bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of healthcare claims to validate the Prevention of Arrhythmia Device Infection Trial cardiac implantable electronic device infection risk score
Authors: Ahmed Fozia Z , Blomström-Lundqvist Carina , Bloom Heather , Cooper Christopher , Ellis Christopher , Goette Andreas , Greenspon Arnold J , Love Charles J , Johansen Jens Brock , Philippon Francois , Tarakji Khaldoun G , Holbrook Reece , Sherfesee Lou , Xia Ying , Seshadri Swathi , Lexcen Daniel R , Krahn Andrew D
Published: January 2021

Aim

The Prevention of Arrhythmia Device Infection Trial (PADIT) infection risk score, developed based on a large prospectively collected data set, identified five independent predictors of cardiac implantable electronic device (CIED) infection. We performed an independent validation of the risk score in a data set extracted from U.S. healthcare claims.

Methods and results

Retrospective identification of index CIED procedures among patients aged ≥18 years with at least one record of a CIED procedure between January 2011 and September 2014 in a U.S health claims database. PADIT risk factors and major CIED infections (with system removal, invasive procedure without system removal, or infection-attributable death) were identified through diagnosis and procedure codes. The data set was randomized by PADIT score into Data Set A (60%) and Data Set B (40%). A frailty model allowing multiple procedures per patient was fit using Data Set A, with PADIT score as the only predictor, excluding patients with prior CIED infection. A data set of 54 042 index procedures among 51 623 patients with 574 infections was extracted. Among patients with no history of prior CIED infection, a 1 unit increase in the PADIT score was associated with a relative 28% increase in infection risk. Prior CIED infection was associated with significant incremental predictive value (HR 5.66, P < 0.0001) after adjusting for PADIT score. A Harrell’s C-statistic for the PADIT score and history of prior CIED infection was 0.76.

Conclusion

The PADIT risk score predicts increased CIED infection risk, identifying higher risk patients that could potentially benefit from targeted interventions to reduce the risk of CIED infection. Prior CIED infection confers incremental predictive value to the PADIT score.
The microbial dimension of submarine groundwater discharge: current challenges and future directions
Authors: Ruiz-González Clara , Rodellas Valentí , Garcia-Orellana Jordi
Published: January 2021

Despite the relevance of submarine groundwater discharge (SGD) for ocean biogeochemistry, the microbial dimension of SGD remains poorly understood. SGD can influence marine microbial communities through supplying chemical compounds and microorganisms, and in turn, microbes at the land–ocean transition zone determine the chemistry of the groundwater reaching the ocean. However, compared with inland groundwater, little is known about microbial communities in coastal aquifers. Here, we review the state of the art of the microbial dimension of SGD, with emphasis on prokaryotes, and identify current challenges and future directions. Main challenges include improving the diversity description of groundwater microbiota, characterized by ultrasmall, inactive and novel taxa, and by high ratios of sediment-attached versus free-living cells. Studies should explore microbial dynamics and their role in chemical cycles in coastal aquifers, the bidirectional dispersal of groundwater and seawater microorganisms, and marine bacterioplankton responses to SGD. This will require not only combining sequencing methods, visualization and linking taxonomy to activity but also considering the entire groundwater–marine continuum. Interactions between traditionally independent disciplines (e.g. hydrogeology, microbial ecology) are needed to frame the study of terrestrial and aquatic microorganisms beyond the limits of their presumed habitats, and to foster our understanding of SGD processes and their influence in coastal biogeochemical cycles.
Accumulation ofcis- andtrans-regulatory variations is associated with phenotypic divergence of a complex trait between yeast species
Authors: Lupo Offir , Krieger Gat , Jonas Felix , Barkai Naama
Published: January 2021

Gene regulatory variations accumulate during evolution and alter gene expression. While the importance of expression variation in phenotypic evolution is well established, the molecular basis remains largely unknown. Here, we examine two closely related yeast species, Saccharomyces cerevisiae and Saccharomyces paradoxus, which show phenotypical differences in morphology and cell cycle progression when grown in the same environment. By profiling the cell cycle transcriptome and binding of key transcription factors (TFs) in the two species and their hybrid, we show that changes in expression levels and dynamics of oscillating genes are dominated by upstream trans-variations. We find that multiple cell cycle regulators show both cis- and trans-regulatory variations, which alters their expression in favor of the different cell cycle phenotypes. Moreover, we show that variations in the cell cycle TFs, Fkh1, and Fkh2 affect both the expression of target genes, and the binding specificity of an interacting TF, Ace2. Our study reveals how multiple variations accumulate and propagate through the gene regulatory network, alter TFs binding, contributing to phenotypic changes in cell cycle progression.
Hox genes are essential for the development of eyespots inBicyclus anynanabutterflies
Authors: Matsuoka Yuji , Monteiro Antónia
Published: January 2021

The eyespot patterns found on the wings of nymphalid butterflies are novel traits that originated first in hindwings and subsequently in forewings, suggesting that eyespot development might be dependent on Hox genes. Hindwings differ from forewings in the expression of Ultrabithorax (Ubx), but the function of this Hox gene in eyespot development as well as that of another Hox gene Antennapedia (Antp), expressed specifically in eyespots centers on both wings, are still unclear. We used CRISPR-Cas9 to target both genes in Bicyclus anynana butterflies. We show that Antp is essential for eyespot development on the forewings and for the differentiation of white centers and larger eyespots on hindwings, whereas Ubx is essential not only for the development of at least some hindwing eyespots but also for repressing the size of other eyespots. Additionally, Antp is essential for the development of silver scales in male wings. In summary, Antp and Ubx, in addition to their conserved roles in modifying serially homologous segments along the anterior–posterior axis of insects, have acquired a novel role in promoting the development of a new set of serial homologs, the eyespot patterns, in both forewings (Antp) and hindwings (Antp and Ubx) of B. anynana butterflies. We propose that the peculiar pattern of eyespot origins on hindwings first, followed by forewings, could be due to an initial co-option of Ubx into eyespot development followed by a later, partially redundant, co-option of Antp into the same network.
Sperm fate is promoted by the mir-44 microRNA family in the Caenorhabditis elegans hermaphrodite germline
Authors: Maniates Katherine A , Olson Benjamin S , Abbott Allison L
Published: January 2021

Posttranscriptional regulation of gene expression, typically effected by RNA-binding proteins, microRNAs (miRNAs), and translation initiation factors, is essential for normal germ cell function. Numerous miRNAs have been detected in the germline; however, the functions of specific miRNAs remain largely unknown. Functions of miRNAs have been difficult to determine as miRNAs often modestly repress target mRNAs and are suggested to sculpt or fine tune gene expression to allow for the robust expression of cell fates. In Caenorhabditis elegans hermaphrodites, cell fate decisions are made for germline sex determination during larval development when sperm are generated in a short window before the switch to oocyte production. Here, analysis of newly generated mir-44 family mutants has identified a family of miRNAs that modulate the germline sex determination pathway in C. elegans. Mutants with the loss of mir-44 and mir-45 produce fewer sperm, showing both a delay in the specification and formation of sperm as well as an early termination of sperm specification accompanied by a premature switch to oocyte production. mir-44 and mir-45 are necessary for the normal period of fog-1 expression in larval development. Through genetic analysis, we find that mir-44 and mir-45 may act upstream of fbf-1 and fem-3 to promote sperm specification. Our research indicates that the mir-44 family promotes sperm cell fate specification during larval development and identifies an additional posttranscriptional regulator of the germline sex determination pathway.
Differential metabolic sensitivity of insulin-like-response- and TORC1-dependent overgrowth inDrosophilafat cells
Authors: Devilliers Maelle , Garrido Damien , Poidevin Mickael , Rubin Thomas , Le Rouzic Arnaud , Montagne Jacques
Published: January 2021

Glycolysis and fatty acid (FA) synthesis directs the production of energy-carrying molecules and building blocks necessary to support cell growth, although the absolute requirement of these metabolic pathways must be deeply investigated. Here, we used Drosophila genetics and focus on the TOR (Target of Rapamycin) signaling network that controls cell growth and homeostasis. In mammals, mTOR (mechanistic-TOR) is present in two distinct complexes, mTORC1 and mTORC2; the former directly responds to amino acids and energy levels, whereas the latter sustains insulin-like-peptide (Ilp) response. The TORC1 and Ilp signaling branches can be independently modulated in most Drosophila tissues. We show that TORC1 and Ilp-dependent overgrowth can operate independently in fat cells and that ubiquitous over-activation of TORC1 or Ilp signaling affects basal metabolism, supporting the use of Drosophila as a powerful model to study the link between growth and metabolism. We show that cell-autonomous restriction of glycolysis or FA synthesis in fat cells retrains overgrowth dependent on Ilp signaling but not TORC1 signaling. Additionally, the mutation of FASN (Fatty acid synthase) results in a drop in TORC1 but not Ilp signaling, whereas, at the cell-autonomous level, this mutation affects none of these signals in fat cells. These findings thus reveal differential metabolic sensitivity of TORC1- and Ilp-dependent growth and suggest that cell-autonomous metabolic defects might elicit local compensatory pathways. Conversely, enzyme knockdown in the whole organism results in animal death. Importantly, our study weakens the use of single inhibitors to fight mTOR-related diseases and strengthens the use of drug combination and selective tissue-targeting.
Cotton Fiber Development Requires the Pentatricopeptide Repeat Protein GhIm for Splicing of Mitochondrial nad7 mRNA
Authors: Zhang Dayong , Chen Chuan , Wang Haitang , Niu Erli , Zhao Peiyue , Fang Shuai , Zhu Guozhong , Shang Xiaoguang , Guo Wangzhen
Published: January 2021

Pentatricopeptide repeat (PPR) proteins encoded by nuclear genomes can bind to organellar RNA and are involved in the regulation of RNA metabolism. However, the functions of many PPR proteins remain unknown in plants, especially in polyploidy crops. Here, through a map-based cloning strategy and Clustered regularly interspaced short palindromic repeats/cas9 (CRISPR/cas9) gene editing technology, we cloned and verified an allotetraploid cotton immature fiber (im) mutant gene (GhImA) encoding a PPR protein in chromosome A03, that is associated with the non-fluffy fiber phenotype. GhImA protein targeted mitochondrion and could bind to mitochondrial nad7 mRNA, which encodes the NAD7 subunit of Complex I. GhImA and its homolog GhImD had the same function and were dosage-dependent. GhImA in the im mutant was a null allele with a 22 bp deletion in the coding region. Null GhImA resulted in the insufficient GhIm dosage, affected mitochondrial nad7 pre-mRNA splicing, produced less mature nad7 transcripts, and eventually reduced Complex I activities, up-regulated alternative oxidase metabolism, caused reactive oxygen species (ROS) burst and activation of stress or hormone response processes. This study indicates that the GhIm protein participates in mitochondrial nad7 splicing, affects respiratory metabolism, and further regulates cotton fiber development via ATP supply and ROS balance.
Regulation of growth and cell fate during tissue regeneration by the two SWI/SNF chromatin-remodeling complexes of Drosophila
Authors: Tian Yuan , Smith-Bolton Rachel K
Published: January 2021

To regenerate, damaged tissue must heal the wound, regrow to the proper size, replace the correct cell types, and return to the normal gene-expression program. However, the mechanisms that temporally and spatially control the activation or repression of important genes during regeneration are not fully understood. To determine the role that chromatin modifiers play in regulating gene expression after tissue damage, we induced ablation in Drosophila melanogaster imaginal wing discs, and screened for chromatin regulators that are required for epithelial tissue regeneration. Here, we show that many of these genes are indeed important for promoting or constraining regeneration. Specifically, the two SWI/SNF chromatin-remodeling complexes play distinct roles in regulating different aspects of regeneration. The PBAP complex regulates regenerative growth and developmental timing, and is required for the expression of JNK signaling targets and the growth promoter Myc. By contrast, the BAP complex ensures correct patterning and cell fate by stabilizing the expression of the posterior gene engrailed. Thus, both SWI/SNF complexes are essential for proper gene expression during tissue regeneration, but they play distinct roles in regulating growth and cell fate.
Proper CycE–Cdk2 activity in endocycling tissues requires regulation of the cyclin-dependent kinase inhibitor Dacapo by dE2F1b in Drosophila
Authors: Kim Minhee , Delos Santos Keemo , Moon Nam-Sung
Published: January 2021

Polyploidy is an integral part of development and is associated with cellular stress, aging, and pathological conditions. The endocycle, comprised of successive rounds of G and S phases without mitosis, is widely employed to produce polyploid cells in plants and animals. In Drosophila, maintenance of the endocycle is dependent on E2F-governed oscillations of Cyclin E (CycE)–Cdk2 activity, which is known to be largely regulated at the level of transcription. In this study, we report an additional level of E2F-dependent control of CycE–Cdk2 activity during the endocycle. Genetic experiments revealed that an alternative isoform of Drosophila de2f1, dE2F1b, regulates the expression of the p27CIP/KIP-like Cdk inhibitor Dacapo (Dap). We provide evidence showing that dE2F1b-dependent Dap expression in endocycling tissues is necessary for setting proper CycE–Cdk2 activity. Furthermore, we demonstrate that dE2F1b is required for proliferating cell nuclear antigen expression that establishes a negative feedback loop in S phase. Overall, our study reveals previously unappreciated E2F-dependent regulatory networks that are critical for the periodic transition between G and S phases during the endocycle.
The conserved regulator of autophagy and innate immunity hlh-30/TFEB mediates tolerance of enterohemorrhagic Escherichia coli in Caenorhabditis elegans
Authors: Tsai Chia-En , Yang Fang-Jung , Lee Ching-Han , Hsueh Yen-Ping , Kuo Cheng-Ju , Chen Chang-Shi
Published: January 2021

Infection with antibiotic-resistant bacteria is an emerging life-threatening issue worldwide. Enterohemorrhagic Escherichia coli O157: H7 (EHEC) causes hemorrhagic colitis and hemolytic uremic syndrome via contaminated food. Treatment of EHEC infection with antibiotics is contraindicated because of the risk of worsening the syndrome through the secreted toxins. Identifying the host factors involved in bacterial infection provides information about how to combat this pathogen. In our previous study, we showed that EHEC colonizes in the intestine of Caenorhabditis elegans. However, the host factors involved in EHEC colonization remain elusive. Thus, in this study, we aimed to identify the host factors involved in EHEC colonization. We conducted forward genetic screens to isolate mutants that enhanced EHEC colonization and named this phenotype enhanced intestinal colonization (Inc). Intriguingly, four mutants with the Inc phenotype showed significantly increased EHEC-resistant survival, which contrasts with our current knowledge. Genetic mapping and whole-genome sequencing (WGS) revealed that these mutants have loss-of-function mutations in unc-89. Furthermore, we showed that the tolerance of unc-89(wf132) to EHEC relied on HLH-30/TFEB activation. These findings suggest that hlh-30 plays a key role in pathogen tolerance in C. elegans.
A microbial gene catalog of anaerobic digestion from full-scale biogas plants
Authors: Ma Shichun , Jiang Fan , Huang Yan , Zhang Yan , Wang Sen , Fan Hui , Liu Bo , Li Qiang , Yin Lijuan , Wang Hengchao , Liu Hangwei , Ren Yuwei , Li Shuqu , Cheng Lei , Fan Wei , Deng Yu
Published: January 2021

Background

Biogas production with anaerobic digestion (AD) is one of the most promising solutions for both renewable energy production and resolving the environmental problem caused by the worldwide increase in organic waste. However, the complex structure of the microbiome in AD is poorly understood.

Findings

In this study, we constructed a microbial gene catalog of AD (22,840,185 genes) based on 1,817 Gb metagenomic data derived from digestate samples of 56 full-scale biogas plants fed with diverse feedstocks. Among the gene catalog, 73.63% and 2.32% of genes were taxonomically annotated to Bacteria and Archaea, respectively, and 57.07% of genes were functionally annotated with KEGG orthologous groups. Our results confirmed the existence of core microbiome in AD and showed that the type of feedstock (cattle, chicken, and pig manure) has a great influence on carbohydrate hydrolysis and methanogenesis. In addition, 2,426 metagenome-assembled genomes were recovered from all digestate samples, and all genomes were estimated to be ≥80% complete with ≤10% contamination.

Conclusions

This study deepens our understanding of the microbial composition and function in the AD process and also provides a huge number of reference genome and gene resources for analysis of anaerobic microbiota.
Detection and source parametrization of small-energy fireball events in Western Alps with ground-based infrasonic arrays
Authors: Belli Giacomo , Pace Emanuele , Marchetti Emanuele
Published: January 2021

We present infrasound signals generated by four fireball events occurred in Western Alps between 2016 and 2019 and that were recorded by small aperture arrays at source-to-receiver distances <300 km. Signals consist in a series of short-lived infrasonic arrivals that are closely spaced in time. Each arrival is identified as a cluster of detections with constant wave parameters (backazimuth and apparent velocity), that change however from cluster to cluster. These arrivals are likely generated by multiple infrasonic sources (fragmentations or hypersonic flow) along the entry trajectory. We developed a method, based on 2-D ray tracing and on the independent optically determined time of the event, to locate the source position of the multiple arrivals from a single infrasonic array data and to reconstruct the 3-D trajectory of a meteoroid in the Earth's atmosphere. The trajectories derived from infrasound array analysis are in excellent agreement with trajectories reconstructed from eyewitnesses reports for the four fireballs. Results suggest that the trajectory reconstruction is possible for meteoroid entries located up to ∼300 km from the array, with an accuracy that depends on the source-to-receiver distance and on the signal-to-noise level. We also estimate the energy of the four fireballs using three different empirical laws, based both on period and amplitude of recorded infrasonic signals, and discuss their applicability for the energy estimation of small energy fireball events ($\le 1{\rm{kt\,\,TNT\,\,equivalent}}$).
Compressive learning with privacy guarantees
Authors: Chatalic A , Schellekens V , Houssiau F , de Montjoye Y A , Jacques L , Gribonval R
Published: January 2021

This work addresses the problem of learning from large collections of data with privacy guarantees. The compressive learning framework proposes to deal with the large scale of datasets by compressing them into a single vector of generalized random moments, called a sketch vector, from which the learning task is then performed. We provide sharp bounds on the so-called sensitivity of this sketching mechanism. This allows us to leverage standard techniques to ensure differential privacy—a well-established formalism for defining and quantifying the privacy of a random mechanism—by adding Laplace of Gaussian noise to the sketch. We combine these standard mechanisms with a new feature subsampling mechanism, which reduces the computational cost without damaging privacy. The overall framework is applied to the tasks of Gaussian modeling, k-means clustering and principal component analysis, for which sharp privacy bounds are derived. Empirically, the quality (for subsequent learning) of the compressed representation produced by our mechanism is strongly related with the induced noise level, for which we give analytical expressions.
Sober in Mecca, Drunk in Byzantium: Antinomian Space in the Poetry of ʿAṭṭār
Authors: Zargar Cyrus Ali
Published: January 2021

This paper investigates premodern conceptions of spaces of otherness, particularly within the context of Persian Sufi poetry. Abbasid-era travel literature describing monasteries, as well as real hostilities between Muslims and Christians, gave symbolic dimensions to spaces of antinomian activity in thirteenth-century eastern Iran. Making use of Edward Soja’s thirdspace, as well as Jorge Luis Borges’s the Aleph, this paper pays particular attention to the pseudo-hagiographical narrative of the “Shaykh of Ṣanʿān” in the poem Manṭiq al-Ṭayr (Speech of the Birds). In this account by the Persian poet Farīd al-Dīn ʿAṭṭār (d. 1221), Byzantium contrasts with the Kaʿba in Mecca, just as the wine-house, the Christian church, and the ruins contrast with normative spaces wherein expectations of decorum can lead to ostentatious and insincere modes of worship. By creating magical spaces of infidelity, spaces devoid of piety, ʿAṭṭār conveys themes of losing oneself to a carnal and ultimately divine Other.
Research Integrated Network of Systems (RINS): a virtual data warehouse for the acceleration of translational research
Authors: He Wenjun , Kirchoff Katie G , Sampson Royce R , McGhee Kimberly K , Cates Andrew M , Obeid Jihad S , Lenert Leslie A
Published: January 2021

Objective

Integrated, real-time data are crucial to evaluate translational efforts to accelerate innovation into care. Too often, however, needed data are fragmented in disparate systems. The South Carolina Clinical & Translational Research Institute at the Medical University of South Carolina (MUSC) developed and implemented a universal study identifier—the Research Master Identifier (RMID)—for tracking research studies across disparate systems and a data warehouse-inspired model—the Research Integrated Network of Systems (RINS)—for integrating data from those systems.

Materials and Methods

In 2017, MUSC began requiring the use of RMIDs in informatics systems that support human subject studies. We developed a web-based tool to create RMIDs and application programming interfaces to synchronize research records and visualize linkages to protocols across systems. Selected data from these disparate systems were extracted and merged nightly into an enterprise data mart, and performance dashboards were created to monitor key translational processes.

Results

Within 4 years, 5513 RMIDs were created. Among these were 726 (13%) bridged systems needed to evaluate research study performance, and 982 (18%) linked to the electronic health records, enabling patient-level reporting.

Discussion

Barriers posed by data fragmentation to assessment of program impact have largely been eliminated at MUSC through the requirement for an RMID, its distribution via RINS to disparate systems, and mapping of system-level data to a single integrated data mart.

Conclusion

By applying data warehousing principles to federate data at the “study” level, the RINS project reduced data fragmentation and promoted research systems integration.
Two Complete Mitochondrial Genomes From Leuctridae (Plecoptera: Nemouroidea): Implications for the Phylogenetic Relationships Among Stoneflies
Authors: Cao Jinjun , Wang Ying , Guo Xuan , Wang Guoquan , Li Weihai , Murányi Dávid
Published: January 2021

The family-level relationships within Plecoptera have been a focused area of research for a long time. Its higher classification remains unstable, and the phylogenetic relationships within Plecoptera should be re-examined. Here, we sequenced and analyzed two complete mitochondrial genomes (mitogenomes) of Paraleuctra cercia and Perlomyia isobeae of the family Leuctridae. We reconstructed the phylogeny of Plecoptera based on 13 protein-coding genes (PCGs) from published stoneflies. Our results showed that the Bayesian inference and maximum-likelihood tree had similar topological structures except for the positions of two families, Peltoperlidae and Scopuridae. The Plecoptera is divided into two clades, the suborder Antarctoperlaria and the suborder Arctoperlaria. The two suborders subsequently formed two groups, Eusthenioidea and Gripopterygoidea, and Euholognatha and Systellognatha, which is consistent with the results of morphological studies. In addition, the Leuctridae is the earliest branch within the superfamily Nemouroidea. But the monophyly of Perloidea and Pteronarcyoidea are still not well supported.
Palliative brachytherapy and external beam radiotherapy for dysphagia from esophageal cancer: a nationwide survey in Japan
Authors: Kawamoto Terufumi , Nakamura Naoki , Saito Tetsuo , Tonari Ayako , Wada Hitoshi , Harada Hideyuki , Kubota Hikaru , Nagakura Hisayasu , Heianna Joichi , Miyazawa Kazunari , Yamada Kazunari , Tago Masao , Fushiki Masato , Nozaki Miwako , Uchida Nobue , Araki Norio , Sekii Shuhei , Kosugi Takashi , Takahashi Takeo , Shikama Naoto
Published: January 2021

Background

International guidelines recommend brachytherapy for patients with dysphagia from esophageal cancer, whereas brachytherapy is infrequently used to palliate dysphagia in some countries. To clarify the availability of palliative treatment for dysphagia from esophageal cancer and explain why brachytherapy is not routinely performed are unknown, this study investigated the use of brachytherapy and external beam radiotherapy for dysphagia from esophageal cancer.

Methods

Japanese Radiation Oncology Study Group members completed a survey and selected the treatment that they would recommend for hypothetical cases of dysphagia from esophageal cancer.

Results

Of the 136 invited facilities, 61 completed the survey (44.9%). Four (6.6%) facilities performed brachytherapy of the esophagus, whereas brachytherapy represented the first-line treatment at three (4.9%) facilities. Conversely, external beam radiotherapy alone and chemoradiotherapy were first-line treatments at 61 and 58 (95.1%) facilities, respectively. In facilities that performed brachytherapy, the main reason why brachytherapy of the esophagus was not performed was high invasiveness (30.2%). Definitive-dose chemoradiotherapy with (≥50 Gy) tended to be used in patients with expected long-term survival.

Conclusions

Few facilities routinely considered brachytherapy for the treatment of dysphagia from esophageal cancer in Japan. Conversely, most facilities routinely considered external beam radiotherapy. In the future, it will be necessary to optimize external beam radiotherapy.
How Are Disputes Resolved under Bilateral Air Services Agreements? A Typology
Authors: Zhang Luping
Published: January 2021

After a dispute between India and Pakistan broke out concerning overflight rights, the International Civil Aviation Organisation (ICAO) Secretariat reviewed 204 bilateral aeronautical agreements between 1941 and 1951 and listed them according to the categories of dispute resolution clauses that they contained. Around 68 years have passed and the ICAO Council has exercised its dispute settlement power in multiple occasions. This article builds upon the research carried out by the ICAO Secretariat, which it supplements with up-to-date data of 709 agreements. It then provides a typology, a study of different types, of bilateral air services agreements (ASAs). The article concludes that the use of international arbitration is the primary forum for dispute resolution chosen by drafters of bilateral ASAs. However, a look at the cases brought to ad hoc arbitration reveals deficiencies, which leads us to discuss potential institutionalized reforms.
Fluid–structure interaction simulation on flight performance of a dragonfly wing under different pterostigma weights
Authors: Chu Yung Jeh , Ganesan Poo Balan , Ali Mohamad Azlin
Published: January 2021

The dragonfly wings provide insights for designing an efficient biomimetic micro air vehicle (BMAV). In this regard, this study focuses on investigating the effect of the pterostigma weight loading and its spatial location on the forewings of dragonfly by using the fluid–structure interaction simulation. This study also investigates the effect of change in the wing elasticity and density on the wing performance. The forewing, which mimics the real dragonfly wing, is flat with a 47.5 mm span and a 0.4 mm thickness. The wing was set to cruise at 3 m/s with a constant flapping motion at a frequency of 25 Hz. This study shows that a small increase of pterostigma loading (11% of wing weight) at the tip of the wing significantly improves the lift to drag ratio, CL/CD, which has 129.16% increment in comparison with no loading. The lift to drag ratio depends on the pterostigma location, pterostigma loading, elastic modulus and density. The results of this study can be used as a reference in future BMAV wing optimization design.
Observations and spectral modelling of the narrow-lined Type Ic SN 2017ein
Authors: Teffs J J , Prentice S J , Mazzali P A , Ashall C
Published: January 2021

SN 2017ein is a narrow-lined Type Ic SN that was found to share a location with a point-like source in the face on spiral galaxy NGC 3938 in pre-supernova images, making SN 2017ein the first credible detection of a Type Ic progenitor. Results in the literature suggest that this point-like source is likely a massive progenitor of 60–80 M⊙, depending on if the source is a binary, a single star, or a compact cluster. Using new photometric and spectral data collected for 200 d, including several nebular spectra, we generate a consistent model covering the photospheric and nebular phase using a Monte Carlo radiation transport code. Photospheric phase modelling finds an ejected mass 1.2–2.0 M⊙ with an Ek of ∼(0.9 ± 0.2) × 1051 erg, with approximately 1 M⊙ of material below 5000 km s−1 found from the nebular spectra. Both photospheric and nebular phase modelling suggests a 56Ni mass of 0.08–0.1 M⊙. Modelling the [O i] emission feature in the nebular spectra suggests that the innermost ejecta are asymmetric. The modelling results favour a low-mass progenitor of 16–20 M⊙, which is in disagreement with the pre-supernova derived high-mass progenitor. This contradiction is likely due to the pre-supernova source not representing the actual progenitor.
Structural basis for RNA recognition by the N-terminal tandem RRM domains of human RBM45
Authors: Chen Xiaolei , Yang Zhongmei , Wang Wenfeng , Qian Kaiyue , Liu Mingjie , Wang Junchao , Wang Mingzhu
Published: January 2021

RBM45 is an RNA-binding protein involved in neural development, whose aggregation is associated with neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTLD). However, the mechanisms of RNA-binding and aggregation of RBM45 remain unelucidated. Here, we report the crystal structure of the N-terminal tandem RRM domains of human RBM45 in complex with single-stranded DNA (ssDNA). Our structural and biochemical results revealed that both the RRM1 and RRM2 of RBM45 recognized the GAC sequence of RNA/ssDNA. Two aromatic residues and an arginine residue in each RRM were critical for RNA-binding, and the interdomain linker was also involved in RNA-binding. Two RRMs formed a pair of antiparallel RNA-binding sites, indicating that the N-terminal tandem RRM domains of RBM45 bound separate GAC motifs in one RNA strand or GAC motifs in different RNA strands. Our findings will be helpful in the identification of physiologic targets of RBM45 and provide evidence for understanding the physiologic and pathologic functions of RBM45.
Industry-Sponsored Research Payments in Neurosurgery—Analysis of the Open Payments Database From 2014 to 2018
Authors: Vanood Aimen , Sharrak Aryana , Karabon Patrick , Fahim Daniel K
Published: January 2021

BACKGROUND

The Open Payments Database (OPD) started in 2013 to combat financial conflicts of interest between physicians and medical industry.

OBJECTIVE

To evaluate the first 5 yr of the OPD regarding industry-sponsored research funding (ISRF) in neurosurgery.

METHODS

The Open Payments Research Payments dataset was examined from 2014 to 2018 for payments where the clinical primary investigator identified their specialty as neurosurgery.

RESULTS

Between 2014 and 2018, a $106.77 million in ISRF was made to 731 neurosurgeons. Fewer than 11% of neurosurgeons received ISRF yearly. The average received $140 000 in total but the median received $30,000. This was because the highest paid neurosurgeon received $3.56 million. A greater proportion ISRF was made to neurosurgeons affiliated with teaching institutions when compared to other specialties (26.74% vs 20.89%, P = .0021). The proportion of the total value of ISRF distributed to neurosurgery declined from 0.43% of payments to all specialties in 2014 to 0.37% in 2018 (P < .001), but no steady decline was observed from year to year.

CONCLUSION

ISRF to neurosurgeons comprises a small percentage of research payments made to medical research by industry sponsors. Although a greater percentage of payments are made to neurosurgeons in teaching institutions compared to other specialties, the majority is given to neurosurgeons not affiliated with a teaching institution. A significant percentage of ISRF is given to a small percentage of neurosurgeons. There may be opportunities for more neurosurgeons to engage in industry-sponsored research to advance our field as long as full and complete disclosures can always be made.
Impact of Coronavirus Disease 2019 on Infectious Diseases Fellows in the United States: Perspectives From the First National Infectious Diseases Fellows Call
Authors: Nematollahi Saman , Konold Victoria J L , Gaston David C , Howard-Anderson Jessica , Kiley John L , Masters Mary C , Melia Michael T , Balba Gayle P , Chiang Augusto Dulanto , Gupta Nupur
Published: January 2021

The coronavirus disease 2019 (COVID-19) pandemic has affected many providers, but its impact on Infectious Diseases (ID) fellows in the United States is largely undescribed. In this study, we discuss key issues that emerged from the first national ID Fellows Call with respect to the ID fellow’s role during the COVID-19 pandemic, teaching/learning, and research.
Professional Development for Industrial-Organizational Psychology Master’s Graduates
Authors: Shoenfelt Elizabeth L.
Published: January 2021

This chapter addresses the important postgraduate experience of continuing training and development for industrial-organizational (I-O) psychology master’s graduates. I-O master’s students often leave school with fewer networking ties, academic mentors, and overall skills in their toolbox than do PhD students. This chapter discusses common certifications and continuing education opportunities that are relevant to those pursuing I-O psychology careers. Mentoring experience are discussed based on experiences of I-O master’s graduates and their employers. Three best-practice suggestions for maximizing mentoring relationships are described. I-O psychology master’s practitioners should use professional development opportunities that increase their knowledge, skills, and the power of their résumé and that help advance their careers.
An atlas of wheat epigenetic regulatory elements reveals subgenome divergence in the regulation of development and stress responses
Authors: Wang Meiyue , Li Zijuan , Zhang Yu’e , Zhang Yuyun , Xie Yilin , Ye Luhuan , Zhuang Yili , Lin Kande , Zhao Fei , Guo Jingyu , Teng Wan , Zhang Wenli , Tong Yiping , Xue Yongbiao , Zhang Yijing
Published: January 2021

Wheat (Triticum aestivum) has a large allohexaploid genome. Subgenome-divergent regulation contributed to genome plasticity and the domestication of polyploid wheat. However, the specificity encoded in the wheat genome determining subgenome-divergent spatio-temporal regulation has been largely unexplored. The considerable size and complexity of the genome are major obstacles to dissecting the regulatory specificity. Here, we compared the epigenomes and transcriptomes from a large set of samples under diverse developmental and environmental conditions. Thousands of distal epigenetic regulatory elements (distal-epiREs) were specifically linked to their target promoters with coordinated epigenomic changes. We revealed that subgenome-divergent activity of homologous regulatory elements is affected by specific epigenetic signatures. Subgenome-divergent epiRE regulation of tissue specificity is associated with dynamic modulation of H3K27me3 mediated by Polycomb complex and demethylases. Furthermore, quantitative epigenomic approaches detected key stress responsive cis- and trans-acting factors validated by DNA Affinity Purification and sequencing, and demonstrated the coordinated interplay between epiRE sequence contexts, epigenetic factors, and transcription factors in regulating subgenome divergent transcriptional responses to external changes. Together, this study provides a wealth of resources for elucidating the epiRE regulomics and subgenome-divergent regulation in hexaploid wheat, and gives new clues for interpreting genetic and epigenetic interplay in regulating the benefits of polyploid wheat.
Predominantly inverse modulation of gene expression in genomically unbalanced disomic haploid maize
Authors: Yang Hua , Shi Xiaowen , Chen Chen , Hou Jie , Ji Tieming , Cheng Jianlin , Birchler James A
Published: January 2021

The phenotypic consequences of the addition or subtraction of part of a chromosome is more severe than changing the dosage of the whole genome. By crossing diploid trisomies to a haploid inducer, we identified 17 distal segmental haploid disomies that cover ∼80% of the maize genome. Disomic haploids provide a level of genomic imbalance that is not ordinarily achievable in multicellular eukaryotes, allowing the impact to be stronger and more easily studied. Transcriptome size estimates revealed that a few disomies inversely modulate most of the transcriptome. Based on RNA sequencing, the expression levels of genes located on the varied chromosome arms (cis) in disomies ranged from being proportional to chromosomal dosage (dosage effect) to showing dosage compensation with no expression change with dosage. For genes not located on the varied chromosome arm (trans), an obvious trans-acting effect can be observed, with the majority showing a decreased modulation (inverse effect). The extent of dosage compensation of varied cis genes correlates with the extent of trans inverse effects across the 17 genomic regions studied. The results also have implications for the role of stoichiometry in gene expression, the control of quantitative traits, and the evolution of dosage-sensitive genes.
Ethylene-regulated asymmetric growth of the petal base promotes flower opening in rose (Rosa hybrida)
Authors: Cheng Chenxia , Yu Qin , Wang Yaru , Wang Hong , Dong Yuhan , Ji Yuqi , Zhou Xiaofeng , Li Yonghong , Jiang Cai-Zhong , Gan Su-Sheng , Zhao Liangjun , Fei Zhangjun , Gao Junping , Ma Nan
Published: January 2021

Flowers are the core reproductive structures and key distinguishing features of angiosperms. Flower opening to expose stamens and gynoecia is important in cases where pollinators much be attracted to promote cross-pollination, which can enhance reproductive success and species preservation. The floral opening process is accompanied by the coordinated movement of various floral organs, particularly petals. However, the mechanisms underlying petal movement and flower opening are not well understood. Here, we integrated anatomical, physiological, and molecular approaches to determine the petal movement regulatory network using rose (Rosa hybrida) as a model. We found that PETAL MOVEMENT-RELATED PROTEIN1 (RhPMP1), a homeodomain transcription factor (TF) gene, is a direct target of ETHYLENE INSENSITIVE3, a TF that functions downstream of ethylene signaling. RhPMP1 expression was upregulated by ethylene and specifically activated endoreduplication of parenchyma cells on the adaxial side of the petal (ADSP) base by inducing the expression of RhAPC3b, a gene encoding the core subunit of the Anaphase-Promoting Complex. Cell expansion of the parenchyma on the ADSP base was subsequently enhanced, thus resulting in asymmetric growth of the petal base, leading to the typical epinastic movement of petals and flower opening. These findings provide insights into the pathway regulating petal movement and associated flower-opening mechanisms.�
The receptor-like cytoplasmic kinase CDG1 negatively regulates Arabidopsis pattern-triggered immunity and is involved in AvrRpm1-induced RIN4 phosphorylation
Authors: Yang Qiujiao , Guo Jianhang , Zeng Hairuo , Xu Lahong , Xue Jiao , Xiao Shi , Li Jian-Feng
Published: January 2021

Arabidopsis CDG1 negatively regulates flg22- and chitin-triggered immunity by promoting FLS2 and CERK1 degradation and is partially required for bacterial effector AvrRpm1-induced RIN4 phosphorylation.

Negative regulators play indispensable roles in pattern-triggered immunity in plants by preventing sustained immunity impeding growth. Here, we report Arabidopsis thaliana CONSTITUTIVE DIFFERENTIAL GROWTH1 (CDG1), a receptor-like cytoplasmic kinase VII member, as a negative regulator of bacterial flagellin/flg22- and fungal chitin-triggered immunity. CDG1 can interact with the flg22 receptor FLAGELLIN SENSITIVE2 (FLS2) and chitin co-receptor CHITIN ELICITOR RECEPTOR KINASE1 (CERK1). CDG1 overexpression impairs flg22 and chitin responses by promoting the degradation of FLS2 and CERK1. This process requires the kinase activity of MEK KINASE1 (MEKK1), but not the Plant U-Box (PUB) ubiquitin E3 ligases PUB12 and PUB13. Interestingly, the Pseudomonas syringae effector AvrRpm1 can induce CDG1 to interact with its host target RPM1-INTERACTING PROTEIN4 (RIN4), which depends on the ADP-ribosyl transferase activity of AvrRpm1. CDG1 is capable of phosphorylating RIN4 in vitro at multiple sites including Thr166 and the AvrRpm1-induced Thr166 phosphorylation of RIN4 is diminished in cdg1 null plants. Accordingly, CDG1 knockout attenuates AvrRpm1-induced hypersensitive response and increases the growth of AvrRpm1-secreting bacteria in plants. Unexpectedly, AvrRpm1 can also induce FLS2 depletion, which is fully dependent on RIN4 and partially dependent on CDG1, but does not require the kinase activity of MEKK1. Collectively, this study reveals previously unknown functions of CDG1 in both pattern-triggered immunity and effector-triggered susceptibility in plants.
A model system for studying plant–microbe interactions under snow
Authors: Kuwabara Chikako , Sasaki Kentaro , Umeki Natsuki , Hoshino Tamotsu , Saburi Wataru , Matsui Hirokazu , Imai Ryozo
Published: January 2021

A model plant–pathogen system using Arabidopsis and its natural snow mold pathogen Typhula ishikariensis demonstrated Arabidopsis plants develop disease resistance through cold acclimation.
Association Between Clinical Symptoms and Radiographic Features in Late-Stage Knee Osteoarthritis Using a New Radiographic Parameter
Authors: Zhu Tengjiao , Xin Xing , Yang Bin , Liu Chen , Kou Bolong , Chen Zhongqiang , Zhang Ke
Published: January 2021

Objective

In this study, we proposed a new radiographic parameter, the plateau attrition index (PAI), and the PAI grades (PAIs) to explore the relationship between subchondral attrition of the tibial plateau and symptoms of knee osteoarthritis (OA) in patients with late-stage knee osteoarthritis.

Method

One hundred nineteen patients with late-stage knee osteoarthritis were enrolled. The Kellgren and Lawrence (K/L) grades and hip-knee-ankle (HKA) angle were used to characterize the radiographic features of knee OA. The bone attrition of the tibial plateau was determined by the PAI and PAIs. The symptoms of knee OA were assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), which is composed of the WOMAC pain (WOMP), WOMAC stiffness (WOMS), and WOMAC function (WOMF) subscores. WOMAC pain scores were divided into non-weight-bearing pain (NWBP) and weight-bearing pain (WBP) subcategories. The Pearson correlation coefficient was used to determine the relationship between the PAI, HKA angle, and WOMAC scores. The Spearman rank correlation coefficient was used to evaluate the correlation between the WOMAC score and the PAIs and K/L grades.

Results

The distribution of the WOMAC scores according to the PAIs was significant (P < .01). A positive correlation was identified between the PAI and the WOMAC, WOMP, WOMF and WBP scores (r = 0.29, 0.34, 0.26 and 0.34, P < .01, respectively). In addition, the PAIs was also significantly correlated with the WOMAC, WOMP, WOMF, and WBP scores (r = 0.37, 0.38, 0.35 and 0.44, P < .01, respectively).

Conclusions

The attrition of tibial subchondral bone determined by the new parameter, the plateau attrition index, was correlated with symptoms, especially weight-bearing pain in late-stage knee OA.
Systemic Opioid Prescribing Patterns and Total Cost of Care in Patients Initiating Spinal Cord Stimulation Therapy: A Retrospective Analysis
Authors: Fraifeld Eduardo M , Hatheway John A , Ricker Christine N
Published: January 2021

Background

Few studies have evaluated patterns of systemic opioid use among patients initiating spinal cord stimulation therapy for chronic pain. This study evaluated systemic opioid discontinuation and/or dose reduction and total health care cost after the start of spinal cord stimulation therapy.

Methods

Using a commercial insurance claims database (2008–2017), we analyzed opioid utilization patterns in patients initiating spinal cord stimulation therapy over a 1-year baseline and 2-year follow-up. The primary end point was defined as either discontinuation (≥365-day gap between prescription fills or total days’ supply in follow-up ≤30 days) or ≥50% reduction in average daily morphine milligram equivalent dose. “Costs” were defined as total payer plus patient out-of-pocket payments.

Results

A total of 5,878 patients met the selection criteria. Of these, 152 (2.6%) showed no opioid prescription data at any point in the study period. Among patients with one or more prescriptions, 42.0% met the primary end point (22.0% discontinued, and 20.0% reduced their dose by 50% or more). Mean total adjusted costs were significantly reduced in years 1 and 2 of follow-up relative to baseline (excluding device insertion costs). The average time to breakeven when accounting for device trial and permanent insertion cost was 3.1 years among those who met the composite end point and 4.2 years among those who did not.

Conclusions

This analysis shows that among patients who continued spinal cord stimulation therapy for at least 2 years, a significant proportion were able to reduce and/or discontinue systemic opioid use, with costs after the start of therapy significantly reduced relative to baseline.