bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fat Induces Glucose Metabolism in Nontransformed Liver Cells and Promotes Liver Tumorigenesis
Authors: Broadfield Lindsay A. , Duarte João André Gonçalves , Schmieder Roberta , Broekaert Dorien , Veys Koen , Planque Mélanie , Vriens Kim , Karasawa Yasuaki , Napolitano Francesco , Fujita Suguru , Fujii Masashi , Eto Miki , Holvoet Bryan , Vangoitsenhoven Roman , Fernandez-Garcia Juan , Van Elsen Joke , Dehairs Jonas , Zeng Jia , Dooley James , Rubio Rebeca Alba , van Pelt Jos , Grünewald Thomas G.P. , Liston Adrian , Mathieu Chantal , Deroose Christophe M. , Swinnen Johannes V. , Lambrechts Diether , di Bernardo Diego , Kuroda Shinya , De Bock Katrien , Fendt Sarah-Maria 
Published: March 2021

Abstract

Hepatic fat accumulation is associated with diabetes and hepatocellular carcinoma (HCC). Here, we characterize the metabolic response that high-fat availability elicits in livers before disease development. After a short term on a high-fat diet (HFD), otherwise healthy mice showed elevated hepatic glucose uptake and increased glucose contribution to serine and pyruvate carboxylase activity compared with control diet (CD) mice. This glucose phenotype occurred independently from transcriptional or proteomic programming, which identifies increased peroxisomal and lipid metabolism pathways. HFD-fed mice exhibited increased lactate production when challenged with glucose. Consistently, administration of an oral glucose bolus to healthy individuals revealed a correlation between waist circumference and lactate secretion in a human cohort. In vitro, palmitate exposure stimulated production of reactive oxygen species and subsequent glucose uptake and lactate secretion in hepatocytes and liver cancer cells. Furthermore, HFD enhanced the formation of HCC compared with CD in mice exposed to a hepatic carcinogen. Regardless of the dietary background, all murine tumors showed similar alterations in glucose metabolism to those identified in fat exposed nontransformed mouse livers, however, particular lipid species were elevated in HFD tumor and nontumor-bearing HFD liver tissue. These findings suggest that fat can induce glucose-mediated metabolic changes in nontransformed liver cells similar to those found in HCC.

Significance:
With obesity-induced hepatocellular carcinoma on a rising trend, this study shows in normal, nontransformed livers that fat induces glucose metabolism similar to an oncogenic transformation.
Hexavalent TRAIL Fusion Protein Eftozanermin Alfa Optimally Clusters Apoptosis-Inducing TRAIL Receptors to Induce On-Target Antitumor Activity in Solid Tumors
Authors: Phillips Darren C. , Buchanan Fritz G. , Cheng Dong , Solomon Larry R. , Xiao Yu , Xue John , Tahir Stephen K. , Smith Morey L. , Zhang Haichao , Widomski Deborah , Abraham Vivek C. , Xu Nan , Liu Zhihong , Zhou Li , DiGiammarino Enrico , Lu Xin , Rudra-Ganguly Nandini , Trela Bruce , Morgan-Lappe Susan E. 
Published: March 2021

Abstract

TRAIL can activate cell surface death receptors, resulting in potent tumor cell death via induction of the extrinsic apoptosis pathway. Eftozanermin alfa (ABBV-621) is a second generation TRAIL receptor agonist engineered as an IgG1-Fc mutant backbone linked to two sets of trimeric native single-chain TRAIL receptor binding domain monomers. This hexavalent agonistic fusion protein binds to the death-inducing DR4 and DR5 receptors with nanomolar affinity to drive on-target biological activity with enhanced caspase-8 aggregation and death-inducing signaling complex formation independent of FcγR-mediated cross-linking, and without clinical signs or pathologic evidence of toxicity in nonrodent species. ABBV-621 induced cell death in approximately 36% (45/126) of solid cancer cell lines in vitro at subnanomolar concentrations. An in vivo patient-derived xenograft (PDX) screen of ABBV-621 activity across 15 different tumor indications resulted in an overall response (OR) of 29% (47/162). Although DR4 (TNFSFR10A) and/or DR5 (TNFSFR10B) expression levels did not predict the level of response to ABBV-621 activity in vivo, KRAS mutations were associated with elevated TNFSFR10A and TNFSFR10B and were enriched in ABBV-621–responsive colorectal carcinoma PDX models. To build upon the OR of ABBV-621 monotherapy in colorectal cancer (45%; 10/22) and pancreatic cancer (35%; 7/20), we subsequently demonstrated that inherent resistance to ABBV-621 treatment could be overcome in combination with chemotherapeutics or with selective inhibitors of BCL-XL. In summary, these data provide a preclinical rationale for the ongoing phase 1 clinical trial (NCT03082209) evaluating the activity of ABBV-621 in patients with cancer.

Significance:
This study describes the activity of a hexavalent TRAIL-receptor agonistic fusion protein in preclinical models of solid tumors that mechanistically distinguishes this molecular entity from other TRAIL-based therapeutics.
Platelet TLR4-ERK5 Axis Facilitates NET-Mediated Capturing of Circulating Tumor Cells and Distant Metastasis after Surgical Stress
Authors: Ren Jinghua , He Jiayi , Zhang Hongji , Xia Yujia , Hu Zhiwei , Loughran Patricia , Billiar Timothy , Huang Hai , Tsung Allan 
Published: March 2021

Abstract

Surgical removal of malignant tumors is a mainstay in controlling most solid cancers. However, surgical insult also increases the risk of tumor recurrence and metastasis. Tissue trauma activates the innate immune system locally and systemically, mounting an inflammatory response. Platelets and neutrophils are two crucial players in the early innate immune response that heals tissues, but their actions may also contribute to cancer cell dissemination and distant metastasis. Here we report that surgical stress–activated platelets enhance the formation of platelet-tumor cell aggregates, facilitating their entrapment by neutrophil extracellular traps (NET) and subsequent distant metastasis. A murine hepatic ischemia/reperfusion (I/R) injury model of localized surgical stress showed that I/R promotes capturing of aggregated circulating tumor cells (CTC) by NETs and eventual metastasis to the lungs, which are abrogated when platelets are depleted. Hepatic I/R also increased deposition of NETs within the lung microvasculature, but depletion of platelets had no effect. TLR4 was essential for platelet activation and platelet-tumor cell aggregate formation in an ERK5-GPIIb/IIIa integrin-dependent manner. Such aggregation facilitated NET-mediated capture of CTCs in vitro under static and dynamic conditions. Blocking platelet activation or knocking out TLR4 protected mice from hepatic I/R-induced metastasis with no CTC entrapment by NETs. These results uncover a novel mechanism where platelets and neutrophils contribute to metastasis in the setting of acute inflammation. Targeted disruption of the interaction between platelets and NETs holds therapeutic promise to prevent postoperative distant metastasis.

Significance:
Targeting platelet activation via TLR4/ERK5/integrin GPIIb/IIIa signaling shows potential for preventing NET-driven distant metastasis in patients post-resection.
Transradial Versus Transfemoral Access for Percutaneous Coronary Intervention in ST-Segment–Elevation Myocardial Infarction
Authors: Di Santo Pietro , Simard Trevor , Wells George A. , Jung Richard G. , Ramirez F. Daniel , Boland Paul , Marbach Jeffrey A. , Parlow Simon , Kyeremanteng Kwadwo , Coyle Doug , Fergusson Dean , Russo Juan J. , Chong Aun-Yeong , Froeschl Michael , So Derek Y. , Dick Alexander , Glover Christopher , Labinaz Marino , Hibbert Benjamin , Le May Michel 
Published: March 2021

Background:
Transradial access (TRA) has emerged as the preferred vascular access site for coronary angiography and percutaneous coronary intervention. This systematic review and meta-analysis was performed to evaluate 30-day all-cause mortality comparing TRA with transfemoral access for percutaneous coronary intervention in patients with ST-segment–elevation myocardial infarction.

Methods:
We performed a systematic literature search and meta-analysis of randomized controlled studies published from inception until January 7, 2020, in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science Core Collection. Preferred Reported Items for Systematic Reviews and Meta-Analyses guidelines were used for abstracting data. The primary outcome was all-cause mortality at 30 days. Secondary outcomes included myocardial infarction, major bleeding, stroke, and access site complications.

Results:
A total of 14 studies representing 11 707 patients (5802 patients with TRA; 5905 patients with transfemoral access) were included in this systematic review. All-cause mortality (N=8 studies) was significantly reduced in the TRA group with an overall risk ratio (RR) of 0.72 (95% CI, 0.56–0.92) in the pooled analysis. Major bleeding (N=12 studies; RR, 0.60 [95% CI, 0.45–0.80]) and access site complications (N=9 studies; RR, 0.40 [95% CI, 0.30–0.53]) were significantly higher in the transfemoral access group. There was no statistical difference in reinfarction (N=10 studies; RR, 0.96 [95% CI, 0.75–1.25]) or stroke (N=8 studies; RR, 1.47 [95% CI, 0.87–2.50]).

Conclusions:
TRA is associated with lower 30-day mortality, major bleeding, and access site complications when compared with transfemoral access in ST-segment–elevation myocardial infarction patients who undergo percutaneous coronary intervention.

Registration:

URL:
https://www.crd.york.ac.uk/PROSPERO/
; Unique identifier: 127955.
Shared Identity of Horses and Men in Oromia, Ethiopia
Authors: Baynes-Rock Marcus , Teressa Tigist 
Published: March 2021

Abstract
In this paper, we draw attention to human-horse relations among the Oromo of West Shewa and the importance that men in particular ascribe to horses known as farrda mia. These horses are not a distinct breed; they attain their status through a process of selection based on attractiveness and mutual compatibility with their owners. Farrda mia are important in ceremonies, racing, and personal prestige to the degree that they constitute a cognitive affective unity with the men they allow on their backs. The relationships between Oromo men and their horses evoke novel conceptions of identity. Through reciprocal trust, exclusivity, naming, and performance, Oromo men and their horses constitute cognitive, affective centaurs that challenge conceptions of self- contained, self-embodied, human individuals.
Leaving the Market, Taking the Square: Space and Mobility in the Revolts of Late Medieval Tournai
Authors: Gonzalez Martin Pablo 
Published: March 2021

Abstract
This article studies the relation between the movement of people and objects and the use of urban places during revolts in late medieval Tournai. It posits that fixed locations were but one ingredient in the construction of medieval spaces of protest and contestation, and that most other essential elements, such as people, objects, and performances, were in fact mobile. As shown here through the case of Tournai, the mobile nature of these elements allowed rebels to transform urban space and its meanings as they moved across the town. The first part of the article looks at how rebels utilized mobility to disrupt and re-appropriate ordinary itineraries. The second part focuses on the “Becquerel revolts,” a series of uprisings that took place in a small, peripheral square. This is to show how urban guilds, by effectively managing to move people, objects, and performances to unexpected locations, not only took control of specific places, but also created their own spaces of contestation.
Mobility and Urban Space in Early Modern Europe: An Introduction
Authors: Zenobi Luca 
Published: March 2021

Abstract
Early modernists have explored a range of mobile practices taking place in cities: from religious and civic rituals to the multisensory experience of traversing streets and squares. Research has also shown the pivotal role played by cities as hubs where people came and went, ideas circulated, and goods passed through. Yet mobility did not just “take place” in cities. In presenting a new collection of articles on the subject, this paper suggests that urban spaces were more than just a stage for the streams of trade and migration. Rather, mobility had a transformative effect on cities: it assigned new meaning to urban locations, altered the ways in which space was ordered, and often refashioned the built environment itself. In addition, the paper argues that the relationship between movement and urban spaces was reciprocal: by channelling the flow of people through spaces of control and reception, cities shaped mobility as much as mobility shaped cities.
November, 1494: Politics in Motion in the Streets of Florence
Authors: Atkinson Niall S. 
Published: March 2021

Abstract
The spectacular entry of Charles VIII into Florence in 1494 initiated a series of political negotiations and maneuvers in which the French monarch, the local government, and the embattled Medici family vied for control over the city. With the threat of violence so present and reliable information so scarce, Florentines had to perform subtle interpretations of the movements of these actors in order to determine what was happening to their city. These eye-witness accounts reveal that the most elaborately staged ritual and the most improvised single gesture were part of a moving tableau whose meaning was contingent on understanding the relationship between the paths taken, the places visited, and the manner in which the protagonists moved through the city. As a result, we can learn how early modern cities were constituted by the ceaseless exchanges between the ephemeral movements of communities and the solidity of the built environment.
Chinese Storytelling in the Xi Jinping Era
Authors: Brown Kerry 
Published: March 2021

Summary
In the era of Xi Jinping in China, the international profile of the country has risen. So too has its need to proactively spell out what its rise means to the rest of the world. This essay looks at the ways in which China has attempted to tell its story, and the challenges it has faced from a world that often knows little about it but also has strong, antipathetic opinions about its political system.
Consular Protection with Chinese Characteristics: Challenges and Solutions
Authors: Xia Liping 
Published: March 2021

Summary
In today’s globalised world, giving consular protection to an increasing number of overseas citizens has become a common challenge to foreign ministries. China, as the most populous country witnessing fast economic development, is facing more severe challenges in this field. Since the 18th National Congress of the Chinese Communist Party, China’s consular protection has demonstrated new trends such as involving more actors in service delivery, constructing a co-ordination network, legalizing the management and taking targeted preventive measures. Compared with developed countries, ‘whole government involvement’ is the most prominent feature of China’s consular protection practice.
Mass Atrocities in Myanmar and the Responsibility to Protect in a Digital Age
Authors: Buzzi Camilla 
Published: March 2021

Abstract
Liberalisation of the telecommunications sector is a significant part of the political changes that were initiated in 2011 in Myanmar, making smartphones, sim cards, and access to the internet more widely available. Social media (SoMe) platforms, notably Facebook, have emerged as the main access to the internet for many people. But as the transition has proceeded, SoMe has become a space both for human rights activism and for inciting human rights abuses against vulnerable minorities. It is well documented that both the state and civil society in Myanmar have used Facebook to foment violence and mass atrocities against the Rohingya and other vulnerable minorities. This article examines some challenges for internet and SoMe governance drawing on the response of Facebook and various internet service providers in Myanmar in order to explore how to apply the norm of R2P on the net. The article aims to provide input for lessons learnt on mass atrocity prevention in a digital age.
Navigating between Pragmatism and Principle: Australia’s Foreign Policy Response to the 2017 Rohingya Crisis
Authors: Jacob Cecilia 
Published: March 2021

Abstract
The escalation of violence by Myanmar’s military forces against ethnic Rohingya populations in Rakhine State in 2017 served as a test case for Australia’s commitment to R2P, and its capacity to protect populations from widespread and systematic atrocities in its own regional neighbourhood. Australia’s response to the crisis in Myanmar was mixed; it co-sponsored a UN Human Rights Council resolution to establish the Independent International Fact-Finding Mission on Myanmar that was instrumental in determining the extent and nature of violence committed by Myanmar’s armed forces during the so-called ‘clearance operations’, and provided substantial humanitarian aid for affected Rohingya populations. Australia has, however, been criticised for not doing enough to pressure the government of Myanmar on the issue, for maintaining defence cooperation with Myanmar throughout the crisis, and for its reluctance to accept Rohingya refugees fleeing the violence. This article examines Australia’s response to the Rohingya crisis in the areas of international, regional, and bilateral diplomacy, humanitarian assistance, and defence cooperation. It asks why Australia did not take a more proactive role in confronting atrocities committed by the Myanmar government, and identifies lessons learnt and recommendations for strengthening Australia’s atrocity prevention architecture that is consistent with Australia’s pragmatic approach to regional assistance and its principled international advocacy.
Constructing Spiritual Blackness
Authors: Ramadan-Santiago Omar 
Published: March 2021

Abstract
In this article, I address how my interlocutors, members of the Rastafari community in Puerto Rico, claim that they identify with Blackness and Africanness in a manner different from other Black-identifying Puerto Ricans. Their identification process presents a spiritual and global construction of Blackness that does not fit within the typical narratives often used to discuss Black identity in Puerto Rico. I argue that their performance of a spiritually Black identity creates a different understanding of Blackness in Puerto Rico, one that is not nation-based but rather worldwide. This construction of Blackness and Black identity allows my interlocutors to create an imagined community of Blackness and African descent that extends past Puerto Rico’s borders toward the greater Caribbean region and African continent. In the first section, I discuss how Blackness is understood and emplaced in Puerto Rico and why this construction is considered too limiting by my interlocutors. I then address their own construction of Blackness, what I refer to as “spiritual Blackness,” and how they believe it diverges from Afro-Boricua/Black Puerto Rican identity. In the final section, I direct focus to how Africa is centralized in the construction of spiritual Blackness.
The Sanskrit Inscription of Śaṅkara and Its Interpretation in the National History of Indonesia
Authors: Griffiths Arlo 
Published: March 2021

Abstract
It is a well-known fact that Sanskrit had a relatively shorter and less prolific lifespan in the epigraphy of Indonesia, particularly in the Javanese epigraphic record, than in that of other Southeast Asian regions. All the more precious, therefore, are the rare opportunities to add a Sanskrit inscription to the historical record of Java and learn more of how the Sanskrit language was deployed on the island to represent events recorded for posterity. In this article, I offer my edition and interpretation of the inscription referred to in Indonesian publications as Prasasti Sankhara (sic, with kh), that is, the Inscription of Śaṅkara; debunk the entirely unfounded interpretation which it has received in successive reprints and editions of the greatly influential Sejarah nasional Indonesia (National history of Indonesia); and show the real historical interest of this inscription.
The Returnee as an Outsider: Reunion and Division in Wang Quan’an’s Apart Together (團圓, tuan yuan)
Authors: Huang Phyllis Yu-ting 
Published: March 2021

Abstract
Mainland Chinese director Wang Quan’an’s Apart Together, which won the Silver Bear Award for Best Screenplay in 2010, tackles the issue of cross-Strait relations by telling the story of Kuomintang veteran Liu Yansheng’s return to mainland China after nearly 40 years of separation from his wife and son. Shanghainese is the main language of the film, a dialect that is used to suggest a local attitude towards the national issue. While earlier Chinese films on similar themes often emphasise the cultural and emotional ties between Taiwan and China, in Wang’s film Liu is characterised as an unwelcome Taiwanese guest, an intruder in his wife’s Chinese family. This essay argues that Wang’s Apart Together contests the People’s Republic of China’s official discourse of cross-Strait reunification by demonstrating the cultural and identity divisions between the Taiwanese character and his Chinese family. Wang provides an alternative perspective on the ‘Taiwan issue’, showing that ordinary people’s experience of cross-Strait reunion might be painful and problematic.
A Shield for the Tip of the Spear
Authors: White Samuel 
Published: March 2021

AbstractThe defence of superior orders is not new. However, within Australia, its statutory codification is lamentably underexplored. The 2018 Amendments to Part IIIAAA of the Defence Act 1903 (Cth) provides a neat catalyst to expand the defence and look at possible manners in which it can be constructed. Utilising a theoretical case study of Australian Defence Force members killing a possible terrorist, ‘this article addresses’ the key elements of the defence—what an order is, when can it be constructed as being manifestly unlawful and what does reasonable and necessary force mean for Australian Defence Force members.
The intraoral growth patterns of parapharyngeal tumors: A proposed classification system
Authors: Feng Yanjun , Wang Jianhong , Li Xiping , Meng Lingzhao , Rao Yuansheng , Yang Fan 
Published: March 2021

Objective:Nearly half of parapharyngeal space (PPS) tumors present as an intraoral mass, which is diagnostically challenging. In this study, we studied whether preoperative growth patterns were associated with histopathological diagnosis for planning surgery.Methods:We performed a cross-sectional study in patients with PPS tumors. A simplified classification scheme based on intraoral tumor growth patterns (patterns 1 and 2) was then proposed. In pattern 1, tumors bulge submucosally to the oropharynx from the soft palate, with the center convexity above the uvula. In pattern 2, tumors bulge submucosally to the oropharynx from the lateral oropharynx wall, with the center convexity below the uvula. The association of this classification with postoperative histopathological diagnosis and surgical-related events was studied.Results:Twenty-two patients were enrolled in this study (12 with pattern 1, 10 with pattern 2). Of these, 91.7% (11/12) of pattern 1 tumors were salivary gland tumors ( P < .001), and 90% (9/10) of pattern 2 tumors were neurogenic ( P < .001). Pattern 2 tumors had fewer bleeding complications or needed external approaches when a transoral approach was chosen.Conclusions:This new classification of PPS tumors facilitates the prediction of salivary gland and neurogenic tumors and can improve the accuracy of preoperative radiologic diagnosis. This system will be helpful for planning surgical interventions, such as implementing transoral approaches.