bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extreme Low‐Latitude Total Electron Content Enhancement and Global Positioning System Scintillation at Dawn
Authors: Mrak Sebastijan , Semeter Joshua , Nishimura Yukitoshi , Coster Anthea J. 
Published: May 2021

AbstractWe report on an extreme ionospheric plasma density enhancement and Global Positioning System (GPS) scintillation at dawn, observed within the expanding equatorial ionization anomaly (EIA). The total electron content (TEC) in central America reached 50 TECu at sunrise, the value almost twice as high as the normal afternoon peak. The enhanced EIA expanded poleward and westward from just below 20° magnetic latitude (MLAT) to beyond 30° MLAT at sunrise. The chief ramification of the enhanced EIA was strong GPS scintillation which was observed poleward of 30° northern MLAT and lasted until 8:00 local time. In total, the amplitude scintillation and phase fluctuations lasted for ∼5 h at latitudes north of 20°MLAT in central America.
Days out of role and somatic, anxious-depressive, hypo-manic, and psychotic-like symptom dimensions in a community sample of young adults
Authors: Crouse Jacob J. , Ho Nicholas , Scott Jan , Martin Nicholas G. , Couvy-Duchesne Baptiste , Hermens Daniel F. , Parker Richard , Gillespie Nathan A. , Medland Sarah E. , Hickie Ian B. 
Published: May 2021

AbstractImproving our understanding of the causes of functional impairment in young people is a major global challenge. Here, we investigated the relationships between self-reported days out of role and the total quantity and different patterns of self-reported somatic, anxious-depressive, psychotic-like, and hypomanic symptoms in a community-based cohort of young adults. We examined self-ratings of 23 symptoms ranging across the four dimensions and days out of role in >1900 young adult twins and non-twin siblings participating in the “19Up” wave of the Brisbane Longitudinal Twin Study. Adjusted prevalence ratios (APR) and 95% confidence intervals (95% CI) quantified associations between impairment and different symptom patterns. Three individual symptoms showed significant associations with days out of role, with the largest association for impaired concentration. When impairment was assessed according to each symptom dimension, there was a clear stepwise relationship between the total number of somatic symptoms and the likelihood of impairment, while individuals reporting ≥4 anxious-depressive symptoms or five hypomanic symptoms had greater likelihood of reporting days out of role. Furthermore, there was a stepwise relationship between the total number of undifferentiated symptoms and the likelihood of reporting days out of role. There was some suggestion of differences in the magnitude and significance of associations when the cohort was stratified according to sex, but not for age or twin status. Our findings reinforce the development of early intervention mental health frameworks and, if confirmed, support the need to consider interventions for subthreshold and/or undifferentiated syndromes for reducing disability among young people.
Diagnostic intervals in oropharyngeal cancers from a primary care perspective: a ten-year case note review
Authors: Wilcock Jane , Grafton-Clarke Ciaran 
Published: May 2021

AbstractBackground Rates of oropharyngeal (OP) cancer are increasing and mortality is related to stage at diagnosis. Early diagnosis is vital to improving patient outcomes.Aim To describe current general practice pathways and time intervals in OP cancer and: a) compare to current National Institute for Health and Care Excellence guidance to refer from general practitioners (GPs) to general medical dentists (dentists); and b) referral pathways for pharyngeal cancers.Design and setting A ten-year retrospective study of patients diagnosed with OP cancer in one suburban general practice in England using GP notes, including secondary care correspondence.Results There were 12 cases of OP cancer; six oral and six pharyngeal. There were marked differences in referral pathways and time intervals for people with visible, or palpable, oral cancers and those with non-visible, or impalpable, pharyngeal cancers. No one had GP to dentist referral. General practice 'safety-netting' or follow-up was not commonly recorded.Conclusion GPs are pivotal in diagnosing symptomatic OP cancers. General practice and dental teams encountering symptoms of uncertain aetiology (for example, pharyngitis) should offer safety-netting to shorten patient intervals to re-attendance. Pathways for oral cancer referral were usually clear and linear. Pathways for pharyngeal cancer were usually complex, with much longer time intervals in primary and secondary care, and would benefit from a single national referral pathway to ENT.
A KLF4/PiHL/EZH2/HMGA2 regulatory axis and its function in promoting oxaliplatin-resistance of colorectal cancer
Authors: Deng Xuan , Kong Fanyang , Li Si , Jiang Haoqin , Dong Liu , Xu Xiao , Zhang Xinju , Yuan Hong , Xu Ying , Chu Yimin , Peng Haixia , Guan Ming 
Published: May 2021

AbstractLong noncoding RNAs (lncRNAs) have emerged as a new class of regulatory molecules implicated in therapeutic resistance, yet the mechanisms underlying lncRNA-mediated oxaliplatin resistance in colorectal cancer (CRC) are poorly understood. In this study, lncRNA P53 inHibiting LncRNA (PiHL) was shown to be highly induced in oxaliplatin-resistant CRC cells and tumor tissues. In vitro and in vivo models clarified PiHL’s role in conferring resistance to oxaliplatin-induced apoptosis. PiHL antagonized chemosensitivity through binding with EZH2, repressing location of EZH2 to HMGA2 promoter, and downregulating methylation of histone H3 lysine 27 (H3K27me3) level in HMGA2 promoter, thus activating HMGA2 expression. Furthermore, HMGA2 upregulation induced by PiHL promotes PI3K/Akt phosphorylation, which resulted in increased oxaliplatin resistance. We also found that transcription factor KLF4 was downregulated in oxaliplatin-resistant cells, and KLF4 negatively regulated PiHL expression by binding to PiHL promoter. In vivo models further demonstrated that treatment of oxaliplatin-resistant CRC with locked nucleic acids targeting PiHL restored oxaliplatin response. Collectively, this study established lncRNA PiHL as a chemoresistance promoter in CRC, and targeting PiHL/EZH2/HMGA2/PI3K/Akt signaling axis represents a novel choice in the investigation of drug resistance.
p27 controls autophagic vesicle trafficking in glucose-deprived cells via the regulation of ATAT1-mediated microtubule acetylation
Authors: Nowosad Ada , Creff Justine , Jeannot Pauline , Culerrier Raphael , Codogno Patrice , Manenti Stephane , Nguyen Laurent , Besson Arnaud 
Published: May 2021

AbstractThe cyclin-dependent kinase inhibitor p27Kip1 (p27) has been involved in promoting autophagy and survival in conditions of metabolic stress. While the signaling cascade upstream of p27 leading to its cytoplasmic localization and autophagy induction has been extensively studied, how p27 stimulates the autophagic process remains unclear. Here, we investigated the mechanism by which p27 promotes autophagy upon glucose deprivation. Mouse embryo fibroblasts (MEFs) lacking p27 exhibit a decreased autophagy flux compared to wild-type cells and this is correlated with an abnormal distribution of autophagosomes. Indeed, while autophagosomes are mainly located in the perinuclear area in wild-type cells, they are distributed throughout the cytoplasm in p27-null MEFs. Autophagosome trafficking towards the perinuclear area, where most lysosomes reside, is critical for autophagosome–lysosome fusion and cargo degradation. Vesicle trafficking is mediated by motor proteins, themselves recruited preferentially to acetylated microtubules, and autophagy flux is directly correlated to microtubule acetylation levels. p27−/− MEFs exhibit a marked reduction in microtubule acetylation levels and restoring microtubule acetylation in these cells, either by re-expressing p27 or with deacetylase inhibitors, restores perinuclear positioning of autophagosomes and autophagy flux. Finally, we find that p27 promotes microtubule acetylation by binding to and stabilizing α-tubulin acetyltransferase (ATAT1) in glucose-deprived cells. ATAT1 knockdown results in random distribution of autophagosomes in p27+/+ MEFs and impaired autophagy flux, similar to that observed in p27−/− cells. Overall, in response to glucose starvation, p27 promotes autophagy by facilitating autophagosome trafficking along microtubule tracks by maintaining elevated microtubule acetylation via an ATAT1-dependent mechanism.
Circular RNA circACSL1 aggravated myocardial inflammation and myocardial injury by sponging miR-8055 and regulating MAPK14 expression
Authors: Zhang Li , Han Bo , Liu Huanlong , Wang Jing , Feng Xinxin , Sun Wei , Cai Dongxiao , Jia Hailin , Jiang Diandong 
Published: May 2021

AbstractMyocarditis (MC) is a common, potentially life-threatening inflammatory disease of the myocardium. A growing body of evidence has shown that mitogen-activated protein kinase 14 (MAPK14) participates in the pathogenesis of MC. However, the upstream regulators of MAPK14 remain enigmatic. Circular RNAs (circRNAs) have been identified to play vital roles in the pathophysiology of cardiovascular diseases. Nevertheless, the clinical significance, biological function, and regulatory mechanisms of circRNAs in MC remain ﻿poorly understood. In this study, we determined a novel circRNA, circACSL1 (ID: hsa_circ_0071542), which was significantly upregulated in the acute phase of MC, and its dynamic change in expression was related to the progression of MC. We used lipopolysaccharide (LPS) to induce the inflammatory responses in the human cardiomyocytes (HCM) line for in vitro and in cellulo experiments﻿. The pro-inflammatory factors (IL-1β, IL-6, and TNF-α), myocardial injury markers (cTnT, CKMB, and BNP), cell viability, and cell apoptosis were measured to evaluate the extent of myocardial inflammation and myocardial injury level. Functional experiments, including gain-of-function and loss-of-function, were then performed to investigate the pro-inflammatory roles of circACSL1. The results revealed that circACSL1 could aggravate inflammation, myocardial injury, and apoptosis in HCM. ﻿Mechanistically, circACSL1 acted as a sponge for miR-8055-binding sites to regulate the downstream target MAPK14 expression. Furthermore, overexpression of miR-8055 rescued the pro-inflammatory effects of circACSL1 on HCM, and the upregulation of MAPK14 induced by circACSL1 was attenuated by miR-8055 overexpression. Knockdown of circACSL1 or overexpression of miR-8055 reduced myocardial inflammation and myocardial injury level and these effects were rescued by overexpression of MAPK14. In summary, our study demonstrated that circACSL1 could aggravate myocardial inflammation and myocardial injury through competitive absorption of miR-8055, thereby upregulating MAPK14 expression. Moreover, circACSL1 may represent a potential novel biomarker for the precise diagnosis of MC and offer a promising therapeutic target for MC treatment.
Vitamin D status in Armenian women: a stratified cross-sectional cluster analysis
Authors: Hutchings Nicholas , Babalyan Varta , Heijboer Annemieke C. , Baghdasaryan Sisak , Qefoyan Mushegh , Ivanyan Arus , Ackermans Mariëtte T. , Formenti Anna Maria , Lesnyak Olga , Giustina Andrea , Bilezikian John P. 
Published: May 2021

Abstract
Background
Vitamin D plays a critical role in skeletal development and maintenance, thus sufficiency is an important goal for public health programs. Given the absence of foods fortified in vitamin D in Armenia, we hypothesized that vitamin D insufficiency would be widespread.

Methods
We conducted a random modified cluster model survey of vitamin D status of women in the country. We measured 25-hydroxyvitamin D [25(OH)D] by liquid chromatography mass spectrometry in dried blood spot samples and utilized a questionnaire to assess lifestyle factors.

Results
In summer, we sampled 1206 participants from 40 communities in Armenia. Mean 25-OH D level among women aged 18–24 was 20 ± 8 ng/mL; aged 25–64 was 21 ± 7 ng/mL; and >65 was 18 ± 8 ng/mL. The country-wide mean of the entire female population was 20 ± 8 ng/mL. A majority (>54%) had 25-OH D levels <20 ng/mL with nearly 13% having 25-OH D levels <12 ng/mL. Participants who reported calcium, vitamin D, or multivitamin supplementation had higher levels of 25-OH D (p values 0.004, 0.0002, and 0.03 respectively) as did pre- vs. postmenopausal women (p = 0.01), pregnant vs. nonpregnant women (p = <0.0001), and women who had experienced a sunburn in the past year (p = 0.004).

Conclusion
In Armenia, there is a high prevalence of vitamin D insufficiency. This information provides data that can be used to inform public health directives to address this pervasive threat to optimal health.
Analysis of Zika virus capsid-Aedes aegypti mosquito interactome reveals pro-viral host factors critical for establishing infection
Authors: Gestuveo Rommel J. , Royle Jamie , Donald Claire L. , Lamont Douglas J. , Hutchinson Edward C. , Merits Andres , Kohl Alain , Varjak Margus 
Published: May 2021

AbstractThe escalating global prevalence of arboviral diseases emphasizes the need to improve our understanding of their biology. Research in this area has been hindered by the lack of molecular tools for studying virus-mosquito interactions. Here, we develop anAedes aegypticell line which stably expresses Zika virus (ZIKV) capsid proteins in order to study virus-vector protein-protein interactions through quantitative label-free proteomics. We identify 157 interactors and show that eight have potentially pro-viral activity during ZIKV infection in mosquito cells. Notably, silencing of transitional endoplasmic reticulum protein TER94 prevents ZIKV capsid degradation and significantly reduces viral replication. Similar results are observed if the TER94 ortholog (VCP) functioning is blocked with inhibitors in human cells. In addition, we show that an E3 ubiquitin-protein ligase, UBR5, mediates the interaction between TER94 and ZIKV capsid. Our study demonstrates a pro-viral function for TER94/VCP during ZIKV infection that is conserved between human and mosquito cells.
Unusual layer-by-layer growth of epitaxial oxide islands during Cu oxidation
Authors: Li Meng , Curnan Matthew T. , Gresh-Sill Michael A. , House Stephen D. , Saidi Wissam A. , Yang Judith C. 
Published: May 2021

AbstractElucidating metal oxide growth mechanisms is essential for precisely designing and fabricating nanostructured oxides with broad applications in energy and electronics. However, current epitaxial oxide growth methods are based on macroscopic empirical knowledge, lacking fundamental guidance at the nanoscale. Using correlated in situ environmental transmission electron microscopy, statistically-validated quantitative analysis, and density functional theory calculations, we show epitaxial Cu2O nano-island growth on Cu is layer-by-layer along Cu2O(110) planes, regardless of substrate orientation, contradicting classical models that predict multi-layer growth parallel to substrate surfaces. Growth kinetics show cubic relationships with time, indicating individual oxide monolayers follow Frank-van der Merwe growth whereas oxide islands follow Stranski-Krastanov growth. Cu sources for island growth transition from step edges to bulk substrates during oxidation, contrasting with classical corrosion theories which assume subsurface sources predominate. Our results resolve alternative epitaxial island growth mechanisms, improving the understanding of oxidation dynamics critical for advanced manufacturing at the nanoscale.
CryoEM structure of the antibacterial target PBP1b at 3.3 Å resolution
Authors: Caveney Nathanael A. , Workman Sean D. , Yan Rui , Atkinson Claire E. , Yu Zhiheng , Strynadka Natalie C. J. 
Published: May 2021

AbstractThe pathway for the biosynthesis of the bacterial cell wall is one of the most prolific antibiotic targets, exemplified by the widespread use of β-lactam antibiotics. Despite this, our structural understanding of class A penicillin binding proteins, which perform the last two steps in this pathway, is incomplete due to the inherent difficulty in their crystallization and the complexity of their substrates. Here, we determine the near atomic resolution structure of the 83 kDa class A PBP from Escherichia coli, PBP1b, using cryogenic electron microscopy and a styrene maleic acid anhydride membrane mimetic. PBP1b, in its apo form, is seen to exhibit a distinct conformation in comparison to Moenomycin-bound crystal structures. The work herein paves the way for the use of cryoEM in structure-guided antibiotic development for this notoriously difficult to crystalize class of proteins and their complex substrates.
Sub-5 nm single crystalline organic p–n heterojunctions
Authors: Xiao Mingchao , Liu Jie , Liu Chuan , Han Guangchao , Shi Yanjun , Li Chunlei , Zhang Xi , Hu Yuanyuan , Liu Zitong , Gao Xike , Cai Zhengxu , Liu Ji , Yi Yuanping , Wang Shuai , Wang Dong , Hu Wenping , Liu Yunqi , Sirringhaus Henning , Jiang Lang 
Published: May 2021

AbstractThe cornerstones of emerging high-performance organic photovoltaic devices are bulk heterojunctions, which usually contain both structure disorders and bicontinuous interpenetrating grain boundaries with interfacial defects. This feature complicates fundamental understanding of their working mechanism. Highly-ordered crystalline organic p–n heterojunctions with well-defined interface and tailored layer thickness, are highly desirable to understand the nature of organic heterojunctions. However, direct growth of such a crystalline organic p–n heterojunction remains a huge challenge. In this work, we report a design rationale to fabricate monolayer molecular crystals based p–n heterojunctions. In an organic field-effect transistor configuration, we achieved a well-balanced ambipolar charge transport, comparable to single component monolayer molecular crystals devices, demonstrating the high-quality interface in the heterojunctions. In an organic solar cell device based on the p–n junction, we show the device exhibits gate-tunable open-circuit voltage up to 1.04 V, a record-high value in organic single crystalline photovoltaics.
Pairing a high-resolution statistical potential with a nucleobase-centric sampling algorithm for improving RNA model refinement
Authors: Xiong Peng , Wu Ruibo , Zhan Jian , Zhou Yaoqi 
Published: May 2021

AbstractRefining modelled structures to approach experimental accuracy is one of the most challenging problems in molecular biology. Despite many years’ efforts, the progress in protein or RNA structure refinement has been slow because the global minimum given by the energy scores is not at the experimentally determined “native” structure. Here, we propose a fully knowledge-based energy function that captures the full orientation dependence of base–base, base–oxygen and oxygen–oxygen interactions with the RNA backbone modelled by rotameric states and internal energies. A total of 4000 quantum-mechanical calculations were performed to reweight base–base statistical potentials for minimizing possible effects of indirect interactions. The resulting BRiQ knowledge-based potential, equipped with a nucleobase-centric sampling algorithm, provides a robust improvement in refining near-native RNA models generated by a wide variety of modelling techniques.
High-isolation antenna array using SIW and realized with a graphene layer for sub-terahertz wireless applications
Authors: Alibakhshikenari Mohammad , Virdee Bal S. , Salekzamankhani Shahram , Aïssa Sonia , See Chan H. , Soin Navneet , Fishlock Sam J. , Althuwayb Ayman A. , Abd-Alhameed Raed , Huynen Isabelle , McLaughlin James A. , Falcone Francisco , Limiti Ernesto 
Published: May 2021

AbstractThis paper presents the results of a study on developing an effective technique to increase the performance characteristics of antenna arrays for sub-THz integrated circuit applications. This is essential to compensate the limited power available from sub-THz sources. Although conventional array structures can provide a solution to enhance the radiation-gain performance however in the case of small-sized array structures the radiation properties can be adversely affected by mutual coupling that exists between the radiating elements. It is demonstrated here the effectiveness of using SIW technology to suppress surface wave propagations and near field mutual coupling effects. Prototype of 2 × 3 antenna arrays were designed and constructed on a polyimide dielectric substrate with thickness of 125 μm for operation across 0.19–0.20 THz. The dimensions of the array were 20 × 13.5 × 0.125 mm3. Metallization of the antenna was coated with 500 nm layer of Graphene. With the proposed technique the isolation between the radiating elements was improved on average by 22.5 dB compared to a reference array antenna with no SIW isolation. The performance of the array was enhanced by transforming the patch to exhibit metamaterial characteristics. This was achieved by embedding the patch antennas in the array with sub-wavelength slots. Compared to the reference array the metamaterial inspired structure exhibits improvement in isolation, radiation gain and efficiency on average by 28 dB, 6.3 dBi, and 34%, respectively. These results show the viability of proposed approach in developing antenna arrays for application in sub-THz integrated circuits.
Serum alanine aminotransferase as an early marker of outcomes in patients receiving anti-PD-1 or anti-CTLA-4 antibody
Authors: Azuma Takeshi , Takeuchi Takumi , Matayoshi Yukihide , Namiki Shin , Obara Tetsuya , Imamura Kazuhiro , Takamori Mikio 
Published: May 2021

AbstractImmune-oncology (IO) drug therapy is effective against various types of cancer. Although several, potential, clinical predictive markers have been identified, none so far have proven reliable. Herein we evaluated changes in serum alanine aminotransferase (ALT), which is upregulated by the accumulation of activated CD8+T cells in the liver, as a potentially reliable predictive marker. We retrospectively analyzed 265 patients with advanced malignancies at three institutions between 2016 and 2019. The patients received IO drug therapy. We defined the ALT ratio (ALR) as the serum ALT value at baseline / the highest serum ALT during IO drug therapy, then determined whether the ALR correlated with the objective response rate or progression-free survival. The median follow-up was 3.1 months. We observed objective responses in 65 patients. The ALR ranged from 0.19 to 32.2 (median 1.5), and a significant ALR increase was observed in responders (p < 0.001). In receiver operating characteristic analysis, ALR = 1.55 had the highest sensitivity and specificity. The patients with ALR < 1.55 had a significantly poorer PFS than those with ALR ≥ 1.55. A high ALR was associated with a tumor response and good PFS in patients with advanced malignancies. The ALR based on activated cytotoxic T lymphocyte dynamics is therefore a reliable predictive marker.