bluuebunny/crossref_metadata_2025_split huggingface dataset:
Medical therapies for prevention of cardiovascular and renal events in patients with atrial fibrillation and diabetes mellitus
Authors: Fauchier Laurent , Boriani Giuseppe , de Groot Joris R , Kreutz Reinhold , Rossing Peter , Camm A John 
Published: July 2021

Abstract
Atrial fibrillation (AF), type 2 diabetes mellitus (DM), and chronic kidney disease (CKD) are three global epidemics with significant effects on morbidity and mortality. Diabetes is a risk factor for AF, and a risk factor for thromboembolism, comorbidity, and mortality when AF is present. The pathophysiology of diabetes-related AF and interrelationships with cardiovascular events and renal events is not fully understood but is in part related to structural, electrical, electromechanical, and autonomic remodelling. The current practice guidelines offer limited recommendations on the management of patients with AF (or risk of AF) and diabetes with its own heterogeneity for the prevention of cardiovascular and renal events. This document discusses possible clinical approaches for these patients. In the last decade, there have been major improvements for the prevention of stroke in AF patients with direct oral anticoagulants, which are preferable to vitamin K antagonists for stroke prevention in DM. Because of the increased risk rate for several cardiovascular adverse events in diabetic patients, a similar relative risk reduction generally translates into greater absolute risk reduction in the diabetic population. Recent trials with non-insulin diabetes drugs using glucagon-like peptide-1 agonists and sodium-glucose cotransporter-2 inhibitors showed a significant reduction for the risk of major adverse cardiovascular events in patients with type 2 DM. Sodium-glucose cotransporter-2 inhibitors also showed a large reduction in hospitalization for heart failure and renal events, which need to be more completely evaluated in patients with AF. Mechanisms, risks, and optimal management of AF patients with DM who have or are under risk of developing heart failure or CKD are also discussed in this document. The benefits of medical therapies for these patients still need to be put into perspective, and gaps in evidence on some of these issues are likely to be addressed in future years.
Early onset atrial lesions in a patient with a novel LMNA frameshift mutation
Authors: Lin Yongping , Liu Hailei , Cui Chang , Lin Zhiqiao , Zhang Yike , Zhu Yue , Ju Weizhu , Chen Minglong 
Published: July 2021

Abstract
Genetic mutations in the lamin A/C gene (LMNA) have been linked to cardiomyopathy. Different mutational sites exhibit different clinical manifestations and prognoses. Herein, we identified a novel LMNA frameshift mutation, p.P485Tfs*67, from a patient with early-onset atrial disease. To verify the pathogenicity of this variation, a transgenic zebrafish model was constructed, which demonstrated that adult zebrafish with the LMNA mutation showed an abnormal ECG and impaired myocardial structure. Our study suggests the atrial pathogenicity of the LMNA-P485Tfs mutation, which is helpful to understand the function of the Ig-like domain of lamin A/C.
Transnational identity and the Gulf crisis: changing narratives of belonging in Qatar
Authors: Mitchell Jocelyn Sage 
Published: July 2021

Abstract
What does the recent Gulf diplomatic crisis of June 2017 to January 2021 mean for the future of the region's signature transnationalism: the khalījī [Gulf] identity? This identity narrative encompasses the shared sociocultural backgrounds of the people of the region, but the unprecedented separations, caused by the regional crisis, may have shifted the discourse of belonging in the Gulf. To investigate the impact of the recent crisis on regional identity narratives, this article explores the new National Museum of Qatar's presentation of Qatar's political history from 1848 to 1868, as well as museum-goers' reactions to this presentation, through original fieldwork and ethnographic interviews with Qatari and expatriate residents. The analysis highlights the museum's purposeful portrayal of parallels between intra-Gulf conflicts of the past and the recent crisis, a presentational choice that stands in sharp contrast to previous regional norms of tactful diplomacy. Further, museum-goers recognized the linguistic and symbolic parallels, provoking both engagement with and rejection of the concept of khalījī identity. In summary, this analysis suggests that the crisis has shifted the norms of discourse in the region in ways that may make social reconciliation difficult, even as political bonds resume. As the region moves forward from crisis, policy-makers should reduce the tension between national and transnational identity narratives by creating space for the renewal of khalījī ties.
Turkish foreign policy in the Middle East: power projection and post-ideological politics
Authors: Dalacoura Katerina 
Published: July 2021

Abstract
Power projection, security, pragmatic considerations and a disparate mix of national interests and narrower party-political objectives have driven the foreign policy of Turkey's Justice and Development Party (AKP) in the Middle East since it came to power in 2002. Ideological concerns, consisting of a fluid blend of Islamist, neo-Ottoman and ‘civilizationalist’ ideas, mingled with a hefty dose of Turkish nationalism, have played a variable, auxiliary but none the less significant role. The Arab uprisings of 2011 opened up opportunities for the AKP to pursue its ideological objectives and they became more central to its policies, if only in some areas or clusters of relationships. However, they receded after 2015, when a confluence of domestic and regional factors caused the onset of a transactional, ‘post-ideological’ phase. The article places the Middle East in the wider context of Turkish foreign policy, both historically and in comparison with other regions, arguing in the process that categories of ‘East’ and ‘West’ are of limited value for its proper understanding and interpretation. It then divides it into four sub-regions, distinct in geographical and issue terms: Syria and Iraq (the ‘near abroad’), the wider Arab world, Israel–Palestine, and Iran. It analyses Turkish foreign policy towards them in sequence, illustrating the ways in which power-political considerations have predominated in all, albeit in different ways and to varying degrees, over the past five years.
Bahrain's transnational Arab Spring: repression, oil and human rights activism
Authors: Moritz Jessie 
Published: July 2021

Abstract
Studies of the Middle East following the Arab Spring have concluded that ‘repression works’, especially in the oil- and gas-rich countries of the Gulf. Drawing on primary materials collected during fieldwork trips to Bahrain, the United States and Britain, this article nuances the ‘repression effect’ by tracing the emergence of a transnational Bahraini opposition, mapping the relationships and joint activities between domestic and exiled Bahraini groups, international NGOs and western policy-makers. It finds that even in the context of domestic repression and continuing ideological divides within Bahrain's opposition, transnational networks have not only sustained opposition organizations, but also maintained access to foreign policy-makers, producing repeated criticisms of the Bahraini regime and legal challenges to ruling elites who visit western states. The successes of this advocacy are modest: while it has not drastically reshaped the domestic state–society relationship, it has created significant costs for the Bahraini regime and damaged Bahrain's international brand. As a result, state and opposition networks now compete for influence over western policy-makers: international ‘arenas of advocacy’—such as the UK parliament, US Congress, UNHRC and European Parliament—have now become ‘arenas of contestation’, as state and opposition narratives of Bahraini politics, filtered through western policy-makers, play out during debates over foreign policy towards Bahrain. The article positions transnational activism as a direct outcome of the ‘repression effect’, highlighting ongoing contests for influence between state and society occurring in international and transnational spaces, even as the domestic scope for opposition mobilization remains highly restricted.
Compensation Funds as a Remedial Mechanism for Victims of Corporate Pollution in Kenya: A Feasibility Study
Authors: Mwanza Rosemary 
Published: July 2021

Abstract
This article explores the potential of a public-run, risk-based compensation fund to provide compensation for victims of corporate pollution in Kenya. Existing remedial mechanisms are severely limited by the uncertainty of recovery attributable to doctrinal barriers in liability rules, the length of time and cost involved in settling claims and the impact of corruption as a hindrance to access to justice. Depending on their design, compensation funds could offer prompt compensation at lower personal costs to claimants. Considering that victims of corporate pollution in Kenya tend to be poor, prompt compensation can cushion their welfare by providing much-needed funds to cover medical expenses and support livelihoods. While claimants would likely obtain less compensation in absolute amounts than in tort litigation, they would still retain the right to pursue supplemental compensation through alternative mechanisms. Thus, a pragmatic approach would be to develop a compensation fund while introducing effective reforms to existing mechanisms.
Protein–lipid interplay at the neuromuscular junction
Authors: Unwin Nigel 
Published: July 2021

Abstract
Many new structures of membrane proteins have been determined over the last decade, yet the nature of protein–lipid interplay has received scant attention. The postsynaptic membrane of the neuromuscular junction and Torpedo electrocytes has a regular architecture, opening an opportunity to illuminate how proteins and lipids act together in a native membrane setting. Cryo electron microscopy (Cryo-EM) images show that cholesterol segregates preferentially around the constituent ion channel, the nicotinic acetylcholine receptor, interacting with specific sites in both leaflets of the bilayer. In addition to maintaining the transmembrane α-helical architecture, cholesterol forms microdomains – bridges of rigid sterol groups that link one channel to the next. This article discusses the whole protein–lipid organization of the cholinergic postsynaptic membrane, its physiological implications and how the observed details relate to our current concept of the membrane structure. I suggest that cooperative interactions, facilitated by the regular protein–lipid arrangement, help to spread channel activation into regions distant from the sites of neurotransmitter release, thereby enhancing the postsynaptic response.
Constraining the formation of NGC 1052-DF2 from its unusual globular cluster population
Authors: Trujillo-Gomez Sebastian , Kruijssen J M Diederik , Keller Benjamin W , Reina-Campos Marta 
Published: July 2021

ABSTRACT
The ultra-diffuse galaxy (UDG) NGC 1052-DF2 has a low dark matter content and hosts a very unusual globular cluster (GC) population, with a median luminosity ∼4 times higher than in most galaxies and containing about 5 per cent of the galaxy’s stars. We apply a theoretical model that predicts the initial cluster mass function as a function of the galactic environment to investigate the origin of DF2’s peculiar GC system. Using the GC mass function, the model constrains the star-forming conditions in the galaxy during the formation of its GCs, ∼9 Gyr ago. We predict that the GCs formed in an environment with very high gas surface density, $\Sigma _{\rm ISM}\gtrsim 10^3\rm \,{M_\odot}\rm \,{pc}^{-2}$, and strong centrifugal support, $\Omega \gtrsim 0.7\rm \,{Myr}^{-1}$, similar to nearby circumnuclear starbursts and the central region of the Milky Way. The extreme conditions required to form the observed GC population imply a very high cluster formation efficiency of ≈87 per cent, and contrast strongly with the current diffuse nature of the galaxy. Since a nuclear starburst would lead to the rapid in-spiral of the GCs and is ruled out by the absence of a nuclear star cluster, we propose that the GCs plausibly formed during a major merger at z ∼ 1.3. The merger remnant must have undergone significant expansion of its stellar (and perhaps also its dark matter) component to reach its low present surface brightness, leading to the interesting possibility that it was the formation of DF2’s extreme GC population that caused it to become a UDG. If true, this strong structural evolution would have important implications for understanding the origins of UDGs.
Radio emission from dust-obscured galaxies
Authors: Gabányi Krisztina É , Frey Sándor , Perger Krisztina 
Published: July 2021

ABSTRACT
The coevolution of galaxies and their central supermassive black holes is a subject of intense research. A class of objects, the dust-obscured galaxies (DOGs) are particularly interesting in this respect as they are thought to represent a short evolutionary phase when violent star formation activity in the host galaxy may coexist with matter accretion on to the black hole powering the active nucleus. Here, we investigate different types of DOGs classified by their mid-infrared spectral energy distributions to reveal whether they can be distinguished by their arcsec-scale radio properties. Radio emission is unaffected by dust obscuration and may originate from both star formation and an active nucleus. We analyse a large sample of 661 DOGs complied from the literature and find that only a small fraction of them (∼2 per cent) are detected with flux densities exceeding ∼1 mJy in the Faint Images of the Radio Sky at Twenty-Centimeters (FIRST) survey. These radio-detected objects are almost exclusively ‘power-law’ DOGs. Stacking analysis of the FIRST image cutouts centred on the positions of individually radio-undetected sources suggests that weak radio emission is present in ‘power-law’ DOGs. On the other hand, radio emission from ‘bump’ DOGs is only marginally detected in the median-stacked FIRST image.
MOMC-2. Glioblastoma Metabolic Symbiosis: When Lactate Takes The Lead
Authors: Guyon Joris , Larrieu Claire , Bouchez Cyrielle , Moncada Ignacio Fernandez , Coffe Aurelien , Nikolski Macha , Bikfalvi Andreas , Daubon Thomas 
Published: July 2021

Abstract
Glioblastoma (GBM) is a common and devastating brain tumor, associated with a low median survival, despite standard therapeutic management. Among its major features, GBMs are highly angiogenic and exhibit paradoxically an elevated glycolysis. Most of differentiated cells convert glucose into pyruvate that enters into the Krebs cycle to maximize energy production in the presence of oxygen. For cancer cells, glucose uptake and catabolism are increased regardless of oxygen level. However, their energy needs are important – mainly for rapid growth – that it requires a much faster production flow. It is at this step that lactate dehydrogenase (LDH) are involved: LDHA converts efficiently pyruvate into lactate and generates NAD+ to maintain glycolysis. Thus, the lactate formed is exported into the extracellular compartment inducing an unfavourable acidification of the microenvironment. Moreover, LDHB, another LDH isoform, metabolizes lactate into pyruvate for generating energy in mitochondria. Though LDHA has already been studied in many cancers including GBM, the simultaneous role of LDH enzymes have not yet been investigated in GBM development.
Hypoxia-driven LDHA expression and lactate production increased cell invasion. Infusing 13C-lactate in starved cells rescued TCA cycle. Then, we showed that, under hypoxia, double sgLDHA/B cell growth and invasion was dramatically decreased in comparison to control cells, mainly caused by an increase in apoptosis. Moreover, double impairment of LDHA and B significantly reduced tumor growth and cell invasion, and induces a massive increase in mouse survival. Tracing experiments with 13C-Glucose coupled with RNA sequencing revealed how metabolism adapts to these contraints, by modifying electron transport chain subunit expressions or by increasing lipid droplet formation.
Considered for a long time as a metabolic waste, lactate is shown here to play a critical role in GBM cell symbiosis. This study highlighted GBM adaptability through the LDH isoforms and their involvement in GBM development.
OPTC-2. Identification of enriched genes and pathways associated to hypoxia induced migration in patient-derived glioma stem cell lines by RNAseq
Authors: Hanon Olivia Morris , Mahmoud Yamil , Vera Mariana , Girotti Romina , Rabinovich Gabriel , Sevlever Gustavo , Scassa Maria Elida , Richardson Guillermo Videla 
Published: July 2021

Abstract
Glioblastomas (GBM), the most prevalent and lethal primary brain tumors, are characterized by high intertumoral heterogeneity, diffuse infiltration, and resistance to conventional therapies. Notably, the ability of tumor cells to invade surrounding tissues is one of their most damaging characteristics, it not only causes resistance to therapies such as surgery and radiotherapy but is ultimately the primary cause of death. Therapies that cause hypoxia (e.g. anti-angiogenic therapies) have been shown to increase invasiveness, leading to resistance to the therapy itself and further complications for the patients. Using patient-derived glioma stem cell lines (GSCL) we have discovered cell lines that display heterogeneous migratory behavior in response to hypoxia. As expected we observed that four GSCLs studied had increased migration in hypoxia. Strikingly, two other cell lines studied showed decreased migration in hypoxia. This unforeseen result reflects the heterogeneous nature of GBM and the difference between these GSCLs could be key to understanding this variable. To delve into the molecular context that could explain these differences we performed an exploratory RNAseq analysis on four of the GSCLs, two that showed hypoxia-induced migration and two with decreased migration in hypoxia, and evaluated genes differentially expressed in hypoxia versus normoxia. We also carried out gene ontology and pathway enrichment analysis to discover molecular and pathway patterns consistent with the migratory behaviors observed in each group of GSCLs. The results show how that a similar migratory response to hypoxia coincides with particular sets of enriched genes and pathways. Specifically, we found NOTCH and WNT signaling pathways upregulated in GSCLs which showed increased migration in hypoxia while the IFN-gamma pathway upregulated in GSCLs with decreased migration in hypoxia. Knowing the individual molecular mechanisms responsible for the migratory behavior could allow for tailor-made therapies that reduce the dissemination of these tumors.
OMRT-3. Longitudinal analysis of diffuse glioma reveals cell state dynamics at recurrence associated with changes in genetics and the microenvironment
Authors: Varn Frederick , Johnson Kevin , Barthel Floris , Kim Hoon , Wade Taylor , Malta Tathiane , Sabedot Thais , Lodha Disha , Ajaib Shoaib , Ahmed Nazia , Garofano Luciano , D’Angelo Fulvio , Stead Lucy , Poisson Laila , Noushmehr Houtan , Iavarone Antonio , Verhaak Roel ,   GLASS Consortium
Published: July 2021

Abstract
Diffuse glioma is an aggressive brain cancer that is characterized by a poor prognosis and a universal resistance to therapy. The evolutionary processes behind this resistance remain unclear. Previous studies by the Glioma Longitudinal Analysis (GLASS) Consortium have indicated that therapy-induced selective pressures shape the genetic evolution of glioma in a stochastic manner. However, single-cell studies have revealed that malignant glioma cells are highly plastic and transition their cell state in response to diverse challenges, including changes in the microenvironment and the administration of standard-of-care therapy. Interactions between these factors remain poorly understood, making it difficult to predict how a patient’s tumor will evolve from diagnosis to recurrence. To interrogate the factors driving therapy resistance in diffuse glioma, we collected and analyzed RNA- and/or DNA-sequencing data from temporally separated tumor pairs of 292 adult patients with IDH-wild-type or IDH-mutant glioma. Recurrent tumors exhibited diverse changes that were attributable to changes in anatomic composition, somatic alterations, and microenvironment interactions. Hypermutation and acquired CDKN2A homozygous deletions associated with an increase in proliferating stem-like malignant cells at recurrence in both glioma subtypes, reflecting active tumor expansion. IDH-wild-type tumors were more invasive at recurrence, and their malignant cells exhibited increased expression of neuronal signaling programs that reflected a possible role for neuronal interactions in promoting glioma progression. Mesenchymal transition was associated with the presence of a specific myeloid cell state defined by unique ligand-receptor interactions with malignant cells, providing opportunities to target this transition through therapy. Collectively, our results uncover recurrence-associated changes in genetics and the microenvironment that can be targeted to shape disease progression following initial diagnosis.
OTEH-5. Characterization of long-non coding RNA associated ceRNA network hub gene involved in glioblastoma multiforme lipid metabolism
Authors: Rizalhanafi Fatin Nabihah , Ramli Norlisah , Narayanan Vairavan , Rashid Khairunnisa , Singh Jesminder Kaur , Ibrahim Kamariah 
Published: July 2021

Abstract

Background
Glioblastoma multiforme (GBM) are the major death contributor in primary brain tumour. Despite having an improved diagnostic criterion by integrating both histological and molecular features such as Isocitrate Dehydrogenase (IDH) detection, the prognosis of GBM patients still remain poor. Lipid metabolism is an essential pathway that fuel GBM aggressiveness. IDH1 one of the key enzyme that regulates it. Long non-coding RNAs (lncRNAs) act as competing endogenous RNAs (ceRNAs) in tumour initiation and progression. In parallel, miRNA-mediate ceRNA crosstalk between lncRNAs and mRNAs. In this study, we aim to investigate the IDH1 subgroup lncRNA associated ceRNA network hub gene responsible in the coordination of glioblastoma multiforme lipid metabolism using bioinformatics approach.

Methods
TCGA-GBM dataset consist of 168 GBM RNA-seq (159 IDH1 wt and 9 IDH1 mutation) were downloaded. Differentially expressed genes (DEG) were then obtained using Limma. Gene sets related with lipid metabolism from GSEA-MSigDB were overlapped with DEG using Venn diagram to identify the DEmRNA that are related with lipid metabolism. Construction of mRNA-miRNA and lncRNA-miRNA interaction networks were performed using miRNet. The ceRNA interaction network were later combined in the Cytoscape software. Potential lncRNA hub genes were identified by CytoHubba analysis.

Results
From 1389 DEG, 67 genes were identified to be significant in the regulation of lipid metabolism. By analysing the lncRNA-miRNA-mRNA interaction network, candidate hub lncRNAs consists of three genes with highest connective nodes; CYTOR, LOXL1-AS1 and HOTAIR. These genes are significantly upregulated in glioma. LOXL1-AS1 serve as an excellent prognostic biomarker for both glioma and glioblastoma as the effect of high and low LOXL1-AS1 expression on patients’ survival is significant (p&lt;0.05).

Conclusions
Data mining and bioinformatics approach guided the identification of the potential hub lncRNAs associated ceRNA network in GBM lipid metabolism. This allows us to uncover the novel role of lncRNA in GBM tumorigenesis.