bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of sarcopenia on post-operative outcomes following nephrectomy and tumor thrombectomy for renal cell carcinoma with inferior vena cava thrombus
Authors: Watanabe Shun , Ishihara Hiroki , Takagi Toshio , Kondo Tsunenori , Ishiyama Ryo , Fukuda Hironori , Yoshida Kazuhiko , Iizuka Junpei , Kobayashi Hirohito , Ishida Hideki , Tanabe Kazunari 
Published: January 2021

Abstract

Objective
Sarcopenia is associated with oncological outcomes in various types of cancer. However, the impact of sarcopenia in renal cell carcinoma with inferior vena cava thrombus remains unclear. We herein evaluated the prognostic significance of sarcopenia for renal cell carcinoma with inferior vena cava thrombus following nephrectomy and thrombectomy.

Methods
Patients who underwent nephrectomy and thrombectomy for renal cell carcinoma with inferior vena cava thrombus at our department between 2004 and 2019 were retrospectively evaluated. Their sarcopenic status, determined by sex, body mass index and skeletal muscle index, was calculated using pre-surgical radiographic imaging. We compared the post-operative cancer-specific survival and overall survival, surgical data and duration of post-operative hospitalization of sarcopenic and non-sarcopenic patients.

Results
Out of 83 patients, 54 (65%) were sarcopenic. Sarcopenic patients had significantly shorter cancer-specific survival (median: 33.3 months vs. not reached, P = 0.0323) and overall survival (32.0 months vs. not reached, P = 0.0173) than non-sarcopenic patients. Furthermore, multivariate analyses showed that sarcopenia was an independent factor for cancer-specific survival (hazard ratio: 2.76, P = 0.0212) and overall survival (hazard ratio: 2.93, P = 0.014). The incidence rate of surgical complications (any grade: 35.2% vs. 27.6%, P = 0.482; grades ≥ 3: 7.4% vs. 10.3%, P = 0.648) or duration of post-operative hospitalization (median: 11 vs. 10 days, P = 0.148) was not significantly different between sarcopenic and non-sarcopenic patients.

Conclusions
In conclusion, this study showed that sarcopenia was an independent prognostic factor for renal cell carcinoma with inferior vena cava thrombus after nephrectomy and tumor thrombectomy. Thus, sarcopenia evaluation can be utilized as an effective prognosticator of post-operative survival.
Tangeretin as an adjuvant and chemotherapeutic sensitizer against various types of cancers: a comparative overview
Authors: Alhamad Dima W , Elgendy Sara M , Al-Tel Taleb H , Omar Hany A 
Published: January 2021

Abstract

Objectives
Cancer is a leading cause of disabling morbidities and death worldwide. Although there are various strategies for the management of cancer, the severe adverse effects negatively impact the patient’s quality of life. In addition, the development of resistance limits the efficacy of many chemotherapeutics. Many natural agents are capable of reducing the adverse effects associated with chemotherapy and improving the therapeutic outcome. Tangeretin, a polymethoxy flavone, is one of the promising natural anticancer agents.

Key findings
Tangeretin not only targets various malignancies but also synergizes chemotherapeutic agents and reverses cancer resistance. Hence, the application of tangeretin as an adjuvant in cancer chemotherapy would be a promising strategy.

Summary
This work critically highlighted the proposed anticancer activity of tangeretin and discussed its potential combination with various chemotherapeutic agents. Additionally, it shed light on tangeretin chemical derivatives with improved pharmacokinetic and pharmacodynamic activity. Finally, this review described flavonoid biosynthetic pathways and how bioengineering can be employed to enhance the production yield of tangeretin. Thus, this work paves the way for the rational clinical utilization of tangeretin as a safe and effective adjuvant in chemotherapeutic protocols.
Pre-harvest sprouting in cereals: genetic and biochemical mechanisms
Authors: Tai Li , Wang Hong-Jin , Xu Xiao-Jing , Sun Wei-Hang , Ju Lan , Liu Wen-Ting , Li Wen-Qiang , Sun Jiaqiang , Chen Kun-Ming 
Published: January 2021

Abstract
With the growth of the global population and the increasing frequency of natural disasters, crop yields must be steadily increased to enhance human adaptability to risks. Pre-harvest sprouting (PHS), a term mainly used to describe the phenomenon in which grains germinate on the mother plant directly before harvest, is a serious global problem for agricultural production. After domestication, the dormancy level of cultivated crops was generally lower than that of their wild ancestors. Although the shortened dormancy period likely improved the industrial performance of cereals such as wheat, barley, rice, and maize, the excessive germination rate has caused frequent PHS in areas with higher rainfall, resulting in great economic losses. Here, we systematically review the causes of PHS and its consequences, the major indicators and methods for PHS assessment, and emphasize the biological significance of PHS in crop production. Wheat quantitative trait loci functioning in the control of PHS are also comprehensively summarized in a meta-analysis. Finally, we use Arabidopsis as a model plant to develop more complete PHS regulatory networks for wheat. The integration of this information is conducive to the development of custom-made cultivated lines suitable for different demands and regions, and is of great significance for improving crop yields and economic benefits.
Coordination between MIDASIN 1-mediated ribosome biogenesis and auxin modulates plant development
Authors: Li Ke , Zhou Ximeng , Sun Xueping , Li Guanghui , Hou Lei , Zhao Shuzhen , Zhao Chuanzhi , Ma Changle , Li Pengcheng , Wang Xingjun 
Published: January 2021

Abstract
Ribosomes are required for plant growth and development, and ribosome biogenesis-deficient mutants generally display auxin-related phenotypes. Although the relationship between ribosome dysfunction and auxin is known, many aspects of this subject remain to be understood. We previously reported that MIDASIN 1 (MDN1) is an essential pre-60S ribosome biogenesis factor (RBF) in Arabidopsis. In this study, we further characterized the aberrant auxin-related phenotypes of mdn1-1, a weak mutant allele of MDN1. Auxin response is disturbed in both shoots and roots of mdn1-1, as indicated by the DR5:GUS reporter. By combining transcriptome profiling analysis and reporter gene detection, we found that expression of genes involved in auxin biosynthesis, transport, and signaling is changed in mdn1-1. Furthermore, MDN1 deficiency affects the post-transcriptional regulation and protein distribution of PIN-FORMED 2 (PIN2, an auxin efflux facilitator) in mdn1-1 roots. These results indicate that MDN1 is required for maintaining the auxin system. More interestingly, MDN1 is an auxin-responsive gene, and its promoter can be targeted by multiple AUXIN RESPONSE FACTORs (ARFs), including ARF7 and ARF19, in vitro. Indeed, in arf7 arf19, the auxin sensitivity of MDN1 expression is significantly reduced. Together, our results reveal a coordination mechanism between auxin and MDN1-dependent ribosome biogenesis for regulating plant development.
The Experience of Religious Same-Sex Marriage in England and Wales: Understanding the Opportunities and Limits Created by the Marriage (Same Sex Couples) Act 2013
Authors: Falcetta Silvia , Johnson Paul , Vanderbeck Robert M 
Published: January 2021

Abstract
Following the enactment of the Marriage (Same Sex Couples) Act 2013, same-sex couples in England and Wales have the same opportunities as different-sex couples to marry by way of a civil ceremony. However, same-sex couples who wish to marry by way of a religious ceremony are at a significant disadvantage to different-sex couples because only a small number of religious organisations, and a tiny number of places of worship, permit same-sex marriage. Drawing on semi-structured interviews, this article provides the first analysis of the experiences of same-sex couples who have married in a certified place of worship that has been registered for same-sex marriage. We argue that these experiences are shaped in complex ways within an environment in which same-sex religious marriage is lawful but nevertheless difficult to access. The analysis examines the experiences of couples at different stages of the marriage process, including the decision to have a religious marriage, seeking a place of worship, and negotiating the form of the ceremony. We show how many couples, unable to marry within the religious traditions with which they are most familiar, are effectively ‘funnelled’ towards particular traditions about which they have little prior knowledge. The article offers a unique insight into how English marriage law sustains faith-based discrimination against same-sex couples, and how some couples are able to overcome this.
Insights in the molecular mechanisms of an azole stress adapted laboratory-generated Aspergillus fumigatus strain
Authors: Aruanno Marion , Gozel Samantha , Mouyna Isabelle , Parker Josie E , Bachmann Daniel , Flamant Patricia , Coste Alix T , Sanglard Dominique , Lamoth Frederic 
Published: January 2021

Abstract

Aspergillus fumigatus is the main cause of invasive aspergillosis, for which azole drugs are the first-line therapy. Emergence of pan-azole resistance among A. fumigatus is concerning and has been mainly attributed to mutations in the target gene (cyp51A). However, azole resistance may also result from other mutations (hmg1, hapE) or other adaptive mechanisms. We performed microevolution experiment exposing an A. fumigatus azole-susceptible strain (Ku80) to sub-minimal inhibitory concentration of voriconazole to analyze emergence of azole resistance. We obtained a strain with pan-azole resistance (Ku80R), which was partially reversible after drug relief, and without mutations in cyp51A, hmg1, and hapE. Transcriptomic analyses revealed overexpression of the transcription factor asg1, several ATP-binding cassette (ABC) and major facilitator superfamily transporters and genes of the ergosterol biosynthesis pathway in Ku80R. Sterol analysis showed a significant decrease of the ergosterol mass under voriconazole exposure in Ku80, but not in Ku80R. However, the proportion of the sterol compounds was similar between both strains. To further assess the role of transporters, we used the ABC transporter inhibitor milbemycine oxime (MLB). MLB inhibited transporter activity in both Ku80 and Ku80R and demonstrated some potentiating effect on azole activity. Criteria for synergism were reached for MLB and posaconazole against Ku80. Finally, deletion of asg1 revealed some role of this transcription factor in controlling drug transporter expression, but had no impact on azole susceptibility.
This work provides further insight in mechanisms of azole stress adaptation and suggests that drug transporters inhibition may represent a novel therapeutic target.

Lay Summary
A pan-azole-resistant strain was generated in vitro, in which drug transporter overexpression was a major trait. Analyses suggested a role of the transporter inhibitor milbemycin oxime in inhibiting drug transporters and potentiating azole activity.
A numerical approach to the non-uniqueness problem of cosmic ray two-fluid equations at shocks
Authors: Gupta Siddhartha , Sharma Prateek , Mignone Andrea 
Published: January 2021

ABSTRACT
Cosmic rays (CRs) are frequently modelled as an additional fluid in hydrodynamic (HD) and magnetohydrodynamic (MHD) simulations of astrophysical flows. The standard CR two-fluid model is described in terms of three conservation laws (expressing conservation of mass, momentum, and total energy) and one additional equation (for the CR pressure) that cannot be cast in a satisfactory conservative form. The presence of non-conservative terms with spatial derivatives in the model equations prevents a unique weak solution behind a shock. We investigate a number of methods for the numerical solution of the two-fluid equations and find that, in the presence of shock waves, the results generally depend on the numerical details (spatial reconstruction, time stepping, the CFL number, and the adopted discretization). All methods converge to a unique result if the energy partition between the thermal and non-thermal fluids at the shock is prescribed using a subgrid prescription. This highlights the non-uniqueness problem of the two-fluid equations at shocks. From our numerical investigations, we report a robust method for which the solutions are insensitive to the numerical details even in absence of a subgrid prescription, although we recommend a subgrid closure at shocks using results from kinetic theory. The subgrid closure is crucial for a reliable post-shock solution and also its impact on large-scale flows because the shock microphysics that determines CR acceleration is not accurately captured in a fluid approximation. Critical test problems, limitations of fluid modelling, and future directions are discussed.
Overlapping but distinct: a new model for G-quadruplex biochemical specificity
Authors: Volek Martin , Kolesnikova Sofia , Svehlova Katerina , Srb Pavel , Sgallová Ráchel , Streckerová Tereza , Redondo Juan A , Veverka Václav , Curtis Edward A 
Published: January 2021

Abstract
G-quadruplexes are noncanonical nucleic acid structures formed by stacked guanine tetrads. They are capable of a range of functions and thought to play widespread biological roles. This diversity raises an important question: what determines the biochemical specificity of G-quadruplex structures? The answer is particularly important from the perspective of biological regulation because genomes can contain hundreds of thousands of G-quadruplexes with a range of functions. Here we analyze the specificity of each sequence in a 496-member library of variants of a reference G-quadruplex with respect to five functions. Our analysis shows that the sequence requirements of G-quadruplexes with these functions are different from one another, with some mutations altering biochemical specificity by orders of magnitude. Mutations in tetrads have larger effects than mutations in loops, and changes in specificity are correlated with changes in multimeric state. To complement our biochemical data we determined the solution structure of a monomeric G-quadruplex from the library. The stacked and accessible tetrads rationalize why monomers tend to promote a model peroxidase reaction and generate fluorescence. Our experiments support a model in which the sequence requirements of G-quadruplexes with different functions are overlapping but distinct. This has implications for biological regulation, bioinformatics, and drug design.
Experimental Constraints on the Crystallization of Silica Phases in Silicic Magmas
Authors: Martel C , Pichavant M , Di Carlo I , Champallier R , Wille G , Castro J M , Devineau K , Davydova V O , Kushnir A R L 
Published: January 2021

Abstract
Low-pressure silica polymorphs, e.g. quartz (Qtz), tridymite (Trd), and cristobalite (Crs), are common in silicic magmas, but the conditions of their formation are still unclear. The stability fields of these polymorphs have been determined in the SiO2, SiO2–H2O, and haplogranite systems, but these simple systems are not directly applicable to silica polymorph crystallization in natural silicic magmas. The present study compiles an experimental database of new and previously-published data documenting the crystallization of silica phases in natural silicic magmas and simple synthetic systems. Silica polymorphs are identified using Raman spectroscopy and their pressure-temperature domains of occurrence and chemical compositions are determined at pressures between 0·1 and 200 MPa, temperatures between 685 to 1200° C, and under H2O-saturated and H2O-undersaturated conditions.
Qtz is the stable silica polymorph at pressures higher than 25–30 MPa, temperatures between ∼700 and 950° C, and occurs for a narrow range of melt SiO2 contents (∼79–81 wt %). Constraints on Qtz stability derived from simple systems are mutually compatible with, and thus applicable to natural compositions. This is consistent with Qtz compositions being close to ‘pure’ SiO2, both in experiments and nature. In volcanic systems, Qtz crystallization may occur in magmatic reservoirs and deep volcanic conduits.
Trd did not crystallize in the experiments conducted as part of this study despite several experiments having been performed in the Trd stability field. This is consistent with results from the literature which show that Trd crystallization is kinetically inhibited in particular relative to Crs. Natural Trd have compositions deviating substantially from ‘pure’ SiO2, so that stability limits determined in simple systems should not be applied directly to natural cases.
Crs was encountered at pressures below 20–30 MPa (or H2O contents &lt; ∼1·5 wt %), from sub-solidus (∼800° C) to near-liquidus (up to 1040° C), and coexisting with melts having a large range of SiO2 contents (70–81 wt %). The Crs stability field is much larger in natural magmas compared to pure SiO2 systems. Crs is a metastable phase stabilized by components (Al, Na, K; about 3 wt %) present in the silicic melt. In volcanic systems, Crs crystallization may thus be restricted to subsurface manifestations such as lava domes.
Ubiquitylome analysis reveals a central role for the ubiquitin-proteasome system in plant innate immunity
Authors: Ma Xiyu , Zhang Chao , Kim Do Young , Huang Yanyan , Chatt Elizabeth , He Ping , Vierstra Richard D , Shan Libo 
Published: January 2021

Abstract
Protein ubiquitylation profoundly expands proteome functionality and diversifies cellular signaling processes, with recent studies providing ample evidence for its importance to plant immunity. To gain a proteome-wide appreciation of ubiquitylome dynamics during immune recognition, we employed a two-step affinity enrichment protocol based on a 6His-tagged ubiquitin (Ub) variant coupled with high sensitivity mass spectrometry to identify Arabidopsis proteins rapidly ubiquitylated upon plant perception of the microbe-associated molecular pattern (MAMP) peptide flg22. The catalog from 2-week-old seedlings treated for 30 min with flg22 contained 690 conjugates, 64 Ub footprints, and all seven types of Ub linkages, and included previously uncharacterized conjugates of immune components. In vivo ubiquitylation assays confirmed modification of several candidates upon immune elicitation, and revealed distinct modification patterns and dynamics for key immune components, including poly- and monoubiquitylation, as well as induced or reduced levels of ubiquitylation. Gene ontology and network analyses of the collection also uncovered rapid modification of the Ub-proteasome system itself, suggesting a critical auto-regulatory loop necessary for an effective MAMP-triggered immune response and subsequent disease resistance. Included targets were UBIQUITIN-CONJUGATING ENZYME 13 (UBC13) and proteasome component REGULATORY PARTICLE NON-ATPASE SUBUNIT 8b (RPN8b), whose subsequent biochemical and genetic analyses implied negative roles in immune elicitation. Collectively, our proteomic analyses further strengthened the connection between ubiquitylation and flg22-based immune signaling, identified components and pathways regulating plant immunity, and increased the database of ubiquitylated substrates in plants.
Nectar biosynthesis is conserved among floral and extrafloral nectaries
Authors: Chatt Elizabeth C , Mahalim Siti-Nabilla , Mohd-Fadzil Nur-Aziatull , Roy Rahul , Klinkenberg Peter M , Horner Harry T , Hampton Marshall , Carter Clay J , Nikolau Basil J 
Published: January 2021

AbstractNectar is a primary reward mediating plant–animal mutualisms to improve plant fitness and reproductive success. Four distinct trichomatic nectaries develop in cotton (Gossypium hirsutum), one floral and three extrafloral, and the nectars they secrete serve different purposes. Floral nectar attracts bees for promoting pollination, while extrafloral nectar attracts predatory insects as a means of indirect protection from herbivores. Cotton therefore provides an ideal system for contrasting mechanisms of nectar production and nectar composition between different nectary types. Here, we report the transcriptome and ultrastructure of the four cotton nectary types throughout development and compare these with the metabolomes of secreted nectars. Integration of these datasets supports specialization among nectary types to fulfill their ecological niche, while conserving parallel coordination of the merocrine-based and eccrine-based models of nectar biosynthesis. Nectary ultrastructures indicate an abundance of rough endoplasmic reticulum positioned parallel to the cell walls and a profusion of vesicles fusing to the plasma membranes, supporting the merocrine model of nectar biosynthesis. The eccrine-based model of nectar biosynthesis is supported by global transcriptomics data, which indicate a progression from starch biosynthesis to starch degradation and sucrose biosynthesis and secretion. Moreover, our nectary global transcriptomics data provide evidence for novel metabolic processes supporting de novo biosynthesis of amino acids secreted in trace quantities in nectars. Collectively, these data demonstrate the conservation of nectar-producing models among trichomatic and extrafloral nectaries.
Patient and Provider Acceptability of a Patient Preauthorized Concealed Opioid Reduction
Authors: Bedford Theresa , Adediran Timileyin , Haycock Nathaniel R , Mullins C Daniel , Medeiros Michelle , Wright Thelma , Curatolo Michele , Hamlin Lynette , Colloca Luana 
Published: January 2021

AbstractObjectiveLimited research of how to best taper opioids brings about an ethical and clinical dilemma. Experiments using overt and concealed administration of opioids have demonstrated the benefits of a concealed reduction to eliminate negative expectations and prolong analgesic benefits. This may allow for opioid tapering without significant increases in pain. Based on this, we investigated patient and provider acceptance of a concealed opioid reduction for chronic pain.MethodsWe conducted a cross-sectional survey via REDcap with 74 patients, who are currently taking or have taken high dose opioids, and 49 providers using a validated questionnaire based on two hypothetical clinical trials comparing a patient preauthorized concealed opioid reduction vs standard tapering.ResultsWe found that patients and providers have positive attitudes toward a concealed reduction of opioid dosages. More than 60% of providers and patients surveyed viewed the hypothetical clinical trial as helpful to reduce pain, side effects, and withdrawal symptoms. Sixty-one percent of patients and 77.6% of providers recognized that there would be differences in pain relief depending upon which group the hypothetical participants would be enrolled in.ConclusionsPatients and providers appear to understand the benefits of a concealed opioid reduction. Our findings support future randomized controlled trials that compare concealed and overt opioid tapering in patients with chronic pain. More research is needed to understand the difference in attitudes between research and clinical practice and to test the acceptability of a concealed reduction following a participation in an active clinical trial.