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Γδ T cells are non-conventional T cells that are not MHC restricted and have T cell receptors (TCRs) that are stimulated by phosphoantigens, stress-induced proteins, lipids, and other antigens. These cells are prognostic across cancer types in The Cancer Genome Atlas (TCGA) but have not been well studied in endometrial cancer, which has a rising incidence and mortality rate. Endometrial cancer patients have variable responses to checkpoint inhibitors which are related to the molecular subtype of their cancer. As such, there is a pressing need to understand the immune microenvironment in endometrial cancer. This study addresses this gap in knowledge by investigating γδ T cell repertoires and transcriptomes in this disease site. γδ T cell repertoires were obtained for 543 endometrial cancer patients within the TCGA and from 5 endometrial cancer patients in the single cell dataset SRP349751 using TRUST4. GLIPH2 was used to identify TCRs predicted to bind the same antigen. Transcriptomes were investigated in the single cell dataset. DNA Polymerase Epsilon Exonuclease (POLE) and Microsatellite Instability High (MSI-H) endometrial cancer subtypes had the most γδ T cell infiltration. Vδ1 and Vδ3 γδ T cell infiltration was prognostic independent of stage and molecular subtype. GLIPH2 analysis revealed TCRδ motifs for TDK, YTD, and GEL were public across all four molecular subtypes and were present in the single cell data set. Vδ1 γδ T cell transcriptomes were associated with cytotoxicity and recent TCR stimulation. These data support further investigation of immunotherapies targeting γδ T cells in endometrial cancer.

In ovarian cancer, there is no current method to accurately predict recurrence after a complete response to chemotherapy. Here, we develop a machine learning risk score using serum proteomics for the prediction of early recurrence of ovarian cancer after initial treatment. The developed risk score was validated in an independent cohort with serum collected prospectively during the remission period. In the discovery cohort, patients scored as low-risk had a median time to recurrence (TTR) that was not reached at 10 years compared to 10.5 months (HR 4.66, p < 0.001) in high-risk patients. In the validation cohort, low-risk patients had a median TTR which was not reached compared to 4.7 months in high-risk patients (HR 4.67, p = 0.009). In advanced-stage patients with a CA125 < 10, low-risk patients had a median TTR of 68 months compared to 6 months in high-risk patients (HR 2.91, p = 0.02). The developed risk score was capable of distinguishing the duration of remission in ovarian cancer patients. This score may help guide maintenance therapy and develop innovative treatments in patients at risk at high-risk of recurrence.

Launched in 2009, the State Action on Avoidable Rehospitalizations initiative, known as STAAR, aims to reduce rates of avoidable rehospitalization in Massachusetts, Michigan, Ohio, and Washington by mobilizing state-level leadership to improve care transitions. With the program two years into its four-year cycle, 148 hospitals are working in partnership with more than 500 cross-continuum team partners. Although there are no publicly available data on whether the project is achieving its primary goal of reducing avoidable rehospitalizations, the effort has so far been successful in aligning numerous complementary initiatives within a state, developing statewide rehospitalization data reports, and mobilizing a sizable number of hospitals to work on reducing rehospitalizations. More than 90 percent of participating hospitals have formed teams to routinely review rehospitalizations with their community-based colleagues. Adapted from the source document.

PurposeTo propose a categorization model of uterine carcinosarcoma (UCS) based on tumor cell types (carcinoma and sarcoma) and sarcoma dominance.MethodsThis secondary analysis of a prior multicenter retrospective study examined 889 cases of UCS with available histologic evaluation. Based on survival outcome, cases were clustered into three groups: low-grade carcinoma with nondominant homologous sarcoma [type A, n = 96 (10.8%)], (1) low-grade carcinoma with heterologous sarcoma or any sarcoma dominance and (2) high-grade carcinoma with nondominant homologous sarcoma [type B, n = 412 (46.3%)], and high-grade carcinoma with heterologous sarcoma or any sarcoma dominance [type C, n = 381 (42.9%)]. Tumor characteristics and outcome were examined based on the categorization.ResultsWomen in type C category were more likely to be older, obese, and Caucasian, whereas those in type A category were younger, less obese, Asian, and nulligravid (all P < 0.01). Type C tumors were more likely to have metastatic implants, large tumor size, lymphovascular space invasion with sarcoma cells, and higher lymph node ratio, whereas type A tumors were more likely to be early-stage disease and small (all P < 0.05). On multivariate analysis, tumor categorization was independently associated with progression-free survival (5-year rates: 70.1% for type A, 48.3% for type B, and 35.9% for type C, adjusted P < 0.01) and cause-specific survival (5-year rates: 82.8% for type A, 63.0% for type B, and 47.1% for type C, adjusted P < 0.01).ConclusionCharacteristic differences in clinicopathological factors and outcomes in UCS imply that different underlying etiologies and biological behaviors may be present, supporting a new classification system.

ObjectiveThe aim of this study was to examine the significance of lymphovascular space invasion (LVSI) with a sarcomatous component on the tumor characteristics and clinical outcomes of women with uterine carcinosarcoma (UCS).MethodsThis was a secondary analysis of a prior multicenter retrospective study that examined women with stage I–IV UCS who underwent primary hysterectomy. Archived histopathology slides were reviewed and LVSI was scored as follows: LVSI with a carcinomatous component alone (LVSI-carcinoma; n = 375, 76.8%) or LVSI containing a sarcomatous component with or without a carcinomatous component (LVSI-sarcoma; n = 113, 23.2%). Qualitative metrics of LVSI were correlated to clinicopathological factors and survival outcome.ResultsTumors in the LVSI-sarcoma group were more likely to have sarcoma dominance (82.1 vs. 26.4%) heterologous sarcomatous component (51.3 vs. 37.9%), low-grade carcinoma (42.5 vs. 22.4%), and large tumor size (81.0 vs. 70.2%) in the primary tumor site compared with tumors in the LVSI-carcinoma group (all p < 0.05). On multivariate analysis, LVSI-sarcoma was independently associated with decreased progression-free survival (5-year rates: 34.9 vs. 40.8%, adjusted hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.36–2.50, p < 0.001), and cause-specific survival (5-year rates: 41.8 vs. 55.9%, adjusted HR 1.95, 95% CI 1.39–2.75, p < 0.001) compared with LVSI-carcinoma. Postoperative radiotherapy for women with LVSI-sarcoma had a higher reduction rate of recurrence/progression of disease (54% reduction, p = 0.04) compared with postoperative radiotherapy for women with LVSI-carcinoma (26% reduction, p = 0.08).ConclusionIn UCS, the presence of a sarcomatous component in LVSI is particularly prevalent when a tumor has sarcoma dominance. Our study suggests that LVSI containing a sarcomatous component may be a predictor of decreased survival for women with UCS.

Examples of categories include adults under 65 with disabilities, frail older adults, people with multiple chronic conditions, and people with behavioral health and social needs; however, stronger links to population-specific care would bolster the usefulness of these categories, as discussed in Overview ofSegmentation of High-Need, High-Cost Patient Population, published by the National Academy of Medicine in January 2016. Share Information on Outcomes Early user testing of The Playbook suggests that audiences, especially health system leaders and payers, value detailed case studies with guidance on a granular level about how to implement promising models and programs; however, few care models highlighted in The Playbook have been replicated or spread to multiple settings. From the body of work that was synthesized for The Playbook-including Models ofCare for High-Need, High-Cost Patients: An Evidence Synthesis, an October 2015 issue brief from The Commonwealth Fund-we found that many of the strongest models of care shared the following three core elements: * Identifying the population segment most likely to benefit * Connecting individuals to appropriate follow-up and support services outside of healthcare * Providing care coordination and facilitating communication across all providers Successful models bolster these elements with operational structures, including leadership buy-in, interdisciplinary teamwork, workforce...

The replication of simian virus 40 DNA and protein synthesis in BSC-1 cells was analyzed in vitro after treatment with 5,6-dihydro-5-azacytidine (DH-5-AzaCR) or 5-azacytidine (5-AzaCR). Results demonstrated that after a 3-h treatment period with 100 µg/ml, DH-5-AzaCR exhibited a 77% inhibition of viral DNA synthesis, whereas 5-AzaCR resulted in a 50% inhibition. Stimulation of DNA synthesis occurred when infected cultures were treated with low doses (0.1 to 0.5 µg/ml) of 5-AzaCR for 3 h and after 1 and 2 h of treatment with 100 µg/ml of 5-AzaCR; however, stimulation did not occur with DH-5-AzaCR. DNA synthesized in the presence of either drug demonstrated altered conformations when analyzed on agarose gels; however this alteration was negligible after DH-5-AzaCR treatment, but more pronounced in the presence of 5-AzaCR. Restriction enzyme analysis suggests that DH-5-AzaCR may not be a hypomethylating agent as is 5-AzaCR. Inhibition of total protein synthesis (cellular and viral) was essentially complete 6 h after treatment with DH-5-AzaCR, whereas 5-AzaCR completely inhibited protein synthesis after 3 h. These data indicate that 5-AzaCR does not exhibit a direct dose relationship to the inhibition of DNA synthesis whereas DH-5-AzaCR may show some dose relationship, and that DH-5-AzaCR is a more potent inhibitor of DNA synthesis as compared to 5-AzaCR.

A Nation at Risk: The Imperative for Educational Reform (National Commission on Excellence in Education, 1983) drew public attention to the need for articulating standards in American education and developing assessments to measure student achievement of those standards. The Alabama High School Graduation Examination Language subtest is a multiple-choice, high-stakes examination addressing the state's five standards for the English language arts: recognizing correct grammar and usage, demonstrating appropriate word choice, recognizing correct sentence structure, using correct capitalization and punctuation, and using appropriate organizational skills for writing/revising. Because research indicates that the teaching of traditional school grammar has little or no positive impact upon students' composition skills, it is generally ignored in the literature addressing the teaching of English language arts. Research further indicates that students from low-income families tend to perform at a lower level on standardized examinations than do students from higher-income families. This research was corroborated by the statistical analysis conducted to identify the schools that would be invited to participate in this study. Data analysis revealed that as schools' free and reduced-price lunch population increased scores on the AHSGE language subtest decreased. The purpose of this study was to identify curricular and instructional practices in schools whose free and reduced-price lunch qualifying population was 50% or higher and whose student passing percentage on the AHSGE language subtest exceeded the state average, thereby challenging the statistical expectation. Teachers and administrators in the 11 participating schools responded to survey items addressing curriculum, instruction, the English language arts, and Alabama standards and assessment. Findings indicated that years of experience, level of certification, and participation in school-level curriculum decisions among teachers in the survey schools are significantly higher than the state averages, and the teachers use traditional methodologies and materials most frequently. Administrators in those schools tend to rely upon their teachers' recommendations regarding curriculum, and they support the traditional approaches to grammar instruction.