bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protocol for a scoping review of implementation research approaches to universal health coverage in Africa
Authors: Nnaji Chukwudi A , Wiysonge Charles S , Okeibunor Joseph , Malinga Thobile , Adamu Abdu A , Tumusiime Prosper , Karamagi Humphrey 
Published: February 2021

IntroductionImplementation research has emerged as part of evidence-based decision-making efforts to plug current gaps in the translation of research evidence into health policy and practice. While there has been a growing number of institutions and initiatives promoting the uptake of implementation research in Africa, their role and effectiveness remain unclear, particularly in the context of universal health coverage (UHC). This review aims to extensively identify and characterise the nature, facilitators and barriers to the use of implementation research for assessing or evaluating UHC-related interventions or programmes in Africa.Methods and analysisThis scoping review will be developed based on the methodological framework proposed by Arksey and O’Malley and enhanced by the Joanna Briggs Institute. It will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. A comprehensive search of the following electronic databases will be conducted: Medline (via PubMed), Scopus and the Cochrane Library. Relevant grey literature and reference lists will also be searched. All publications describing the application of implementation research in the context of UHC will be considered for inclusion. Findings will be narratively synthesised and analysed using a predefined conceptual framework. Where applicable, quantitative evidence will be aggregated using summary statistics. There will be consultation of stakeholders, including UHC-oriented health professionals, programme managers, implementation researchers and policy-makers; to provide methodological, conceptual and practical insights.Ethics and disseminationThe data used in this review will be sourced from publicly available literature; hence, this study will not require ethical approval. Findings and recommendations will be disseminated to reach a diverse audience, including UHC advocates, implementation researchers and key health system stakeholders within the African region. Additionally, findings will be disseminated through an open-access publication in a relevant peer-reviewed journal.
Instruments for measuring nursing research competence: a protocol for a scoping review
Authors: Chen Qirong , Huang Chongmei , Castro Aimee R , Tang Siyuan 
Published: February 2021

IntroductionNursing research competence of nursing personnel has received much attention in recent years, as nursing has developed as both an independent academic discipline and an evidence-based practiing profession. Instruments for appraising nursing research competence are important, as they can be used to assess nursing research competence of the target population, showing changes of this variable over time and measuring the effectiveness of interventions for improving nursing research competence. There is a need to map the current state of the science of the instruments for nursing research competence, and to identify well validated and reliable instruments. This paper describes a protocol for a scoping review to identify, evaluate, compare and summarise the instruments designed to measure nursing research competence.Methods and analysisThe scoping review will be conducted following Arksey and O’Malley’s methodological framework and Levacet al’s additional recommendations for applying this framework. The scoping review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. The protocol is registered through the Open Science Framework (https://osf.io/ksh43/). Eight English databases and two Chinese databases will be searched between 1 December 2020 and 31 December 2020 to retrieve manuscripts which include instrument(s) of nursing research competence. The literature screening and data extraction will be conducted by two researchers, independently. A third researcher will be involved when consensus is needed. The COnsensus-based Standards for the selection of health Measurement INstruments methodology will be used to evaluate the methodological quality of the included studies on measurement properties of the instruments, as well as the quality of all the instruments identified.Ethics and disseminationEthical approval is not needed. We will disseminate the findings through a conference focusing on nursing research competence and publication of the results in a peer-reviewed journal.
WHSC1/NSD2 regulates immune infiltration in prostate cancer
Authors: Want Muzamil Y , Tsuji Takemasa , Singh Prashant K , Thorne James L , Matsuzaki Junko , Karasik Ellen , Gillard Bryan , Cortes Gomez Eduardo , Koya Richard C. , Lugade Amit , Odunsi Kunle , Battaglia Sebastiano 
Published: February 2021

BackgroundImmunotherapy in prostate cancer (PCa) lags behind the progresses obtained in other cancer types partially because of its limited immune infiltration. Tumor-resident immune cells have been detected in the prostate, but the regulatory mechanisms that govern tumor infiltration are still poorly understood. To address this gap, we investigated the role of Wolf-Hirschhorn syndrome candidate 1 (WHSC1), a histone methyltransferase enzyme that targets dimethyl and trimethyl H3K36. WHSC1 is known to promote malignant growth and progression in multiple tumors, but its role in the interface between PCa and immune system is unknown.MethodsRNA Sequencing (RNASeq) data from patients with PCa from The Cancer Genome Atlas (TCGA) were collected and divided into top/bottom 30% based on the expression of WHSC1 and disease-free survival was calculated. Publicly available chromatin immunoprecipitation (ChIPSeq) data were obtained from Cistrome and integrated with the available RNASeq data. RNASeq, ATACSeq and methylomic were analyzed using R Bioconductor packages comparing C42 cells with or without stable knockdown on WHSC1. Flow cytometry was used to measure Major Histocompatibility complex (MHC) levels, MHC-bound ovalbumin and tumor infiltration. C57B6 and NOD scid gamma (NSG) mice were subcutaneously grafted with TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) C2 cells and treated with MCTP39 (10 mg/kg); tumor size was monitored over time and curves were compared using permutation analyses. All analyses used a significance threshold of 0.05.ResultsLeveraging TCGA data, we demonstrated that elevated WHSC1 levels positively correlate with the presence of an immunosuppressive microenvironment. We validated those results in vitro, demonstrating that genetic and pharmacological inhibition of WHSC1 restores antigen presentation. This occurs via an elegant epigenetic regulation of gene expression at the chromatin and DNA methylation levels. In vivo studies in immunocompetent mice also show an increased frequency of CD8+ T cells in tumors from mice treated with WHSC1 inhibitor, supporting the hypothesis that the antitumor effect following WHSC1 inhibition requires a fully functional immune system.ConclusionsThis study demonstrates a novel role for WHSC1 in defining immune infiltration in PCa, with significant future implications for the use of immunotherapies in prostate malignancies.
Integrating genome-wide CRISPR immune screen with multi-omic clinical data reveals distinct classes of tumor intrinsic immune regulators
Authors: Hou Jiakai , Wang Yunfei , Shi Leilei , Chen Yuan , Xu Chunyu , Saeedi Arash , Pan Ke , Bohat Ritu , Egan Nicholas A. , McKenzie Jodi A. , Mbofung Rina M. , Williams Leila J. , Yang Zhenhuang , Sun Ming , Liang Xiaofang , Rodon Ahnert Jordi , Varadarajan Navin , Yee Cassian , Chen Yiwen , Hwu Patrick , Peng Weiyi 
Published: February 2021

BackgroundDespite approval of immunotherapy for a wide range of cancers, the majority of patients fail to respond to immunotherapy or relapse following initial response. These failures may be attributed to immunosuppressive mechanisms co-opted by tumor cells. However, it is challenging to use conventional methods to systematically evaluate the potential of tumor intrinsic factors to act as immune regulators in patients with cancer.MethodsTo identify immunosuppressive mechanisms in non-responders to cancer immunotherapy in an unbiased manner, we performed genome-wide CRISPR immune screens and integrated our results with multi-omics clinical data to evaluate the role of tumor intrinsic factors in regulating two rate-limiting steps of cancer immunotherapy, namely, T cell tumor infiltration and T cell-mediated tumor killing.ResultsOur studies revealed two distinct types of immune resistance regulators and demonstrated their potential as therapeutic targets to improve the efficacy of immunotherapy. Among them, PRMT1 and RIPK1 were identified as a dual immune resistance regulator and a cytotoxicity resistance regulator, respectively. Although the magnitude varied between different types of immunotherapy, genetically targetingPRMT1andRIPK1sensitized tumors to T-cell killing and anti-PD-1/OX40 treatment. Interestingly, a RIPK1-specific inhibitor enhanced the antitumor activity of T cell-based and anti-OX40 therapy, despite limited impact on T cell tumor infiltration.ConclusionsCollectively, the data provide a rich resource of novel targets for rational immuno-oncology combinations.
Abstract PD1-08: Oral paclitaxel and encequidar (oPac+E) versus IV paclitaxel (IVPac) in the treatment of metastatic breast cancer (mBC) patients (study KX-ORAX-001): Progression free survival (PFS) and overall survival (OS) updates
Authors: Umanzor G , Rugo H S , Barrios F J , Vasallo R H , Chivalan M A , Bejarano S , Ramirez J R , Fein L , Kowalyszyn R D , Cutler D L , Kramer D , Goldfinch J , Wang H , Moore T , Kwan R MF 
Published: February 2021

Abstract
Background: IVPac is widely used to treat patients with breast cancer. oPac+E is oral paclitaxel in combination with Encequidar, an oral, minimally absorbed, specific p-glycoprotein inhibitor that enables the absorption of oral paclitaxel. Results of the phase III trial, KX-ORAX-001, were presented at SABCS, 2019, Abstract # GS6-01. At the time of the database lock for the final analysis of the primary endpoint of confirmed tumor response rate, analyses of PFS and OS were performed. The confirmed tumor response rate was significantly higher in the oPac+E group vs IVPac (35.8% vs 23.4%, p=0.011 ITT, population). The median overall survival was 27.7 months vs 16.7 months, respectively favoring oPac. An update of the duration of response, PFS and OS data comprising an additional 14 months follow-up will be presented. At the time of the update it is projected that approximately 60% of subjects will have had a survival event.
Methods: Study KX-ORAX-001 was a phase III, randomized, international study in women with mBC for whom treatment with IVPac was recommended. Eligible patients were randomized 2:1 to receive oPac+E or IVPac. Patients continued treatment until discontinuation due to progressive disease or toxicity. oPac 205 mg/m2 was given once daily for 3 days weekly. E 12.9 mg was given 1 hour before each dose of oPac. IVPac 175 mg/m2 was infused over 3 hours every 3 weeks. The primary endpoint was efficacy defined as tumor response confirmed by BICR at two consecutive evaluations. Key secondary endpoints included PFS, OS. Safety was monitored throughout the study.
Results: A total of 402 mBC patients were randomized (oPac+E 265: IVPac 137) and represent the ITT population of which 399 subjects were dosed. Updated data for duration of response, PFS and OS for the ITT and prespecified mITT populations will be presented. (NCT 02594371)
Citation Format: G Umanzor, H S Rugo, F J Barrios, R H Vasallo, M A Chivalan, S Bejarano, J R Ramirez, L Fein, R D Kowalyszyn, D L Cutler, D Kramer, J Goldfinch, H Wang, T Moore, R MF Kwan. Oral paclitaxel and encequidar (oPac+E) versus IV paclitaxel (IVPac) in the treatment of metastatic breast cancer (mBC) patients (study KX-ORAX-001): Progression free survival (PFS) and overall survival (OS) updates [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD1-08.
Abstract PD12-07: Incidences of endometrial events and frequencies of endometrial invasive diagnostic procedures in breast cancer survivors on tamoxifen: A nationwide study
Authors: Choi Soojeong , Jeong Jae ho , Jung Jinhong , Lee Young Jae , Lee Jong Won , Ko Beom Seok , Son Byung Ho , Ahn Sei Hyun , Lee Yura , Kim Hee jeong , Chung Il Yong 
Published: February 2021

Abstract
BackgroundBreast cancer survivors who taking tamoxifen as adjuvant therapy have been reported to have more endometrial lesions. According to guidelines, a gynecological assessment is recommended for postmenopausal women, but there is no mention of premenopausal women. The purpose of this study is to compare the risk of endometrial cancer by age at diagnosis, and to investigate frequencies of gynecological exam in breast cancer patients taking tamoxifen in South Korea.
MethodsA nationwide retrospective cohort study was conducted using South Korea Health Insurance Review and Assessment Service claims data. Between 2010 and 2015, a total of 60,545 (mean follow-up, 66.0 months) newly diagnosed female breast cancer survivors were included. Endometrial evaluation and Dilatation & Curettage (D&C) proportion were analyzed by age at diagnosis. The incidence of endometrial cancer and benign lesions were calculated as incident cases per person-year and analyzed with the Kaplan-Meier method. ResultsThe 26,374 patients who taking tamoxifen were divided into four groups by age at diagnosis. The incidence rate of endometrial cancer per 1,000 person-years was 1.13 and 1.45 for age range 50-59 and over 60 and 0.62 and 0.82 for in age under 40 and range 40-49. However, D&C proportion did not all differ from 10 to 11% in each subgroup.
ConclusionsThis nationwide cohort study showed that the risk of endometrial cancer in premenopausal breast cancer women taking tamoxifen was lower than that of postmenopausal women. However, the invasive diagnostic procedure such as aspiration, biopsy, polypectomy and D&C was proceeding at a level that makes no difference with those in postmenopausal women.
Citation Format: Soojeong Choi, Jae ho Jeong, Jinhong Jung, Young Jae Lee, Jong Won Lee, Beom Seok Ko, Byung Ho Son, Sei Hyun Ahn, Yura Lee, Hee jeong Kim, Il Yong Chung. Incidences of endometrial events and frequencies of endometrial invasive diagnostic procedures in breast cancer survivors on tamoxifen: A nationwide study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD12-07.
Abstract PD15-08: The role of purinergic signaling in the chemotherapy response of triple negative breast cancer
Authors: Manouchehri Jasmine , Datta Jharna , Cherian Mathew 
Published: February 2021

Abstract
Triple negative breast cancer (TNBC) affects women worldwide with a higher incidence in minority populations. Patients with TNBCs often have poorer prognoses in comparison to other breast cancer sub-types due to a lack of effective therapeutic options. Chemotherapy and immunotherapy are the only effective treatments, but these modalities generally result in short-term response. Therefore, there is a need to identify additional therapies to intensify the chemotherapeutic response in TNBC. When cancer cells are exposed to chemotherapy, they release adenosine triphosphate (ATP) into the extracellular space. Extracellular ATP is degraded by CD39 (E-NTPDase) to adenosine diphosphate (ADP) and then adenosine monophosphate (AMP), and AMP is broken down to adenosine by CD73. We examined the potential role of extracellular ATP in chemotherapy- induced cancer cell death. We hypothesized that extracellular ATP sensitizes TNBC cells to chemotherapy and that ATP degrading enzymes such as CD39 and CD73 attenuate this effect. TNBC MDA-MB 231, MDA-MB 468, and Hs 578t cell lines were treated with the chemotherapeutic agent paclitaxel for different time courses. Extracellular ATP was measured via the ATPlite 1step luminescence assay, and cell viability was assessed by applying PrestoBlue HS cell viability reagent. Paclitaxel-treated TNBC cell lines revealed a dose-dependent increase in extracellular ATP release in the presence of an inhibitor of CD39 (POM-1), accompanied by a dose-dependent decrease in cell viability. In addition, the general P2X receptor (P2RX) inhibitor iso-PPADS and the P2RX7 specific inhibitor (A438079) were added separately to observe if the P2X receptors are necessary for the release of ATP upon paclitaxel treatment. After paclitaxel treatment, TNBC cell lines showed a decline in the amount of ATP released with the addition of the inhibitors iso-PPADS and A438079. Treatment of non-tumorigenic immortalized MCF-10A mammary epithelial cells with paclitaxel in the presence and absence of the inhibitors iso-PPADS and A438079 did not result in a significant increase in extracellular ATP or a decrease in cell viability. These results indicate that P2RX7 is necessary for ATP release in TNBC cell lines exposed to chemotherapy. Furthermore, when TNBC cell lines were treated with increasing concentrations of ATP, there was a dose-dependent decrease in cell viability. Overall, these findings suggest that extracellular ATP may impact the chemotherapeutic response in TNBC cell lines through the activation of the ATP-gated channel P2RX7.
Citation Format: Jasmine Manouchehri, Jharna Datta, Mathew Cherian. The role of purinergic signaling in the chemotherapy response of triple negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD15-08.
Abstract PD5-07: Mapping the tumor and microenvironmental evolution underlying DCIS progression throughmultiplexed ion beam imaging
Authors: Angelo Michael 
Published: February 2021

Abstract
Ductal Carcinoma in Situ (DCIS) is a pre-invasive lesion that accounts for nearly 20% of new breast cancer diagnoses. Of these cases, about half will progress to invasive breast cancer (IBC) within ten years. However, because diagnostic criteria for delineating low risk lesions from those likely to progress to IBC have not been identified, many patients are receiving unnecessary chemotherapy and surgery that can result in therapy-related morbidity and death. With this in mind, we used Multiplexed Ion Beam Imaging by time of flight (MIBI-TOF) and RNA-seq laser-capture microdissection (SMART-3SEQ) to construct a comprehensive spatial atlas describing the structure, function, and cellular composition of DCIS. MIBI-TOF and SMART-3SEQ were used to compare lesions from patients that later developed IBC with those from age- and history matched DCIS controls without recurrence. Using a 37-marker staining panel to interrogate 137 lesions, we identified 17 distinct cell populations of epithelial, stromal, and immune cells that were arranged in recurrent cellular microenvironments specific for DCIS or invasive disease. We observe a coordinated shift in the immune and stromal compartments as invasive disease arises, including a robust influx of lymphocytes and expansion reactive stromal phenotypes in synchronous DCIS + IBC, which was distinct from the macrophage-dominant, highly vascularized microenvironment of recurrent IBC. Further, single cell segmentation using a deep learning model was combined with pixel-level coexpression analysis to extensively evaluate how the thickness, continuity, and phenotype of ductal myoepithelium changes as tumors progress from a pre-invasive state. These data were incorporated into a comprehensive model which was subsequently used to identify a subset of features that correlate with disease-free survival following DCIS tumor resection. Taken together, these features represent important prognostic metrics that can be used to separate pre-invasive from indolent DCIS tumors, and allow for tailored therapy that improves patient outcomes and quality of life in this disease.
Citation Format: Michael Angelo. Mapping the tumor and microenvironmental evolution underlying DCIS progression throughmultiplexed ion beam imaging [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD5-07.
Abstract PD9-12: Concordance and use patterns of tissue and cell-free based genomic testing in metastatic breast cancer
Authors: Liu Minetta , Schaffer Jeff , Piwowarczyk Aneta , Beaubier Nike , Blackwell Kimberly , Park Ben 
Published: February 2021

Abstract
Genomic testing has transformed clinical care in metastatic breast cancer. Cell-free DNA (cfDNA) has made sequential testing feasible, however, concordance between tissue and cfDNA, sensitivity of cfDNA, and optimal sampling frequency have not been examined on large data sets with clinical annotation. Of the 648 genes in the tissue NGS Tempus xT assay, 105 genes are also included in the Tempus xF cfDNA plasma-based test. Both platforms are run on Illumina and detect SNVs, indels, CNVs, and rearrangements/fusions with high sensitivity and specificity (&gt;90%). This study used the Tempus Labs LENS™ tool to identify the most recent ~3,300 metastatic breast cancer patients who underwent clinical testing and had either tissue-based testing, cfDNA testing or both. Of the 212 patients with xF and xT testing, 87 had xT before xF, 135 had xF before xT, and 7 had the testing performed at the same time. The most common pathogenic germline versus somatic alterations on tissue-based testing and their concordance will also be reported. In summary, this data suggests a variable amount of concordance between tissue-based and plasma-based assays. Timing of assay performance and inclusion of germline DNA might play an important role in contributing to these differences which need further exploration.
Table: Count of Reported Variants and xT/xF Concordance by GeneSomatic GenesxF frequency (n)xT frequency(n)Concordance Between xF and xTTP5313911043%PIK3CA848058%ESR1584141%BRCA238217%ERBB2372629%NF1322113%RB1272416%ATM30165%GATA3213441%FGFR13353%PTEN193036%ARID1A251823%
Citation Format: Minetta Liu, Jeff Schaffer, Aneta Piwowarczyk, Nike Beaubier, Kimberly Blackwell, Ben Park. Concordance and use patterns of tissue and cell-free based genomic testing in metastatic breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD9-12.