidance, from their care team and from peers, may help overcome psychological barriers to treatment and facilitate the start of therapy. CONCLUSIONS: Patients feel an urgency to start cancer therapy, desiring time frames shorter than those included in guidelines. Psychological distress is frequently both a contributor to, and a consequence of, treatment delays. Addressing multilevel barriers, including psychological ones, may facilitate timely treatment and reduce distress.

Development of a Multilevel Model to Identify Patients at Risk for Delay in Starting Cancer Treatment.

Importance: Delays in starting cancer treatment disproportionately affect vulnerable populations and can influence patients' experience and outcomes. Machine learning algorithms incorporating electronic health record (EHR) data and neighborhood-level social determinants of health (SDOH) measures may identify at-risk patients. Objective: To develop and validate a machine learning model for estimating the probability of a treatment delay using multilevel data sources. Design, Setting, and Participants: This cohort study evaluated 4 different machine learning approaches for estimating the likelihood of a treatment delay greater than 60 days (group least absolute shrinkage and selection operator [LASSO], bayesian additive regression tree, gradient boosting, and random forest). Criteria for selecting between approaches were discrimination, calibration, and interpretability/simplicity. The multilevel data set included clinical, demographic, and neighborhood-level census data derived from the EHR, cancer registry, and American Community Survey. Patients with invasive breast, lung, colorectal, bladder, or kidney cancer diagnosed from 2013 to 2019 and treated at a comprehensive cancer center were included. Data analysis was performed from January 2022 to June 2023. Exposures: Variables included demographics, cancer characteristics, comorbidities, laboratory values, imaging orders, and neighborhood variables. Main Outcomes and Measures: The outcome estimated by machine learning models was likelihood of a delay greater than 60 days between cancer diagnosis and treatment initiation. The primary metric used to evaluate model performance was area under the receiver operating characteristic curve (AUC-ROC). Results: A total of 6409 patients were included (mean [SD] age, 62.8 [12.5] years; 4321 [67.4%] female; 2576 [40.2%] with breast cancer, 1738 [27.1%] with lung cancer, and 1059 [16.5%] with kidney cancer). A total of 1621 (25.3%) experienced a delay greater than 60 days. The selected group LASSO model had an AUC-ROC of 0.713 (95% CI, 0.679-0.745). Lower likelihood of delay was seen with diagnosis at the treating institution; first malignant neoplasm; Asian or Pacific Islander or White race; private insurance; and lacking comorbidities. Greater likelihood of delay was seen at the extremes of neighborhood deprivation. Model performance (AUC-ROC) was lower in Black patients, patients with race and ethnicity other than non-Hispanic White, and those living in the most disadvantaged neighborhoods. Though the model selected neighborhood SDOH variables as contributing variables, performance was similar when fit with and without these variables. Conclusions and Relevance: In this cohort study, a machine learning model incorporating EHR and SDOH data was able to estimate the likelihood of delays in starting cancer therapy. Future work should focus on additional ways to incorporate SDOH data to improve model performance, particularly in vulnerable populations.

Defining aggressive prostate cancer: a geospatial perspective.

BACKGROUND: Spatial analysis can identify communities where men are at risk for aggressive prostate cancer (PCan) and need intervention. However, there are several definitions for aggressive PCan. In this study, we evaluate geospatial patterns of 3 different aggressive PCan definitions in relation to PCan-specific mortality and provide methodologic and practical insights into how each definition may affect intervention targets. METHODS: Using the Pennsylvania State Cancer Registry data (2005-2015), we used 3 definitions to assign "aggressive" status to patients diagnosed with PCan. Definition one (D1, recently recommended as the primary definition, given high correlation with PCan death) was based on staging criteria T4/N1/M1 or Gleason score ≥ 8. Definition two (D2, most frequently-used definition in geospatial studies) included distant SEER summary stage. Definition three (D3) included Gleason score ≥ 7 only. Using Bayesian spatial models, we identified geographic clusters of elevated odds ratios for aggressive PCan (binomial model) for each definition and compared overlap between those clusters to clusters of elevated hazard ratios for PCan-specific mortality (Cox regression). RESULTS: The number of "aggressive" PCan cases varied by definition, and influenced quantity, location, and extent/size of geographic clusters in binomial models. While spatial patterns overlapped across all three definitions, using D2 in binomial models provided results most akin to PCan-specific mortality clusters as identified through Cox regression. This approach resulted in fewer clusters for targeted intervention and less sensitive to missing data compared to definitions that rely on clinical TNM staging. CONCLUSIONS: Using D2, based on distant SEER summary stage, in future research may facilitate consistency and allow for standardized comparison across geospatial studies.

Acyl-CoA thioesterase-2 facilitates ß-oxidation in glycolytic skeletal muscle in a lipid supply dependent manner.

Acyl-Coenzyme A (acyl-CoA) thioesters are compartmentalized intermediates that participate in in multiple metabolic reactions within the mitochondrial matrix. The limited availability of free CoA (CoASH) in the matrix raises the question of how the local acyl-CoA concentration is regulated to prevent trapping of CoASH from overload of any specific substrate. Acyl-CoA thioesterase-2 (ACOT2) hydrolyzes long-chain acyl-CoAs to their constituent fatty acids and CoASH, and is the only mitochondrial matrix ACOT refractory to inhibition by CoASH. Thus, we reasoned that ACOT2 may constitutively regulate matrix acyl-CoA levels. Acot2 deletion in murine skeletal muscle (SM) resulted in acyl-CoA build-up when lipid supply and energy demands were modest. When energy demand and pyruvate availability were elevated, lack of ACOT2 activity promoted glucose oxidation. This preference for glucose over fatty acid oxidation was recapitulated in C2C12 myotubes with acute depletion of Acot2 , and overt inhibition of ß-oxidation was demonstrated in isolated mitochondria from Acot2 -depleted glycolytic SM. In mice fed a high fat diet, ACOT2 enabled the accretion of acyl-CoAs and ceramide derivatives in glycolytic SM, and this was associated with worse glucose homeostasis compared to when ACOT2 was absent. These observations suggest that ACOT2 supports CoASH availability to facilitate ß-oxidation in glycolytic SM when lipid supply is modest. However, when lipid supply is high, ACOT2 enables acyl-CoA and lipid accumulation, CoASH sequestration, and poor glucose homeostasis. Thus, ACOT2 regulates matrix acyl-CoA concentration in glycolytic muscle, and its impact depends on lipid supply.

Voltage-Gated Sodium Channel NaV1.7 Inhibitors with Potent Anticancer Activities in Medullary Thyroid Cancer Cells.

Our results from quantitative RT-PCR, Western blotting, immunohistochemistry, and the tissue microarray of medullary thyroid cancer (MTC) cell lines and patient specimens confirm that VGSC subtype NaV1.7 is uniquely expressed in aggressive MTC and not expressed in normal thyroid cells and tissues. We establish the druggability of NaV1.7 in MTC by identifying a novel inhibitor (SV188) and investigate its mode of binding and ability to inhibit INa current in NaV1.7. The whole-cell patch-clamp studies of the SV188 in the NaV1.7 channels expressed in HEK-293 cells show that SV188 inhibited the INa current in NaV1.7 with an IC50 value of 3.6 µM by a voltage- and use-dependent blockade mechanism, and the maximum inhibitory effect is observed when the channel is open. SV188 inhibited the viability of MTC cell lines, MZ-CRC-1 and TT, with IC50 values of 8.47 µM and 9.32 µM, respectively, and significantly inhibited the invasion of MZ-CRC-1 cells by 35% and 52% at 3 µM and 6 µM, respectively. In contrast, SV188 had no effect on the invasion of TT cells derived from primary tumor, which have lower basal expression of NaV1.7. In addition, SV188 at 3 µM significantly inhibited the migration of MZ-CRC-1 and TT cells by 27% and 57%, respectively.

Childhood and Adult Sexual Violence Exposures as Predictors of PTSD, Dissociation, and Substance Use in Women in Jail.

Women involved in the criminal legal system report high rates of interpersonal violence, particularly sexual violence, and mental health problems. Although existing research has linked experiences of interpersonal violence to multiple negative mental health outcomes, few researchers have examined concurrent psychopathology as an outcome of child and adult sexual violence in system-involved women. The purpose of this study was to examine child sexual abuse (CSA) and adult sexual violence, while controlling for other forms of interpersonal violence, as predictors of current symptoms of posttraumatic stress disorder (PSTD), substance use disorder (SUD), and dissociation in women in jail in the Mountain West. Randomly selected participants (N = 146) completed clinician-administered measures of trauma histories and mental health symptoms. The majority of the women (73%) reported experiences of CSA and about half reported experiences of adult sexual violence. Over half of the women reported symptoms consistent with current probable PTSD, about 20% reported dissociation symptoms in a clinical range, and over 70% met criteria for a SUD in the past year. The proposed model was tested with path analysis. CSA significantly predicted current symptoms of PTSD while adult sexual violence exposure predicted symptoms of SUD and dissociation. These results illustrate the high rates of sexual violence exposure as well as the complexity of mental health needs associated with these exposures in system-involved women. Findings highlight the need to comprehensively assess incarcerated women's trauma exposure and psychological distress to better meet the needs of this population.

Trends in prostate cancer incidence among Black men in the Caribbean and the United States.

BACKGROUND: Prostate cancer incidence is highest for Black men of the African diaspora in the United States and Caribbean. Recent changes in recommendations for prostate cancer screening have been shown to decrease overall prostate cancer incidence and increase the likelihood of late stage disease. However, it is unclear how trends in prostate cancer characteristics among high risk Black men differ by geographic region during the changes in screening recommendations. METHODS: In this study, we used population-based prostate cancer registry data to describe age-adjusted prostate cancer incidence trends from 2008 to 2015 among Black men from six geographic regions. We obtained data on incident Black prostate cancer patients from six cancer registries (in the United States: Florida, Alabama, Pennsylvania, and New York; and in the Caribbean: Guadeloupe and Martinique). After age standardization, we used descriptive analyses to compare the demographics and tumor characteristics by cancer registry site. The Joinpoint regression program was used to compare the trends in incidence by site. RESULTS: A total of 59,246 men were analyzed. We found the highest incidence rates (per 100,000) for prostate cancer in the Caribbean countries (181.99 in Martinique and 176.62 in Guadeloupe) and New York state (178.74). Incidence trends decreased significantly over time at all sites except Martinique, which also showed significantly increasing rates of late stage (III/IV) and Gleason score 7+ tumors. CONCLUSIONS: We observed significant differences in prostate cancer incidence trends among Black men after major changes prostate screening recommendations. Future studies will examine the factors that differentially influence prostate cancer trends among the African diaspora.

Current Status and Future Direction to Address Disparities in Diversity, Equity, and Inclusion in Prostate Cancer Care.

PURPOSE OF REVIEW: Disparities in prostate cancer care and outcomes have been well recognized for decades. The purpose of this review is to methodically highlight known racial disparities in the care of prostate cancer patients, and in doing so, recognize potential strategies for overcoming these disparities moving forward. RECENT FINDINGS: Over the past few years, there has been a growing recognition and push towards addressing disparities in cancer care. This has led to improvements in care delivery trends and a narrowing of racial outcome disparities, but as we highlight in the following review, there is more to be addressed before we can fully close the gap in prostate cancer care delivery. While disparities in prostate cancer care are well recognized in the literature, they are not insurmountable, and progress has been made in identifying areas for improvement and potential strategies for closing the care gap.

Venous thromboembolism in metastatic pancreatic cancer.

BACKGROUND: Pancreatic cancer (PC) carries a high risk of venous thromboembolism (VTE). Several risk assessment models (RAMs) predict benefit of thromboprophylaxis in solid tumors; however, none are verified in metastatic pancreatic cancer (mPC). METHODS: A retrospective mPC cohort treated at an academic cancer center from 2010 to 2016 was investigated for VTE incidence (VTEmets). Multivariable regression analysis was used to assess multiple VTE risk factors. Overall survival (OS) was compared between mPC groups with and without VTE. Survival was analyzed using Kaplan-Meier survival plots and Cox proportional hazards regressions. RESULTS: 400 mPC patients (median age 66; 52% males) were included. 87% had performance status of ECOG 0-1; 70% had advanced stage at PC diagnosis. Incidence of VTEmets was 17.5%; median time of occurrence 3.48 months after mPC diagnosis. Survival analysis started at median VTE occurrence. Median OS was 10.5 months in VTEmets vs. 13.4 in non-VTE group. Only advanced stage (OR 3.7, p = .001) correlated with increased VTE risk. CONCLUSIONS: The results suggest mPC carries a significant VTE burden. VTE predicts poor outcomes from the point of median VTE occurrence. Advanced stage disease is the strongest risk factor. Future studies are needed to define risk stratification, survival benefit, and choice of thromboprophylaxis.

The changing dynamics of ant-tree cholla mutualisms along a desert urbanization gradient.

Urbanization, among the most widespread and multifaceted anthropogenic change drivers, exerts strong influences on a diversity of ecological communities worldwide. We have begun to understand how urbanization affects species diversity, yet we still have limited knowledge about the ways that species interactions are altered by urbanization. We have an especially poor understanding of how urbanization influences stress-buffering mutualisms, despite the high levels of multivariate stress that urban organisms must overcome and the importance of these interactions to the fitness of many organisms. In this study, we investigated the effects of urbanization on a mutualism between tree cholla cacti (Cylindropuntia imbricata) and visiting ants. We first examined how plant size, ant species composition, and ant activity varied on C. imbricata across an urbanization gradient (urban, suburban, wild) in and around Albuquerque, NM. Ant species composition and activity varied significantly across the urbanization gradient, with ant communities from wildlands having the highest activity and the most dissimilar species composition compared to both suburban and urban sites. In contrast, plant size remained constant regardless of site type. We then experimentally assessed how nectar levels influenced ant aggressive encounters with proxy prey (Drosophila melanogaster larvae) on C. imbricata across urban and wild sites. Ants were more likely to discover, attack, and remove proxy prey in wild sites compared to urban sites; they also performed these behaviors more quickly in wild sites. Nectar supplementation had weaker effects on ant aggression than urbanization, but consistently increased the speed at which aggressive behaviors occurred. Future studies that examine nectar quality and herbivorous arthropod abundance may help explain why this strong difference in ant composition and aggression was not associated with lower plant fitness proxies (i.e. size traits). Nevertheless, this study provides unique insight into the growing body of work demonstrating that mutualisms vary significantly across urbanization gradients.