bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss ofZic3impairs planar cell polarity leading to abnormal left–right signaling, heart defects and neural tube defects
Authors: Bellchambers Helen M , Ware Stephanie M 
Published: July 2021

AbstractLoss of function of ZIC3 causes heterotaxy (OMIM #306955), a disorder characterized by organ laterality defects including complex heart defects. Studies using Zic3 mutant mice have demonstrated that loss of Zic3 causes heterotaxy due to defects in establishment of left–right (LR) signaling, but the mechanistic basis for these defects remains unknown. Here, we demonstrate Zic3 null mice undergo cilia positioning defects at the embryonic node consistent with impaired planar cell polarity (PCP). Cell-based assays demonstrate that ZIC3 must enter the nucleus to regulate PCP and identify multiple critical ZIC3 domains required for regulation of PCP signaling. Furthermore, we show that Zic3 displays a genetic interaction with the PCP membrane protein Vangl2 and the PCP effector genes Rac1 and Daam1 resulting in increased frequency and severity of neural tube and heart defects. Gene and protein expression analyses indicate that Zic3 null embryos display disrupted expression of PCP components and reduced phosphorylation of the core PCP protein DVL2 at the time of LR axis determination. These results demonstrate that ZIC3 interacts with PCP signaling during early development, identifying a novel role for this transcription factor, and adding additional evidence about the importance of PCP function for normal LR patterning and subsequent heart development.
WNT2 activation through proximal germline deletion predisposes to small intestinal neuroendocrine tumors and intestinal adenocarcinomas
Authors: Aavikko Mervi , Kaasinen Eevi , Andersson Noora , Pentinmikko Nalle , Sulo Päivi , Donner Iikki , Pihlajamaa Päivi , Kuosmanen Anna , Bramante Simona , Katainen Riku , Sipilä Lauri J , Martin Samantha , Arola Johanna , Carpén Olli , Heiskanen Ilkka , Mecklin Jukka-Pekka , Taipale Jussi , Ristimäki Ari , Lehti Kaisa , Gucciardo Erika , Katajisto Pekka , Schalin-Jäntti Camilla , Vahteristo Pia , Aaltonen Lauri A 
Published: July 2021

Abstract
Many hereditary cancer syndromes are associated with an increased risk of small and large intestinal adenocarcinomas. However, conditions bearing a high risk to both adenocarcinomas and neuroendocrine tumors are yet to be described.
We studied a family with 16 individuals in four generations affected by a wide spectrum of intestinal tumors, including hyperplastic polyps, adenomas, small intestinal neuroendocrine tumors, and colorectal and small intestinal adenocarcinomas.
To assess the genetic susceptibility and understand the novel phenotype, we utilized multiple molecular methods, including whole genome sequencing, RNA sequencing, single cell sequencing, RNA in situ hybridization and organoid culture.
We detected a heterozygous deletion at the cystic fibrosis locus (7q31.2) perfectly segregating with the intestinal tumor predisposition in the family. The deletion removes a topologically associating domain border between CFTR and WNT2, aberrantly activating WNT2 in the intestinal epithelium. These consequences suggest that the deletion predisposes to small intestinal neuroendocrine tumors and small and large intestinal adenocarcinomas, and reveals the broad tumorigenic effects of aberrant WNT activation in the human intestine.
Complex Temporal Biology: Towards a Unified Multi-Scale Approach to Predict the Flow of Information
Authors: Alicea Bradly , Yuan Chongli 
Published: July 2021

Synopsis
Two hallmarks of biological processes are complexity and time. While complexity can have many meanings, in this paper we propose an explicit link to the flow of time and how it is experienced by the organism. While the flow of time is rooted in constraints of fundamental physics, understanding the operation of biological systems in terms of processual flow and tempo is more elusive. Fortunately, the convergence of new computational and methodological perspectives will provide a means to transform complicated, nonlinear paths between related phenomena at different time scales into dynamic four-dimensional perspectives. According to the complex temporal biology approach, information flow between time scales of multiple lengths is a transformational process that acts to regulate life's complexity. Interactions between temporal intervals of differing magnitude and otherwise loosely-related mechanisms can be understood as inter-timescale information flow. We further propose that informational flow between time scales is the glue that binds the multiple vertical layers of biocomplexity, as well as yielding surprising outcomes ranging from complex behaviors to the persistence of lineages. Building a foundation of rules based on common interactions between orders of time and common experiential contexts would help to reintegrate biology. Emerging methodologies such as state-of-the-art imaging, visualization techniques, and computational data analysis can help us uncover these interactions. In conclusion, we propose educational and community-level changes that would better enable our vision.
Does Social Science Inform Foreign Policy? Evidence from a Survey of US National Security, Trade, and Development Officials
Authors: Avey Paul C , Desch Michael C , Parajon Eric , Peterson Susan , Powers Ryan , Tierney Michael J 
Published: July 2021

Abstract
Scholars continue to debate the relationship of academic international relations to policy. One of the most straightforward ways to discern whether policymakers find IR scholarship relevant to their work is to ask them. We analyzed an elite survey of US policy practitioners to better understand the conditions under which practitioners use academic knowledge in their work. We surveyed officials across three different policy areas: international development, national security, and trade. We also employed multiple survey experiments in an effort to causally identify the impact of academic consensus on the views of policy officials and to estimate the relative utility of different kinds of research outputs. We found that policymakers frequently engage with academic ideas, find an array of research outputs and approaches useful, and that scholarly findings can shift their views. Key obstacles to using academic knowledge include practitioners' lack of time as well as academic work being too abstract and not timely, but not that it is overly quantitative. Additionally, we documented important differences between national security officials and their counterparts who work in the areas of development and trade. We suggest that this variation is rooted in the nature of the different policy areas.
Between Deference and Defiance: Hierarchical Status Roles and International Conflict
Authors: Wolf Reinhard 
Published: July 2021

AbstractAccording to recent international relations research, an actor's status ultimately depends on commonly accepted ratings of that actor's valued attributes (e.g., wealth, competence, culture, or coercive capabilities). This manuscript argues that asymmetric reciprocal roles (leaders versus followers, patrons versus clients, teachers versus students, etc.) constitute another, even more fundamental, kind of stratification that can provoke far more acrimonious status conflicts. Such role-based hierarchies remain stable as long as subordinate actors deem their superiors entitled to deferential treatment. Disputes over asymmetrical roles arise when subaltern actors begin to question the right of dominant actors to command, or when actors fear that co-equal parties are trying to establish their social dominance through a series of faits accomplis. In such circumstances, defiance is the status tactic of choice because it directly undercuts disconcerting patterns of deference. By systematically theorizing defiance in status hierarchies, the paper provides an overdue addition to the literature on the breakdown of cooperation and the dissolution of order. It first sketches a theory that lays out the motives and forms of defiant behavior in international status disputes and then illustrates its value in explaining Russian and Greek resistance to domineering Western “partners.”
International Cooperation and Natural Disasters: Evidence from Trade Agreements
Authors: Conevska Aleksandra 
Published: July 2021

Abstract
Environmental shocks in the form of natural disasters are well known for their impact on domestic economies. Less known, however, is their impact on the global economy. The scant existing literature suggests that macro-economic impacts manifest in observed empirical decreases in international trade. The literature, however, does not examine whether the impact of natural disasters on trade varies for trading partners with differing levels of market integration. This paper examines if preferential liberalization serves to protect or buffer against the negative economic consequences of natural disasters. I show that deep preferential liberalization can not only protect countries against the negative macro-economic impact of natural disasters but can actually allow countries to increase exports during natural disaster events that otherwise induce trade decline. These findings suggest that by allowing countries to expand the quantity and the range of exports, preferential trade agreements lead to enhanced resilience against exogenous shocks.
GraphSynergy: a network-inspired deep learning model for anticancer drug combination prediction
Authors: Yang Jiannan , Xu Zhongzhi , Wu William Ka Kei , Chu Qian , Zhang Qingpeng 
Published: July 2021

AbstractObjectiveTo develop an end-to-end deep learning framework based on a protein–protein interaction (PPI) network to make synergistic anticancer drug combination predictions.Materials and MethodsWe propose a deep learning framework named Graph Convolutional Network for Drug Synergy (GraphSynergy). GraphSynergy adapts a spatial-based Graph Convolutional Network component to encode the high-order topological relationships in the PPI network of protein modules targeted by a pair of drugs, as well as the protein modules associated with a specific cancer cell line. The pharmacological effects of drug combinations are explicitly evaluated by their therapy and toxicity scores. An attention component is also introduced in GraphSynergy, which aims to capture the pivotal proteins that play a part in both PPI network and biomolecular interactions between drug combinations and cancer cell lines.ResultsGraphSynergy outperforms the classic and state-of-the-art models in predicting synergistic drug combinations on the 2 latest drug combination datasets. Specifically, GraphSynergy achieves accuracy values of 0.7553 (11.94% improvement compared to DeepSynergy, the latest published drug combination prediction algorithm) and 0.7557 (10.95% improvement compared to DeepSynergy) on DrugCombDB and Oncology-Screen datasets, respectively. Furthermore, the proteins allocated with high contribution weights during the training of GraphSynergy are proved to play a role in view of molecular functions and biological processes, such as transcription and transcription regulation.ConclusionThe introduction of topological relations between drug combination and cell line within the PPI network can significantly improve the capability of synergistic drug combination identification.
Amplification and Characterization of DDT Metabolizing Delta Class GST in Sand Fly,Phlebotomus argentipes(Diptera: Psychodidae) From Bihar, India
Authors: Hassan Faizan , Singh Krishn Pratap , Shivam Pushkar , Ali Vahab , Dinesh Diwakar Singh 
Published: July 2021

AbstractPhlebotomus argentipes is an established vector for Visceral leishmaniasis prevalent in the Indian subcontinent. Insect Glutathione S-transferases (GST) enzyme plays a pivotal role in the metabolism of xenobiotics and chemical insecticides. We report herein the identification and characterization of a delta class GST from the sandfly, P. argentipes. The resulting clone (rParg-GSTδ) is successfully sequenced, which revealed 76.43% and 66.32% gene identity with GST from Phlebotomus papatasi (Scopoli; Diptera: Psychodidae) and Lutzomiya longipalpis (Lutz and Neiva; Diptera: Psychodidae), respectively. The identified rParg-GST amino acid Blast results revealed 82.6% homology to delta class GST of Phlebotomus papatasi and more than 50% homology to Lepidoptera which comprises butterflies and moths. The Phylogenetic analysis of Parg-GST with different classes of Insect GSTs further supported its classification as delta class. A functional recombinant Parg-GSTδ protein (rParg-GSTδ) was expressed in Escherichia coli (Migula; Enterobacterales: Enterobacteriaceae) cells in a soluble form, purified to homogeneity and found to be active against a substrate 1-chloro-2,4-dintrobenzene (CDNB) and lipid peroxidation by-product 4-Hydrxynonenal (4-HNE). Interestingly, rParg-GSTδ demonstrates high dehydrochlorination activity against dichlorodiphenyltrichloroethane (DDT) i.e., 16.27 nM/µg in high performance liquid chromatography (HPLC) assay. These results provide evidence of direct DDT metabolism property exhibited by P. argentipes GST and set the foundation to decipher the metabolic resistance mechanism in P. argentipes against insecticides.
Cancer Misinformation and Harmful Information on Facebook and Other Social Media: A Brief Report
Authors: Johnson Skyler B , Parsons Matthew , Dorff Tanya , Moran Meena S , Ward John H , Cohen Stacey A , Akerley Wallace , Bauman Jessica , Hubbard Joleen , Spratt Daniel E , Bylund Carma L , Swire-Thompson Briony , Onega Tracy , Scherer Laura D , Tward Jonathan , Fagerlin Angela 
Published: July 2021

Abstract
There are few data on the quality of cancer treatment information available on social media. Here, we quantify the accuracy of cancer treatment information on social media and its potential for harm. Two cancer experts reviewed 50 of the most popular social media articles on each of the 4 most common cancers. The proportion of misinformation and potential for harm were reported for all 200 articles and their association with the number of social media engagements using a 2-sample Wilcoxon rank-sum test. All statistical tests were 2-sided. Of 200 total articles, 32.5% (n = 65) contained misinformation and 30.5% (n = 61) contained harmful information. Among articles containing misinformation, 76.9% (50 of 65) contained harmful information. The median number of engagements for articles with misinformation was greater than factual articles (median [interquartile range] = 2300 [1200-4700] vs 1600 [819-4700], P = .05). The median number of engagements for articles with harmful information was statistically significantly greater than safe articles (median [interquartile range] = 2300 [1400-4700] vs 1500 [810-4700], P = .007).
Urosymphyseal fistulas in women: identification and characterization of a previously undescribed phenomenon
Authors: Anele Uzoma A , Wood Hadley M , Angermeier Kenneth W 
Published: July 2021

Abstract
Urosymphyseal fistula (USF) is a very uncommon but catastrophic condition which typically occurs in the setting of previous radiation treatment for prostate cancer. As a result, USF has only been described in male populations. For the first time, we characterize this phenomenon in a series consisting of four women managed at our quaternary institution. We found that most patients presented with pubic pain and all were diagnosed with USF on CT or MRI. Imaging commonly demonstrated features suggesting osteomyelitis which was confirmed on histology. Patients experienced significant decreases in peri-operative pain scores following extirpative surgery with urinary diversion, bone debridement/resection and tissue interposition. This case series highlights the rarity of USF in women in order to help promote increased recognition and timely management.
Adjunctive efficacy of intra-arterial cone-beam computed tomography angiography in the endovascular treatment of vertebra–venous fistula
Authors: Lu Yu-Chun , Wen Chung-Yu , Yang Shun-Tai , Lu Yueh-Hsun , Su I-Chang 
Published: July 2021

Abstract
Vertebro–venous fistula (VVF) refers to an abnormal arteriovenous shunt connecting the extracranial vertebral artery and the paraspinal venous structures. Coil embolization is the mainstay treatment of choice for VVF, and accurate definition of the endovascular target is mandatory. Traditionally, catheter-based angiograms are used for treatment planning, but those images lack bony information to delineate the precise relationship of the drainage veins to the spinal structure. Herein, we presented two VVF cases and demonstrated how we used intra-arterial cone-beam computed tomography angiography (IA-CBCTA) to determine the safe embolization zone for dense coil packing. We propose that IA-CBCTA is a useful adjunct in the endovascular planning of VVF by offering an image consisting of bony and vascular information.
Nonsense-mediated mRNA decay modulates Arabidopsis flowering time via the SET DOMAIN GROUP 40–FLOWERING LOCUS C module
Authors: Nasim Zeeshan , Fahim Muhammad , Hwang Hocheol , Susila Hendry , Jin Suhyun , Youn Geummin , Ahn Ji Hoon 
Published: July 2021

Abstract
The nonsense-mediated mRNA decay (NMD) surveillance system clears aberrant mRNAs from the cell, thus preventing the accumulation of truncated proteins. Although loss of the core NMD proteins UP-FRAMESHIFT1 (UPF1) and UPF3 leads to late flowering in Arabidopsis, the underlying mechanism remains elusive. Here, we showed that mutations in UPF1 and UPF3 cause temperature- and photoperiod-independent late flowering. Expression analyses revealed high FLOWERING LOCUS C (FLC) mRNA levels in upf mutants; in agreement with this, the flc mutation strongly suppressed the late flowering of upf mutants. Vernalization accelerated flowering of upf mutants in a temperature-independent manner. FLC transcript levels rose in wild-type plants upon NMD inhibition. In upf mutants, we observed increased enrichment of H3K4me3 and reduced enrichment of H3K27me3 in FLC chromatin. Transcriptome analyses showed that SET DOMAIN GROUP 40 (SDG40) mRNA levels increased in upf mutants, and the SDG40 transcript underwent NMD-coupled alternative splicing, suggesting that SDG40 affects flowering time in upf mutants. Furthermore, NMD directly regulated SDG40 transcript stability. The sdg40 mutants showed decreased H3K4me3 and increased H3K27me3 levels in FLC chromatin, flowered early, and rescued the late flowering of upf mutants. Taken together, these results suggest that NMD epigenetically regulates FLC through SDG40 to modulate flowering time in Arabidopsis.
Spectroscopic frequency and mode identification of γ Doradus stars HD 109799 and HD 103257
Authors: Shutt T R , Brunsden E , Pollard K R 
Published: July 2021

ABSTRACT
Following frequency and mode identification of two candidate γ Doradus stars, HD 103257 and HD 109799, both can be categorized as bona-fide members of the class. Over 250 high-resolution spectra of the two stars were collected at University of Canterbury Mount John Observatory (UCMJO) using the High Efficiency and Resolution Canterbury University Large Echelle Spectrograph (HERCULES) spectrograph. The spectra were cross-correlated with a synthetic δ-function template to produce line-profiles and further augmented with high-quality photometry from the Transiting Exoplanet Survey Satellite (TESS) mission, the Wide Angle Search for Planets (WASP) archive, and HIPPARCOS catalogue for frequency and mode analysis. Frequency analysis was carried out using FAMIAS and SigSpec. Two pulsation frequencies were identified in the spectra for HD 103257: 1.22496 ± 0.00001 and 1.14569 ± 0.00002 d−1, explaining 58.9 ${{\ \rm per\ cent}}$ of the variation across the line profiles. Both frequencies were characterized with best-fitting modes of (ℓ, m) = (1, 1). Two pulsation frequencies were identified in the spectra for HD 109799: 1.48679 ± 0.00002 and 1.25213 ± 0.00002 d−1, explaining 32.6 ${{\ \rm per\ cent}}$ of the variation across the line profiles. Both frequencies also yielded individual mode fits of modes (ℓ, m) = (1, 1). The excellent quality photometry from TESS observations has proven complementary to the work herein, and will provide a meaningful opportunity for deeper analysis of additional stars in the HERCULES catalogue. This will be a key component in the continued development of models relating to the processes within γ Doradus stars.
Quantitative comparison of opacities calculated using the R-matrix and distorted-wave methods: Fe xvii
Authors: Delahaye F , Ballance C P , Smyth R T , Badnell N R 
Published: July 2021

ABSTRACT
We present here a detailed calculation of opacities for Fe xvii at the physical conditions corresponding to the base of the Solar convection zone. Many ingredients are involved in the calculation of opacities. We review the impact of each ingredient on the final monochromatic and mean opacities (Rosseland and Planck). The necessary atomic data were calculated with the R-matrix and the distorted-wave (DW) methods. We study the effect of broadening, of resolution, of the extent of configuration sets and of configuration interaction to understand the differences between several theoretical predictions as well as the existing large disagreement with measurements. New Dirac R-matrix calculations including all configurations up to the n = 4, 5, and 6 complexes have been performed as well as corresponding Breit–Pauli DW calculations. The DW calculations have been extended to include autoionizing initial levels. A quantitative contrast is made between comparable DW and R-matrix models. We have reached self-convergence with n = 6 R-matrix and DW calculations. Populations in autoionizing initial levels contribute significantly to the opacities and should not be neglected. The R-matrix and DW results are consistent under the similar treatment of resonance broadening. The comparison with the experiment shows a persistent difference in the continuum while the filling of the windows shows some improvement. This study defines our path to the next generation of opacities and opacity tables for stellar modelling.
Degeneracies between baryons and dark matter: the challenge of constraining the nature of dark matter with JWST
Authors: Khimey Diana , Bose Sownak , Tacchella Sandro 
Published: July 2021

ABSTRACT
The James Webb Space Telescope (JWST) will revolutionize our understanding of early galaxy formation, and could potentially set stringent constraints on the nature of dark matter. We use a semi-empirical model of galaxy formation to investigate the extent to which uncertainties in the implementation of baryonic physics may be degenerate with the predictions of two different models of dark matter – cold dark matter (CDM) and a 7 keV sterile neutrino, which behaves as warm dark matter (WDM). Our models are calibrated to the observed UV luminosity function at z = 4 using two separate dust attenuation prescriptions, which manifest as high and low star formation efficiency in low-mass haloes. These efficiencies capture the net effect of processes that regulate star formation. We find that while at fixed star formation efficiency, ε, there are marked differences in the abundance of faint galaxies in the two dark matter models at high-z; these differences are mimicked easily by varying ε in the same dark matter model. We find that a high ε WDM and a low ε CDM model – which provide equally good fits to the z = 4 UV luminosity function – exhibit nearly identical evolution in the cosmic stellar mass and star formation rate densities. We show that differences in the star formation rate at fixed stellar mass are larger for variations in ε in a given dark matter model than they are between dark matter models; however, the scatter in star formation rates is larger between the two models than they are when varying ε. Our results suggest that JWST will likely be more informative in constraining baryonic processes operating in high-z galaxies than it will be in constraining the nature of dark matter.