bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PO022: Metabolic and transcriptional adaptations under hypoxic stress promote breast cancer progression
Authors: Dai Tao , Novickis Aaron , Katsuta Eriko , Takabe Kazuaki , Abrams Scott I. , Dasgupta Subhamoy 
Published: March 2021

Abstract
To sustain energy production for survival in hypoxia, tumor cells undergo metabolic rewiring predominantly by accentuating glucose uptake through hypoxia-driven enhanced expression of glycolytic enzymes. 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 4 (PFKFB4) is one of the hypoxia response glycolytic enzyme which primarily balances the glucose flux between glycolysis and pentose phosphate pathway. However, the necessity to increase PFKFB4 expression under hypoxia is poorly understood. Here, we show that PFKFB4 dependent adaptation in hypoxia promotes a tumor-intrinsic genetic alteration acquiring invasive phenotype in breast cancer. Specifically, we found that CRISPR-Cas9 PFKFB4-knock-out (KO) breast cancer cells were defective in migration under normoxic condition (21% O2) compared to wild-type (WT) cells; while this migratory defect was found more severe under hypoxic stress (1% O2). To elucidate the mechanisms of PFKFB4-driven migration, we performed RNA-sequencing which revealed that PFKFB4 induces expression of focal adhesion pathway genes including ITGB3 (integrin β3), which are essential regulators of migration and invasion. While validating the target genes by qPCR and immunoblotting, we found that a great number of focal adhesion target genes were hypoxia-response genes including ITGB3, as their expression was significantly enhanced in hypoxia, which was completely abrogated in the absence of PFKFB4. Rescuing ITGB3-expression in PFKFB4-KO cells was sufficient to restore the migratory defects in both normoxic and hypoxic conditions, suggesting that PFKFB4 promotes migration by inducing focal adhesion genes such as ITGB3 expression. Previously we have shown that PFKFB4 directly activates steroid receptor coactivator 3 (SRC-3, also known as NCOA3) so we analyzed promoter occupancy of SRC-3 on the proximal promoter of ITGB3. Our data revealed strong occupancy of SRC-3 on the ITGB3 promoter, which also contains a canonical hypoxia response element (HRE), suggesting that PFKFB4/SRC-3 signaling axis may stimulate HIF-1A transcriptional response. By further elucidating the roles of PFKFB4/SRC-3/HIF-1A axis in hypoxia in breast tumor mouse models, we will demonstrate how metabolic and transcriptional adaptations in the TME stimulates breast cancer progression and metastasis.
Citation Format: Tao Dai, Aaron Novickis, Eriko Katsuta, Kazuaki Takabe, Scott I. Abrams, Subhamoy Dasgupta. Metabolic and transcriptional adaptations under hypoxic stress promote breast cancer progression [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr PO022.
Abstract PO043: TERT expression increases with tumor grade in a cohort of IDH mutant gliomas
Authors: Caniglia John L. , Jalasutram Anvesh , Velpula Kiran K. , Guda Maheedhara R. , Bach Sarah E. , Tsung Andrew J. 
Published: March 2021

Abstract
Glioblastoma multiforme is the most deadly primary brain tumor, exhibiting a median survival of just 13 months despite aggressive treatments including surgery, radiation, and chemotherapy. There are two main subtypes of glioblastoma, denoted primary and secondary glioblastoma, respectively. While the former begins as a grade IV tumor, secondary glioblastomas evolve from a lineage that may include grade II astrocytomas and grade III anaplastic astrocytomas, a class of tumors which are molecularly defined by mutations in isocitrate dehydrogenase (IDH). The molecular mechanisms underlying progression of these tumors are poorly understood. Telomerase reverse transcriptase (TERT), a gene encoding for the catalytic subunit of telomerase, is upregulated in a plethora of cancers and represents a probable mechanism by which malignant cells delay senescence and evade cell death. TERT activity is the primary mechanism by which malignant cells replenish telomeres with the other being the alternative lengthening of telomeres (ALT) system, known to become active in tumors harboring loss of function mutations in ATRX. In data obtained from The Cancer Genome Atlas, significantly lower rates of survival were observed in low grade glioma patients with tumors highly expressing TERT as compared to tumors with low/medium expression. However, studies comparing the expression of TERT across different grades of glioma have not been performed to date. Using immunohistochemical staining we show that, controlling for ATRX and IDH mutational status, TERT expression increases as a function of tumor grade in a cohort of patient-derived astrocytoma, anaplastic astrocytoma, and secondary glioblastoma samples. These findings indicate that as astrocytomas progress to more aggressive tumors, TERT expression likely increases to provide enhanced genomic stability.
Citation Format: John L. Caniglia, Anvesh Jalasutram, Kiran K. Velpula, Maheedhara R. Guda, Sarah E. Bach, Andrew J. Tsung. TERT expression increases with tumor grade in a cohort of IDH mutant gliomas [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr PO043.
Abstract PR006: Infiltration of TRPV1+ nerves influences the ovarian cancer immune landscape
Authors: Reavis Hunter D. , Vermeer Daniel W. , Restaino Anthony C. , Kruse Allison , Knarr Matthew , Vermeer Paola D. , Drapkin Ronny 
Published: March 2021

Abstract
High-grade serous ovarian carcinoma (HGSC) is the most lethal gynecological malignancy, with poor survival rates attributable to both late diagnosis and resistance of tumors to standard-of-care chemotherapies. Recent therapeutic strategies aim to circumvent chemoresistance by targeting tumor-extrinsic factors that support the tumor microenvironment (TME). While TME-targeted therapies such as immunotherapy and anti-angiogenics have shown promise in other chemoresistant disease states, no substantial benefit has been observed in HGSC. We have recently observed that HGSC tumors are densely infiltrated by transient receptor potential vanilloid 1 (TRPV1+) sensory nerves that are otherwise absent in normal gynecological tissues. Tumor innervation has been shown to correlate with poor prognostic outcomes in other solid tumor types and thus warrants investigation in the context of HGSC. Our preliminary data using a syngeneic mouse model of HGSC shows that diphtheria toxin-mediated ablation of TRPV1+ nerves (Trpv1-DTA) attenuates HGSC tumor growth in vivo. Furthermore, preliminary immunohistochemical analysis of HGSC tumors from wild-type versus Trpv1-DTA mice has revealed differential infiltration of immune cell populations, indicating that tumor innervation may influence immunoreactivity within the TME. These results provide us with a basis for understanding how therapeutic targeting of tumor infiltrating nerve populations may sensitize HGSC tumors to immunotherapy.
Citation Format: Hunter D. Reavis, Daniel W. Vermeer, Anthony C. Restaino, Allison Kruse, Matthew Knarr, Paola D. Vermeer, Ronny Drapkin. Infiltration of TRPV1+ nerves influences the ovarian cancer immune landscape [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr PR006.
Abstract PR-07: ORCESTRA: A platform for orchestrating and sharing high-throughput multimodal data analyses
Authors: Mammoliti Anthony , Smirnov Petr , Nakano Minoru , Safikhani Zhaleh , Nair Sisira , Mer Arvind Singh , Ho Chantal , Beri Gangesh , Haibe-Kains Benjamin 
Published: March 2021

Abstract
Reproducibility is essential to Open Science. If a finding cannot be reproduced by independent research groups its relevance is extremely limited, regardless of its validity. It is therefore crucial for scientists to describe their experiments in sufficient detail so they can be reproduced, challenged, and built upon. However, due to recent technological advances in the biological and computational sciences, experimental protocols, data analysis and interpretation have become increasingly complex. This has made reproducing research findings more challenging, with some researchers going as far as suggesting that the biomedical sciences are experiencing a "reproducibility crisis". In order to overcome these issues we developed ORCESTRA, a cloud-based platform that provides a transparent, reproducible and flexible computational framework for processing and sharing high-throughput multimodal biomedical data. The platform enables processing of genomic and pharmacological profiles of cancer samples through the use of automated processing pipelines executed by Pachyderm, a data versioning and orchestration tool. ORCESTRA creates an integrated and fully documented data object known as a PharmacoSet (PSet) for future analyses using the Bioconductor PharmacoGx package. A PSet includes cell line and drug annotations, along with molecular and pharmacological data from the largest studies and consortia. Our platform is currently being expanded to additional data types, which includes toxicogenomics, xenographic pharmacogenomic data, radiomics, and clinical genomic data. The automated pipelines can be accessed via a web interface (www.orcestra.ca). Users can view and download existing dataset or request a new one by selecting pipeline parameters. The web application provides features to improve user experience, and to accommodate different scenarios for ORCESTRA deployment. They include a personal account to save PSets, a dashboard to check the status of a requested pipeline, email notification upon the pipeline completion, handling pipeline requests while the Pachyderm cluster is offline, and “manual push” of the pipeline requests once the cluster becomes online. Funding: This project is supported by CIHR, under the frame of ERA PerMed.
Citation Format: Anthony Mammoliti, Petr Smirnov, Minoru Nakano, Zhaleh Safikhani, Sisira Nair, Arvind Singh Mer, Chantal Ho, Gangesh Beri, Benjamin Haibe-Kains. ORCESTRA: A platform for orchestrating and sharing high-throughput multimodal data analyses [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr PR-07.
Shifting Paradigms of Chinese Diaspora Studies and the Changing Dynamics of Transnational Chinese Communities: a Holistic Review
Authors: WU Xiao An 
Published: March 2021

Abstract
This article considers the pathbreaking developments that are quickly changing the field of Chinese diaspora studies. China’s rise and its ongoing integration in the world and the concomitantly changing international position of Hong Kong, Macao, and Taiwan launched a wave of Chinese elite students studying abroad, of nouveau riche emigrating to the West, and of returning Chinese recent emigrants. This brought forth a new discourse on the Chineseness and the Sinophone world that reshaped the meaning of how an ancestral hometown and host countries connect, and of the imagery and meaning of being Chinese, including being Chinese Overseas. Ironically, the new discourse, however sophisticated, global, and multidisciplinary, is primarily produced by non-Chinese and expatriate Chinese scholars. The challenge here is that, for many decades, political and ideological considerations worldwide have motivated the scholarship on Chinese diaspora, by both Chinese and non-Chinese scholars. A holistic approach, which frames Chinese diaspora as an integral part of world history, may help to meet this challenge.
Repositioning Taiwan: Historical Representation and Transformative Identity in Taiwanese American Literature
Authors: Hsieh Hsin-Chin 
Published: March 2021

Abstract
This article investigates how Taiwanese American writers represent Taiwan history in literary works with a focus on a female perspective as a way of reconstructing identities and repositioning Taiwan on a global scale. With the case studies of the first-generation Taiwanese American writer Joyce Huang’s Yangmei Trilogy (2001–2005) and the multiethnic second-generation writer Shawna Yang Ryan’s Green Island (2016), this article employs Shu-mei Shih’s “relational comparison” as a theoretical approach to analyze generational differences and transformative identities in these novels and argues that these authors’ writings on Taiwan history in the United States embody the transnational connection between the homeland and the host state. More importantly, by adopting similar historical materials and distinct narrative strategies, these novels demonstrate the involved multifaceted political meanings and cultural interventions by situating Taiwan in the related national, transnational and world histories and in doing so connect and compare Taiwan with other parts of the world.
An Adaptive Tracking Algorithm for Convection in Simulated and Remote Sensing Data
Authors: Raut Bhupendra A. , Jackson Robert , Picel Mark , Collis Scott M. , Bergemann Martin , Jakob Christian 
Published: March 2021

AbstractA robust and computationally efficient object tracking algorithm is developed by incorporating various tracking techniques. Physical properties of the objects, such as brightness temperature or reflectivity, are not considered. Therefore, the algorithm is adaptable for tracking convection-like features in simulated data and remotely sensed two-dimensional images. In this algorithm, a first guess of the motion, estimated using the Fourier phase shift, is used to predict the candidates for matching. A disparity score is computed for each target–candidate pair. The disparity also incorporates overlapping criteria in the case of large objects. Then the Hungarian method is applied to identify the best pairs by minimizing the global disparity. The high-disparity pairs are unmatched, and their target and candidate are declared expired and newly initiated objects, respectively. They are tested for merger and split on the basis of their size and overlap with the other objects. The sensitivity of track duration is shown for different disparity and size thresholds. The paper highlights the algorithm’s ability to study convective life cycles using radar and simulated data over Darwin, Australia. The algorithm skillfully tracks individual convective cells (a few pixels in size) and large convective systems. The duration of tracks and cell size are found to be lognormally distributed over Darwin. The evolution of size and precipitation types of isolated convective cells is presented in the Lagrangian perspective. This algorithm is part of a vision for a modular platform [viz., TINT is not TITAN (TINT) and Tracking and Object-Based Analysis of Clouds (tobac)] that will evolve into a sustainable choice to analyze atmospheric features.
Single-dose MGTA-145/plerixafor leads to efficient mobilization and in vivo transduction of HSCs with thalassemia correction in mice
Authors: Li Chang , Goncalves Kevin A. , Raskó Tamás , Pande Amit , Gil Sucheol , Liu Zhinan , Izsvák Zsuzsanna , Papayannopoulou Thalia , Davis John C. , Kiem Hans-Peter , Lieber André 
Published: March 2021

Abstract
We have developed an in vivo hemopoietic stem cell (HSC) gene therapy approach without the need for myelosuppressive conditioning and autologous HSC transplantation. It involves HSC mobilization and IV injection of a helper-dependent adenovirus HDAd5/35++ vector system. The current mobilization regimen consists of granulocyte colony-stimulating factor (G-CSF) injections over a 4-day period, followed by the administration of plerixafor/AMD3100. We tested a simpler, 2-hour, G-CSF–free mobilization regimen using truncated GRO-β (MGTA-145; a CXCR2 agonist) and plerixafor in the context of in vivo HSC transduction in mice. The MGTA-145+plerixafor combination resulted in robust mobilization of HSCs. Importantly, compared with G-CSF+plerixafor, MGTA-145+plerixafor led to significantly less leukocytosis and no elevation of serum interleukin-6 levels and was thus likely to be less toxic. With both mobilization regimens, after in vivo selection with O6-benzylguanine (O6BG)/BCNU, stable GFP marking was achieved in &gt;90% of peripheral blood mononuclear cells. Genome-wide analysis showed random, multiclonal vector integration. In vivo HSC transduction after mobilization with MGTA-145+plerixafor in a mouse model for thalassemia resulted in &gt;95% human γ-globin+ erythrocytes at a level of 36% of mouse β-globin. Phenotypic analyses showed a complete correction of thalassemia. The γ-globin marking percentage and level were maintained in secondary recipients, further demonstrating that MGTA145+plerixafor mobilizes long-term repopulating HSCs. Our study indicates that brief exposure to MGTA-145+plerixafor may be advantageous as a mobilization regimen for in vivo HSC gene therapy applications across diseases, including thalassemia and sickle cell disease.
Consumer acceptance of genetic-based personalized nutrition in Hungary
Authors: Szakály Zoltán , Kovács Bence , Szakály Márk , T. Nagy-Pető Dorka , Popovics Péter , Kiss Marietta 
Published: March 2021

Abstract
Background
Despite the increasing number of personalized nutrition services available on the market, nutrigenomics-based level of personalization is still the exception rather than a mainstream activity. This can be partly explained by various factors of consumer acceptance of the new technology. While consumer attitudes toward genetic tests aiming to reveal the risks of a predisposition to various illnesses have already been examined by several research studies worldwide; consumer acceptance of nutrigenomics-based personalized nutrition has only been examined by a significantly lower number of papers, especially in the Central and Eastern European region.

Objective
The purpose of this paper is to examine consumer acceptance of genetic-based personalized nutrition in Hungary. Therefore a national representative survey was conducted involving 1000 individuals. The starting point of the model used is the assumption that the consumer acceptance of personalized nutrition is influenced by its consumer perceptions, which are affected by psychological processes that, in a more general sense, determine acceptance of food innovations.

Results
The results show that 23.5% of respondents accept genetic test-based personalized nutrition. Women were found to reject the new technology in a significantly smaller proportion than men. The relationship between other demographic variables (i.e. age groups, education and subjective income level) and the perception of genetic-based personalized nutrition is also significant. Our results indicate that it is perceived cost/benefit that is most strongly related to genetically based personalized dietary preferences, followed by perceived risk and subjective norms. Perceived uncertainty and perceived behavioural control, however, have only a weak relationship with genetic-based personalized dietary preferences.

Conclusions
Compared with the magnitude of the effect of socio-demographic criteria, it can be concluded that, on the whole, psychological processes in the individual have a greater influence on the development of preferences for genetic-based personalized nutrition than any socio-demographic factor. This also confirms the trend that there are more and more value-added products or value propositions (where a significant part of the value added is to be found in product innovation), for which psychological characteristics are/should be given more emphasis among the segmentation criteria.
Common bacterial causes of external ocular infections, associated risk factors and antibiotic resistance among patients at ophthalmology unit of Felege Hiwot Referral Hospital, Northwest Ethiopia: a cross-sectional study
Authors: Ayehubizu Zimam , Mulu Wondemagegn , Biadglegne Fantahun 
Published: March 2021

AbstractBackgroundOcular infections are a serious public health problem in Ethiopia with increased incidence of morbidity and blindness. Empirical therapy with topical ophthalmic broad spectrum antibiotic formulations is also a prevailing practice. The aim of this study was to determine the bacterial causes of external ocular infections (EOIs), antimicrobial resistance and its associated risk factors among patients at Felege Hiwot Referral Hospital, Northwest Ethiopia.MethodsA hospital based cross - sectional study was conducted from 1 February to 30 April 2019. Patients with EOIs were consecutively included from 1 February to 30 April, 2019. Data were collected using structured questionnaire by face-to-face interview and complemented with patient card review. Conjunctival, eyelid margin and lacrimal sac swabs were collected aseptically. Bacterial species were identified using standard bacteriological techniques. Antimicrobial susceptibility testing was done using Kirby-Bauer disk diffusion method. Binary logistic regression analysis was calculated to identify the factors associated with EOIs. P.value (p) < < 0.05 was considered as statistically significant.ResultsA total of 360 patients took part in the study and majority of them were males (64.7%). The median age of study participants was 59.5 years. Overall, 208(57.8%) (95%CI = 52.6– - 62.8%) of patients had culture confirmed bacterial EOIs. The proportion of culture confirmed EOIs was 60.4% among conjunctivitis cases and 55.8% among blepharitis. Ocular trauma (P < < 0.001), ocular disease (P < < 0.001) and having eye allergy (P = 0.027) were significantly associated with EOIs. The most frequent isolates were S. aureus (37%), K. pneumoniae (13.5%), Proteus(7.2%) spp., S. pneumoniae (4.3%), Citrobacter spp. (3.4%) and P. aeruginosa (2.9%). Gram positive isolates were resistant to penicillin in 87% and ampicillin in 86.2%. Gram negative isolates were resistant to ampicillin (87.5%). P.aeruginosa isolates (85.3%) were resistant to piperacillin and 50% were resistant to tobramycin. Overall, 45.2% of the isolates were multi-drug resistant. The percentage of multi-drug resistance was 80% among Enterobacter isolates and 64.3% among K. pneumoniae.ConclusionsBacterial external ocular infections linked with multi-drug resistance and resistance to penicillin, ampicillin, tetracycline and piperacillin are high. Therefore, empirical treatment of eye infections in the study area needs to be monitored by regular antimicrobial-susceptibility testing of isolates.