bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circular RNAs and complex diseases: from experimental results to computational models
Authors: Wang Chun-Chun , Han Chen-Di , Zhao Qi , Chen Xing 
Published: July 2021

AbstractCircular RNAs (circRNAs) are a class of single-stranded, covalently closed RNA molecules with a variety of biological functions. Studies have shown that circRNAs are involved in a variety of biological processes and play an important role in the development of various complex diseases, so the identification of circRNA-disease associations would contribute to the diagnosis and treatment of diseases. In this review, we summarize the discovery, classifications and functions of circRNAs and introduce four important diseases associated with circRNAs. Then, we list some significant and publicly accessible databases containing comprehensive annotation resources of circRNAs and experimentally validated circRNA-disease associations. Next, we introduce some state-of-the-art computational models for predicting novel circRNA-disease associations and divide them into two categories, namely network algorithm-based and machine learning-based models. Subsequently, several evaluation methods of prediction performance of these computational models are summarized. Finally, we analyze the advantages and disadvantages of different types of computational models and provide some suggestions to promote the development of circRNA-disease association identification from the perspective of the construction of new computational models and the accumulation of circRNA-related data.
Differential network analysis by simultaneously considering changes in gene interactions and gene expression
Authors: Tu Jia-Juan , Ou-Yang Le , Zhu Yuan , Yan Hong , Qin Hong , Zhang Xiao-Fei 
Published: July 2021

Abstract

Motivation
Differential network analysis is an important tool to investigate the rewiring of gene interactions under different conditions. Several computational methods have been developed to estimate differential networks from gene expression data, but most of them do not consider that gene network rewiring may be driven by the differential expression of individual genes. New differential network analysis methods that simultaneously take account of the changes in gene interactions and changes in expression levels are needed.

Results
: In this article, we propose a differential network analysis method that considers the differential expression of individual genes when identifying differential edges. First, two hypothesis test statistics are used to quantify changes in partial correlations between gene pairs and changes in expression levels for individual genes. Then, an optimization framework is proposed to combine the two test statistics so that the resulting differential network has a hierarchical property, where a differential edge can be considered only if at least one of the two involved genes is differentially expressed. Simulation results indicate that our method outperforms current state-of-the-art methods. We apply our method to identify the differential networks between the luminal A and basal-like subtypes of breast cancer and those between acute myeloid leukemia and normal samples. Hub nodes in the differential networks estimated by our method, including both differentially and nondifferentially expressed genes, have important biological functions.

Availability and implementation
All the datasets underlying this article are publicly available. Processed data and source code can be accessed through the Github repository at https://github.com/Zhangxf-ccnu/chNet.

Supplementary information
Supplementary data are available at Bioinformatics online.
Tumor heterogeneity assessed by sequencing and fluorescence in situ hybridization (FISH) data
Authors: Lei Haoyun , Gertz E Michael , Schäffer Alejandro A , Fu Xuecong , Tao Yifeng , Heselmeyer-Haddad Kerstin , Torres Irianna , Li Guibo , Xu Liqin , Hou Yong , Wu Kui , Shi Xulian , Dean Michael , Ried Thomas , Schwartz Russell 
Published: July 2021

Abstract

Motivation
Computational reconstruction of clonal evolution in cancers has become a crucial tool for understanding how tumors initiate and progress and how this process varies across patients. The field still struggles, however, with special challenges of applying phylogenetic methods to cancers, such as the prevalence and importance of copy number alteration (CNA) and structural variation events in tumor evolution, which are difficult to profile accurately by prevailing sequencing methods in such a way that subsequent reconstruction by phylogenetic inference algorithms is accurate.

Results
In this work, we develop computational methods to combine sequencing with multiplex interphase fluorescence in situ hybridization to exploit the complementary advantages of each technology in inferring accurate models of clonal CNA evolution accounting for both focal changes and aneuploidy at whole-genome scales. By integrating such information in an integer linear programming framework, we demonstrate on simulated data that incorporation of FISH data substantially improves accurate inference of focal CNA and ploidy changes in clonal evolution from deconvolving bulk sequence data. Analysis of real glioblastoma data for which FISH, bulk sequence and single cell sequence are all available confirms the power of FISH to enhance accurate reconstruction of clonal copy number evolution in conjunction with bulk and optionally single-cell sequence data.

Availability and implementation
Source code is available on Github at https://github.com/CMUSchwartzLab/FISH_deconvolution.

Supplementary information
Supplementary data are available at Bioinformatics online.
2DProts: database of family-wide protein secondary structure diagrams
Authors: Hutařová Vařeková Ivana , Hutař Jan , Midlik Adam , Horský Vladimír , Hladká Eva , Svobodová Radka , Berka Karel 
Published: July 2021

Abstract

Summary
Secondary structures provide a deep insight into the protein architecture. They can serve for comparison between individual protein family members. The most straightforward way how to deal with protein secondary structure is its visualization using 2D diagrams. Several software tools for the generation of 2D diagrams were developed. Unfortunately, they create 2D diagrams based on only a single protein. Therefore, 2D diagrams of two proteins from one family markedly differ. For this reason, we developed the 2DProts database, which contains secondary structure 2D diagrams for all domains from the CATH and all proteins from PDB databases. These 2D diagrams are generated based on a whole protein family, and they also consider information about the 3D arrangement of secondary structure elements. Moreover, 2DProts database contains multiple 2D diagrams, which provide an overview of a whole protein family's secondary structures. 2DProts is updated weekly and is integrated into CATH.

Availability and Implementation
Freely accessible at https://2dprots.ncbr.muni.cz. The web interface was implemented in JavaScript. The database was implemented in Python.

Supplementary information
Supplementary data are available at Bioinformatics online.
Uncertainty and inequality in early financial thought: John Hicks as a reader of Knight and Keynes
Authors: Hirsch Roni 
Published: July 2021

Abstract
The article examines the early reception of Knight’s and Keynes’ accounts of uncertainty and their overlooked role in the development of financial economics. Knight’s famous distinction between risk and uncertainty bore a deep social and political significance, dividing humanity into risk-takers and the risk-averse. This same distinction, I argue, along with its asymmetries of power and rewards, was reproduced in Hicks’ 1939 dynamic equilibrium model. It was recast as an opposition between hedgers and speculators in a market for risk, on the one hand, and between institutional investors and the general public, on the other. Hicks’s synthesis heeds both Knightian and Keynesian notions of uncertainty, adopting the former’s idea of profit-earning uncertainty-bearers and the latter’s definition of money as an imperfect though widely used hedge against uncertainty. Closer to Knight than to Keynes, Hicks’s model raises a fundamental political question: is inequality a price worth paying for greater certainty in economic life?
British Nationals’ Preferences Over Who Gets to Be a Citizen According to a Choice-Based Conjoint Experiment
Authors: Donnaloja Victoria 
Published: July 2021

Abstract
This article contributes new evidence about the types of immigrants that British nationals would accept as fellow citizens. I analyse the preferences of a large, nationally representative UK sample employing a choice-based conjoint-analysis experiment. Respondents were presented with paired vignettes of applicant types characterized by a combination of attributes chosen randomly. The attributes of immigrants with the largest impact on the probability of granting citizenship were occupation and religion: respondents especially penalized applicants who were Muslim or with no occupation. Respondents granted citizenship at different rates on average (from 64 per cent to 80 per cent): rates were lower among respondents who had voted to leave the EU, were older, less educated, and earned less. The types of immigrant who were most likely to be granted citizenship did not, however, vary by respondents’ income, education, or age, and varied little between Brexit Leave and Remain voters. My findings about nationals’ citizen preferences reflect the inclusive–exclusive nature of British citizenship and national identity, whereby inclusion is conditional on productivity and on the endorsement of liberal values.
Genomic Expansions in the Human Gut Microbiome
Authors: Moeller Andrew H 
Published: July 2021

Abstract
Bacteria inhabiting the human body vary in genome size by over an order of magnitude, but the processes that generate this diversity are poorly understood. Here, we show that evolutionary forces drive divergence in genome size between bacterial lineages in the gut and their closest relatives in other body sites. Analyses of thousands of reference bacterial isolate genomes and metagenome-assembled genomes from the human microbiome indicated that transitions into the gut from other body sites have promoted genomic expansions, whereas the opposite transitions have promoted genomic contractions. Bacterial genomes in the gut are on average ∼127 kb larger than their closest congeneric relatives from other body sites. Moreover, genome size and relative abundance are positively associated within the gut but negatively associated at other body sites. These results indicate that the gut microbiome promotes expansions of bacterial genomes relative to other body sites.
Is a National Court Competent to Introduce a Disclaimer into a Trade Mark Registration? The Latvian Supreme Court Finally Says ‘No’
Authors: Rozenfelds JĀnis , Mantrov Vadim 
Published: July 2021

Abstract
It was a longstanding practice of Latvian courts to acknowledge their competence to introduce a disclaimer into a challenged trade mark registration. This had come to be considered as settled court practice. However, the Latvian Supreme Court recently decided to withdraw this practice and explicitly admitted a change of approach concerning the competence of Latvian national courts to introduce a disclaimer into a trade mark registration. In this way, the Latvian Supreme Court finally abolished a disputable practice in the Latvian courts, having formerly allowed themselves to introduce a disclaimer which could – by way of a misunderstanding of trade mark law – be introduced by a court in addition to a trade mark applicant and the Patent Office. The consequences of this Latvian case have led to the situation that only a trade mark applicant may – either on their own initiative or following a request from the Patent Office – introduce a disclaimer into a trade mark registration. This opinion discusses the situation which existed before the Latvian Supreme Court judgment in question and its consequences.
Postwar statebuilding in Burundi: ruling party elites and illiberal peace
Authors: Burihabwa Ntagahoraho Z , Curtis Devon E A 
Published: July 2021

Abstract
The widespread enthusiasm for internationally-supported liberal statebuilding since the 1990s has become much more tempered, due in part to the mixed record of postwar liberal statebuilding. Over time, many postwar countries have adopted more authoritarian statebuilding trajectories, despite the fact that negotiated peace agreements tend to reflect liberal principles. This is often attributed to ‘liberal’ international actors encountering resistant ‘illiberal’ domestic elites. The postwar statebuilding trajectory in Burundi appears to fit this dominant narrative, with the ruling party, the Conseil National pour la Défense de la Démocratie-Forces pour la Défense de la Démocratie (CNDD-FDD), deviating from some of the liberal principles that underpinned the Burundian peace agreement. Drawing on a detailed analysis of the internal politics of Burundi's ruling party, we show that this account is flawed. We question overly simplified accounts of ‘illiberal’ ruling party elites and we argue that tensions, competition and fragmentation within the ruling party were decisive in Burundi's statebuilding path. Rather than seeing Burundi as an inevitable failure of liberal statebuilding, we highlight how there was some commitment to liberal principles even within the ruling party. Internal struggles within the ruling CNDD-FDD led to current outcomes in Burundi, which should not be interpreted as predestined or definitive. We show that understanding the complexities, diversities and contingencies within ruling parties opens new spaces for thinking about the creation and recreation of political orders after war.
Clerical associations in Qatar and the United Arab Emirates: soft power competition in Islamic politics
Authors: Diwan Kristin 
Published: July 2021

Abstract
In the wake of the 2011 Arab uprisings, the wealthy Gulf states of Qatar and the United Arab Emirates began hosting and establishing associations of influential Islamic scholars. These clerical associations, the Doha-based International Union for Muslim Scholars (IUMS) and the Abu Dhabi-based Muslim Council of Elders (MCE) and associated peace initiatives, have afforded a platform for more credibly entering into religious and political debates, for cultivating new networks of influence among Muslim publics, and engaging non-Islamic countries and organizations. Drawing upon interviews and primary resources, this study investigates this exercise in religious statecraft, comparing the discourse and policy interventions of these associations, and analysing their improbable challenge to the predominant religious terms set by the traditional heavyweight in the Gulf, Saudi Arabia. It finds that the effectiveness, or resonance, of these religious soft power projects depends upon credibility—their alignment with national religious traditions and policy directions—and positioning—the targeting of particular audiences and stakeholders. It concludes that the UAE holds certain advantages over Qatar in its soft power positioning in the current nationalist moment, as states gain ground over transnational Islamic movements and relations with powers such as India, Russia, China and Israel—all hostile to independent Islamic movements—gain in importance. Policy-makers acknowledging the surprising hard power projection of these small states through military interventions and economic leverage may benefit from this study of their new religious soft power influence.
Post-Termination Responsibility of States?—The Impact of Amendment/Modification, Suspension and Termination of Investment Treaties on (Vested) Rights of Investors
Authors: Reinisch August , Mansour Fallah Sara 
Published: July 2021

Abstract
The recent practice of States to amend, suspend or terminate investment treaties has moved questions of potential ‘post-termination responsibility’ to the forefront of the contemporary legal discourse in international investment law. Although States have often included provisions in their respective treaties to regulate post-termination protection of investments, some aspects of the aftermath of treaty terminations are still unsettled. This article defines and discusses various types of ‘post-termination responsibility’ by reviewing current practice, doctrine and jurisprudence on the matter. In that vein, it examines terminations, modifications and suspensions that were unlawful and ineffective, or effective but not capable of releasing the State from all treaty obligations either by virtue of survival clauses or separate principles of vested or third-party rights. It then elaborates on denunciations of the ICSID Convention or terminations of BITs and their effects on pending proceedings or the right to initiate proceedings in the future. Moreover, the article discusses whether survival clauses apply solely to unilateral or also to mutual terminations of investment treaties. It will also address the question whether investor rights may continue to be protected as a result of acquired/vested rights or third-party rights. By analysing the most recent jurisprudence and practice of States, as well as more general foundations of general international law, this article aims to contribute to a clarification of these questions.
Review: optimizing genomic selection for crossbred performance by model improvement and data collection
Authors: Duenk Pascal , Bijma Piter , Wientjes Yvonne C J , Calus Mario P L 
Published: July 2021

AbstractBreeding programs aiming to improve the performance of crossbreds may benefit from genomic prediction of crossbred (CB) performance for purebred (PB) selection candidates. In this review, we compared genomic prediction strategies that differed in 1) the genomic prediction model used or 2) the data used in the reference population. We found 27 unique studies, two of which used deterministic simulation, 11 used stochastic simulation, and 14 real data. Differences in accuracy and response to selection between strategies depended on i) the value of the purebred crossbred genetic correlation (rpc), ii) the genetic distance between the parental lines, iii) the size of PB and CB reference populations, and iv) the relatedness of these reference populations to the selection candidates. In studies where a PB reference population was used, the use of a dominance model yielded accuracies that were equal to or higher than those of additive models. When rpc was lower than ~0.8, and was caused mainly by G × E, it was beneficial to create a reference population of PB animals that are tested in a CB environment. In general, the benefit of collecting CB information increased with decreasing rpc. For a given rpc, the benefit of collecting CB information increased with increasing size of the reference populations. Collecting CB information was not beneficial when rpc was higher than ~0.9, especially when the reference populations were small. Collecting only phenotypes of CB animals may slightly improve accuracy and response to selection, but requires that the pedigree is known. It is, therefore, advisable to genotype these CB animals as well. Finally, considering the breed-origin of alleles allows for modeling breed-specific effects in the CB, but this did not always lead to higher accuracies. Our review shows that the differences in accuracy and response to selection between strategies depend on several factors. One of the most important factors is rpc, and we, therefore, recommend to obtain accurate estimates of rpc of all breeding goal traits. Furthermore, knowledge about the importance of components of rpc (i.e., dominance, epistasis, and G × E) can help breeders to decide which model to use, and whether to collect data on animals in a CB environment. Future research should focus on the development of a tool that predicts accuracy and response to selection from scenario specific parameters.
DNA G-quadruplex structures: more than simple roadblocks to transcription?
Authors: Robinson Jenna , Raguseo Federica , Nuccio Sabrina Pia , Liano Denise , Di Antonio Marco 
Published: July 2021

AbstractIt has been &gt;20 years since the formation of G-quadruplex (G4) secondary structures in gene promoters was first linked to the regulation of gene expression. Since then, the development of small molecules to selectively target G4s and their cellular application have contributed to an improved understanding of how G4s regulate transcription. One model that arose from this work placed these non-canonical DNA structures as repressors of transcription by preventing polymerase processivity. Although a considerable number of studies have recently provided sufficient evidence to reconsider this simplistic model, there is still a misrepresentation of G4s as transcriptional roadblocks. In this review, we will challenge this model depicting G4s as simple ‘off switches’ for gene expression by articulating how their formation has the potential to alter gene expression at many different levels, acting as a key regulatory element perturbing the nature of epigenetic marks and chromatin architecture.
ECOA-4. Hypoxia alters the DNA methylation profile of glioblastoma tumor cells
Authors: Mansouri Sheila , Mamatjan Yasin , Karimi Shirin , Singh Olivia , Tung Takyee , Velasquez Carlos , Nassiri Farshad , Aldape Kenneth , Zadeh Gelareh 
Published: July 2021

Abstract
Glioblastoma (GBM) is the deadliest and most vascularized brain tumor in adults; however, blood circulation is highly inefficient in these tumors, contributing to areas of cell death (necrosis) within the tumor, which is likely due to oxygen deprivation (hypoxia). Hypoxia plays a major role in tumor growth, invasion, and resistance to therapy. Hypoxic stress has been linked to several changes that are fundamental to the malignant progression of GBM and other tumor types. Pimonidazole (PIMO) is an exogenous marker of hypoxia that is used to delineate hypoxic regions in several tumor types. To date, a clear hypoxia gene signature has not been specifically described for GBM. We hypothesize that specific cellular pathways are differentially regulated in hypoxic tumor niches and can serve as novel actionable targets for treatment-resistant tumor cells in GBM. Over the past 3 years, we have administered PIMO to 35 patients with primary IDH1/2 wild-type GBM and isolated PIMO-positive and PIMO-negative tumor cells by laser capture microdissection using a PIMO-specific antibody on frozen tumor specimens. Total genomic DNA was isolated and subjected to DNA methylation profiling using the Illumina Infinium Methylation EPIC array. Our preliminary results suggest that PIMO-positive (hypoxic) tumor cells display a distinct DNA methylation profile that corresponds to changes in expression of a set of genes associated with immune regulation, angiogenesis, and proliferation. Furthermore, multiple CpG sites within the promoter of some genes are differentially methylated in hypoxic cells, suggesting these genes may be epigenetically regulated under hypoxia. In conclusion, our results indicate that hypoxia is associated with distinct epigenetic alterations in tumor cells which may alter how these cells respond to low oxygen levels and can further be utilized to uncover the epigenomic vulnerabilities of hypoxic tumor cells in GBM.