bluuebunny/crossref_metadata_2025_split huggingface dataset:
59. A RADIOMICS-BASED MACHINE LEARNING MODEL FOR DISTINGUISHING RADIATION NECROSIS FROM PROGRESSION OF BRAIN METASTASES TREATED WITH STEREOTACTIC RADIOSURGERY (SRS)
Authors: Chen Xuguang , Parekh Vishwa , Peng Luke , Chan Michael , Soike Michael , McTyre Emory , Jacobs Michael , Kleinberg Lawrence 
Published: August 2020

Abstract

PURPOSE
This study aims to test whether MRI radiomic signatures can distinguish radiation necrosis (RN) from tumor progression (TP) in a multi-institution dataset using machine learning.

METHODS
Brain metastases treated with SRS were followed by serial MRI, and those showing evidence of RN or TP underwent pathologic confirmation. Radiomic features were extracted from T1 post-contrast (T1c) and T2 fluid attenuated inversion recovery (T2 FLAIR) MRI. High dimensional radiomic feature space was visualized in a two-dimensional space using t-distributed stochastic neighbor embedding (t-SNE). Cases from 2 institutions were combined and randomly assigned to training (2/3) and testing (1/3) cohorts. Backward elimination was used for feature selection, followed by random forest algorithm for predictive modeling.

RESULTS
A total of 135 individual lesions (37 RN and 98 TP) were included. The majority (72.6%) received single-fraction SRS to a median dose of 18Gy. Clear clustering of cases around the institutional origin was observed on t-SNE analysis. 21 T1c and 4 FLAIR features were excluded from subsequent modeling due to significant correlation with the institutional origin. Backward elimination yielded 6 T1c and 6 FLAIR features used for model construction. A random forest model based on the 6 FLAIR features (cluster shade, neighborhood gray tone difference matrix (NGTDM) coarseness, NGTDM texture strength, run length nonuniformity, run percentage, and short run high gray-level emphasis) achieved sensitivity of 76% and specificity of 70% on the training cohort (AUC 0.74, 95% CI 0.60–0.88), and sensitivity of 67% and specificity of 83% on the testing cohort (AUC 0.75, 95% CI 0.59–0.93). Addition of the T1c features resulted in overfitting of the training cohort (AUC 1.00), but did not improve model performance on the testing cohort (AUC 0.69, 95% CI 0.51–0.87).

CONCLUSION
MRI radiomics based machine learning can distinguish RN from TP after brain SRS in a heterogeneous image dataset.
62. PRESENCE OF EXTRACRANIAL TUMORS INFLUENCES RESPONSE TO IMMUNE CHECKPOINT INHIBITORS IN A PRE-CLINICAL MODEL OF MELANOMA BRAIN METASTASIS
Authors: Nayyar Naema , Singh Mohini , Stocking Jackson , Brehm Michael , Brastianos Priscilla 
Published: August 2020

Abstract
Up to 75% of patients with melanoma develop brain metastases. While immune checkpoint inhibitors (ICI) targeting PD-1 and CTLA4 have revolutionized the treatment of metastatic melanoma, responses within the immune-specialized microenvironment of the brain are not well understood and there is a paucity of animal models to investigate the effect of ICI intracranially. We characterized responses to checkpoint inhibitors in a syngeneic mouse model of melanoma brain metastasis with concurrent intracranial and subcutaneous melanoma. D3UV3 cells (obtained from David Fisher’s laboratory) were derived using UVB irradiation from D4M.3A melanoma cell line and implanted into the striatum using stereotactic injection or subcutaneously injected into the flank of C57BL/6 mice. Mice were then treated with anti-PD-1 antibody, anti-CTLA4 antibody, a combination of anti-PD-1 and anti-CTLA4, or isotype controls. While mice with intracranial melanoma alone had no response to monotherapy with anti-PD-1 or anti-CTLA4 antibody (p=1 and 0.1, respectively), and only a slight response to combination therapy (p=0.049), mice with concurrent subcutaneous tumors had significantly improved responses to anti-PD-1, anti-CTLA4 and combination treatment (p=0.002, 0.01 and 0.01 respectively compared to mice with intracranial tumors alone with equivalent treatment). These results demonstrate that the presence of an extracranial tumor influences response to ICI in pre-clinical mouse models of melanoma brain metastasis. We have therefore established a pre-clinical model with concurrent intracranial and extracranial tumors to better recapitulate the clinically observed context of melanoma brain metastases and lead to a better understanding of the setting in which ICI are effective for patients with this devastating complication.
70. A PHASE 1–2 CLINICAL TRIAL OF EO1001, A NOVEL IRREVERSIBLE pan-ErbB INHIBITOR WITH PROMISING BRAIN PENETRATION
Authors: Wheeler Helen , Bacha Jeffrey , Kanekal Sarath , Pedersen Harry , Sankar Neil , Wang Shen , Nesbit Ian , Skoff Kathy , Brown Dennis 
Published: August 2020

Abstract
CNS metastasis has become a prominent driver of morbidity and mortality in recent years as new targeted therapies have improved systemic outcomes. Mutations in the ErbB family of kinases are known oncodrivers in many of these cancers. ErbB family member “crosstalk” is associated with rapid development acquired resistance to ErbB TKIs. The development of agents targeting multiple ErbB receptors has shown promise but has been limited by toxicity and poor brain penetration. EO1001 is a first-in-class, oral, brain penetrating, irreversible pan-ErbB inhibitor with superior CNS penetration targeting ErbB1, ErbB2 and ErbB4. Preclinical data suggests a favorable pharmacokinetic and safety profile and promising activity against ErbB-driven cancers in patient-derived xenograft models. Male or female adult participants with confirmed ErbB-positive cancer, including patients with CNS involvement, who have progressed after standard of care therapy, with adequate bone marrow, renal and liver function are eligible. An accelerated dose-escalation design is employed. One subject per dose cohort will be recruited until drug related toxicity (≥G2) is observed in the first dosing cycle, after which dose escalation will revert to a 3 + 3 design to determine the maximum tolerated dose (MTD). Dose Escalation: Cycle 1: Patients will receive a single dose EO1001 on day 1 and single dose pharmacokinetics will be performed. Beginning on day 8, EO1001 will be administered once daily for 21 days; multi-dose pharmacokinetics will be performed. Cycles 2–6: Oral EO1001 will be administered once daily in continuous 28-day cycles for up to 20 weeks. MTD Expansion: Oral EO1001 will be administered once daily at the MTD in continuous 28-day cycles for up to 6 cycles (24 weeks). Toxicity is assessed based on NCI CCTCAEv5 and tumor response will be assessed by RECIST 1.1 or RANO for CNS disease. CNS exposure is evaluated in patients via CSF collection with confirmed CNS disease involvement.
72. THE COMBINED USE OF STEROIDS AND IMMUNE CHECKPOINT INHIBITORS IN BRAIN METASTASES PATIENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Jessurun Charissa , Hulsbergen Alexander , de Wit Anouk , Tewarie Ishaan Ramlochan , Broekman Marike 
Published: August 2020

Abstract

INTRODUCTION
Immune checkpoint inhibitors (ICI) are increasingly being administered to cancer patients, including those with brain metastases (BMs). However, little is known about the interaction between ICI and steroids such as dexamethasone. The aim of this study was to perform a systematic literature review and meta-analysis on the association between steroid use and overall survival (OS) in BM patients receiving ICI.

METHODS
A systematic literature search was performed in PubMed, Embase, Web of Science, Cochrane, Academic Search Premier, and PsycINFO. Pooled effect estimates were calculated using random-effects models; analysis was performed across all included studies and stratified by tumor type.

RESULTS
After screening 978 abstracts, thirteen studies were included for systematic review. Ten studies reported sufficient data for meta-analysis, comprising 838 BM patients of which 335 (40%) had received steroids. In the steroid group, median OS ranged from 2.9 months to 10.2 months across studies. In the non-steroid group, median OS ranged from 4.9 to 25.1 months. Pooling results demonstrated significantly worse survival in the steroid group (HR 1.97; 95% CI 1.65–2.36); no significant heterogeneity (I2 = 0%) or publication bias (Egger’s p = 0.29) was identified. Stratified analysis showed a consistent effect across melanoma (HR 1.71, 95% CI 1.34–2.18) and non-small cell lung cancer (HR 2.26, 95% CI 1.49–3.43) subgroups.

CONCLUSION
Administration of steroids is associated with a significantly worse OS in BM patients receiving ICI. Further investigation on dose, timing and duration of steroids in this population is needed to elucidate the cause of this association and optimize outcomes in BM patients receiving ICI.
POINCARÉ DUALITY, CAP PRODUCT AND BOREL–MOORE INTERSECTION HOMOLOGY
Authors: Saralegi-Aranguren Martintxo , Tanré Daniel 
Published: August 2020

Abstract
Using a cap product, we construct an explicit Poincaré duality isomorphism between the blown-up intersection cohomology and the Borel–Moore intersection homology, for any commutative ring of coefficients and second-countable, oriented pseudomanifolds.
The effect of competitive public funding on scientific output: A comparison between China and the EU
Authors: Wang Lili , Wang Xianwen , Piro Fredrik Niclas , Philipsen Niels J 
Published: August 2020

Abstract
Public funding is believed to play an important role in the development of science and technology. However, whether public funding and, in particular, competitive funding from public agencies actually helps to increase scientific output (i.e. publications) remains a matter of debate. By analysing a dataset of co-publications between China and the EU and a dataset of joint project collaborations in European Framework Programs for Research and Innovation [FP7 and Horizon 2020 (H2020)], we investigate whether different public funding agencies’ competitive assets have different impact on the volume of publication output. Our results support the hypotheses that competitively funded research output varies by funding sources, so that a high level of funding does not necessarily lead to high scientific output. Our results show that FP7/H2020 funded projects do not have a positive contribution to the output of joint publications between China and the EU. Interestingly, cooperation in the form of jointly writing proposals to these EU programmes, especially when they are not granted by the European Commission, can contribute significantly to joint scientific publications in a later stage. This applies in particular to cases where funding from China is involved. Our findings highlight the key role that funding agencies play in influencing research behaviour. Our results indicate that Chinese funding triggers a high number of publications, whereas research funded by the EU does so to a much lower extent, arguably due to the EU’s strong focus on social impact and its funding schemes as tools to promote European integration.
Informational Robustness in Intertemporal Pricing
Authors: Libgober Jonathan , Mu Xiaosheng 
Published: August 2020

Abstract
We introduce a robust approach to study dynamic monopoly pricing of a durable good in the face of buyer learning. A buyer receives information about her willingness-to-pay for the seller’s product over time, and decides when to make a one-time purchase. The seller does not know how the buyer learns but commits to a pricing strategy to maximize profits against the worst-case information arrival process. We show that a constant price path delivers the robustly optimal profit, with profit and price both lower than under known values. Thus, under the robust objective, intertemporal incentives do not arise at the optimum, despite the possibility for information arrival to influence the timing of purchases. We delineate whether constant prices remain optimal (or not) when the seller seeks robustness against a subset of information arrival processes. As part of the analysis, we develop new techniques to study dynamic Bayesian persuasion.
US rheumatologists’ beliefs and knowledge about biosimilars: a survey
Authors: Gibofsky Allan , McCabe Dorothy 
Published: August 2020

Abstract

Objectives
We sought to evaluate perceptions of biosimilar products among US rheumatologists who prescribe TNF-α inhibitors, given that 10 TNF-α inhibitor biosimilars and two rituximab biosimilars have Food and Drug Administration (FDA) approval.

Methods
A 19-question self-administered online survey was conducted from 6 May to 1 June 2019, and fielded by WebMD, LLC. Rheumatologists (n = 9050) who were members of Medscape.com and its partner panels were invited to participate. Likert and other rating scales were used to collect responses, which were summarized descriptively.

Results
Responses were obtained from 320 board-certified US rheumatologists, 85% of whom were fellows of the ACR. Nearly all respondents were familiar with the FDA definition of a biosimilar product and were aware that an infliximab biosimilar was FDA approved; fewer realized that adalimumab, etanercept and rituximab biosimilars were also FDA approved. Most respondents (84%) were aware that an approved biosimilar was not automatically deemed interchangeable by the FDA. Rheumatologists were more likely to initiate biosimilar treatment for a biologic treatment-naïve patient with RA (73%) than they were to switch to the biosimilar for a patient with RA doing well on the reference product (35%).

Conclusions
The results of this survey suggest that US rheumatologists have a good understanding and acceptance of biosimilar products, particularly for the initiation of treatment in biologic-naïve individuals. They were hesitant to switch from a reference product to a biosimilar for a patient doing well on the reference product. Additional education on biosimilars is required to help inform treatment decisions by rheumatologists.
A plain language summary of this article has been uploaded as supplementary material, available at Rheumatology online.
Cannabis use assessment and its impact on pain in rheumatologic diseases: a systematic review and meta-analysis
Authors: Guillouard M , Authier N , Pereira B , Soubrier M , Mathieu S 
Published: August 2020

AbstractObjectivesDespite classic analgesic or effective treatments in rheumatic diseases, such as synthetic DMARDs in RA, patients remain in pain and often turn to non-prescribed pharmacological alternatives, such as cannabis self-therapeutic use. However, this medical use of cannabis has not been thoroughly studied.MethodsWe performed a systematic literature review up to June 2020. The incidence of cannabis consumption was calculated by metaproportion. Differences between cannabis users and non-users were expressed as standardized mean differences using the inverse-variance method. We also assessed the effects of cannabis on pain.ResultsA total of 2900 patients reported cannabis consumption in a sample of 10 873 patients [incidence 40.4% (95% confidence interval (CI): 0.28, 0.54)], and 15.3% (95% CI: 0.07, 0.27) specified that they were currently taking cannabis. Cannabis use was higher in the four fibromyalgia studies [68.2% (95% CI: 0.41, 0.90), n = 611] compared with seven articles concerning RA or lupus [26.0% (95% CI: 0.14, 0.41), n = 8168]. Cannabis consumption was associated with a decrease in pain intensity [VAS pain at baseline 8.2 (2.9) vs 5.6 (3.5) mm over time; pooled effect size −1.75 (95% CI: −2.75, −0.76)]. Cannabis users were younger [58.4 (11.4) vs 63.6 (12.1) years; P &lt;0.001], more often smokers [OR 2.91 (95% CI: 1.84, 4.60)] or unemployed [OR 2.40 (95% CI: 1.31, 4.40)], and had higher pain intensity [5.0 (2.4) vs 4.1(2.6) mm; P &lt;0.001] than non-users.ConclusionNearly 20% of patients suffering from rheumatologic diseases actively consume cannabis, with an improvement in pain. The issue of cannabis use in the management of these patients should be addressed during medical consultation, essentially with cannabis-based standardized pharmaceutical products.
Morbidity and mortality in antiphospholipid syndrome based on cluster analysis: a 10-year longitudinal cohort study
Authors: Ogata Yusuke , Fujieda Yuichiro , Sugawara Masanari , Sato Taiki , Ohnishi Naoki , Kono Michihito , Kato Masaru , Oku Kenji , Amengual Olga , Atsumi Tatsuya 
Published: August 2020

Abstract

Objective
Using cluster analysis, to identify the subgroup of patients with APS with the poorest prognosis and clarify the characteristics of that subgroup.

Methods
This is a longitudinal retrospective cohort study of APS patients. Using clinical data and the profile of aPL, cluster analysis was performed to classify the patients into subgroups. Events were defined as thrombosis, severe bleeding, and mortality.

Results
A total of 168 patients with APS were included. Cluster analysis classified the patients into three subgroups; Cluster A (n = 61): secondary APS, Cluster B (n = 56): accumulation of cardiovascular risks and arterial thrombosis, Cluster C (n = 61): triple positivity of aPL and venous thrombosis. Cluster B showed significantly higher frequency of the events and higher mortality compared with the other clusters (P = 0.0112 for B vs A and P = 0.0471 for B vs C).

Conclusion
Using cluster analysis, we clarified the characteristics of the APS patients with the poorest prognosis. Risk factors for cardiovascular disease may further increase events in patients with APS.
ASSESSING RADIATION EXPOSURE INSIDE THE EARTH’S ATMOSPHERE
Authors: Tezari Anastasia , Paschalis Pavlos , Mavromichalaki Helen , Karaiskos Pantelis , Crosby Norma , Dierckxsens Mark 
Published: August 2020

Abstract
The study of the particle showers created inside the Earth’s atmosphere due to interactions of cosmic rays of solar and galactic origin is of great importance for the determination of the radiation impact on technological and biological systems. DYASTIMA is a Geant4-based software application that simulates the evolution of secondary particle cascades inside the atmosphere of Earth. DYASTIMA-R is a new feature especially created for assessing the exposure of flight-personnel and frequent flyers to cosmic radiation by performing calculations of radiobiological quantities, such as dose and equivalent dose rates for several air-flight scenarios. In this work, the validation of DYASTIMA/DYASTIMA-R, according to internationally accepted ICRP and ICRU standards, is discussed. Initial results for radiobiological quantities for several air-flight scenarios are also included. The results for specific scenarios calculated by DYASTIMA/DYASTIMA-R are provided as a federated product through the European Space Agency Space Situational Awareness Space Weather Service Centre Network.
Getting a Job, Again: New Evidence against Subjective Well-Being Scarring
Authors: Rauf Tamkinat 
Published: August 2020

Abstract
Previous research finds that unemployment leaves permanent “scars” on subjective well-being (SWB) that remain even after reemployment. However, this research systematically overweighs long-term unemployment, inaccurately measures employment transitions, often does not track individuals long enough to substantiate scarring, and does not always account for age-related changes in well-being. This paper uses event history calendars from the Panel Study of Income Dynamics to track complete monthly employment histories of prime working age Americans over a 17-year period, and accounts for the temporal relationships between SWB, age, and employment transitions using a novel fixed-effects formulation. The results suggest that there is some variation in patterns of recovery by employment stability after job loss, but no significant differences were observed by the duration of unemployment spells. Within 2 years of reemployment, average SWB levels reverted toward baseline trajectories across all groups, showing no evidence of scarring. This study brings unemployment literature into better alignment with research on resilience and adaptation. The findings also highlight some limitations of the construct of SWB for assessing the long-term costs of unemployment.
Threat and Emotions: Mobilizing and Attitudinal Outcomes of a Ballistic Missile Scare
Authors: Bergstrand Kelly , Robertson Christopher 
Published: August 2020

Abstract
This study examines the false ballistic missile alert that occurred in Hawaii in 2018, which presented a unique opportunity for assessing the civic and mobilizing outcomes of a threat. In the days that followed the scare, we conducted an online experiment to investigate its effects on willingness to engage in activism and concerns about broader issues. Our results show that emotions serve as an important mechanism for channeling threat experiences into concern about specific causes. Those most emotionally affected by the missile scare in Hawaii thought it more important to engage in activities to control the spread of nuclear weapons, protect the environment, and address climate change, relative to a control group on the mainland. Both the intensity and type of emotion play a role. These results shed light on the role of threats and grievances in shaping concern about social and environmental issues. They also suggest that emotions may serve as a bridge that can connect personal, concrete, lived-experiences to more abstract, complex, or future-oriented issues and grievances.
Development of an online tool for linking behavior change techniques and mechanisms of action based on triangulation of findings from literature synthesis and expert consensus
Authors: Johnston Marie , Carey Rachel N , Connell Bohlen Lauren E , Johnston Derek W , Rothman Alexander J , de Bruin Marijn , Kelly Michael P , Groarke Hilary , Michie Susan 
Published: August 2020

Abstract
Researchers, practitioners, and policymakers develop interventions to change behavior based on their understanding of how behavior change techniques (BCTs) impact the determinants of behavior. A transparent, systematic, and accessible method of linking BCTs with the processes through which they change behavior (i.e., their mechanisms of action [MoAs]) would advance the understanding of intervention effects and improve theory and intervention development. The purpose of this study is to triangulate evidence for hypothesized BCT–MoA links obtained in two previous studies and present the results in an interactive, online tool. Two previous studies generated evidence on links between 56 BCTs and 26 MoAs based on their frequency in literature synthesis and on expert consensus. Concordance between the findings of the two studies was examined using multilevel modeling. Uncertainties and differences between the two studies were reconciled by 16 behavior change experts using consensus development methods. The resulting evidence was used to generate an online tool. The two studies showed concordance for 25 of the 26 MoAs and agreement for 37 links and for 460 “nonlinks.” A further 55 links were resolved by consensus (total of 92 [37 + 55] hypothesized BCT–MoA links). Full data on 1,456 possible links was incorporated into the online interactive Theory and Technique Tool (https://theoryandtechniquetool.humanbehaviourchange.org/). This triangulation of two distinct sources of evidence provides guidance on how BCTs may affect the mechanisms that change behavior and is available as a resource for behavior change intervention designers, researchers and theorists, supporting intervention design, research synthesis, and collaborative research.