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PurposeThe purpose of this study was to evaluate RB1 expression and survival across ovarian carcinoma histotypes and how co-occurrence of BRCA1 or BRCA2 (BRCA) alterations and RB1 loss influences survival in tubo-ovarian high-grade serous carcinoma (HGSC).Experimental designRB1 protein expression was classified by immunohistochemistry in ovarian carcinomas of 7,436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined RB1 expression and germline BRCA status in a subset of 1,134 HGSC, and related genotype to overall survival (OS), tumor-infiltrating CD8+ lymphocytes, and transcriptomic subtypes. Using CRISPR-Cas9, we deleted RB1 in HGSC cells with and without BRCA1 alterations to model co-loss with treatment response. We performed whole-genome and transcriptome data analyses on 126 patients with primary HGSC to characterize tumors with concurrent BRCA deficiency and RB1 loss.ResultsRB1 loss was associated with longer OS in HGSC but with poorer prognosis in endometrioid ovarian carcinoma. Patients with HGSC harboring both RB1 loss and pathogenic germline BRCA variants had superior OS compared with patients with either alteration alone, and their median OS was three times longer than those without pathogenic BRCA variants and retained RB1 expression (9.3 vs. 3.1 years). Enhanced sensitivity to cisplatin and paclitaxel was seen in BRCA1-altered cells with RB1 knockout. Combined RB1 loss and BRCA deficiency correlated with transcriptional markers of enhanced IFN response, cell-cycle deregulation, and reduced epithelial-mesenchymal transition. CD8+ lymphocytes were most prevalent in BRCA-deficient HGSC with co-loss of RB1.ConclusionsCo-occurrence of RB1 loss and BRCA deficiency was associated with exceptionally long survival in patients with HGSC, potentially due to better treatment response and immune stimulation.

All teachers need ongoing coaching that helps them recognize areas of strength and need for teaching students with disabilities. Unfortunately, the amount, quality, and speed with which teachers receive feedback from coaches, administrators, mentors, or other instructional leaders on their academic and behavior management practices is limited. In this article, we describe a multimedia professional development option for documenting teacher practice, generating feedback, and delivering targeted instruction.

BackgroundWomen with low-grade ovarian serous carcinoma (LGSC) benefit from surgical treatment; however, the role of chemotherapy is controversial. We examined an international database through the Ovarian Cancer Association Consortium to identify factors that affect survival in LGSC.MethodsWe performed a retrospective cohort analysis of patients with LGSC who had had primary surgery and had overall survival data available. We performed univariate and multivariate analyses of progression-free survival and overall survival, and generated Kaplan-Meier survival curves.ResultsOf the 707 patients with LGSC, 680 (96.2%) had available overall survival data. The patients' median age overall was 54 years. Of the 659 patients with International Federation of Obstetrics and Gynecology stage data, 156 (23.7%) had stage I disease, 64 (9.7%) had stage II, 395 (59.9%) had stage III, and 44 (6.7%) had stage IV. Of the 377 patients with surgical data, 200 (53.0%) had no visible residual disease. Of the 361 patients with chemotherapy data, 330 (91.4%) received first-line platinum-based chemotherapy. The median follow-up duration was 5.0 years. The median progression-free survival and overall survival were 43.2 months and 110.4 months, respectively. Multivariate analysis indicated a statistically significant impact of stage and residual disease on progression-free survival and overall survival. Platinum-based chemotherapy was not associated with a survival advantage.ConclusionThis multicentre analysis indicates that complete surgical cytoreduction to no visible residual disease has the most impact on improved survival in LGSC. This finding could immediately inform and change practice.

Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi-institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36-3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11-2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC.

BackgroundCyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC.MethodsWithin the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated.ResultsHigh-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss.ConclusionThis study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC.

We investigated the content of liberal and conservative news media Facebook posts on race and ethnic health disparities. A total of 3,327,360 liberal and conservative news Facebook posts from the United States (US) from January 2015 to May 2022 were collected from the Crowd Tangle platform and filtered for race and health-related keywords. Qualitative content analysis was conducted on a random sample of 1750 liberal and 1750 conservative posts. Posts were analyzed for a continuum of hate speech using a newly developed method combining faceted Rasch item response theory with deep learning. Across posts referencing Asian, Black, Latinx, Middle Eastern, and immigrants/refugees, liberal news posts had lower hate scores compared to conservative posts. Liberal news posts were more likely to acknowledge and detail the existence of racial/ethnic health disparities, while conservative news posts were more likely to highlight the negative consequences of protests, immigration, and the disenfranchisement of Whites. Facebook posts from liberal and conservative news focus on different themes with fewer discussions of racial inequities in conservative news. Investigating the discourse on race and health in social media news posts may inform our understanding of the public's exposure to and knowledge of racial health disparities, and policy-level support for ameliorating these disparities.

Vocabulary is a critical building block for establishing mastery of content area knowledge. Two technology-based tools (InferCabulary and Content Acquisition Podcasts for Students [CAP-S]) have been found to have beneficial effects on students' vocabulary knowledge, but efficacy of device features across varied presentation formats is unknown. The purpose of this study was to compare InferCabulary and CAP-S on four measures of vocabulary performance. Fifth-grade students (n = 656) drawn from 30 classrooms across three states participated in one of three conditions to learn 100 new vocabulary terms. Teachers (n = 30) taught student participants new word meanings via the InferCabulary program, CAP-S instructional slides, or their business-as-usual (BAU) approach to instruction. Results indicate that when students learned vocabulary using InferCabulary or CAP-S approaches, they significantly outperformed their peers who participated in BAU vocabulary instruction. In addition, students with disabilities in the CAP-S and InferCabulary conditions scored similarly to students without disabilities in the BAU condition on most measures. Implications for research and practice are discussed.

Background: Technology and its use within mental health services has advanced dramatically over recent years. Opportunities for mental health services to utilise technology to introduce novel, effective, and more efficient means of delivering assessment, and treatment are increasing. Objective: The current rapid-evidence paper reviews evidence regarding the introduction of novel technology to support young people's mental health and psychological well-being. Methods: A rapid evidence review was conducted. PSYCHINFO and CINAHL were searched for research articles between 2016 and 2021 that were specific to young people, mental health, and technology developments within this domain. N = 27 studies which explored the introduction, feasibility, and value of technology for mental health purposes were included in a narrative synthesis. Quality or risk of bias analyses were not completed. Results: Overall, technological advancements in young people's care were considered positive and engaging for young people. Factors including resources, efficiency of care, engagement, therapeutic effectiveness, ethical considerations, therapeutic alliance, and flexibility were considered within this review. Nevertheless, potential barriers include clinician concerns, socioeconomic factors, and motivation. Conclusion: Effective and sustained use of technology within young people's mental health services will depend on the technology's usability, efficiency, and ability to engage young people. This paper expands on existing research by reviewing a broader range of technology proposed to support young people's mental health and well-being. This will assist in the application of novel technological advancements by indicating effectiveness, preferences, potential barriers, and recommendations for the feasibility and efficacy of introducing technology into young people's services.

BackgroundRecently, we showed a >60% difference in 5-year survival for patients with tubo-ovarian high-grade serous carcinoma (HGSC) when stratified by a 101-gene mRNA expression prognostic signature. Given the varied patient outcomes, this study aimed to translate prognostic mRNA markers into protein expression assays by immunohistochemistry and validate their survival association in HGSC.MethodsTwo prognostic genes, FOXJ1 and GMNN, were selected based on high-quality antibodies, correlation with protein expression and variation in immunohistochemical scores in a preliminary cohort (n = 134 and n = 80, respectively). Six thousand four hundred and thirty-four (FOXJ1) and 5470 (GMNN) formalin-fixed, paraffin-embedded ovarian neoplasms (4634 and 4185 HGSC, respectively) represented on tissue microarrays from the Ovarian Tumor Tissue Analysis consortium underwent immunohistochemical staining and scoring, then univariate and multivariate survival analysis.ResultsConsistent with mRNA, FOXJ1 protein expression exhibited a linear, increasing association with improved overall survival in HGSC patients. Women with >50% expression had the most favourable outcomes (HR = 0.78, 95% CI 0.67-0.91, p 35% GMNN expression showed a trend for better outcomes, though this was not significant.ConclusionWe provide foundational evidence for the prognostic value of FOXJ1 in HGSC, validating the prior mRNA-based prognostic association by immunohistochemistry.

BackgroundLos Angeles County Department of Health Services provides medical care to a diverse group of patients residing in underresourced communities. To improve patients' access to addiction medications during the COVID-19 pandemic, Los Angeles County Department of Health Services established a low-barrier telephone service for DHS providers in March 2020, staffed by DATA-2000-waivered providers experienced with prescribing addiction medications. This study describes the patient population and medications prescribed through this service during its initial 12 months.MethodsWe performed a retrospective evaluation of a provider-entered call registry for the telephone consult line. Information was collected between March 31, 2020, and March 30, 2021. The registry includes information related to patient demographics, the reason for visit, and which addiction medications were prescribed. We conducted descriptive statistics in each of these domains.ResultsDuring the study period, 11 providers on the MAT telephone service logged 713 calls. These calls represented a total of 557 unique patients (mean age of 40 years, 75% male, 41% Latino, 49% experiencing homelessness). Most patients either had Medicaid insurance (77%) or were uninsured (20%). The most prescribed addiction medication was buprenorphine-naloxone (90%), followed by nicotine replacement therapy (5.3%), naltrexone (4.2%), and buprenorphine monotherapy (1.8%).ConclusionA telephone addiction medication service is feasible to deliver low-barrier medications to treat addiction in underresourced communities, especially to individuals experiencing homelessness. This can mitigate but does not eliminate disparities in access to addiction medications for communities of color.

PurposeAdvanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features.Experimental designDiscovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55).ResultsInfiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77; 95% confidence interval (CI), 1.04-7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04-1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01-1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%).ConclusionsAn infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies.

PurposeTo identify molecular subclasses of clear cell ovarian carcinoma (CCOC) and assess their impact on clinical presentation and outcomes.Experimental designWe profiled 421 primary CCOCs that passed quality control using a targeted deep sequencing panel of 163 putative CCOC driver genes and whole transcriptome sequencing of 211 of these tumors. Molecularly defined subgroups were identified and tested for association with clinical characteristics and overall survival.ResultsWe detected a putative somatic driver mutation in at least one candidate gene in 95% (401/421) of CCOC tumors including ARID1A (in 49% of tumors), PIK3CA (49%), TERT (20%), and TP53 (16%). Clustering of cancer driver mutations and RNA expression converged upon two distinct subclasses of CCOC. The first was dominated by ARID1A-mutated tumors with enriched expression of canonical CCOC genes and markers of platinum resistance; the second was largely comprised of tumors with TP53 mutations and enriched for the expression of genes involved in extracellular matrix organization and mesenchymal differentiation. Compared with the ARID1A-mutated group, women with TP53-mutated tumors were more likely to have advanced-stage disease, no antecedent history of endometriosis, and poorer survival, driven by their advanced stage at presentation. In women with ARID1A-mutated tumors, there was a trend toward a lower rate of response to first-line platinum-based therapy.ConclusionsOur study suggests that CCOC consists of two distinct molecular subclasses with distinct clinical presentation and outcomes, with potential relevance to both traditional and experimental therapy responsiveness. See related commentary by Lheureux, p. 4838.

Student achievement disparities in inclusive science classrooms are concerning, as knowledge about science, technology, engineering, and mathematics (STEM) is increasingly important for upward mobility. When students identify with multiple marginalized sociocultural groups, progress becomes more troubling, as the interplay among these factors is rarely accounted for in quantitative intervention research. The purpose of the present study, therefore, was to evaluate performance on measures of science vocabulary and general science knowledge among students with intersectional identities (i.e., students with disabilities from marginalized racial/ethnic groups, n = 33; and students with disabilities from low SES households, n = 167) following teacher participation in a multimedia professional development (PD) process. Using a series of multilevel models, results suggest students who learned from teachers who participated in the multimedia professional development process experienced greater gains than peers with the same intersectional identities in comparison classrooms across all measures. Implications and future directions are discussed.

The 21st century has ushered in accelerated new technologies, new knowledge and new information and the fourth industrial revolution (4IR) -- causing rapid changes in the way humans live and work and resulting in an outcry for educational reforms globally. Many frameworks and debates centred on rethinking and reshaping the curriculum including what knowledge, skills, values and attitudes should be taught to prepare learners to thrive in the 21st century, have been developed. This study examined the students' conceptions of 21st century education in four diverse schools in Zimbabwe. The study is framed by the powerful theory and the complexity theory. The study used a quantitative non-experimental correlation design to collect data from four secondary schools, three of which follow the ZIMSEC syllabus and the other, a private school that follows a Cambridge syllabus. The questionnaire was adapted from the Partnership for 21st century framework (P21) and (Ravitz, 2014) to fit the Zimbabwean context. A total of 236 students and 93 took part. Exploratory and confirmatory factor analyses and ANOVA were used to analyse the data.The results showed that the students' conception of 21st century skills is defined by three factors: the learning of self-management, learning skills and values and learning process. Students most strongly endorsed self-management.It is envisaged that the proposed model of Zimbabwean students' conceptions of 21st century skills will act as a baseline for theory, policymakers, head teachers, teachers and teacher education colleges to realign the current teaching to fit the 21st century curricula.

Understanding science allows students with and without developmental and behavioral-based (DB) disabilities to better appreciate the world around them as well as prepare them for the growing science-related job market. However, students in the United States consistently underperform on science achievement tests compared to students from other nations. This underperformance could be attributed, in part to science having many specialized vocabulary terms that are not often taught explicitly, leaving students with incomplete or inaccurate understandings of word meanings. Improving science vocabulary instructional practices may support students with and without DB disabilities in enhancing their science achievement. To address this need, researchers implemented multicomponent multimedia professional development (PD) to support middle-school science teachers in delivering high-quality vocabulary instruction in inclusive settings. In this paper, data collected from a study evaluating the efficacy of the PD were analyzed to determine the influence on student outcomes using ANOVA and multilevel modeling methodologies. Though initial results indicate a promising impact on teacher instructional practices, little is known whether teacher participation in the PD affected student science vocabulary and content knowledge growth. Using multilevel modeling, student science knowledge growth was evaluated following their teachers' exposure to the PD. The findings from this study indicate having indirect exposure to PD had a positive effect on science content knowledge for students with and without DB disabilities (N = 980). In addition, the authors found students with DB disabilities whose teachers had access to PD showed a larger gain in science knowledge than general education students whose teachers did not have access to the PD.

High-leverage practices (HLPs) are instructional approaches educators in K-12 can use to teach different types of learners and content. They are deemed "high leverage" because they are foundational to effective instruction, they help with managing and intervening in students' behavior, and they support successful implementation of the Individuals with Disabilities Education Act (the legislation guaranteeing that students with disabilities receive a free and appropriate education with their nondisabled peers to the extent that is possible). This article describes two HLPs that are foundational for delivering effective instruction: (1) use explicit instruction; and (2) provide high-quality feedback. Research shows that teachers can use these two practices in general and special education classrooms to improve student outcomes. In addition, they are a great starting place for implementing other HLPs. In describing these two HLPs, the authors provide examples of how teachers might use them. A a list of resources teachers can use to support their implementation is also provided.

Curriculum reform was high on the agenda of South Africa's post-apartheid governments. Yet as time passed, the initial reforms were seen as increasingly problematic, especially when pedagogical realities met policy priorities. There was reluctance on the part of policymakers to give up what was seen as the democratic imperative behind the reforms. Yet as schools struggled, public responses blamed inadequate attention to practical issues as undermining the implementation of the reforms. This perspective on curriculum implementation, blaming teachers for the failure of policy reforms, is not uncommon. This paper argues, however, that such a perspective is very often misinformed because it deflects attention from the specific nature of policies and the role of policymaking in neglecting key issues that might have better facilitated implementation. South Africa's democratic curriculum reforms were essential for dismantling a key aspect of the apartheid state. The paper highlights this point arguing that an understanding of policies rather than a focus on the failure of schools provides a better lens for understanding the trajectory of curriculum reform processes in South Africa.

Science includes a multitude of specialized terms that are not consistently taught using effective practices. Often, students with disabilities rely on ineffective strategies in order to memorize word definitions, which inhibits their science achievement. Using a counter-balanced design, we tested whether having access to multimedia videos that incorporate evidence-based practices would influence participating students' scores on vocabulary assessments. Additionally, we investigated whether the number of video views by students predicted assessment scores. Results from this study demonstrated positive science assessment outcomes when students have access to the multimedia videos. Overall, a greater number of video views predicted better student assessment outcomes. Implications for multimedia video use and future research are discussed.