bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PR011: DCIS-associated myoepithelial cells drive tumor progressive inflammation through up-regulation of integrin αvβ6
Authors: Allen Michael D. , Roozitalab M. Reza , Murtough Stephen , Maniati Eleni , Jones J. Louise 
Published: December 2022

Abstract
Background: Ductal carcinoma in-situ (DCIS) is a pre-invasive stage of breast cancer, however &lt;50% will progress to invasion. A key component in promoting tumor invasion is inflammation, though its role in DCIS progression is unclear. We previously, showed αvβ6 expression on DCIS myoepithelial cells promotes tumor cell invasion. We hypothesized that altered myoepithelial phenotype in DCIS may modulate periductal inflammation to contribute to disease progression. Methods: The inflammatory infiltrate in DCIS cases (20 αvβ6+ and 20 αvβ6-) was characterized by immunohistochemistry (IHC) and immunofluorescence-IHC, focusing on Tumor Associated Macrophages (TAM) and Regulatory T cell markers. A myoepithelial cell line over-expressing αvβ6 (β6-1089) and a control counterpart (N-1089) were analyzed for cytokine and signaling molecule expression with proteome profilers and western blotting. The monocyte cell line (THP-1) was exposed to conditioned media from β6-1089 or N-1089 followed by qPCR for TAM markers (IL4, IL10 and IL8), MTS proliferation assay and western blotting for NFkB and STAT6 activation (involved in macrophage differentiation). 3D models were used to examine if the in vivo changes to macrophages can be modelled in vitro. Results: IHC analysis revealed a significant association between myoepithelial αvβ6 expression and increased T-reg cell infiltrate (p&lt; 0.0001). Similarly, αvβ6 expression associated with increased presence of TAM (p=0.0026), αvβ6 positive DCIS with exhibited a microenvironment comprising 15% TAMs compared to 3% in αvβ6 negative DCIS cases. This shift in macrophage phenotype was recapitulated in 3D organotypic assays incorporating macrophages and myoepithelial cells. Proteome profiler analysis of THP-1 cells grown with conditioned media from αvβ6 positive myoepithelial cells demonstrated increased expression of CCL5 while all other proteins analyzed where generally suppressed. Nuclear and cytoplasmic western blotting of THP-1s demonstrated NfκB and STAT activation were altered by CM from myoepithelial cells +/- avb6. Conclusion: DCIS myoepithelial cells upregulate αvβ6 and exhibit changes in the periductal inflammatory infiltrate indicating a switch to a tumor promoting phenotype. Further investigation is required to determine the prognostic value and underlying mechanisms of this change.
Citation Format: Michael D. Allen, M. Reza Roozitalab, Stephen Murtough, Eleni Maniati, J. Louise Jones. DCIS-associated myoepithelial cells drive tumor progressive inflammation through up-regulation of integrin αvβ6 [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr PR011.
Abstract A004: Chemoprevention of head and neck cancers by the combination of epigallocatechin gallate (EGCG) and resveratrol
Authors: Adeluola Adeoluwa , Raji Lukmon , Sigdel Saroj , Anisuzzaman A.S.M. , Amin A. R. M. Ruhul 
Published: December 2022

Abstract
Head and neck cancer (HNC) is a devastating disease and the 6th most common cancer worldwide. Most HNC patients are diagnosed with advanced stage disease for which the 5-year survival is below 50%, stressing the need for chemoprevention. Recently, we have reported that the combination of resveratrol and EGCG induces synergistic apoptosis and inhibits xenografted HNC growth by inhibiting AKT-mTOR pathway. In this study, we have investigated the chemopreventive efficacy of resveratrol, EGCG and their combination using 4NQO-induced oral carcinogenesis model. C57BL/6 mice were exposed to 4-NQO (50 μg/ml) via drinking water for 10 weeks, followed by treatment with vehicle (50% sweetened condense milk), resveratrol (30 mg/kg), EGCG (30 mg/kg) and their combination for 8 weeks, 5 days/week. The mice were sacrificed on week 24 and the number of visible and microscopic lesions were counted. Resveratrol alone and in combination with EGCG significantly inhibited the number of visible lesions whereas the number of microscopic lesions and lesion area were significantly inhibited only in the combination group. Furthermore, RNASeq and qPCR analysis using a HNC cell line identified GDF15, ATF3, p21, p27 and Bim as significantly upregulated genes with GDF15 being the most upregulated one. Expression of GDF15 and ATF3 proteins were confirmed by western blotting. Taken together, our data strongly demonstrate the chemopreventive potential of the combination of EGCG and resveratrol and paves the way for further clinical developments. (Supported by NIH Grant P20GM103434 to the West Virginia IDeA Network for Biomedical Research Excellence)
Citation Format: Adeoluwa Adeluola, Lukmon Raji, Saroj Sigdel, A.S.M. Anisuzzaman, A. R. M. Ruhul Amin. Chemoprevention of head and neck cancers by the combination of epigallocatechin gallate (EGCG) and resveratrol [abstract]. In: Proceedings of the Second Biennial NCI Meeting: Translational Advances in Cancer Prevention Agent Development (TACPAD); 2022 Sep 7-9. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_2): Abstract nr A004.
Abstract A020: Exploring the effects of resveratrol on the gut microbiome in high fat diet-fed BRAFV600E mutant mice
Authors: Theofanous Despoina , Cai Hong , Brown Karen 
Published: December 2022

Abstract
The polyphenol resveratrol, widely known for its cancer protective activities has been shown to protect against the pro-tumorigenic effects induced by high-fat diets (HFD) in mouse models of colorectal cancer (CRC). Although, the mechanisms of actions of this compound in humans still remain elusive, recent studies suggest its effects may be mediated partly through its interaction with the gut microbiota. Here we sought to determine the changes induced by HFD on the intestinal microbiome and the impact of resveratrol supplementation on these alterations in a mouse model of BRAFV600E mutant CRC.
BRAFV600E; BRAFWT (wild-type) mice were randomised into 8 groups and fed either a standard diet or HFD supplemented with low or high-dose of resveratrol (0.7mg/kg/day and 14mg/kg/day, respectively) for 6-weeks. The mouse faecal microbial profile was then assessed by targeting the V3-V4 area of the bacterial 16S rRNA gene.
Consumption of HFD was associated with significant alternations in the gut microbiome composition in both BRAFV600E and BRAFWT based on beta-diversity analysis (PADONIS&lt;0.05). HFD increased the Firmicutes and Clostridia abundance in BRAFWT compared to animals on a standard diet (P&lt;0.01, P&lt;0.008 respectively), while in BRAFV600E mice, alterations were observed in lower taxonomic levels including the enrichment of Faecalibaculum (P&lt;0.02) and growth inhibition of Lactobacillus johnsonhii (P&lt;0.05). High-dose resveratrol resulted in significant differences in the microbial composition compared to HFD-treated group in the BRAFV600E mice (PADONIS&lt;0.05) but not in BRAFWT . Resveratrol administration did not counteract the HF-induced taxonomic changes but high-dose resveratrol changed Muribaculum, and UBA181 genera abundances in BRAFV600E mice (P&lt;0.001 and P&lt;0.05 respectively) compared to HF-treated mice. Low dose resveratrol had no significant effects on bacterial abundance in both BRAFV600E and BRAFWT mice. It was also observed that BRAFV600E mutation influenced the gut microbiome independently of diet based on beta and alpha-diversity (PADONIS&lt;0.05, PChao1&lt;0.05 respectively).
Resveratrol administration modified the gut microbiota composition of BRAFV600E mice but did not completely reverse the HFD-induced changes indicating that alternative mechanisms may contribute to the protective effects of resveratrol in this mouse model.
Citation Format: Despoina Theofanous, Hong Cai, Karen Brown. Exploring the effects of resveratrol on the gut microbiome in high fat diet-fed BRAFV600E mutant mice [abstract]. In: Proceedings of the Second Biennial NCI Meeting: Translational Advances in Cancer Prevention Agent Development (TACPAD); 2022 Sep 7-9. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_2): Abstract nr A020.
Abstract IA004: Targeting STAT3 with TTI-101, an oral small molecule, to prevent colorectal and hepatocellular cancer
Authors: Robinson Prema , Hamana Leticia , Beretta Laura , Kasembeli Moses , Bharadwaj Uddalak , Chun Yun Shin , Wang Yinghong , Wang Xeumei , Reyes Laura , Solis Luisa , Rashid Asif , Maru Dipen , Vila Eduardo , Tsimberidou Apostolia , Kaseb Ahmed , Kopetz Scott , Tweardy David 
Published: December 2022

Abstract
Persistent STAT3 activation contributes to 10 of 14 hallmarks of cancer, including inflammation; successful targeting of STAT3 has the potential to prevent and/or treat cancer. However, no small molecule that directly targets STAT3 has been FDA approved. The Tweardy lab used computer-based docking of drug-like compounds into the SH2 domain of STAT3, along with hit-to-lead optimization and medicinal chemistry, to identify TTI-101; TTI-101 treatment was safe, hit its target in tumor cells, and resulted in clinical benefit in a Phase I trial of patients with advanced solid tumors.
The incidence of colorectal cancer (CRC) is increased 20-30 fold in patients with inflammatory bowel disease (IBD), while 90% of hepatocellular carcinomas (HCC) arise in the setting of chronic inflammation. To assess the contribution of STAT3 to CRC secondary to IBD and to HCC, we performed immunohistochemistry (IHC) staining and computer-based scoring for activated STAT3 (phosphorylated on Y705, pY-STAT3) of epithelial and stromal cells within colonic endoscopic biopsies and surgically resected CRC from IBD patients, as well as of tumor cells and hepatocytes within surgically resected HCC tumors. Compared to epithelium of normal tissue, levels of pY-STAT3 were increased 1.9-fold in dysplastic epithelium (p=0.05) and 1.8-fold in the stroma of normal tissue (p&lt;0.0001). In surgically resected HCC tumors, lower pY-STAT3 scores in tumor cells, but not hepatocytes, correlated with longer recurrence free survival (RFS; p=0.003).
TTI-101 administration in three AOM-DSS mouse models of IBD resulted in a dose-dependent reduction in polyps, adenomas, and/or adenocarcinomas. TTI-101 administration to the HepPten- mouse model of NASH-induced HCC resulted in a dose-dependent reduction in liver pY-STAT3 levels. Thus, STAT3 may be a valid target for chemoprevention using TTI-101 in CRC arising from IBD and in HCC.
We thank Tvardi Therapeutics for providing TTI-101 for these studies.
Citation Format: Prema Robinson, Leticia Hamana, Laura Beretta, Moses Kasembeli, Uddalak Bharadwaj, Yun Shin Chun, Yinghong Wang, Xeumei Wang, Laura Reyes, Luisa Solis, Asif Rashid, Dipen Maru, Eduardo Vila, Apostolia Tsimberidou, Ahmed Kaseb, Scott Kopetz, David Tweardy. Targeting STAT3 with TTI-101, an oral small molecule, to prevent colorectal and hepatocellular cancer [abstract]. In: Proceedings of the Second Biennial NCI Meeting: Translational Advances in Cancer Prevention Agent Development (TACPAD); 2022 Sep 7-9. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_2): Abstract nr IA004.
Tropoelastin Improves Post-Infarct Cardiac Function
Authors: Hume Robert D. , Kanagalingam Shaan , Deshmukh Tejas , Chen Siqi , Mithieux Suzanne M. , Rashid Fairooj N. , Roohani Iman , Lu Juntang , Doan Tram , Graham Dinny , Clayton Zoe E. , Slaughter Eugene , Kizana Eddy , Stempien-Otero April S. , Brown Paula , Thomas Liza , Weiss Anthony S. , Chong James J.H. 
Published: December 2022

Background:
Myocardial infarction (MI) is among the leading causes of death worldwide. Following MI, necrotic cardiomyocytes are replaced by a stiff collagen-rich scar. Compared to collagen, the extracellular matrix protein elastin has high elasticity and may have more favorable properties within the cardiac scar. We sought to improve post-MI healing by introducing tropoelastin, the soluble subunit of elastin, to alter scar mechanics early after MI.

METHODS AND RESULTS:

We developed an ultrasound-guided direct intramyocardial injection method to administer tropoelastin directly into the left ventricular anterior wall of rats subjected to induced MI. Experimental groups included shams and infarcted rats injected with either PBS vehicle control or tropoelastin. Compared to vehicle treated controls, echocardiography assessments showed tropoelastin significantly improved left ventricular ejection fraction (64.7±4.4% versus 46.0±3.1% control) and reduced left ventricular dyssynchrony (11.4±3.5 ms versus 31.1±5.8 ms control) 28 days post-MI. Additionally, tropoelastin reduced post-MI scar size (8.9±1.5% versus 20.9±2.7% control) and increased scar elastin (22±5.8% versus 6.2±1.5% control) as determined by histological assessments. RNA sequencing (RNAseq) analyses of rat infarcts showed that tropoelastin injection increased genes associated with elastic fiber formation 7 days post-MI and reduced genes associated with immune response 11 days post-MI. To show translational relevance, we performed immunohistochemical analyses on human ischemic heart disease cardiac samples and showed an increase in tropoelastin within fibrotic areas. Using RNA-seq we also demonstrated the tropoelastin gene
ELN
is upregulated in human ischemic heart disease and during human cardiac fibroblast-myofibroblast differentiation. Furthermore, we showed by immunocytochemistry that human cardiac fibroblast synthesize increased elastin in direct response to tropoelastin treatment.

Conclusions:
We demonstrate for the first time that purified human tropoelastin can significantly repair the infarcted heart in a rodent model of MI and that human cardiac fibroblast synthesize elastin. Since human cardiac fibroblasts are primarily responsible for post-MI scar synthesis, our findings suggest exciting future clinical translation options designed to therapeutically manipulate this synthesis.
Clinical, Neuroimaging, and Genetic Markers in Cerebral Amyloid Angiopathy-Related Inflammation: A Systematic Review and Meta-Analysis
Authors: Theodorou Aikaterini , Palaiodimou Lina , Malhotra Konark , Zompola Christina , Katsanos Aristeidis H. , Shoamanesh Ashkan , Boviatsis Efstathios , Dardiotis Efthimios , Spilioti Martha , Sacco Simona , Werring David J. , Cordonnier Charlotte , Alexandrov Andrei V. , Paraskevas George P. , Tsivgoulis Georgios 
Published: December 2022

Background:
There are limited data regarding the prevalence of distinct clinical, neuroimaging and genetic markers among patients diagnosed with cerebral amyloid angiopathy–related inflammation (CAA-ri). We sought to determine the prevalence of clinical, radiological, genetic and cerebrospinal fluid biomarker findings in patients with CAA-ri.

Methods:

A systematic review and meta-analysis of published studies including patients with CAA-ri was conducted to determine the prevalence of clinical, neuroimaging, genetic and cerebrospinal fluid biomarker findings. Subgroup analyses were performed based on (1) prospective or retrospective study design and (2) CAA-ri diagnosis with or without available biopsy. We pooled the prevalence rates using random-effects models and assessed the heterogeneity using Cochran-Q and I
2
-statistics.

Results:

We identified 4 prospective and 17 retrospective cohort studies comprising 378 patients with CAA-ri (mean age, 71.5 years; women, 52%). The pooled prevalence rates were as follows: cognitive decline at presentation 70% ([95% CI, 54%–84%]; I
2
=82%), focal neurological deficits 55% ([95% CI, 40%–70%]; I
2
=82%), encephalopathy 54% ([95% CI, 39%–68%]; I
2
=43%), seizures 37% ([95% CI, 27%–49%]; I
2
=65%), headache 31% ([95% CI, 22%–42%]; I
2
=58%), T2/fluid-attenuated inversion recovery-hyperintense white matter lesions 98% ([95% CI, 93%–100%]; I
2
=44%), lobar cerebral microbleeds 96% ([95% CI, 92%–99%]; I
2
=25%), gadolinium enhancing lesions 54% ([95% CI, 42%–66%]; I
2
=62%), cortical superficial siderosis 51% ([95% CI, 34%–68%]; I
2
=77%) and lobar macrohemorrhage 40% ([95% CI, 11%–73%]; I
2
=88%). The prevalence rate of the ApoE (Apolipoprotein E) ε4/ε4 genotype was 34% ([95% CI, 17%–53%]; I
2
=76%). Subgroup analyses demonstrated no differences in these prevalence rates based on study design and diagnostic strategy.

Conclusions:
Cognitive decline was the most common clinical feature. Hyperintense T2/fluid-attenuated inversion recovery white matter lesions and lobar cerebral microbleeds were by far the most prevalent neuroimaging findings. Thirty-four percent of patients with CAA-ri have homozygous ApoE ε4/ε4 genotype and scarce data exist regarding the cerebrospinal fluid biomarkers and its significance in these patients.
Lexical Frequency Effects on the Acquisition of Syntactic Properties in Heritage Spanish: A Study on Unaccusative and Unergative Predicates
Authors: López Otero Julio César 
Published: December 2022

Abstract
This study investigates the acquisition of subject placement in unergative and unaccusative predicates among heritage speakers of Spanish by addressing two constraints ruling the distribution of subject placement (i.e., verb type and focus) as well as by examining whether lexical frequency impacts their acquisition. Sixty-three heritage speakers and twenty-five Spanish-dominant bilinguals completed an oral elicited production task and an acceptability judgment task. Results show that verb type constraints in the heritage speakers are shaped by their proficiency and self-reported lexical frequency: more proficient heritage speakers rated VS sentences higher than their lower-proficient counterparts, and more instances of VS sentences were produced with more frequent unaccusative verbs. Focus constraints only impact the heritage speakers’ acceptability: in narrow focus contexts, heritage speakers rate SV higher than VS sentences. Lexical frequency effects in unaccusative predicates are argued to be the result of spell-outs favoring compatible linear orders as a way to reduce computational costs.
The Protestant Missions to South-East Asia: Experimental Laboratory of Missionary Concepts and of Human Relations (Circa 1780–1840)
Authors: Laamann Lars Peter 
Published: December 2022

Abstract
The relationship between the Anglo-Scottish Ultra-Ganges Mission and the Dutch missionaries in South East Asia, both missions based at Batavia and at Melaka (Malacca), could be described as “distant but cordial” – even during times of colonial conflict – but the same cannot always be said about the internal conditions of the British mission. This article will attempt to place the relationship between the Anglo-Dutch missionary enterprises into a historical context which includes the complex networks built up by the missionaries with the colonial administrations, as well as with the local Malay and Chinese communities. Ultimately, the success of their mission depended as much on such external factors as on the internal cohesion between the individual missionaries. Much of the historical sources for this article has been derived from the Special Collections archives kept at the School of Oriental and African Studies (SOAS), University of London.
Serving and Sustaining Diasporic Connectivities: Hindu Sindhi Women’s Seva in Hong Kong
Authors: Chakraborty Radhika Mathrani 
Published: December 2022

Abstract
This article highlights the role of Hindu Sindhi women in building and sustaining transnational diasporic connectivities through the discourse and practice of “seva” (loosely translated as “selfless service”). Scholars note how the heterodox and syncretic character of Hindu Sindhi religious and cultural identity stretches the contours of textualized Hinduism. However, an analysis of women’s seva demonstrates how Sindhis also deploy an explicitly Hindu identity to negotiate and perform belonging in the diaspora locale of Hong Kong. Through ethnographic fieldwork in Hong Kong, this article explores how women perform acts of seva (e.g., cooking, serving, and maintaining religious spaces) to sustain diaspora ties. Seva positions the community as performing “local civic virtue” and frames Sindhis’ perceived “ethnic difference” in Hong Kong by presenting a legible Hindu identity. Women are pivotal in sacralizing food offerings and facilitating the religio-spiritual meanings of seva in Hong Kong. During the pandemic, the religious connectivities and spaces of seva women maintained, created, shaped, and expanded global Sindhi diaspora ties. For these women, participating in seva becomes a means of personal spiritual growth, fostering social connections, and negotiating/performing gendered roles and expectations.
Does Surgeon Experience Correlate with Crowd-Sourced Skill Assessment in Robotic Bariatric Surgery?
Authors: Addison Poppy , Bitner Daniel P. , Addy Jermyn , Dechario Samuel , Husk Gregg , Antonacci Anthony , Talamini Mark , Giangola Gary , Filicori Filippo 
Published: December 2022

Background The Global Evaluative Assessment of Robotic Skills (GEARS) rubric provides a measure of skill in robotic surgery. We hypothesize surgery performed by more experienced operators will be associated with higher GEARS scores. Method Patients undergoing sleeve gastrectomy from 2016 to 2020 were analyzed. Three groups were defined by time in practice: less than 5, between 5 and 15, and more than 15 years. Continuous variables were compared with ANOVA and multivariable regression was performed. Results Fourteen operators performing 154 cases were included. More experienced surgeons had higher GEARS scores and shorter operative times. On multivariable regression, operative time (P = 0.027), efficiency (P = .022), depth perception (P = 0.033), and bimanual dexterity (P = 0.047) were associated with experience. Conclusions In our video-based assessment (VBA) model, operative time and several GEARS subcomponent scores were associated with surgical experience. Further studies should determine the association between these metrics and surgical outcomes.