bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PO076: Development of a CD137 (4-1BB) receptor occupancy assay using fluorescently labelled Bicycles®
Authors: Kanakia Drasti N. , Upadhyaya Punit , Lahdenranta Johanna , Repash Elizabeth , Haines Eric , McDonnell Kevin , Hurov Kristen , Brandish Philip , Keen Nicholas 
Published: February 2021

Abstract
Receptor occupancy (RO) assays are designed to quantify the binding of therapeutics to their cell surface targets and are frequently used to generate both pre-clinical and clinical pharmacodynamic biomarker data. Flow cytometry is a commonly used technique to measure receptor occupancy on immune cell populations within fresh blood specimens. Yet, receptor occupancy assays are subject to numerous technical and logistical challenges. To ensure that reliable and high-quality results are generated from receptor occupancy assays, careful assay design and key reagent selection, characterization, and utilization are of critical importance. Antibodies are commonly conjugated with fluorophores and used in receptor occupancy assays for related therapeutics. Bicycles® are a new therapeutic modality - fully synthetic, constrained bicyclic peptides with high affinity and excellent target selectivity. Here, we describe a novel utility for fluorescently-labeled Bicycles in the development of a CD137 (4-1BB) receptor occupancy assay. CD137 is a member of the TNFR superfamily involved in stimulation of several immune cell types, including T cells and NK cells. CD137 is well validated pre-clinically, as agonism with anti-CD137 antibodies is effective in vivo, however, clinical utility to date has been limited by dose dependent hepatotoxicity. We have demonstrated that tumor-targeted immune cell agonists (TICAsTM) comprised of CD137 binding Bicycles coupled to tumor antigen binding Bicycles exert anti tumoral properties with a favorable safety profile. Here, we demonstrate another functionality for the Bicycle platform, as a measurement of CD137 TICA target engagement and receptor occupancy. Using fluorescently-labeled CD137 Bicycles, we measured RO on immune populations in isolated human peripheral blood mononuclear cells (PBMCs), as well as in whole blood. The assay shows high specificity as no Bicycle binding was observed in CD137 negative cell populations. Additionally, RO was shown to be dependent on the presence of CD137-binding Bicycles. Together, this novel approach of measuring receptor occupancy may be used to inform on both the pre-clinical and clinical therapeutic properties of Bicycle TICAs.
Citation Format: Drasti N. Kanakia, Punit Upadhyaya, Johanna Lahdenranta, Elizabeth Repash, Eric Haines, Kevin McDonnell, Kristen Hurov, Philip Brandish, Nicholas Keen. Development of a CD137 (4-1BB) receptor occupancy assay using fluorescently labelled Bicycles® [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Cancer Immunol Res 2021;9(2 Suppl):Abstract nr PO076.
Abstract PR004: Genetic ablation of adipocyte PD-L1 reduces tumor growth but accentuates obesity-associated inflammation
Authors: Wu Bogang , Chiang Huai-Chin , Sun Xiujie , Yuan Bin , Mitra Payal , Hu Yanfen , Curiel Tyler J. , Li Rong 
Published: February 2021

Abstract
The programmed death-ligand 1 (PD-L1)-dependent immune checkpoint attenuates host immunity and maintains self-tolerance. Imbalance between protective immunity and immunopathology due to altered PD-L1 signaling can lead to autoimmunity or tumor immunosuppression. The role of the PD-L1-dependent checkpoint in non-immune system is less reported. We previously found that white adipocytes highly express PD-L1. Here we show that adipocyte-specific PD-L1 knockout mice exhibit enhanced host anti-tumor immunity against mammary tumors and melanoma with low or no tumor PD-L1. However, adipocyte PD-L1 ablation in tumor-free mice also exacerbates diet-induced body weight gain, pro-inflammatory macrophage infiltration into adipose tissue, and insulin resistance. Low PD-L1 mRNA levels in human adipose tissue correlate with high body mass index and presence of type 2 diabetes. Therefore, our mouse genetic approach unequivocally demonstrates a cell-autonomous function of adipocyte PD-L1 in promoting tumor growth and inhibiting anti-tumor immunity. In addition, our work uncovers a previously unrecognized role of adipocyte PD-L1 in mitigating obesity-related inflammation and metabolic dysfunction.
This abstract is also being presented as PO031.
Citation Format: Bogang Wu, Huai-Chin Chiang, Xiujie Sun, Bin Yuan, Payal Mitra, Yanfen Hu, Tyler J. Curiel, Rong Li. Genetic ablation of adipocyte PD-L1 reduces tumor growth but accentuates obesity-associated inflammation [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Cancer Immunol Res 2021;9(2 Suppl):Abstract nr PR004.
Abstract PR013: Microfluidic purification of T lymphocytes separated from blood for chimeric antigen receptor T-cell manufacturing
Authors: Elsemary Mona T. , Maritz Michelle F. , Smith Louise , Warkiani Majid , Thierry Benjamin 
Published: February 2021

Abstract
The CAR T cell manufacturing process is complex and expensive. In addition, the quality of the final product suffers from great variability, which is in part due to the personalized nature of the therapy. An important source of variability of final CAR T cells products is the starting cellular material for manufacture. The percentage of T-cells separated from a patient’s blood used for CAR T cell manufacture is highly variable and influenced by many factors. The percentage of ‘other’ cells typically range anywhere from 10 to 90%, and these cells interfere with the downstream T-cell modification and expansion processes, potentially preventing the production of high-quality end products. Microfluidic technologies which separate cells based on their physical attributes have previously shown great success in separating circulating cancer cells from blood but have not yet been applied in the CAR T cell manufacturing process. Early research has shown the possibility of depleting red blood cells and platelets, however little has been done in the specific purification of T-cells and depletion of other lymphocytic cells. This research therefore aimed to investigate the use of microfluidics in the separation and purification of T-cells towards addressing known bottlenecks/issues in the CAR T cells manufacturing process. We have designed and optimized microfluidic devices of various dimensions with enrichment and depletion outlets. We will report on the successful utilization of these devices in various critical steps of the manufacturing process.
This abstract is also being presented as PO080.
Citation Format: Mona T. Elsemary, Michelle F. Maritz, Louise Smith, Majid Warkiani, Benjamin Thierry. Microfluidic purification of T lymphocytes separated from blood for chimeric antigen receptor T-cell manufacturing [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Cancer Immunol Res 2021;9(2 Suppl):Abstract nr PR013.
Shared Decision-Making for Left Ventricular Assist Devices
Authors: Thompson Jocelyn S. , Fitzgerald Monica D. , Allen Larry A. , McIlvennan Colleen K. , Glasgow Russell E. , Wynia Matthew , Morris Megan A. , Beilenson John , Gherst Chris , Matlock Dan D. 
Published: February 2021

Background
The left ventricular assist device (LVAD) has become a common medical option for patients with end-stage heart failure. Although patients’ chances of survival may increase with an LVAD compared with medical therapy, the LVAD poses many risks and requires major lifestyle changes, thus making it a complex medical decision. Our prior work found that a decision aid for LVADs significantly increased decision quality for both patients and caregivers and was successfully implemented at 6 LVAD programs.

Methods
In follow-up, we are conducting a nationwide dissemination and implementation project, with the goal of implementing the decision aid at as many of the 176 LVAD programs in the United States as possible. Guided by the Theory of Diffusion of Innovations, the project consists of 4 phases: (1) building a network; (2) promoting adoption; (3) supporting implementation; and (4) encouraging maintenance. Developing an LVAD network of contacts occurs by using a national baseline survey of LVAD clinicians, existing professional relationships, and an internet-based strategy. A suite of resources targeted to promote adoption and support implementation of the decision aid into standard LVAD education processes are provided to the network. Evaluation is guided by the Reach, Effectiveness, Adoption, Implementation, Maintenance framework, where clinician and patient surveys and qualitative interviews determine the reach, effectiveness, adoption, implementation, and maintenance achieved.

Conclusions
This project is a true dissemination study in that it targets the entire population of LVAD programs in the United States and is unique in its use of social marketing principles to promote adoption and implementation. The implementation plan is intended to serve as a test case and model for dissemination and implementation of other evidence-based decision support aids and strategies.
An evaluation of CMIP6 historical simulations of the cold season teleconnection between tropical Indo-Pacific sea surface temperatures and precipitation in Southwest Asia, the coastal Middle East, and Northern Pakistan and India
Authors: Barlow Mathew , Hoell Andrew , Agel Laurie 
Published: February 2021

AbstractThe ability of six CMIP6 models to reproduce the observed cold season teleconnection between tropical Indo-Pacific sea surface temperatures (SSTs) and precipitation in Southwest Asia, the coastal Middle East (CME), and Northern Pakistan and India (NPI) is examined. The 1979-2014 period is analyzed, to maximize observations over both the tropical ocean and the regions. Nine historical simulations for the same period are examined for each model, to account for the internal variability of the coupled system. The teleconnection is examined in terms of SSTs, precipitation, 200 hPa geopotential heights, and derived quantities.All the models capture some of the broadest features of the teleconnections, but there is a wide range in the ability of the models to reproduce the magnitude and details. The differences appear related to both the models’ ability to capture the details of the tropical variability, including the position and strength of the precipitation anomalies in the Indo-west Pacific, as well as the models’ ability to accurately propagate the tropically-forced response into the region. The teleconnections to the CME and NPI regions on the eastern and western margins, respectively, of the strongest signal are very similar in structure and have similar results, except that the models’ ability to reproduce the strength and details of the teleconnection is even more limited, consistent with their marginal locations and known influence of other modes of variability. For all three areas, the wide range in model ability to capture the leading teleconnection suggests caution in interpreting climate regional projections.
Impact of Stochastic Physics and Model Resolution on the Simulation of Tropical Cyclones in Climate GCMs
Authors: Vidale Pier Luigi , Hodges Kevin , Vannière Benoit , Davini Paolo , Roberts Malcolm J. , Strommen Kristian , Weisheimer Antje , Plesca Elina , Corti Susanna 
Published: February 2021

AbstractThe role of model resolution in simulating geophysical vortices with the characteristics of realistic tropical cyclones (TCs) is well established. The push for increasing resolution continues, with general circulation models (GCMs) starting to use sub-10-km grid spacing. In the same context it has been suggested that the use of stochastic physics (SP) may act as a surrogate for high resolution, providing some of the benefits at a fraction of the cost. Either technique can reduce model uncertainty, and enhance reliability, by providing a more dynamic environment for initial synoptic disturbances to be spawned and to grow into TCs. We present results from a systematic comparison of the role of model resolution and SP in the simulation of TCs, using EC-Earth simulations from project Climate-SPHINX, in large ensemble mode, spanning five different resolutions. All tropical cyclonic systems, including TCs, were tracked explicitly. As in previous studies, the number of simulated TCs increases with the use of higher resolution, but SP further enhances TC frequencies by ~30%, in a strikingly similar way. The use of SP is beneficial for removing systematic climate biases, albeit not consistently so for interannual variability; conversely, the use of SP improves the simulation of the seasonal cycle of TC frequency. An investigation of the mechanisms behind this response indicates that SP generates both higher TC (and TC seed) genesis rates, and more suitable environmental conditions, enabling a more efficient transition of TC seeds into TCs. These results were confirmed by the use of equivalent simulations with the HadGEM3-GC31 GCM.
Across establishments, within firms: worker’s mobility, knowledge transfer and survival
Authors: Tavares Marisa Fernanda Figueiredo 
Published: February 2021

AbstractWe analyze the recruitment strategies and the survival of newly created establishments that are affiliated with pre-established _rms. For the new establishments, the existence of ports of entry as well as the importance of internal and external recruitment is assessed. Being affiliated with a pre-established firm may be a source of competitive advantage and improve the new plant’s chances of survival as the parent firm may supply the newly created unit with expertise and firm-specific knowledge. In this research we suggest a channel for knowledge transfer that has been little addressed in previous literature: within firm and across establishments mobility of workers. As firm-specific knowledge is mainly embodied and non-tradable, we suggest that it can be successfully transferred to the new unit embodied in the workers that are internally recruited. We find that internally transferred workers, particularly skilled workers hired at high-rank jobs play an important role in improving the survival of new establishments.
ACEF performed better than other risk scores in non-ST-elevation acute coronary syndrome during long term follow-up
Authors: Kristić Ivica , Crnčević Nikola , Runjić Frane , Čapkun Vesna , Polašek Ozren , Matetic Andrija , Vrsalovic Mislav 
Published: February 2021

AbstractBackgroundRisk stratification of patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) is an important clinical method, but long-term studies on patients subjected to all-treatment strategies are lacking. Therefore, the aim was to compare several established risk scores in the all-treatment NSTE-ACS cohort during long-term follow-up.MethodsConsecutive patients (n = 276) with NSTE-ACS undergoing coronary angiography were recruited between September 2012 and May 2015. Six risk scores for all patients were calculated, namelyGRACE 2.0, ACEF, SYNTAX, Clinical SYNTAX, SYNTAX II PCI and SYNTAX II CABG. The primary end-point was Major Adverse Cardiovascular Events (MACE) which was a composite of cardiac death, nonfatal myocardial infarction, ischemic stroke or urgent coronary revascularization.ResultsDuring a median follow-up of 33 months, 64 MACE outcomes were recorded (23.2%). There was no difference between risk score categories, except in the highest risk group ofACEFandSYNTAX II PCIscores which exhibited significantly more MACE (51.6%, N = 33 and 45.3%, N = 29,P = 0.024, respectively). In the multivariate Cox regression analysis of individual variables, only age and atrial fibrillation were significant predictors for MACE (HR 1.03, 95% CI 1.00–1.05,P = 0.023 and HR 2.02, 95% CI 1.04–3.89,P = 0.037, respectively). Furthermore, multivariate analysis of the risk scores showed significant prediction of MACE only withACEFscore (HR 2.16, 95% CI 1.36–3.44,P = 0.001). The overall performance ofGRACE,SYNTAX,Clinical SYNTAXandSYNTAX II CABGwas poor with AUC values of 0.596, 0.507, 0.530 and 0.582, respectively, whileACEFandSYNTAX II PCIshowed the best absolute AUC values for MACE (0.630 and 0.626, respectively).ConclusionsACEFrisk score showed better discrimination than other risk scores in NSTE-ACS patients undergoing all-treatment strategies over long-term follow-up and it could represent a fast and user-friendly tool to stratify NSTE-ACS patients.
The Frailty In Residential Sector over Time (FIRST) study: methods and baseline cohort description
Authors:   on behalf of the FIRST Study Collaborators, Jadczak Agathe Daria , Robson Leonie , Cooper Tina , Bell J. Simon , Visvanathan Renuka 
Published: February 2021

Abstract
Background
The Frailty In Residential Sector over Time (FIRST) Study is a 3-year prospective cohort study investigating the health of residents living in residential aged care services (RACS) in South Australia. The study aims to examine the change in frailty status and associated health outcomes.

Methods
This interim report presents data from March 2019–October 2020. The study setting is 12 RACS from one organisation across metropolitan and rural South Australia involving 1243 residents. All permanent (i.e. respite or transition care program excluded) residents living in the RACS for at least 8 weeks were invited to participate. Residents who were deemed to be medically unstable (e.g. experiencing delirium), have less than 3 months to live, or not fluent in English were excluded. Data collected included frailty status, medical diagnoses, medicines, pain, nutrition, sarcopenia, falls, dementia, anxiety and depression, sleep quality, quality of life, satisfaction with care, activities of daily living, and life space use at baseline and 12-months. Data Linkage will occur over the 3 years from baseline.

Results
A total of 561 permanent residents (mean age 87.69 ± 7.25) were included. The majority of residents were female (n = 411, 73.3%) with 95.3% (n = 527) being classified as either frail (n = 377, 68.2%) or most-frail (n = 150, 27.1%) according to the Frailty Index (FI). Most residents were severely impaired in their basic activities of daily living (n = 554, 98.8%), and were at-risk of malnutrition (n = 305, 55.0%) and at-risk of sarcopenia (n = 492, 89.5%). Most residents did not experience pain (n = 475, 85.4%), had normal daytime sleepiness (n = 385, 69.7%), and low anxiety and depression scores (n = 327, 58.9%).

Conclusion
This study provides valuable information on the health and frailty levels of residents living in RACS in South Australia. The results will assist in developing interventions that can help to improve the health and wellbeing of residents in aged care services.

Trial registration
Prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12619000500156).
Prognostic value of visual residual tumour cells (VRTC) for patients with esophageal squamous cell carcinomas after neoadjuvant therapy followed by surgery
Authors: Wang Xingxing , Wang Hao , Wang Haixing , Huang Jie , Wang Xin , Jiang Zhengzeng , Tan Lijie , Jiang Dongxian , Hou Yingyong 
Published: February 2021

Abstract
Background
We assessed visual residual tumour cells (VRTC) with both Becker’s tumour regression grading (TRG) system and Japanese TRG system in esophageal squamous cell carcinoma (ESCC) patients treated with neoadjuvant therapy followed by surgery.

Methods
We compared Becker system and Japanese system in 175 ESCC patients treated between 2009 and 2015.

Results
According to Becker system, the 5-year DFS/DSS rates were 70.0%/89.3, 53.8%/56.7, 43.0%/49.0, and 42.4%/39.1% for TRG 1a (VRTC 0), TRG 1b (1–10%), TRG 2 (11–50%), and TRG 3 (> 50%). According to Japanese system, the rates were 38.8%/34.1, 49.5%/58.7, 50.2%/49.0 and 70.0%/89.3% for Grade 0-1a (VRTC> 66.6%), Grade 1b (33.3–66.6%), Grade 2 (1–33.3%) and Grade 3 (0). TRG according to two systems significantly discriminate the patients’ prognosis. TRG according to Becker system (HR 2.662, 95% CI 1.151–6.157), and lymph node metastasis (HR 2.567, 95% CI 1.442–4.570) were independent parameters of DSS.

Conclusions
Both Becker and Japanese system had their advantage in risk stratification of these ESCC patients. It was speculated that dividing 1–10% VRTC into a group might contribute to independently prognostic significance of Becker’s TRG system. Therefore, in addition to TRG of different systems, the percentage of VRTC might be recommended in the pathologic report, which could make the results more comparable among different researches, and more understandable for oncologists in the clinical practice.
An investigation of depression, anxiety, and stress and its relating factors during COVID-19 pandemic in Iran
Authors: Khademian Fatemeh , Delavari Sajad , Koohjani Zahra , Khademian Zahra 
Published: February 2021

Abstract
Background
The COVID-19 (SARS-CoV-2) is an emerging epidemic caused by the new Coronavirus. It has affected more than 200 countries, infected 5,939,234 people, and killed 367,255 in the world until 1 June 2020. While the disease epidemic could affect population mental health, this study aimed to investigate stress, anxiety, and depression during the Corona pandemic in Iran.

Methods
An online survey was designed using the depression, anxiety, and stress scale (DASS-21) questionnaire. The questionnaire was available for all Iranian population from 18 to 28 April 2020. Finally, 1498 participants filled the questionnaire using snowball sampling. Data were analyzed using multivariate regression models.

Results
Findings showed that most participants had experienced a normal level of stress (36.6%), anxiety (57.9%) and depression (47.9%). About 2.5% of respondents report an extremely severe level of stress. This amount of anxiety and depression was 6.3 and 7.9%, respectively. Regression model showed being female (CI: − 1.299; − 0.248), living with a high risk family member (CI: 0.325; 1.400), health status (CI: − 0.857; − 0.595), economic status (CI: − 0.396; − 0.141), social capital (CI: − 0.475; − 0.244), risk of disease (CI: 0.081; 0.729), and following COVID-19 news (CI: 0.111; 0.551) have a relation with stress level. Education level (CI: − 0.252; − 0.017), living with a high risk family member (CI: 0.0301; 1.160), health status (CI: − 0.682; − 0.471), social capital (CI: − 0.236; − 0.048), risk of disease (CI: 0.154; 0.674), and following COVID-19 news (CI: 0.046; 0.401) have a relation with anxiety score. Depression score was in relation with education level (CI: − 0.263; − 0.022), having a high-risk family member (CI: 0.292; 1.155), health status (CI: − 0.687; − 0.476), social capital (CI: − 0.235; − 0.048), risk of disease (CI: 0.144; 0.667), and following Covid-19 news (CI: 0.053; 0.408).

Conclusions
Most of the factors related to depression, anxiety, and stress are related to COVID-19, such as having a vulnerable person in the family, risk of disease, and following COVID-19 news. The findings suggest the factors that should be taken into consideration for improving population mental health during pandemics.