Same People, Different Results: Categorizing Cancer Registry Cases Across the Rural-Urban Continuum.

BACKGROUND: Many rural-urban indexes are utilized in cancer research. This variation introduces inconsistencies between studies. Recommendations on index use have prioritized geographical unit over feasibility of inclusion in analysis. We evaluated rural-urban indexes and recommend one for use to increase comparability across studies. METHODS: We assessed 9 US rural-urban indexes regarding their respective rural and urban code ranges; geographical unit, land area, and population distributions; percent agreement; suitability for analysis; and integration feasibility for national, state, and local cancer research. We referenced 1569 Wisconsin Pancreatic Cancer Registry patients to demonstrate how index choice affects patient categorization. RESULTS: Six indexes categorized rural and urban areas. Indexes agreed on binary rural-urban designation for 88.8% of the US population. As ternary variables, they agreed for 83.4%. For cancer registry patients, this decreased to 73.4% and 60.4% agreement, respectively. Rural-Urban Continuum Codes (RUCC) performed the best in differentiating metropolitan, micropolitan, and rural counties; availability for retrospective and prospective studies; and continuous coding for analysis. CONCLUSIONS: Urban/rural patient categorization changed with index selection. We conclude that RUCC is an appropriate and feasible rural-urban index to include in cancer research, as it is standardly available in national cancer registries, can be matched to patient's county of residence for local research, and it had the least amount of fluctuation of the indices analyzed. Utilizing RUCC as a continuous variable across studies with a rural-urban component will increase reproducibility and comparability of results and eliminate rural-urban index choice as a potential source of discrepancy between studies.

A platform-independent AI tumor lineage and site (ATLAS) classifier.

Histopathologic diagnosis and classification of cancer plays a critical role in guiding treatment. Advances in next-generation sequencing have ushered in new complementary molecular frameworks. However, existing approaches do not independently assess both site-of-origin (e.g. prostate) and lineage (e.g. adenocarcinoma) and have minimal validation in metastatic disease, where classification is more difficult. Utilizing gradient-boosted machine learning, we developed ATLAS, a pair of separate AI Tumor Lineage and Site-of-origin models from RNA expression data on 8249 tumor samples. We assessed performance independently in 10,376 total tumor samples, including 1490 metastatic samples, achieving an accuracy of 91.4% for cancer site-of-origin and 97.1% for cancer lineage. High confidence predictions (encompassing the majority of cases) were accurate 98-99% of the time in both localized and remarkably even in metastatic samples. We also identified emergent properties of our lineage scores for tumor types on which the model was never trained (zero-shot learning). Adenocarcinoma/sarcoma lineage scores differentiated epithelioid from biphasic/sarcomatoid mesothelioma. Also, predicted lineage de-differentiation identified neuroendocrine/small cell tumors and was associated with poor outcomes across tumor types. Our platform-independent single-sample approach can be easily translated to existing RNA-seq platforms. ATLAS can complement and guide traditional histopathologic assessment in challenging situations and tumors of unknown primary.

Association of Neighborhood Disadvantage with Short- and Long-Term Outcomes After Pancreatectomy for Pancreatic Ductal Adenocarcinoma.

BACKGROUND: While lower socioeconomic status has been shown to correlate with worse outcomes in cancer care, data correlating neighborhood-level metrics with outcomes are scarce. We aim to explore the association between neighborhood disadvantage and both short- and long-term postoperative outcomes in patients undergoing pancreatectomy for pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: We retrospectively analyzed 243 patients who underwent resection for PDAC at a single institution between 1 January 2010 and 15 September 2021. To measure neighborhood disadvantage, the cohort was divided into tertiles by Area Deprivation Index (ADI). Short-term outcomes of interest were minor complications, major complications, unplanned readmission within 30 days, prolonged hospitalization, and delayed gastric emptying (DGE). The long-term outcome of interest was overall survival. Logistic regression was used to test short-term outcomes; Cox proportional hazards models and Kaplan-Meier method were used for long-term outcomes. RESULTS: The median ADI of the cohort was 49 (IQR 32-64.5). On adjusted analysis, the high-ADI group demonstrated greater odds of suffering a major complication (odds ratio [OR], 2.78; 95% confidence interval [CI], 1.26-6.40; p = 0.01) and of an unplanned readmission (OR, 3.09; 95% CI, 1.16-9.28; p = 0.03) compared with the low-ADI group. There were no significant differences between groups in the odds of minor complications, prolonged hospitalization, or DGE (all p > 0.05). High ADI did not confer an increased hazard of death (p = 0.63). CONCLUSIONS: We found that worse neighborhood disadvantage is associated with a higher risk of major complication and unplanned readmission after pancreatectomy for PDAC.

PARP inhibitors in metastatic prostate cancer.

Poly-ADP ribose polymerase inhibitors (PARPi) are an emerging therapeutic option for the treatment of prostate cancer. Their primary mechanism of action is via induction of synthetic lethality in cells with underlying deficiencies in homologous recombination repair (HRR). In men with metastatic castrate-resistant prostate cancer (mCRPC) and select HRR pathway alterations, PARPi treatment has been shown to induce objective tumor responses as well as improve progression free and overall survival. Presently, there are two PARPi, olaparib and rucaparib, that are FDA approved in the treatment of mCRPC. Ongoing research is focused on identifying which HRR alterations are best suited to predict response to PARPi so that these therapies can be most effectively utilized in the clinic. While resistance to PARPi remains a concern, combination therapies may represent a mechanism to overcome or delay resistance.

Treatment Inequity: Examining the Influence of Non-Hispanic Black Race and Ethnicity on Pancreatic Cancer Care and Survival in Wisconsin.

INTRODUCTION: We investigated race and ethnicity-based disparities in first course treatment and overall survival among Wisconsin pancreatic cancer patients. METHODS: We identified adults diagnosed with pancreatic adenocarcinoma in the Wisconsin Cancer Reporting System from 2004 through 2017. We assessed race and ethnicity-based disparities in first course of treatment via adjusted logistic regression and overall survival via 4 incremental Cox proportional hazards regression models. RESULTS: The study included 8,490 patients: 91.3% (n = 7,755) non-Hispanic White; 5.1% (n = 437) non-Hispanic Black, 1.8% (n = 151) Hispanic, 0.6% Native American (n = 53), and 0.6% Asian (n = 51) race and ethnicities. Non-Hispanic Black patients had lower odds of treatment than non-Hispanic White patients for full patient (OR, 0.52; 95% CI, 0.41-0.65) and Medicare cohorts (OR, 0.40; 95% CI, 0.29-0.55). Non-Hispanic Black patients had lower odds of receiving surgery than non-Hispanic White patients (full cohort OR, 0.67 [95% CI, 0.48-0.92]; Medicare cohort OR, 0.57 [95% CI, 0.34-0.93]). Non-Hispanic Black patients experienced worse survival than non-Hispanic White patients in the first 2 incremental Cox proportional hazard regression models (model II HR, 1.18; 95% CI, 1.06-1.31). After adding insurance and treatment course, non-Hispanic Black and non-Hispanic White patients experienced similar survival (HR, 0.98; 95% CI, 0.88-1.09). CONCLUSION: Non-Hispanic Black patients were almost 50% less likely to receive any treatment and 33% less likely to receive surgery than non-Hispanic White patients. After including treatment course, non-Hispanic Black and non-Hispanic White patient survival was similar. Increasing non-Hispanic Black patient treatment rates by addressing structural factors affecting treatment availability and employing culturally humble approaches to treatment discussions may mitigate these disparities.

Aquaculture Reuse Water, Genetic Line, and Vaccination Affect Rainbow Trout (Oncorhynchus mykiss) Disease Susceptibility and Infection Dynamics.

Infectious hematopoietic necrosis virus (IHNV) and Flavobacterium psychrophilum are major pathogens of farmed rainbow trout. Improved control strategies are desired but the influence of on-farm environmental factors that lead to disease outbreaks remain poorly understood. Water reuse is an important environmental factor affecting disease. Prior studies have established a replicated outdoor-tank system capable of varying the exposure to reuse water by controlling water flow from commercial trout production raceways. The goal of this research was to evaluate the effect of constant or pulsed reuse water exposure on survival, pathogen prevalence, and pathogen load. Herein, we compared two commercial lines of rainbow trout, Clear Springs Food (CSF) and Troutex (Tx) that were either vaccinated against IHNV with a DNA vaccine or sham vaccinated. Over a 27-day experimental period in constant reuse water, all fish from both lines and treatments, died while mortality in control fish in spring water was <1%. Water reuse exposure, genetic line, vaccination, and the interaction between genetic line and water exposure affected survival (P<0.05). Compared to all other water sources, fish exposed to constant reuse water had 46- to 710-fold greater risk of death (P<0.0001). Tx fish had a 2.7-fold greater risk of death compared to CSF fish in constant reuse water (P ≤ 0.001), while risk of death did not differ in spring water (P=0.98). Sham-vaccinated fish had 2.1-fold greater risk of death compared to vaccinated fish (P=0.02). Both IHNV prevalence and load were lower in vaccinated fish compared to sham-vaccinated fish, and unexpectedly, F. psychrophilum load associated with fin/gill tissues from live-sampled fish was lower in vaccinated fish compared to sham-vaccinated fish. As a result, up to forty-five percent of unvaccinated fish were naturally co-infected with F. psychrophilum and IHNV and the coinfected fish exhibited the highest IHNV loads. Under laboratory challenge conditions, co-infection with F. psychrophilum and IHNV overwhelmed IHNV vaccine-induced protection. In summary, we demonstrate that exposure to reuse water or multi-pathogen challenge can initiate complex disease dynamics that can overwhelm both vaccination and host genetic resistance.

Sirtuin 1 Promotes Deacetylation of Oct4 and Maintenance of Naive Pluripotency.

The enhancer landscape is dramatically restructured as naive preimplantation epiblasts transition to the post-implantation state of primed pluripotency. A key factor in this process is Otx2, which is upregulated during the early stages of this transition and ultimately recruits Oct4 to a different set of enhancers. In this study, we discover that the acetylation status of Oct4 regulates the induction of the primed pluripotency gene network. Maintenance of the naive state requires the NAD-dependent deacetylase, SirT1, which deacetylates Oct4. The activity of SirT1 is reduced during the naive-to-primed transition; Oct4 becomes hyper-acetylated and binds to an Otx2 enhancer to induce Otx2 expression. Induction of Otx2 causes the reorganization of acetylated Oct4 and results in the induction of the primed pluripotency gene network. Regulation of Oct4 by SirT1 may link stem cell development to environmental conditions, and it may provide strategies to manipulate epiblast cell state.

Women's health care utilization and expenditures.

This study examines women's use and expenditures for medical care in the US. In 2000, 91% of women aged 18 years and older used any form of health care services. Overall, 82% of adult women reported an ambulatory care visit, and 11% had an inpatient hospital stay. Mean expense per person with expenses was 3219 dollars for that year. We examined use and expenditures by sociodemographic characteristics. The most notable findings indicate that women with private insurance and those on Medicaid are more likely to use health services than uninsured women. White women, compared to black and Hispanic women, are more likely to have an ambulatory care visit, buy prescription drugs, and use preventive health care services. In addition, white and Hispanic women pay a higher proportion of medical care expenses out-of-pocket than do black women. Finally, nearly 30% of older women in fair or poor health spent 10% or more of their income on medical care. Preventable disparities in access to and receipt of care are unacceptable. To improve the quality of health care for all women, it is important for policymakers to understand the factors that influence their utilization and expenditures for medical care. Data collection, analysis, and reporting by race, ethnicity, and primary language across federally supported health programs are essential to help identify, understand the causes of, monitor, and eventually eliminate disparities.

Latino adults' health insurance coverage: an examination of Mexican and Puerto Rican subgroup differences.

Lack of health insurance is a serious problem in the United States. Using data from the 1996 Medical Expenditure Panel Survey, this paper examines how insurance varies between black, white, and Latino adults. Because Latino subgroups are not homogeneous, the paper also compares the factors associated with health insurance status for Mexican and Puerto Rican adults. Results indicate that access to private health insurance for Latino adults was more closely associated with workplace characteristics than employment itself. Time lived in the United States was a major factor associated with being uninsured for Mexican adults, while language barriers were a major factor limiting Puerto Rican individuals' access to private health insurance. The paper suggests two approaches for decreasing uninsurance among Latino adults: (1) strengthening the link between employment and private health insurance and (2) addressing disparities in access to public coverage for racial and ethnic groups, including recent immigrants.