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Over the course of a two-year curriculum field test study that implemented a curriculum-based professional learning framework, we investigated the factors that influenced teachers' willingness and ability to implement NGSS-aligned, phenomenon-based storylines for teaching the nature of science, evolution, and climate change. Through qualitative data collected from interviews and lesson evaluation surveys from 25 middle and high school science teachers, we identified potential implementation barriers and support structures relating to organizational culture as well as curriculum and instruction at the classroom, school, community, and systemic levels. The data indicate that lack of administrative support, time constraints, difficulty with student sense-making, and mismatched classrooms are the largest barriers to implementation, while curriculum-based professional learning including working through the lessons from a student perspective, peer collaboration, autonomy, and flexibility were the largest predictors of successful implementation. Administrators can play a large role in providing successful supports and removing barriers for teachers implementing NGSS-aligned, phenomenon-based lessons.

Adolescents with disabilities require access to general education and life skills instruction. Knowledge of food safety for this audience is important for health and valuable for work placement. The objective was to implement a survey to assess high school and transition special education teachers in RI, CT, and MA for food safety knowledge and attitudes toward the use of food safety education for special needs students. Respondents answered questions on food safety topics and attitudes toward incorporating food safety principles into curriculum. Agree, disagree, and don't know and Likert scale response formats were used. Descriptive one-way ANOVA and t-test statistics were run. Forty-seven food safety knowledge questions for 220 respondents were assessed. Of the respondents, 69% had primary certification in special education and 15% in Family and Consumer Sciences (FCS). As part of the learning experience, 86% served food in the classroom, and 94% served food classified as potentially hazardous. Using 80% as knowledge mastery, only 24 of 46 items (52%) met the standard, with cooking and chilling categories scoring low (70%). FCS and special education teachers had significant differences (P less than 0.05) in knowledge scores, 87% and 74%, respectively. Special education teachers scored low, 66% to 67%, in key food safety categories. Attitudinal questions reflected a support for food safety information to be taught to this student audience. The survey identified the need for outreach education for special education teachers due to lack of food safety knowledge, food safety risks due to potentially hazardous foods prepared by students, and lack of food safety resources for these students.

Arboricultural employers and non-English speaking workers were surveyed to acquire information about their outreach educational needs. Results suggest that language barriers sometimes reduce job performance and threaten worker safety and relationships. Respondents stated that employee performance would improve if workers received English language and cultural training. Method of education mattered, with face-to-face learner and educator contact as the preferred method. It is recommended that arboriculture employers and outreach educators provide English language and cultural outreach education opportunities to arboriculture workers whose first language is not English, then follow this with arboriculture training and information (such as pesticide safety). [ABSTRACT FROM AUTHOR]

Background: Breast cancer's complex transcriptional landscape requires an improved understanding of cellular diversity to identify effective treatments. The study of genetic variations among breast cancer subtypes at single-cell resolution has potential to deepen our insights into cancer progression., Methods: In this study, we amalgamate single-cell RNA sequencing data from patient tumours and matched lymph metastasis, reduction mammoplasties, breast cancer patient-derived xenografts (PDXs), PDX-derived organoids (PDXOs), and cell lines resulting in a diverse dataset of 117 samples with 506 719 total cells. These samples encompass hormone receptor positive (HR+), human epidermal growth factor receptor 2 positive (HER2+), and triple-negative breast cancer (TNBC) subtypes, including isogenic model pairs. Herein, we delineated similarities and distinctions across models and patient samples and explore therapeutic drug efficacy based on subtype proportions., Results: PDX models more closely resemble patient samples in terms of tumour heterogeneity and cell cycle characteristics when compared with TNBC cell lines. Acquired drug resistance was associated with an increase in basal-like cell proportions within TNBC PDX tumours as defined with SCSubtype and TNBCtype cell typing predictors. All patient samples contained a mixture of subtypes; compared to primary tumours HR+ lymph node metastases had lower proportions of HER2-Enriched cells. PDXOs exhibited differences in metabolic-related transcripts compared to PDX tumours. Correlative analyses of cytotoxic drugs on PDX cells identified therapeutic efficacy was based on subtype proportion., Conclusions: We present a substantial multimodel dataset, a dynamic approach to cell-wise sample annotation, and a comprehensive interrogation of models within systems of human breast cancer. This analysis and reference will facilitate informed decision-making in preclinical research and therapeutic development through its elucidation of model limitations, subtype-specific insights and novel targetable pathways., Key Points: Patient-derived xenografts models more closely resemble patient samples in tumour heterogeneity and cell cycle characteristics when compared with cell lines. 3D organoid models exhibit differences in metabolic profiles compared to their in vivo counterparts. A valuable multimodel reference dataset that can be useful in elucidating model differences and novel targetable pathways., (© 2024 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Motivation: Medical curricula improvement is an ongoing process to keep material relevant and improve the student's learning experience to better prepare them for patient care. Many programs utilize end-of-year evaluations, but these frequently have low response rates and lack actionable feedback. We hypothesized that student reflections written during a fourth year Sub-Internship could be used retrospectively to mine additional information as feedback for future curriculum adjustments. However, reflections contain a large amount of narrative content that would require a cumbersome and essentially infeasible manual review process for busy medical education faculty., Methods: We developed a Natural Language Processing (NLP) pipeline to automatically identify common themes and topics present in the set of reflective writings that could be used to improve the curriculum. The dataset contains required responses to a faculty issued question submitted between August 2016 and July 2018 about challenges experienced during the medical students fourth year Sub-Internship., Results: Eleven distinct topics were identified, with several being subsequently addressed in future iterations of the curriculum., Conclusion: Utilizing NLP on reflective writings was able to identify areas of curriculum improvement, and the NLP results provided a quick and easy way to explore the main themes and challenges expressed by students.

Purpose: - Coronary microvascular dysfunction (CMD) is common in patients with heart failure with preserved ejection fraction (HFpEF) and obesity. Stress cardiovascular magnetic resonance (CMR) has been proposed as a non-invasive tool for detection of CMD. The aim of this study was to determine relationship between CMD and diastolic function in patients with HFpEF using a novel CMR technique., Methods: - Patients with obesity and HFpEF without epicardial coronary artery disease (CAD) underwent Doppler echocardiography to measure diastolic function, followed by vasodilator stress CMR, using a single bolus, dual sequence, quantitative myocardial perfusion mapping to measure myocardial blood flow (MBF) at rest and at peak hyperemia. With this, myocardial perfusion reserve (MPR), global stress endocardial-to-epicardial (endo:epi) perfusion ratio, and total ischemic burden (IB, defined as myocardial segments with MBF < 1.94 mL/min/g) were calculated. Results are reported as median and interquartile range., Results: - Nineteen subjects were enrolled (100% female, 42% Black). Median age was 64 [56-72] years. Global stress MBF was 2.43 ml/min/g [2.16-2.78] and global myocardial perfusion reserve (MPR) was 2.34 [2.07-2.88]. All had an abnormal subendocardial perfusion with an endo:epi of less than 1 (0.87 [0.81-0.90]). Regional myocardial hypoperfusion was detected in 14 (74%) patients with an IB of 6% [0-34.4]. Endo:epi ratio significantly correlated with IB (R=-0.510, p = 0.026) and measures of diastolic function (R = 0.531, p = 0.019 and R=-0.544, p = 0.014 for e' and E/e' respectively)., Conclusion: - Using a novel quantitative stress CMR myocardial perfusion mapping technique, women with obesity and HFpEF were found to have patterns of abnormal subendocardial perfusion which significantly correlated with measures of diastolic dysfunction., (© 2022. The Author(s).)

The goals of this study were to identify transcriptomic changes that arise in basal-like breast cancer cells during the development of resistance to epidermal growth factor receptor inhibitors (EGFRi) and to identify drugs that are cytotoxic once EGFRi resistance occurs. Human patient-derived xenografts (PDXs) were grown in immunodeficient mice and treated with a set of EGFRi; the EGFRi erlotinib was selected for more expansive in vivo studies. Single-cell RNA sequencing was performed on mammary tumors from the basal-like PDX WHIM2 that was treated with vehicle or erlotinib for 9 weeks. The PDX was then subjected to long-term erlotinib treatment in vivo. Through serial passaging, an erlotinib-resistant subline of WHIM2 was generated. Bulk RNA-sequencing was performed on parental and erlotinib-resistant tumors. In vitro high-throughput drug screening with > 500 clinically used compounds was performed on parental and erlotinib-resistant cells. Previously published bulk gene expression microarray data from MMTV-Wnt1 tumors were contrasted with the WHIM2 PDX data. Erlotinib effectively inhibited WHIM2 tumor growth for approximately 4 weeks. Compared to untreated cells, single-cell RNA sequencing revealed that a greater proportion of erlotinib-treated cells were in the G1 phase of the cell cycle. Comparison of WHIM2 and MMTV-Wnt1 gene expression data revealed a set of 38 overlapping genes that were differentially expressed in the erlotinib-resistant WHIM2 and MMTV-Wnt1 tumors. Comparison of all three data types revealed five genes that were upregulated across all erlotinib-resistant samples: IL19, KLK7, LCN2, SAA1, and SAA2. Of these five genes, LCN2 was most abundantly expressed in triple-negative breast cancers, and its knockdown restored erlotinib sensitivity in vitro. Despite transcriptomic differences, parental and erlotinib-resistant WHIM2 displayed similar responses to the majority of drugs assessed for cytotoxicity in vitro. This study identified transcriptomic changes arising in erlotinib-resistant basal-like breast cancer. These data could be used to identify a biomarker or develop a gene signature predictive of patient response to EGFRi. Future studies should explore the predictive capacity of these gene signatures as well as how LCN2 contributes to the development of EGFRi resistance., (© 2022. The Author(s).)

Temporal expression recognition and normalization (TERN) is the foundation for all higher-level temporal reasoning tasks in natural language processing, such as timeline extraction, so it must be performed well to limit error propagation. Achieving new heights in state-of-the-art performance for TERN in clinical texts requires knowledge of where current systems struggle. In this work, we summarize the results of a detailed error analysis for three top performing state-of-the-art TERN systems that participated in the 2012 i2b2 Clinical Temporal Relation Challenge, and compare our own home-grown system Chrono to identify specific areas in need of improvement. Performance metrics and an error analysis reveal that all systems have reduced performance in normalization of relative temporal expressions, specifically in disambiguating temporal types and in the identification of the correct anchor time. To address the issue of temporal disambiguation we developed and integrated a module into Chrono that utilizes temporally fine-tuned contextual word embeddings to disambiguate relative temporal expressions. Chrono now achieves state-of-the-art performance for temporal disambiguation of relative temporal expressions in clinical text, and is the only TERN system to output dual annotations into both TimeML and SCATE schemes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Olex and McInnes.)

TopEx is a natural language processing application developed to facilitate the exploration of topics and key words in a set of texts through a user interface that requires no programming or natural language processing knowledge, thus enhancing the ability of nontechnical researchers to explore and analyze textual data. The underlying algorithm groups semantically similar sentences together followed by a topic analysis on each group to identify the key topics discussed in a collection of texts. Implementation is achieved via a Python library back end and a web application front end built with React and D3.js for visualizations. TopEx has been successfully used to identify themes, topics and key words in a variety of corpora, including Coronavirus disease 2019 (COVID-19) discharge summaries and tweets. Feedback from the BioCreative VII Challenge Track 4 concludes that TopEx is a useful tool for text exploration for a variety of users and tasks., Databse Url: http://topex.cctr.vcu.edu., (© The Author(s) 2022. Published by Oxford University Press.)

An estimated 284,000 Americans will be diagnosed with breast cancer in 2021. Of these individuals, 15-20% have basal-like triple-negative breast cancer (TNBC), which is known to be highly metastatic. Chemotherapy is standard of care for TNBC patients, but chemoresistance is a common clinical problem. There is currently a lack of alternative, targeted treatment strategies for TNBC; this study sought to identify novel therapeutic combinations to treat basal-like TNBCs. For these studies, four human basal-like TNBC cell lines were utilized to determine the cytotoxicity profile of 1363 clinically-used drugs. Ten promising therapeutic candidates were identified, and synergism studies were performed in vitro. Two drug combinations that included KPT-330, an XPO1 inhibitor, were synergistic in all four cell lines. In vivo testing of four basal-like patient-derived xenografts (PDX) identified one combination, KPT-330 and GSK2126458 (a PI3K/mTOR inhibitor), that decreased tumor burden in mice significantly more than monotherapy with either single agent. Bulk and single-cell RNA-sequencing, immunohistochemistry, and analysis of published genomic datasets found that XPO1 was abundantly expressed in human basal-like TNBC cell lines, PDXs, and patient tumor samples. Within basal-like PDXs, XPO1 overexpression was associated with increased proliferation at the cellular level. Within patient datasets, XPO1 overexpression was correlated with greater rates of metastasis in patients with basal-like tumors. These studies identify a promising potential new combination therapy for patients with basal-like breast cancer., (Copyright © 2021. Published by Elsevier Inc.)

Extraction of high-quality RNA from pancreatic tumors for sequencing purposes is technically challenging, as the pancreas is an organ rich in ribonucleases. The majority of the established RNA isolation protocols for use with primary pancreatic tissue involve perfusion of RNA stabilizing reagent into the pancreatic tissue to protect RNA integrity before extraction. However, the additional time needed for this procedure can actually lead to further RNA degradation. We optimized a protocol suitable for high quality RNA isolation from mouse pancreatic tumors that is a simple, fast, and inexpensive modification of existing methods, combining the use of liquid nitrogen and guanidinium thiocyanate-chloroform extraction. Through this procedure, the mean RNA Integrity Number value obtained for RNA isolated from pancreatic tumors was 9.0, and was reproducibly suitable for RNAseq and qPCR.•a protocol suitable for high quality RNA isolation from mouse pancreatic tumors as well as normal pancreas•combining the use of liquid nitrogen and guanidinium thiocyanate-chloroform extraction., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Authors. Published by Elsevier B.V.)

Ctbp2 is a uniquely targetable oncogenic transcriptional coregulator, exhibiting overexpression in most common solid tumors, and critical to the tumor-initiating cell (TIC) transcriptional program. In the "CKP" mouse pancreatic ductal adenocarcinoma (PDAC) model driven by mutant K-Ras, Ctbp2 haploinsufficiency prolonged survival, abrogated peritoneal metastasis, and caused dramatic downregulation of c-Myc, a known critical dependency for TIC activity and tumor progression in PDAC. A small-molecule inhibitor of CtBP2, 4-chloro-hydroxyimino phenylpyruvate (4-Cl-HIPP) phenocopied Ctbp2 deletion, decreasing tumor burden similarly to gemcitabine, and the combination of 4-Cl-HIPP and gemcitabine further synergistically suppressed tumor growth. Pharmacodynamic monitoring revealed that the 4-Cl-HIPP/gemcitabine combination induced robust and synergistic tumor apoptosis and marked downregulation of the TIC marker CD133 in CKP PDAC tumors. Collectively, our data demonstrate that targeting CtBP represents a fruitful avenue for development of highly active agents in PDAC that cooperate with standard therapy to limit both primary and metastatic tumor burden.

Purpose: Angiogenesis is one of the hallmarks of cancer and is essential for cancer progression and metastasis. However, clinical trials with vascular endothelial growth factor (VEGF) pathway inhibitors have failed to show overall survival benefit in breast cancer. Targeted therapy against the angiopoietin pathway, a downstream angiogenesis cascade, could be effective in breast cancer. This study investigates the association of angiopoietin pathway gene expression with breast cancer survival using a "big data" approach employing RNA sequencing data from The Cancer Genome Atlas (TCGA)., Methods: A total of 888 patients with adequate gene expression, disease-free survival (DFS), and overall survival (OS) data were selected for analysis. DFS and OS were calculated for patients with high and low expression of angiopoietin and VEGF pathway genes using TCGA data. Gene-specific thresholds to dichotomize patients into high and low expression were determined and survival plots were generated., Results: The TCGA cohort was representative of national breast cancer patients with respect to stage, pathology, and survival. High Ang2 gene expression was associated with not only decreased DFS (p = 0.05), but also decreased OS (p < 0.05). High co-expression of Ang2 and its receptor Tie2 was associated with both decreased DFS and OS (p < 0.05). There was strong correlation between angiopoietin and VEGF pathway genes. While high expression of VEGFA alone was not associated with survival, high co-expression with Ang2 was associated with decreased OS., Conclusions: This study validates TCGA as a representative database providing genomic data and survival outcomes in breast cancer. Our TCGA data support the angiopoietin pathway as a key mediator in the pathologic angiogenic switch in breast cancer.