bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P4-07-30: Residual lymphovascular invasion: Predicts the outcome of neoadjuvant chemotherapy in locally advanced breast cancer
Authors: Elemam Omima , Elnaghi Khaled , Emarah Ziad , Alghanami Hossam , Abdelkhalek Seham 
Published: March 2022

Abstract
Background: Lymphovascular invasion (LVI) is known to be associated with a poor outcome in breast cancer patients. It indicates a highly proliferative cancer. Few studies examined the value of LVI as a predictor for outcome after neoadjuvant chemotherapy (NAC). The aim of this study to look for an association between survival outcomes and clinicopathological features in locally advanced breast cancer patients treated with NAC and to identify the predictors of nodal pathologic complete response (PCR). Methods:This study is a retrospective analysis of 224 women with locally advanced breast cancer who underwent NAC between 2011-2020. Kaplan-Meier analyses were used to assess the associations between disease-free survival (DFS) and overall survival (OS) and all clinicopathological variables including LVI in breast surgical specimens following NAC. Associations between nodal PCR and all clinicopathologic variables were assessed Results:Median follow-up was 29.9 months. Absence of nodal PCR (p.000), positive family history (p .027), clinical T4 (p.049), pathological TNM staging (p.016), high tumor grade (p .020),triple negative disease(p .016) and absence of tumor PCR (p.001) were associated with worse disease free survival. Absence of nodal PCR (p.002), high BMI (p.039), multicentric disease (p.026), high tumor grade, triple negative disease (p.018), and absence of tumor PCR (p.005) were associated with worse overall survival. LVI was found in 53 of surgical specimens (23.7%). It was associated with worse DFS (HR) (2.967) 95% CI (1.7-4.9), p.000 and overall survival (HR) (3.05) 95% CI (1.525-6.09), p.002). Nodal PCR significantly correlated with T stage (p .013), LVI (p.000), ER status (p.004), PR status (p.003), Her2neu status and IHC score (p.000), tumor subtype (p.000), tumor PCR (p.000), DFS (p.000), and OS (p.000). Conclusion:LVI is significantly associated with worse DFS and OS in locally advanced breast cancer patients treated with NAC. This data confirmed the previously published recommendation to add LVI to the pathological staging system. LVI may be further explored as a guide for adjuvant treatment options in clinical trials. Nodal PCR is another significant predictor of outcome and is associated significantly with tumor PCR and LVI. Both tumor PCR and LVI can be used as criteria for axillary surgery omission in future trials.
Citation Format: Omima Elemam, Khaled Elnaghi, Ziad Emarah, Hossam Alghanami, Seham Abdelkhalek. Residual lymphovascular invasion: Predicts the outcome of neoadjuvant chemotherapy in locally advanced breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-07-30.
Abstract P5-05-10: Inhibition of FASN as a potential treatment of advanced therapy-resistant breast cancer
Authors: Balinda Henriette U 
Published: March 2022

Abstract
INTRODUCTION: The majority of breast cancers are estrogen receptor (ERα) positive making endocrine therapy a mainstay for these patients. Unfortunately, resistance to endocrine therapy is a common occurrence. Fatty acid synthase (FASN) is a key enzyme in lipid biosynthesis and is overexpressed in more aggressive and therapy-resistant tumors, including breast cancers. METHODS: The effect of the FASN inhibitor TVB-3166 on ERα expression and cell growth was characterized in tamoxifen-resistant and fulvestrant-resistant cell lines, xenografts, and patient explants. Subcellular localization of ERα was assessed using subcellular fractionations. Palmitoylation and ubiquitination of ERα were assessed by immunoprecipitation. ERα and p-eIF2α protein levels were analyzed by western blotting after treatment with TVB-3166 with or without the addition of palmitate or BAPTA. RESULTS: TVB-3166 treatment leads to a marked inhibition of proliferation in tamoxifen-resistant and fulvestrant-resistant cells compared to the parental cells. Additionally, TVB-3166 significantly inhibited tamoxifen-resistant breast tumor growth in mice and decreased proliferation of primary tumor explants compared to untreated controls. FASN inhibition significantly reduced ERα levels most prominently in endocrine resistant cells and altered its subcellular localization. Furthermore, we showed that the reduction of ERα expression upon TVB-3166 treatment is mediated through the induction of endoplasmic reticulum stress. CONCLUSION: Our preclinical data provide evidence that FASN inhibition by TVB-3166 presents a promising therapeutic strategy for treatment of endocrine-resistant breast cancer. Further clinical development of FASN inhibitors for endocrine resistant breast cancer should be considered.
Citation Format: Henriette U Balinda. Inhibition of FASN as a potential treatment of advanced therapy-resistant breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-05-10.
Abstract P5-11-03: Altered adipose-derived mesenchymal stem/stromal cells induced by obesity in the breast cancer microenvironment
Authors: Ritter Andreas , Roth Susanne , Friemel Alexandra , Kreis Nina-Naomi , Louwen Frank , Solbach Christine , Yuan Juping 
Published: March 2022

Abstract
It is well documented that obesity, characterized by an increased body mass index (BMI≥30), is an important risk factor for the development of aggressive breast cancer (BC), which is associated with a reduced overall survival rate and decreased treatment response. The tumor microenvironment (TME), a cellular network majorly constructed by adipocytes, adipose-derived mesenchymal stem/stromal cells (bASCs) and immune cells, impacts progression of breast cancer and treatment response of patients. This study aims to examine how obesity influences the functional characteristics of bASCs in comparison to lean bASCs in the TME. To address this issue, various molecular, biological and cellular methods are applied including transcriptomic profiling and functional assays to characterize at first the features of bASCs in the TME (adjacent to tumor; -aT/distant to tumor; -dT) in obese (ob-) and lean (ln-) bASCs (n=5, for each group) patients with breast cancer. Second, based on the transcriptomic data, we investigated the interaction of bASCs with triple negative as well as triple positive BC cell lines in 3D-spheroids and in standard 2D-cell culture conditions.Indicated by the gene signature the TME shifts bASCs towards a cancer supporting phenotype with a significant deregulated protein expression, cytokine/chemokine secretion, and reduced differentiation capacity. These changes affect critically the cell-cell interaction of BC cells with bASCs. bASCs isolated adjacent to the tumor increase the malignancy of BCs by stimulating the proliferation, migration, invasion and chemoresistance of these cells significantly. These observed effects are further enhanced by ob-aT bASCs. In conclusion, this study identifies over 900 genes deregulated in bASCs adjacent to breast cancer. Many of these genes are associated with pathways known for the development of malignant cells. Moreover, it clarifies differences in obese versus lean bASCs and their impacts on progression of breast cancer cells.
Citation Format: Andreas Ritter, Susanne Roth, Alexandra Friemel, Nina-Naomi Kreis, Frank Louwen, Christine Solbach, Juping Yuan. Altered adipose-derived mesenchymal stem/stromal cells induced by obesity in the breast cancer microenvironment [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-11-03.
Abstract WS2-1: Genome editing in human organoids as new models for discovery
Authors: Rosenbluth JM 
Published: March 2022

Abstract
Use of human organoids as new models for discovery. Despite significant advances, there are circumstances where mouse models remain inadequate to model cancer. Human organoid cultures are becoming established as a useful adjunct to mouse models because they enable the propagation of both normal and cancerous tissues in the lab for functional studies, disease modeling, and drug screening. Organoids can be generated from induced pluripotent stem cells or directly from donor tissue samples (e.g. normal breast tissue or tumors). In the latter approach, breast organoid cultures are grown in a hydrogel that mimics the basement membrane and are bathed in a cocktail of growth factors, vitamins, and compounds that mimic the microenvironment provided by stroma, resulting in the growth of cells in a polarized fashion to recapitulate breast acinar- and duct-like structures. Breast epithelial cells within organoids are able to differentiate into all of the major mammary epithelial lineages, and hence organoids can be used to study several types of epithelial lineages and their relative contributions to tumor development. In addition, breast cancer organoids can be used to expand heterogeneous populations of tumor cells for in vitro assays. For example, genome editing approaches can be used to model mutations associated with breast cancer, and compound screening approaches can facilitate target discovery. In this educational talk, we will review some of these recent advances, consider advantages and disadvantages of this model system, and discuss some practical considerations for bio-banking efforts and downstream applications.
Citation Format: JM Rosenbluth. Genome editing in human organoids as new models for discovery [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr WS2-1.
Are You a TMBeliever? Mutations and Atezolizumab Response in Solid Tumors
Authors: Maron Steven B. , Klempner Samuel J. 
Published: March 2022

Summary:
Optimizing the utility of tumor mutational burden in solid tumors remains an unmet need and a clinical knowledge gap. Using a centrally determined cutoff of ≥16 mut/Mb, Friedman and colleagues demonstrate an ability to enrich for atezolizumab response in a pretreated pan-cancer multibasket study.
See related article by Friedman et al., p. 654 (4).
Therapeutic and Prognostic Significance of Arachidonic Acid in Heart Failure
Authors: Ma Ke , Yang Jie , Shao Yihui , Li Ping , Guo Hongchang , Wu Jianing , Zhu Yi , Zhang Hui , Zhang Xu , Du Jie , Li Yulin 
Published: March 2022

Background:
Accurate prediction of death is an unmet need in patients with acute decompensated heart failure (HF). Arachidonic acid (AA) metabolites play an important role in the multiple pathophysiological processes. We aimed to develop an AA score to accurately predict mortality in patients with acute decompensated HF and explore the causal relationship between the AA predictors and HF.

Methods:
The serum AA metabolites was measured in patients with acute decompensated HF (discovery cohort n=419; validation cohort n=386) by mass spectroscopy. We assessed the prognostic importance of AA metabolites for 1-year death using Cox regression and machine learning approaches. A machine learning-based AA score for predicting 1-year death was created and validated. We explored the mechanisms using transcriptome and functional experiments in a mouse model of early ischemic cardiomyopathy.

Results:

Among the 27 AA metabolites, elevated 14,15-DHET/14,15-EET ratio was the strongest predictor of 1-year death (hazard ratio, 2.10,
P
=3.1×10
−6
). Machine learning-based AA score using a combination of the 14,15-DHET/14,15-EET ratio, 14,15-DHET, PGD2, and 9-HETE performed best (area under the curve [AUC]: 0.85). The machine learning-based AA score provided incremental information to predict mortality beyond BNP (B-type natriuretic peptide; ΔAUC: 0.19), clinical score (ΔAUC: 0.09), and preexisting Acute Decompensated Heart Failure National Registry, Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure, and Get With The Guidelines Heart Failure scores (ΔAUC: 0.17, 0.17, 0.15, respectively). In the validation cohort, the AA score accurately predicted mortality (AUC:0.81). False-negative and false-positive findings, as classified by the BNP threshold, were correctly reclassified by the AA score (46.2% of false-negative and 84.5% of false-positive). In a murine model, the expression and enzymatic activity of sEH (soluble epoxide hydrolase) increased after myocardial infarction. Genetic deletion of sEH improved HF and the blockade of 14,15-EET abolished this cardioprotection. We mechanistically revealed the beneficial effect of 14,15-EET by impairing the activation of monocytes/macrophages.

Conclusions:
Our studies propose that the AA score predicts death in patients with acute decompensated HF and inhibiting sEH serves as a therapeutic target for treating HF.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT04108182.
Disparities in Stroke: Associating Socioeconomic Status With Long‐Term Functional Outcome After Mechanical Thrombectomy
Authors: Nguyen Anh V. Tran , Cortez Gustavo M. , Aghaebrahim Amin , Sauvageau Eric , Hanel Ricardo A. 
Published: March 2022

Background
Socioeconomic status is regarded as a significant predictor of poor outcomes after ischemic stroke. However, there is sparse evidence of its effect in patients undergoing mechanical thrombectomy. This study aimed to explore the effect of socioeconomic status on long‐term functional outcomes after mechanical thrombectomy.

Methods
A retrospective, self‐adjudicated, single‐center study comparing favorable and unfavorable functional outcomes through risk factors, demographic factors, and neighborhood socioeconomic status was performed. Functional outcome was defined by modified Rankin scale scores evaluated at 90 days after thrombectomy.

Results

Factors that were independently associated with favorable functional outcome included age (odds ratio [OR], 0.97; 95% CI, 0.96–0.98 [
P
<0.001]), baseline National Institutes of Health Stroke Scale scores (OR, 0.94; 95% CI, 0.92–0.97 [
P
<0.001]), baseline modified Rankin scale scores (OR, 3.02; 95%CI, 1.46–6.25 [
P
=0.003]), ischemic core size at presentation (OR, 0.47; 95% CI, 0.26–0.84 [
P
=0.011]), symptomatic intracranial hemorrhage (OR, 0.3; 95% CI, 0.14–0.66 [
P
=0.003]), puncture‐to‐recanalization time (OR, 0.99; 95% CI, 0.98–1.00 [
P
=0.007]), median income based on zip code (OR, 1.01; 95% CI, 1.00–1.02 [
P
=0.016]), and final modified thrombolysis in cerebral infarction (OR, 6.05; 95% CI, 2.23–16.08 [
P
<0.001]).

Conclusions
Patients from zip codes with higher median income who achieved successful reperfusion during mechanical thrombectomy were more likely to achieve a long‐term favorable functional outcome.
Annotation Curricula to Implicitly Train Non-Expert
Annotators
Authors: Lee Ji-Ung , Klie Jan-Christoph , Gurevych Iryna 
Published: March 2022

Abstract
Annotation studies often require annotators to familiarize themselves with the task, its annotation scheme, and the data domain. This can be overwhelming in the beginning, mentally taxing, and induce errors into the resulting annotations; especially in citizen science or crowdsourcing scenarios where domain expertise is not required. To alleviate these issues, this work proposes annotation curricula, a novel approach to implicitly train annotators. The goal is to gradually introduce annotators into the task by ordering instances to be annotated according to a learning curriculum. To do so, this work formalizes annotation curricula for sentence- and paragraph-level annotation tasks, defines an ordering strategy, and identifies well-performing heuristics and interactively trained models on three existing English datasets. Finally, we provide a proof of concept for annotation curricula in a carefully designed user study with 40 voluntary participants who are asked to identify the most fitting misconception for English tweets about the Covid-19 pandemic. The results indicate that using a simple heuristic to order instances can already significantly reduce the total annotation time while preserving a high annotation quality. Annotation curricula thus can be a promising research direction to improve data collection. To facilitate future research—for instance, to adapt annotation curricula to specific tasks and expert annotation scenarios—all code and data from the user study consisting of 2,400 annotations is made available.1
Efficient Prestimulus Network Integration of Fusiform Face Area Biases Face Perception during Binocular Rivalry
Authors: Rassi Elie , Wutz Andreas , Peatfield Nicholas , Weisz Nathan 
Published: March 2022

Abstract
Ongoing fluctuations in neural excitability and connectivity influence whether or not a stimulus is seen. Do they also influence which stimulus is seen? We recorded magnetoencephalography data while 21 human participants viewed face or house stimuli, either one at a time or under bistable conditions induced through binocular rivalry. Multivariate pattern analysis revealed common neural substrates for rivalrous versus nonrivalrous stimuli with an additional delay of ∼36 msec for the bistable stimulus, and poststimulus signals were source-localized to the fusiform face area. Before stimulus onset followed by a face versus house report, fusiform face area showed stronger connectivity to primary visual cortex and to the rest of the cortex in the alpha frequency range (8–13 Hz), but there were no differences in local oscillatory alpha power. The prestimulus connectivity metrics predicted the accuracy of poststimulus decoding and the delay associated with rivalry disambiguation suggesting that perceptual content is shaped by ongoing neural network states.
The Crusade of the Pen: Developed During the Colonial Period and Dismantling the Discourse of the War on Terror
Authors: Meyler Ruairí 
Published: March 2022

Abstract
In March 2021, Pope Francis visited Iraq, highlighting the challenges faced by the Christian community in Iraq and meeting with the Shia cleric Grand Ayatollah Ali al-Sistani. By engaging in this interreligious dialogue with al-Sistani, Pope Francis reminded us of another interreligious episode from the Crusades between Saint Francis and Sultan al-Kamil and challenged our perspective on the Crusades. This paper submits that in order to facilitate the repairing of relations between Christian and Muslim communities in the Middle East, we must dismantle the War on Terror discourse and in particular the nineteenth century Crusader images that underpin it and follow the example of Pope Francis in recovering not only a more ecumenical vision of the Crusades but also of the relationship between Middle Eastern Christians and Muslims. This article aims to dismantle this discourse which divides Muslim and Christian communities both in the West and in the Middle East by examining the use of Crusader imagery from Napoleon’s invasion of Egypt to the present, arguing that our modern images of the Crusades are developed in the eighteenth, nineteenth and early twentieth centuries, and it is these ahistorical images that also fuel the rhetoric surrounding the War on Terror.
Adaptation and Change among Asian Muslim Immigrants in the West
Authors: Singh David Emmanuel 
Published: March 2022

Abstract
Drawing on a variety of sources, this paper highlights the reality of diverse choices immigrants make as they come to terms with crises. Two theoretical domains are used to explain the disparate responses instead of simply identifying the options adopted by the immigrants and describing them. The first is ‘modernity’ understood here in its expanded sense, i.e.: it is not just an idea unique to the West but that it is ‘variegated’ or ‘multiple’. The second is ‘conversion’, involving the idea of it being a dynamic process, especially for those dealing with crises. The immigrant responses converge around these ideas thus revealing how some of them find answers within Islam (through re-visioning) and others who find them outside Islam (through conversion). This illustrates how ‘Muslim modernity’ expresses itself in the heart of the West but also highlights the agency of some who seek change through a radical affiliation with Christianity and secular humanism. The underlying argument is that Muslim responses are far more diverse and varied than existing literature shows.
The Bible and Women’s Subordination
Authors: Phaipi Chingboi Guite 
Published: March 2022

Abstract
Tribal Christian patriarchal societies promulgate women subordination as biblical by using the creation stories in Gen 2–3. This paper re-examines the narrative of Gen 2–3, whether women subordination is promulgated in the text. Terms and logic often used for women subjugation—such as the woman created to be ‘helper’ for the man, the woman being created later and from the man, the man to ‘rule’ the woman—are not so straightforward as they seem. A close analysis of the biblical narratives demonstrates that these terms, in their root meanings, are rather ambiguous. Rather than subordination, sameness and togetherness between the man and the woman are emphasized throughout the narrative of Gen 2–3.
Cognitive Impairment and Mild to Moderate Dysphagia in Elderly Patients: A Retrospective Controlled Study
Authors: Maniaci Antonino , Lechien Jérome R , La Mantia Ignazio , Iannella Giannicola , Ferlito Salvatore , Albanese Gianluca , Magliulo Giuseppe , Pace Annalisa , Cammaroto Giovanni , Di Mauro Paola , Vicini Claudio , Cocuzza Salvatore 
Published: March 2022

Background: To investigate whether cognitive impairment in elderly patients could correlate with the severity of swallowing disorders detectable through the endoscopic fiber optic evaluation. Methods: Elderly patients (≥65 years) performing a swallowing evaluation were included and divided according to the Dysphagia outcome and severity scale (DOSS). Neurological evaluation and Mini-Mental test examination (MMET) were administered to detect cognitive impairment. Results: Significantly worse swallowing function was reported in the cognitive impairment group than the control one (40% vs 19%; P = .001). A different significant distribution of swallowing performance was detected according to the patient’s MMET score ( P < .001; P < .001; P = .01). At the ANOVA test among dependent variables assessed, only age>65 and MMET<10 were significantly correlated with swallowing function (F = 3.862, P = .028; F = 17.49, P = .000). Conclusions: The elderly patient has an increased risk for unrecognized swallowing disorders, with a prevalence of mild to moderate forms. Assessment of cognitive performance could facilitate the identification of swallowing disorders by providing a higher level of suspicion for silent aspiration in subjects with poor MMET scores.