bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract SY01-03: The gold standard cancer diagnosis: Studies of physician variability, interpretive behavior, and the impact of AI
Authors: Elmore Joann 
Published: July 2021

Abstract
The current gold standard for cancer diagnoses is based on pathologists' visual inspection of tissue sections. However, our research has found concerning levels of inter-observer and intra-observer variability among pathologists. Our prior work in melanoma shows that current diagnoses within the disease spectrum from benign nevi to melanoma in situ to invasive melanoma are neither reproducible nor accurate, yielding estimates that ~17% of all diagnoses for melanocytic lesions in the US are incorrect (Elmore et al. BMJ 2017). A study conducted by our team in breast pathology quantified the magnitude of diagnostic agreement among pathologists compared with a gold standard consensus reference: among DCIS cases, 16% of interpretations were discordant, while among atypia cases 52% of interpretations were discordant (Elmore et al. JAMA 2015). While computer systems, such as computer aided detection (CAD) tools, have been widely integrated into clinical practice to aid the interpretative and diagnostic process, our work has also found that the use of CAD can be associated with increases in potential harms, including higher recall and biopsy rates for screening mammography (Fenton et al. NEJM 2007). Given the critical need to improve the quality of our current diagnostic and prognostic capabilities, our multidisciplinary research team is conducting several studies that involve the development and integration of AI/machine learning and eye-tracking across clinical contexts. The challenges and implications associated with “gold standard” definitions for diagnoses, with data sharing infrastructure and with the eventual impact of AI on the human interface will be discussed.
Citation Format: Joann Elmore. The gold standard cancer diagnosis: Studies of physician variability, interpretive behavior, and the impact of AI [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr SY01-03.
Abstract SY19-01: TGFβ and immune evasion in metastatic cancer
Authors: Massagué Joan 
Published: July 2021

Abstract
TGF-β and Immune Evasion in Metastatic Cancer Transforming growthfactor-β (TGF-β) is a major regulator of development,immune homeostasis, tissue regeneration, and cancer. TGF-β signaling suppresses tumor initiation but promotestumor progression through mechanisms that are increasingly understood. TGF-β inhibitsthe expansion and function of many components of the immune system and itspresence in the tumor microenvironment limits the effectiveness of current immunotherapies. To betterdefine the potential benefit of targeting TGF-β in cancer, we investigated therole of TGF-β in metastasis. Metastasis, the main cause of deathfrom cancer, is driven by stem-like disseminated cancer cells (“metastasisinitiating cells”, MICs) capable of reversible quiescence, immune evasion, organ-specificoutgrowth, and drug resistance. We developed models oflung adenocarcinoma (LUAD) metastatic dormancy and outbreak by isolating MICs thatrecapitulate the developmental and regenerative phenotypes of carcinoma cellsin human metastases. We find that TGF-β in thetumor microenvironment has different tumorigenic effects on early-stageprogenitor MICs and their progenies. In SOX2-rich early progenitor MICs, TGF-βinduces dormancy by imposing a growth-inhibited epithelial to mesenchymaltransition (EMT). Pharmacologic inhibition of TGF-β in this context causes MICsto exit from this immune evasive dormancy and become exposed to immune attack. Incontrast, SOX9-rich MIC progeny cells respond to TGF-β with an EMT that iscoupled to expression of fibrogenic cytokines. Deletion of TGF-β receptor orits fibrogenic target genes in the carcinoma cells prevents intratumoralfibrosis and inhibits metastatic outgrowth. These insights suggest that targetingTGF-β in metastatic cancer can improve treatment outcomes by forcing MICs outof immune evasive quiescence and suppressing intra-tumoral fibrosis, inaddition to relieving innate and adaptive immunity from TGF-β mediated inhibition.
Citation Format: Joan Massagué. TGFβ and immune evasion in metastatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr SY19-01.
Abstract SY26-01: Targeting natural ligands for TCR engineering
Authors: Schoenberger Stephen P. 
Published: July 2021

Abstract
Neoantigens (NeoAg) offer the potential to directtherapeutic T cell responses to immunogenic mutations exclusively expressed bytumors. Most strategies for their identification select potentialligands for CD8+ T cells rather than for CD4+ T cells,despite the extensive literature showing functional cooperation between thesesubsets. To better understand CD4-CD8synergy in anti-tumor immunity, we have applied a novel functional approach toidentify the subset of expressed mutations targeted as NeoAg by natural CD4+and CD8+ T cell responses to a poorly-immunogenic spontaneoussquamous cell tumor, SCC VII. We demonstrate that a single mutation (Cltc H129&gt;Q) that is recognized byboth subsets is capable of eradicating large established SCCVII tumors in thesetting of therapeutic vaccination provided the relevant epitopes whenphysically linked. Single-cell TCR analysis revealed that the endogenous CD4+T cell response against this epitope comprises both low-affinity CD4+-dependentand high-affinity CD4+-independent receptors, with the latterdisplaying superior capacity in promoting prophylactic and therapeutic CD8+T cell-mediated immunity against the MHC class I+ class II−tumors in the setting of adoptive cellular therapy. These findings demonstratethat linked CD4+ T cell help enables potent therapeuticNeoAg-specific vaccination and provides instructive insights into the qualityof TCRs mediating this effect.
Citation Format: Stephen P. Schoenberger. Targeting natural ligands for TCR engineering [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr SY26-01.
Abstract 17: Adaptation and Assessment of a Text Message Cessation Intervention for Tobacco Users in Viet Nam
Authors: Shelley Donna , Jiang Nan , Cleland Charles , Nguyen Trang , Abroms Lorien , Nguyen Nam 
Published: July 2021

Abstract
Purpose: Text message (i.e., short message service, SMS) smoking cessation interventions have demonstrated efficacy, but most evaluations were conducted in high-income countries. We assessed the feasibility, acceptability and preliminary efficacy of a smoking cessation SMS intervention adapted to the sociocultural context, language and communication styles of Vietnamese smokers.
Methods: Participants were current adult cigarette-only or dual cigarette and waterpipe users. We adapted a message library from two SMS smoking cessation programs with proven efficacy in increasing quit rates in the US. The iterative adaptation process included focus groups with 58 smokers to provide data on culturally relevant patterns of tobacco use and to assess message preferences. We then pilot tested (n=40) a 6-week SMS intervention using brief text surveys to obtain real time feedback on messages and conducted post-test interviews (n=10) to inform further adaptation. Finally, we randomized 100 smokers to the SMS intervention (including bidirectional messages and key words to generate additional support) vs. weekly text assessments of tobacco use. Surveys assessed engagement and acceptability at 6 weeks, cessation at 6 and 12 weeks.
Results: Significant modifications were made in terms of content (e.g. preference for negative framing of health risks, and focus on enhancing refusal skills) and tone (e.g., preferences for action-oriented advice for craving management). We found high rates of engagement (e.g. 82% usually or always read messages) and satisfaction with the SMS program (e.g. 70% satisfied, 24% very satisfied).
Conclusion: Intervention participants suggested enhancing the program with additional telephone support, extending the length of the program, and adding images and more interactive content. This pilot study provided support for the feasibility and acceptability of culturally-adapted SMS smoking cessation treatment among smokers in Viet Nam. It also showed promising early efficacy in promoting abstinence. Future studies are needed to assess whether, with additional modifications, the program is associated with long-term abstinence.
Citation Format: Donna Shelley, Nan Jiang, Charles Cleland, Trang Nguyen, Lorien Abroms, Nam Nguyen. Adaptation and Assessment of a Text Message Cessation Intervention for Tobacco Users in Viet Nam [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 17.
Comprehensive Proteomics Profiling Reveals Circulating Biomarkers of Hypertrophic Cardiomyopathy
Authors: Shimada Yuichi J. , Raita Yoshihiko , Liang Lusha W. , Maurer Mathew S. , Hasegawa Kohei , Fifer Michael A. , Reilly Muredach P. 
Published: July 2021

Background:
Hypertrophic cardiomyopathy (HCM) is caused by mutations in the genes coding for proteins essential in normal myocardial contraction. However, it remains unclear through which molecular pathways gene mutations mediate the development of HCM. The objectives were to determine plasma protein biomarkers of HCM and to reveal molecular pathways differentially regulated in HCM.

Methods:
We conducted a multicenter case-control study of cases with HCM and controls with hypertensive left ventricular hypertrophy. We performed plasma proteomics profiling of 1681 proteins. We performed a sparse partial least squares discriminant analysis to develop a proteomics-based discrimination model with data from 1 institution (ie, the training set). We tested the discriminative ability in independent samples from the other institution (ie, the test set). As an exploratory analysis, we executed pathway analysis of significantly dysregulated proteins. Pathways with false discovery rate <0.05 were declared positive.

Results:
The study included 266 cases and 167 controls (n=308 in the training set; n=125 in the test set). Using the proteomics-based model derived from the training set, the area under the receiver operating characteristic curve was 0.89 (95% CI, 0.83–0.94) in the test set. Pathway analysis revealed that the Ras-MAPK (mitogen-activated protein kinase) pathway, along with its upstream and downstream pathways, was upregulated in HCM. Pathways involved in inflammation and fibrosis—for example, the TGF (transforming growth factor)-β pathway—were also upregulated.

Conclusions:
This study serves as the largest-scale investigation with the most comprehensive proteomics profiling in HCM, revealing circulating biomarkers and exhibiting both novel (eg, Ras-MAPK) and known (eg, TGF-β) pathways differentially regulated in HCM.
Interleukin-1α Is a Central Regulator of Leukocyte-Endothelial Adhesion in Myocardial Infarction and in Chronic Kidney Disease
Authors: Schunk Stefan J. , Triem Sarah , Schmit David , Zewinger Stephen , Sarakpi Tamim , Becker Ellen , Hütter Gregor , Wrublewsky Selina , Küting Fabienne , Hohl Mathias , Alansary Dalia , Prates Roma Leticia , Lipp Peter , Möllmann Julia , Lehrke Michael , Laschke Matthias W. , Menger Michael D. , Kramann Rafael , Boor Peter , Jahnen-Dechent Willi , März Winfried , Böhm Michael , Laufs Ulrich , Niemeyer Barbara A. , Fliser Danilo , Ampofo Emmanuel , Speer Thimoteus 
Published: July 2021

Background:
Cardiovascular diseases and chronic kidney disease (CKD) are highly prevalent, aggravate each other, and account for substantial mortality. Both conditions are characterized by activation of the innate immune system. The alarmin interleukin-1α (IL-1α) is expressed in a variety of cell types promoting (sterile) systemic inflammation. The aim of the present study was to examine the role of IL-1α in mediating inflammation in the setting of acute myocardial infarction (AMI) and CKD.

Methods:

We assessed the expression of IL-1α on the surface of monocytes from patients with AMI and patients with CKD and determined its association with atherosclerotic cardiovascular disease events during follow-up in an explorative clinical study. Furthermore, we assessed the inflammatory effects of IL-1α in several organ injury models in
Il1a
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mice and investigated the underlying mechanisms in vitro in monocytes and endothelial cells.

Results:
IL-1α is strongly expressed on the surface of monocytes from patients with AMI and CKD compared with healthy controls. Higher IL-1α surface expression on monocytes from patients with AMI and CKD was associated with a higher risk for atherosclerotic cardiovascular disease events, which underlines the clinical relevance of IL-1α. In mice, IL-1α, but not IL-1β, mediates leukocyte-endothelial adhesion as determined by intravital microscopy. IL-1α promotes accumulation of macrophages and neutrophils in inflamed tissue in vivo. Furthermore, IL-1α on monocytes stimulates their homing at sites of vascular injury. A variety of stimuli such as free fatty acids or oxalate crystals induce IL-1α surface expression and release by monocytes, which then mediates their adhesion to the endothelium via IL-1 receptor-1. IL-1α also promotes expression of the VCAM-1 (vascular cell adhesion molecule-1) on endothelial cells, thereby fostering the adhesion of circulating leukocytes. IL-1α induces inflammatory injury after experimental AMI, and abrogation of IL-1α prevents the development of CKD in oxalate or adenine-fed mice.

Conclusions:
IL-1α represents a key mediator of leukocyte-endothelial adhesion and inflammation in AMI and CKD. Inhibition of IL-1α may serve as a novel anti-inflammatory treatment strategy.
Stoma and intestine ultrastructure of the marine free-living nematode Odontophora deconincki (Nematoda: Araeolaimida: Axonolaimidae)
Authors: Fedyaeva Maria A. , Tchesunov Alexei V. 
Published: July 2021

Summary
The fine morphology of the buccal capsule and intestine (midgut) of the marine free-living nematode Odontophora deconincki was investigated. The cheilostome is armed with six equal claw-like odontia that can evert radially by opening the mouth. Light-refracting accessory buccal structures within the cheilostomatal cuticle alternate with odontia and consist of two elements: anterior armilloids and posterior granular armilliths. The buccal cavity (pharyngostome) is surrounded by a complex of longitudinal and oblique muscles partially attached to the cheilostome cuticle at the sites of the accessory buccal structures and enabling a wide opening of the mouth. With the described stoma condition, the nematode probably scrapes food particles from the substrate surface. In cross-section, the midgut consists of 5-7 cells that appear uniform throughout its length. An extracellular matrix (glycocalyx) over the microvillar brush varies in thickness and stratification depending on presence or absence of food content in the lumen. Abundant spherocrystals (globular inclusions with concentric striations) were present in all gut cells. No indication of endocytosis or digestive vacuoles was observed in the gut cells and extracellular digestion predominates. Most specimens had a gut content formed from a long cylinder of compressed flocculent material with some barely identifiable components and few spherocrystals expelled from the enterocytes. We assume that the nematode diet comprises a wide range of objects, mainly eukariotic epigrowth organisms, which are shorn off and scraped from the surface of sand grains and then ingested.
Lutherans and Pentecostals in Dialogue
Authors: Grenholm Cristina , Habib Zeiler Johannes , Josefsson Ulrik 
Published: July 2021

Abstract
This article provides an analysis of the ongoing ecumenical conversation between Lutherans and Pentecostals in Sweden. The material used in the article consists of written documents combined with references to the experiences from the participants in the dialogue. The aim of the article is threefold: first, to describe the setting, development, and character of the conversation; second, to analyze the contents of the conversation with a focus on the theme of pneumatology; and third, to relate this analysis to the ongoing international Lutheran-Pentecostal dialogue. A theoretical reference point is the growing field of receptive ecumenism, which is described as a third way of ecumenism. One result from this study is that more consensus is reached in areas of societal ministry and advocacy than concerning doctrinal issues. The analysis shows deep ecumenical ambitions built on trust but also reveals some difficulties on the path toward Christian unity.
Development Stages of Islamic Movements in the Pashtun Tribal Environment: The Case of the Rawshaniyya and Beyond
Authors: Andreyev Sergei 
Published: July 2021

The Rawshani movement is the first well-documented example of supra-tribal unification and subsequent successful integration of the movement’s leaders into the alien state structures. But by no means is it an isolated phenomenon in Pashtun history. Similar pattern of religion-motivated supra-tribal unification, which should be considered as a product of historical relationships of power, remerged inter alia during more recent crises in the Afghan history. Due to the volatile nature of the Afghan state fluctuating between tribalism and ethnic pluralistic participation, military and Islamic dimensions have always been of paramount importance for state-community relations where religion, tribalism and ethnicity were often the means of state’s control of social resistance and its vehicles. In the time of crises, religion-inspired militia-type independent military formations were able to challenge the might of the state and occasionally even initiate the incipient state formation opposed to the communal institutions and those of the old regime. When this community-based military activity went beyond the scope of traditional annual cycle of violence it often acquired a supra-tribal or ethnic and regional dimension, which was legitimised by the Islamic ideology and institutions.
This article offers some directions towards making a calibration tool or even identifying a pattern that may be used as an epistemological paradigm that may provide a sense of orientation and bearing in the intricacies of a complex historical interaction between Pashtun Islam, tribes and state.
Reconnecting Forward: Nasjonal Samling’s Apocalyptic Temporality as a Key to the Fascist Regime of Historicity
Authors: Wilhelmsen Fredrik 
Published: July 2021

Abstract
This article analyses the conception of history or ‘regime of historicity’ structuring the ideology of the Norwegian fascist party, Nasjonal Samling (1933–1945). It highlights the value of the theory of palingenetic ultranationalism to the understanding of fascist temporality generically and specifically. Generically, because the findings show how Nasjonal Samling’s regime of historicity followed the same structure of revolution and eternity, decay and rebirth, as other fascist movements did. Specifically, because it also shows how Nasjonal Samling drew heavily on Norwegian national myths. The ideologues of ns recoded these myths, and integrated them into their own palingenetic, apocalyptic, and – after 1935 – antisemitic grand narratives. These crystallized in a triadic scheme, forming a fascist regime of historicity, structured around the myth of past greatness, followed by decadence, combined with a fantasy of a future revolutionary rebirth of the nation.
“People are gazing” — An Interpretative Phenomenological Analysis of Viewing Velázquez
Authors: Starr Rachel A. , Smith Jonathan A. 
Published: July 2021

Abstract
What is it like to look at a painting? Research into art viewing raises challenging considerations. Factors concerning the artwork, the viewer, the role of context, as well as conceptualisation of the response and how to measure it, present a wealth of complexity. Although such a topic might arguably lend itself to qualitative exploration, work of this type is notably sparse. In the research reported here, Interpretative Phenomenological Analysis was used to explore the experience of looking at a painting. Twelve participants were individually interviewed whilst viewing Las Meninas by Diego Velázquez. Three Master Themes were developed, the first of which, ‘The Gaze’, is presented in depth. Experiences of looking and being looked at by figures in the image are described and considered in relation to social and philosophical understandings of eye contact, seeing and being seen.
History of Medicine in Eastern Europe: Sexual Medicine and Women’s Reproductive Health in Czechoslovakia, Poland, and Hungary
Authors: Lišková Kateřina 
Published: July 2021

Abstract
Specific developments in reproductive health occurred in Eastern Europe, especially in the second half of the twentieth century. During state socialism, it was experts, not social movements, who furthered the agenda of women’s health and sexuality. New analyses from the region and written mostly by authors who speak the local languages attest to the wealth of histories, highlighting different timelines of reproductive health developments, the unexpected causes behind them, and the social actors and institutions which played decisive roles.
The impacts of cloud-radiative changes on poleward atmospheric and oceanic energy transport in a warmer climate
Authors: Chen Yong-Jhih , Hwang Yen-Ting , Ceppi Paulo 
Published: July 2021

AbstractBased on theory and climate model experiments, previous studies suggest most of the uncertainties in projected future changes in meridional energy transport and zonal mean surface temperature can be attributed to cloud feedback. To investigate how radiative and dynamical adjustments modify the influence of cloud-radiative changes on energy transport, this study applies a cloud-locking technique in a fully-coupled climate model, CESM. Under global warming, the impacts of cloud-radiative changes on the meridional energy transport are asymmetric in the two hemispheres. In the Northern Hemisphere, the cloud-radiative changes have little impact on energy transport, because 89% of the cloud-induced heating is balanced locally by increasing outgoing longwave radiation. In the Southern Hemisphere, on the other hand, cloud-induced dynamical changes in the atmosphere and the ocean cause enhanced poleward energy transport, accounting for most of the increase in energy transport under warming. Our experiments highlight that the local longwave radiation adjustment induced by temperature variation can partially offset the impacts of cloud-radiative changes on energy transport, making the estimated impacts smaller than those obtained from directly integrating cloud-radiative changes in previous studies. It is also demonstrated that the cloud-radiative impacts on temperature and energy transport can be significantly modulated by the oceanic circulation, suggesting the necessity of considering atmospheric-oceanic coupling when estimating the impacts of cloud-radiative changes on the climate system.