bluuebunny/crossref_metadata_2025_split huggingface dataset:
The cost of improving care: a multisite economic analysis of hospital resource use for implementing recommended postpartum contraception programmes
Authors: Ling Vivian B , Levi Erika E , Harrington Amy R , Zite Nikki B , Rivas Saul D , Dalton Vanessa K , Smith Roger , Moniz Michelle H 
Published: September 2020

BackgroundThe costs of quality improvement efforts in real-world settings are often unquantified. Better understanding could guide appropriate resource utilisation and drive efficiency. Immediate postpartum contraceptive care (ie, placement of an intrauterine device or contraceptive implant during hospitalisation for childbirth) represents an excellent case study for examining costs, because recommended services are largely unavailable and adoption requires significant effort. We therefore evaluated the cost of implementing immediate postpartum contraceptive services at four academic centres and one private hospital in USA.MethodsIn this mixed-methods cost analysis, implementation activities were retrospectively identified using standardised data collection. Activities were categorised as preimplementation activities (infrastructure building, tool creation and stakeholder engagement) or execution activities (workforce training and process refinement). Costs were assigned based on national median salaries for the roles of individuals involved. Cross-case comparison and rapid qualitative analysis guided by the Consolidated Framework for Implementation Research were used to identify factors driving cost variation observed across sites.ResultsOn average, implementation activities required 204 hours (range 119–368), with this time costing $14 433.94 (range $9955.61–$23 690.49), and involving 9 (range 7–11) key team members per site. Preimplementation activities required more resources than execution activities (preimplementation: average 173 hours, $11 573.25; execution: average 31 hours, $2860.67). Sites that used lower-cost employees (eg, shifting tasks from a physician to a project manager) observed lower costs per hour for implementation activities. Implementation activities and costs were associated with local contextual factors, including stakeholder acceptance, integration of employees and infrastructure readiness for the change effort.ConclusionsOur findings provide the first estimates of health system costs for adopting recommended contraceptive care in maternity units in USA. More broadly, our findings suggest that the budget impact of improvement efforts may vary widely depending on local context.
Frequency and prognostic impact of right ventricular involvement in acute myocardial infarction
Authors: Stiermaier Thomas , Backhaus Sören J , Matz Jonas , Koschalka Alexander , Kowallick Johannes , de Waha-Thiele Suzanne , Desch Steffen , Gutberlet Matthias , Hasenfuß Gerd , Thiele Holger , Eitel Ingo , Schuster Andreas 
Published: September 2020

ObjectiveRight ventricular (RV) involvement complicating myocardial infarction (MI) is thought to impact prognosis, but potent RV markers for risk stratification are lacking. Therefore, the aim of this trial was to assess the frequency and prognostic implications of concomitant structural and functional RV injury in MI.MethodsCardiac magnetic resonance (CMR) was performed in 1235 patients with MI (ST-elevation myocardial infarction: n=795; non-STEMI: n=440) 3 days after reperfusion by primary percutaneous coronary intervention. Central core laboratory-masked analyses included structural (oedema representing reversible ischaemia, irreversible infarction, microvascular obstruction (MVO)) and functional (ejection fraction, global longitudinal strain (GLS)) RV alterations. The clinical end point was the 12-month rate of major adverse cardiac events (MACE).ResultsRV ischaemia and infarction were observed in 19.6% and 12.1% of patients, respectively, suggesting complete myocardial salvage in one-third of patients. RV ischaemia was associated with a significantly increased risk of MACE (10.1% vs 6.2%; p=0.035), while patients with RV infarction showed only numerically increased event rates (p=0.075). RV MVO was observed in 2.4% and not linked to outcome (p=0.894). Stratification according to median RV GLS (10.2% vs 3.8%; p<0.001) but not RV ejection fraction (p=0.175) resulted in elevated MACE rates. Multivariable analysis including clinical and left ventricular MI characteristics identified RV GLS as an independent predictor of outcome (HR 1.05, 95% CI 1.00 to 1.09; p=0.034) in addition to age (p=0.001), Killip class (p=0.020) and left ventricular GLS (p=0.001), while RV ischaemia was not independently associated with outcome.ConclusionsRV GLS is a predictor of postinfarction adverse events over and above established risk factors, while structural RV involvement was not independently associated with outcome.
Lack of myeloid cell infiltration as an acquired resistance strategy to immunotherapy
Authors: Beyranvand Nejad Elham , Labrie Camilla , Abdulrahman Ziena , van Elsas Marit J , Rademaker Eva , Kleinovink Jan Willem , van der Sluis Tetje C , van Duikeren Suzanne , Teunisse Amina F A.S , Jochemsen Aart G , Oosting Jan , de Miranda Noel F C C , Van Hall Thorbald , Arens Ramon , van der Burg Sjoerd H 
Published: September 2020

BackgroundImmunotherapy of cancer is successful but tumor regression often is incomplete and followed by escape. Understanding the mechanisms underlying this acquired resistance will aid the development of more effective treatments.MethodsWe exploited a mouse model where tumor-specific therapeutic vaccination results in tumor regression, followed by local recurrence and resistance. In depth studies on systemic, local and tumor intrinsic changes were performed with flow and mass cytometry, immunohistochemistry, transcriptomics and several perturbation studies with inhibitors or agonistic antibodies in mice. Main findings were recapitulated in vaccinated patients.ResultsFull tumor regression and cure of tumor-bearing mice is dependent on the magnitude of the vaccine-induced T-cell response. Recurrence of tumors did not involve classical immune escape mechanisms, such as antigen-presentation alterations, immune checkpoint expression, resistance to killing or local immune suppression. However, the recurrent tumors displayed a changed transcriptome with alterations in p53, tumor necrosis factor-α and transforming growth factor-β signaling pathways and they became immunologically cold. Remarkably, ex vivo cell-sorted recurrent tumors, directly reinjected in naïve hosts retained their resistance to vaccination despite a strong infiltration with tumor-specific CD8+T cells, similar to that of vaccine-responsive tumors. The influx of inflammatory mature myeloid effector cells in the resistant tumors, however, was impaired and this turned out to be the underlying mechanisms as restoration of inflammatory myeloid cell infiltration reinstated the sensitivity of these refractory tumors to vaccination. Notably, impaired myeloid cell infiltration after vaccination was also associated with vaccine resistance in patients.ConclusionAn immunotherapy-induced disability of tumor cells to attract innate myeloid effector cells formed a major mechanism underlying immune escape and acquired resistance. These data not only stresses the importance of myeloid effector cells during immunotherapy but also demands for new studies to harness their tumoricidal activities.
Pre-exposure HIV prophylaxis (PrEP) among transgender women: 3 years of follow-up in a university hospital in Paris
Authors: Isernia Valentina , Phung Bao , Lepretre Annie Marie , Azadi Bahar , Rincon Giovanna , Zelie Julia , Le Gac Sylvie , Deprez Andres , Michard Florence , Yazdanpanah Yazdan , Ghosn Jade 
Published: September 2020

ObjectivesThe principal outcome was to describe clinical characteristics of a transgender male-to-female (TGW) cohort followed for pre-exposure HIV prophylaxis (PrEP).IntroductionFew efforts and preventive interventions have targeted transgender population, despite them being at great risk of HIV infection.MethodsThis was a retrospective transgender male-to-female (TGW) cohort followed for PrEP at Bichat Hospital Sexual Health Clinic between February 2016 and January 2019.The principal outcome was to describe clinical characteristics of this TGW population: modalities of PrEP uptake, treatment adherence and tolerance, sanitary system retention, hormonal therapy and STIs.Data about age, ethnicity, language, sex work and sanitary healthcare insurance coverage were also collected.ResultsForty-nine TGW were included, with a median age of 33 years; 43/49 (87.7%) were from South America and 43/49 (87.7%) were sex workers. Forty-four 44/49 TGW (89.7%) had no regular healthcare insurance coverage. Nineteen out of 49 (38.7%) had a history of STI in the last 12 months. Hormone intake was reported in 16/49 (32.60%). PrEP with oral TDF/FTC was prescribed on a daily basis for 45/49 TG (91.8%). Two TGW discontinued PrEP for gastrointestinal intolerance. No case of renal toxicity or HIV seroconversion has been reported. Retention rate was high (71.4%), but average follow-up was 9 months.ConclusionsOur data showed a very vulnerable population, with a high proportion of migrants, sex workers and with a low healthcare insurance coverage. Retention rate was high (71.4%). Further multi-component interventions are needed to improve global sex health approach, PreP follow-up and sanitary system retention among TGW population.
Distribution and source of Pu in the sediments of the seas and estuaries of China—a review
Authors: Wang Ruirui , Liu Zhiyong 
Published: September 2020

Abstract
The coastal zone is the most concentrated area of human activities, and it is also the main accumulation zone of continental sediments, which is an ideal area for studying anthropocene sedimentary records. This study summarizes the distribution of 239+240Pu activity, 239+240Pu inventory, and 240Pu/239Pu atom ratios in the sediments of the seas and estuaries of China. Studies have shown that the distribution of 239+240Pu activity in sediments is mainly influenced by sediment properties and ocean current dynamics. Furthermore, 239+240Pu activity in sediment cores has obvious peak characteristics, which can be used in sediment dating. In fact, 240Pu/239Pu atom ratios indicate that the Pu in the sediments of the seas and estuaries of China mainly comes from global fallout and the Pacific Proving Grounds (PPG). Pu from the PPG enters the seas of China through the North Equatorial Current and Kuroshio intrusion current. And the contribution of Pu from the PPG in the East China Sea, the South China Sea, and the Yangtze estuary is over 40%. Moreover, Pu has been applied in the tracer of land-sea interactions and ocean dynamics, and it can be used as a background value to study the changes of Pu in the coastal zone of China in the future.
Effects of progressive Orff vocal therapy on BODE index and quality of life in patients with low lung function after non-small cell lung cancer surgery
Authors: Du Yijie , Su Mingyue , Xue Hongli , Ma Mengyu , Wu Xilong , Xue Hanyu , Yi Tao , Tang Zhao , Kong Qing , Xu Yizhe , Cao Yuxue 
Published: September 2020

Objective: To explore the effect of Orff vocal therapy on BODE index and quality of life of patients with low lung function after non-small cell lung cancer surgery. Methods: From March 2014 to March 2019, 231 patients with NSCLC postoperative (their pulmonary functions FEV1 [Formula: see text] of the expected value) in the Huashan Hospital, Fudan University were selected and randomly divided into observation groups and control group. On the basis of conventional treatment of NSCLC, the control group used lung rehabilitation training, and the observation group used the Orff music therapy. They carry out vocal and breath training step by step, using a combination of online and offline methods, 1[Formula: see text]h per day online interactive training, 2[Formula: see text]h of offline group vocal therapy once a week, continuous intervention for 12 months. The patient’s BODE index and FACT-L scores were monthly follow-up. Results: Compared with the control group, the BODE index and FACT-L scores improved more significantly in the vocal therapy group ([Formula: see text]). Especially in the FEV1pred, family/society module and functional status module, the improvement was most significant, compared with the control group ([Formula: see text]). And the loss of follow-up rate in the vocal therapy group was lower than that in the lung rehabilitation group ([Formula: see text]). Conclusion: Orff vocal therapy can improve the BODE index and quality of life of patients with low lung function after non-small cell lung cancer surgery, and its compliance and intervention effects are better than ordinary lung rehabilitation training.
Abstract 1037: Orally available small molecule CD73 inhibitor reverses immunosuppression through blocking of adenosine production
Authors: Du Xiaohui , Blank Brian , Chan Brenda , Chen Xi , Chen Yuping , Duong Frank , Friedman Lori , Huang Tom , Junttila Melissa R. , Kong Wayne , Metzger Todd , Moore Jared , Sun Daqing , Sun Jessica , Sutimantanapi Dena , Yuen Natalie , Zavorotinskaya Tatiana 
Published: September 2020

Abstract
CD73 has emerged as an attractive target for cancer immunotherapy. CD73 (ecto-5-nucleotidase) is a glycosyl phosphatidyl inositol (GPI)-anchored cell surface protein and catalyzes the hydrolysis of AMP into immunosuppressive adenosine and inorganic phosphate. CD73 is widely overexpressed in tumor microenvironments (TME) of many cancers, resulting in elevated levels of extra cellular adenosine (ADO). ADO plays a critical role in tumor progression through immune suppression, chemotherapy resistance, metastasis and angiogenesis. Therefore, reducing the level of adenosine via inhibition of CD73 has become a potential strategy for treating cancers. Here we report our medicinal chemistry efforts in developing orally available small molecule CD73 inhibitors. Based on the binding mode of adenosine 5'-(α,β-methylene)diphosphate (APCP) with CD73, we designed a novel series of monophosphate CD73 inhibitors, which are highly potent and orally bioavailable. In preclinical studies, OP-5244 inhibited ADO production completely in human cancer cells and CD8+ T cells. It also showed dose-dependent inhibitory effects on CD73 activity in various tumors ex vivo. Furthermore, OP-5244 showed PK/PD efficacy through lowering of ADO/AMP ratio and reversal of immunosuppression in vivo.
Citation Format: Xiaohui Du, Brian Blank, Brenda Chan, Xi Chen, Yuping Chen, Frank Duong, Lori Friedman, Tom Huang, Melissa R. Junttila, Wayne Kong, Todd Metzger, Jared Moore, Daqing Sun, Jessica Sun, Dena Sutimantanapi, Natalie Yuen, Tatiana Zavorotinskaya. Orally available small molecule CD73 inhibitor reverses immunosuppression through blocking of adenosine production [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1037.
Abstract 1423: A lncRNA MEG9 protects vasculature from DNA damage
Authors: Espinosa-Diez Cristina , Fraile-Bethencourt Eugenia , Hudson Clayton , Ruhl Rebecca , Anand Sudarshan 
Published: September 2020

Abstract
DNA damaging agents including ionizing radiation (IR) therapy are widely used in cancer patients. Previous studies have suggested that the tumor vasculature, specifically endothelial cell (ECs) dictate responses to IR. We recently showed how IR, among other DNA damaging agents, induced changes in microRNA programs and impacted tumor angiogenesis. Here, we describe how different DNA damaging agents affect long noncoding RNA (lncRNA) programs in vascular cells. Specifically, we identify lncRNA MEG9 (Maternally Expressed Gene 9 in humans, Mirg in mouse) as one of the most differentially expressed lncRNAs in angiogenic stimuli and stress responses. MEG9 is robustly induced by DNA damaging agents and suppressed by vascular growth factors. MEG9 is located in the DLK1-DIO3 imprinted cluster. Previous studies have shown how DLK1-DIO3 genes are associated with stem cell biology and with the pathogenesis of several diseases, such as cancer. Other studies have shown that microRNAs in this cluster are regulated by methylation. Consistent with this observation, we found that inhibition of DNA methylation either via 5-azacytidine or silencing of DNMT3b significantly upregulated de novo expression of MEG9. Gain and loss of function assays indicated an anti-apoptotic role of MEG9 via caspase 3/7 pathways in cultured ECs. Similarly, MEG9 inhibition decreased angiogenesis in a 3D sprouting angiogenesis assay. Interestingly, MEG9 inhibition in ECs accelerated fibrin formation suggesting a regulatory role for this lncRNA in thrombosis. Moreover, we observed that MEG9 inhibition affects vascular permeability in vitro and in vivo in bFGF-Matrigel plugs. Finally, systemic delivery of RNAi targeting Mirg (mouse MEG9) decreased tumor burden in a mouse model of triple negative mammary carcinoma. Our mechanistic studies indicated that MEG9 in ECs impacts pathways related to inflammation and thrombosis, both critical mediators of tumor responses to radiation. Taken together, our results show MEG9 as a novel DNA damage induced lncRNA with a protective role in the tumor vasculature functioning via multiple distinct mechanisms. Therefore, we propose that disruption of lncRNA MEG9 is a potent anti-angiogenic strategy that can synergize with DNA damaging agents.
Citation Format: Cristina Espinosa-Diez, Eugenia Fraile-Bethencourt, Clayton Hudson, Rebecca Ruhl, Sudarshan Anand. A lncRNA MEG9 protects vasculature from DNA damage [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1423.
Abstract 1698: Cellular cytotoxicity is a form of immunogenic cell death
Authors: Minute Luna , Teijeira Alvaro , Sánchez-Paulete Alfonso Rodriguez , del Carmen Ochoa Maria , Alvarez Maite , Otano Itziar , Etxeberria Iñaki , Bolaños Elixabet , Azpilikueta Arantza , Garasa Saray , Casares Noelia , Pérez-Gracia José Luiz , Rodríguez-Ruiz Maria Esperanza , Berraondo Pedro , Melero Ignacio 
Published: September 2020

Abstract
Background: The immune response to cancer is often conceptualized with the Cancer Immunity Cycle. An essential step in this interpretation is that antigens released by dying tumors are presented by dendritic cells to naive or memory T cells in the tumor-draining lymph nodes. Whether tumor cell death resulting from cytotoxicity, as mediated by T cells or NK lymphocytes, is actually immunogenic currently remains unknown.
Methods: In this study, tumor cells were killed by antigen-specific T-cell receptor (TCR) transgenic CD8 T cells or activated natural killer cells. Immunogenic cell death was studied analyzing the membrane exposure of calreticulin and the release of high mobility group box 1 (HMGB1) by the dying tumor cells. Furthermore, the potential immunogenicity of the tumor cell debris was evaluated in immunocompetent mice challenged with an unrelated tumor sharing only one tumor-associated antigen and by class I MHC-multimer stainings. Mice deficient in BATF-3, IFNAR and STING were used to study mechanistic requirements.
Results: We observe in co-cultures of tumor cells and effector cytotoxic cells, the presence of markers of immunogenic cell death such as calreticulin exposure and soluble HMGB1 protein. OVA-transfected MC38 colon cancer cells, exogenously pulsed to present the gp100 epitope are killed in culture by mouse gp100 specific TCR transgenic CD8 T cells. Immunization of mice with the resulting destroyed cells induces epitope spreading as observed by detection of OVA-specific T cells by MHC multimer staining and rejection of OVA+ EG7 lymphoma cells. Similar results were observed in mice immunized with cell debris generated by NK-cell mediated cytotoxicity. Mice deficient in BATF3-dependent dendritic cells (cDC1) fail to develop an anti-OVA response when immunized with tumor cells killed by cytotoxic lymphocytes. In line with this, cultured cDC1 dendritic cells uptake and can readily cross-present antigen from cytotoxicity-killed tumor cells to cognate CD8+ T lymphocytes.
Conclusion: These results support that an ongoing cytotoxic antitumor immune response can lead to immunogenic tumor cell death.
Citation Format: Luna Minute, Alvaro Teijeira, Alfonso Rodriguez Sánchez-Paulete, Maria del Carmen Ochoa, Maite Alvarez, Itziar Otano, Iñaki Etxeberria, Elixabet Bolaños, Arantza Azpilikueta, Saray Garasa, Noelia Casares, José Luiz Pérez-Gracia, Maria Esperanza Rodríguez-Ruiz, Pedro Berraondo, Ignacio Melero. Cellular cytotoxicity is a form of immunogenic cell death [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1698.
Abstract 330: Reconstructed Bone (r-Bone): A patient-derived 3D culture platform for prediction of clinical outcomes in multiple myeloma
Authors: Kirshner Julia , Kirshnan Amrita , Nathwani Nitya , Htut Myo , Rosenzweig Michael , Karanes Chatchada , Firoozeh Sahebi , Rosen Steven 
Published: September 2020

Abstract
Multiple myeloma (MM), an incurable cancer of the bone marrow plasma cells, is a second most common hematological malignancy. While considerable progress has been made towards treatment of MM, the 5-year survival rate continues to hover around 50%. In this study, we aimed to evaluate the capacity of the Reconstructed Bone (r-Bone) model to predict clinical outcomes in patients with multiple myeloma. The r-Bone system incorporates cellular (hematopoietic and stromal) and extracellular (extracellular matrix and secretory factors) components, supports long-term survival (&gt;30 days) and proliferation, and maintains cellular heterogeneity of the primary human bone marrow. The 1-to-1 reconstruction of the bone marrow architecture established by the r-Bone platform provides an ideal in vitro system to evaluate the efficacy of anti-myeloma agents to select those with highest probability of clinical success. Bone marrow aspirates collected from 21 patients with multiple myeloma were processed and set-up in r-Bone cultures. To establish the correct bone marrow architechture, cultures where grown for 5 days, after which the cells were treated according to the clinical regimen selected by the treating physician based on the orginal bone marrow aspirate. Subsequently, cells were isolated from the r-Bone and processed for flow cytometry. Plasma and non-plasma cell populations were evaluated post-treatment and the extent of cell death was correlated with the observed clinical response. r-Bone cultures correctly predicted the outcome of 19 out of 21 cases with 8 true positivies, 11 true negatives, and 2 false positives. This data demonstrate that the r-Bone system could be used for pipeline attrition management to select drug candidates with the highest probability of clinical success and can be developed into a prognostic tool for the selection of treatment regimen for patients with multiple myeloma.
Citation Format: Julia Kirshner, Amrita Kirshnan, Nitya Nathwani, Myo Htut, Michael Rosenzweig, Chatchada Karanes, Sahebi Firoozeh, Steven Rosen. Reconstructed Bone (r-Bone): A patient-derived 3D culture platform for prediction of clinical outcomes in multiple myeloma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 330.