bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the role of resonances in polluting white dwarfs by asteroids
Authors: Smallwood Jeremy L , Martin Rebecca G , Livio Mario , Veras Dimitri 
Published: April 2021

ABSTRACT
Pollution of white dwarf atmospheres may be caused by asteroids that originate from the locations of secular and mean-motion resonances in planetary systems. Asteroids in these locations experience increased eccentricity, leading to tidal disruption by the white dwarf. We examine how the ν6 secular resonance shifts outwards into a previously stable region of the asteroid belt, as the star evolves to a white dwarf. Analytic secular models require a planet to be engulfed in order to shift the resonance. We show with numerical simulations that as a planet gets engulfed by the evolving star, the secular resonance shifts and the rate of tidal disruption events increases with the engulfed planet’s mass and its orbital separation. We also investigate the behaviour of mean-motion resonances. The width of a mean-motion resonance increases as the star loses mass and becomes a white dwarf. The ν6 secular resonance is more efficient at driving tidal disruptions than mean-motion resonances with Jupiter. By examining 230 observed exoplanetary systems whose central star will evolve into a white dwarf, we find that along with an Earth mass planet at $1\, \rm au$, hot Jupiters at a semimajor axis $a\gtrsim 0.05\, \rm au$ and super-Earths of mass $10\, \rm M_\oplus$ at $a\gtrsim 0.3\, \rm au$ represent planet types whose engulfment shifts resonances enough to cause pollution of the white dwarfs to a degree in agreement with observations.
A comprehensive review of m6A/m6Am RNA methyltransferase structures
Authors: Oerum Stephanie , Meynier Vincent , Catala Marjorie , Tisné Carine 
Published: April 2021

Abstract
Gene expression is regulated at many levels including co- or post-transcriptionally, where chemical modifications are added to RNA on riboses and bases. Expression control via RNA modifications has been termed ‘epitranscriptomics’ to keep with the related ‘epigenomics’ for DNA modification. One such RNA modification is the N6-methylation found on adenosine (m6A) and 2′-O-methyladenosine (m6Am) in most types of RNA. The N6-methylation can affect the fold, stability, degradation and cellular interaction(s) of the modified RNA, implicating it in processes such as splicing, translation, export and decay. The multiple roles played by this modification explains why m6A misregulation is connected to multiple human cancers. The m6A/m6Am writer enzymes are RNA methyltransferases (MTases). Structures are available for functionally characterized m6A RNA MTases from human (m6A mRNA, m6A snRNA, m6A rRNA and m6Am mRNA MTases), zebrafish (m6Am mRNA MTase) and bacteria (m6A rRNA MTase). For each of these MTases, we describe their overall domain organization, the active site architecture and the substrate binding. We identify areas that remain to be investigated, propose yet unexplored routes for structural characterization of MTase:substrate complexes, and highlight common structural elements that should be described for future m6A/m6Am RNA MTase structures.
MGMTpromoter methylation testing to predict overall survival in people with glioblastoma treated with temozolomide: a comprehensive meta-analysis based on a Cochrane Systematic Review
Authors: Brandner Sebastian , McAleenan Alexandra , Kelly Claire , Spiga Francesca , Cheng Hung-Yuan , Dawson Sarah , Schmidt Lena , Faulkner Claire L , Wragg Christopher , Jefferies Sarah , Higgins Julian P T , Kurian Kathreena M 
Published: April 2021

AbstractBackgroundThe DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) causes resistance of tumor cells to alkylating agents. It is a predictive biomarker in high-grade gliomas treated with temozolomide, however, there is no consensus on which test method, methylation sites, and cutoff values to use.MethodsWe performed a Cochrane Review to examine studies using different techniques to measure MGMT and predict survival in glioblastoma patients treated with temozolomide. Eligible longitudinal studies included (i) adults with glioblastoma treated with temozolomide with or without radiotherapy, or surgery; (ii) where MGMT status was determined in tumor tissue, and assessed by 1 or more technique; and (iii) where overall survival was an outcome parameter, with sufficient information to estimate hazard ratios (HRs). Two or more methods were compared in 32 independent cohorts with 3474 patients.ResultsMethylation-specific PCR (MSP) and pyrosequencing (PSQ) techniques were more prognostic than immunohistochemistry for MGMT protein, and PSQ is a slightly better predictor than MSP.ConclusionsWe cannot draw strong conclusions about use of frozen tissue vs formalin-fixed paraffin-embedded in MSP and PSQ. Also, our meta-analysis does not provide strong evidence about the best CpG sites or threshold. MSP has been studied mainly for CpG sites 76-80 and 84-87 and PSQ at CpG sites ranging from 72 to 95. A cutoff threshold of 9% for CpG sites 74-78 performed better than higher thresholds of 28% or 29% in 2 of the 3 good-quality studies. About 190 studies were identified presenting HRs from survival analysis in patients in which MGMT methylation was measured by 1 technique only.
Failed supernova remnants
Authors: Tsuna Daichi 
Published: April 2021

Abstract
In a failed supernova, partial ejection of the progenitor’s outer envelope can occur due to weakening of the core’s gravity by neutrino emission in the protoneutron star phase. We consider emission when this ejecta sweeps up the circumstellar material, analogous to supernova remnants (SNRs). We focus on failed explosions of blue supergiants, and find that the emission can be bright in soft X-rays. Due to its soft emission, we find that sources in the Large Magellanic Cloud (LMC) are more promising for detection than those in the Galactic disk. These remnants are characteristic in their small size (≲10 pc) and slow speed (100s of km s−1) compared to typical SNRs. Although the expected number of detectable sources is small (up to a few by the eROSITA four-year all-sky survey), prospects are better for deeper surveys targeting the LMC. Detection of these “failed SNRs” will realize observational studies of mass ejection following black hole formation.
P023 Secondary membranous nephropathy in a patient with a background of rheumatoid arthritis treated with biosimilar etanercept
Authors: Sammut Luke , Leach Tim , Yalakki Leena 
Published: April 2021

Abstract
Background/Aims
There is a growing number of reports of the development of autoimmune processes related to TNF-targeted therapies. This relationship is much more established with the originator biologics as they have been in clinical use for longer, but data for biosimilar safety is still emerging. Here we describe a case of an 80-year-old gentleman with a background of rheumatoid arthritis who developed membranous nephropathy secondary to Benepali®.
Methods
An 80-year-old Caucasian gentleman with a background of seropositive rheumatoid arthritis, diagnosed at the age of 35 years, was maintained in a clinical remission on oral methotrexate 15 mg weekly, until 2017, when his disease started to flare. At that time, his treatment was switched to sulfasalazine, but due to ongoing high disease activity, this was changed again in December 2018 to methotrexate with Benepali®. His rheumatoid arthritis was controlled with these disease-modifying anti-rheumatic drugs (DMARDs) and his blood test monitoring including full blood count, liver and renal profile (eGFR 80 ml/min/1.73m2) remained normal during the first seven months of treatment. In June 2019, his eGFR deteriorated to 46 and methotrexate was held. Despite this, his eGFR continued to worsen to 28 in July. At that point his Benepali® was discontinued and he was referred to the renal physicians.
Results
He was normotensive (blood pressure 120/68) and had no dependent oedema. A renal tract ultrasound scan showed normal appearing (with a couple of simple cysts) 10.7/9.4 cm kidneys. Urine dipstick showed 2+ blood and 2+ protein, urine protein:creatinine ratio was 138 mg/mmol (normal ≤ 23) and serum albumin 31 g/L (normal ≥ 34). Serum electrophoresis, HIV and Hepatitis PCRs and serum anti-phospholipase A2 receptor antibody were negative. Renal biopsy confirmed stage I to II membranous nephropathy with mild focal segmental glomerulosclerosis. Reassuringly his renal function and proteinuria continued to improve off Benepali® and both returned to normal a few months after stopping this agent.
Conclusion
This is the case of an 80-year-old gentleman who developed membranous nephropathy eight months after commencing etanercept biosimilar - Benepali® - for rheumatoid arthritis. Although attribution to a single agent is challenging, we believe that it is likely Benepali® was the main attributing factor for the development of membranous nephropathy. The temporal relationship between the initiation of Benepali® and the subsequent development of biopsy proven membranous nephropathy along with the resolution following withdrawal of Benepali® supports drug-related renal injury. Although TNF inhibitor-induced renal injury is uncommon, this case highlights the need for physicians to maintain a high level of suspicion if a patient on a TNF inhibitor, including biosimilars, develops proteinuria and renal injury.
Disclosure
L. Sammut: None. T. Leach: None. L. Yalakki: None.
P056 Recurrent ACE-inhibitor induced angioedema in a patient with long COVID-19 syndrome
Authors: Crawshaw Helena , Webber Stuart 
Published: April 2021

Abstract
Background/Aims
Here we present the case of a 47-year-old female with long COVID-19 syndrome presenting with four episodes of acute onset angioedema in the absence of urticaria or pruritis affecting the mucosal layer of the lips and tongue.
Methods
She had been taking lisinopril for the last 18 months. She was diagnosed with COVID-19 in March 2020 presenting with fever, cough, shortness of breath and anosmia. She did not require hospital admission initially however has been readmitted twice with profound breathlessness and fever. She has subsequently developed a long COVID-19 syndrome with a daily, fluctuating fever of up to 39 °C for the last six months, profound fatigue, persistent shortness of breath with bilateral ground glass changes seen on high resolution CT chest imaging and mild anaemia. During this time, she subsequently reported four episodes of acute onset of severe angioedema affecting the lips and tongue for which she self-medicated with anti-histamines.
Results
Following disclosure of these episodes her lisinopril was ceased and there have been no further episodes to date. There are two other case reports in the literature that propose a potential relationship between angiotensin-converting enzyme (ACE) inhibitor induced angioedema and COVID-19. It is known that SAR-CoV-2 binds with high affinity to angiotensin converting enzyme 2 receptors which are found in oral tissues, heart, kidneys and the lung. ACE inhibitors can be associated with angioedema in approximately 0.5% of patients prescribed an ACE inhibitor. It occurs most commonly in the first year following instigation of treatment but can occur years later. The proposed mechanism of action is via the degradation of bradykinin. Bradykinin is converted from Kallikrenin by C1 esterase, and ACE in turn metabolises bradykinin.
Conclusion
Bradykinin affects vascular permeability and results in vasodilatation, when patients take an ACE inhibitor there is a slower rate of bradykinin degradation and therefore this accumulation results in ACE inhibitor induced angioedema. SARS-CoV-2 binds to the ACE2 receptors. ACE2 is thought to counterbalance ACE in the renin-angiotensin system, it is theorised that the potential downregulation of ACE2 by the presence of bound SARS-CoV-2 may therefore potentiate angioedema in susceptible individuals. At present we cannot confirm this proposed relationship and global current consensus supports the ongoing use of ACE inhibitors during the pandemic but clinicians should continue to be aware of emergent pathologies related to the COVID-19 pandemic.
Disclosure
H. Crawshaw: None. S. Webber: None.
P066 Telephone clinics: what are our patients saying?
Authors: Abdullah Muhammad Azhar , Heng Nicholas , Noor Sajjad , Ahmed Urooj , Lavery Clare , Bawa Sandeep 
Published: April 2021

Abstract
Background/Aims
Telemedicine has not previously been a regular part of routine rheumatology services.Our department adopted telephone clinics during the COVID-19 pandemic. We assessed patient satisfaction by conducting a feedback survey. Our aim was to obtain a patient perspective on remote consultations and on preferred future follow up options including video or face-to-face consultations.
Methods
The cohort included 160 rheumatology patients who had a telephone consultation between May and mid-June 2020. All patients consented to receive a further phone call by a different member of the team. Patients had to answer a questionnaire about recent consultation and to rate this on a scale of 1-5. Other questions included whether all their queries were answered; clear action plan made; perceived benefits or disadvantages of telephone consultation; and views about future follow up and any additional comments.
Results
71.9% of 160 patients were females while 28.1 % males. Mean age 58.6 yrs. More than half of the patients (60.6%) had a diagnosis of inflammatory arthritis, followed by connective tissue disease (19.3%), other diagnosis (8.1% ) & vasculitis (5.6%). 94.4 % of the patients in this study were return appointments-the remainder new. Feedback results revealed 92.5% patients were satisfied with their consultation with mean score of 4.3/5 (5=best,1= worst). More than 80% agreed that all their queries were answered and a clear action plan was formed during consultation. However ,71.2% would want a face to face consultation if given choice while 54 % happy to have further follow up over the phone. 65% of patients preferred not to have video consultation. Subgroup analysis showed that majority of patients who would accept video consultation were aged between 30-39. Most common benefits described were noted to be convenience; reduced time of work; travel time and safety during pandemic, whilst difficulty in describing symptoms; hearing problems; and severity of disease were disadvantages raised, but numbers were small in our cohort.
Conclusion
Telephone clinics were the mainstay during the COVID-19 pandemic.The large majority of the rheumatology patients in our cohort were highly satisfied with this form of consultation. However, interestingly the majority (71% ) would still prefer face-to-face consultation as follow up in the future. Regular follow up in carefully selected patient groups can successfully be performed by telephone clinics with good patient satisfaction. This would help increase capacity within the clinic setting.
Disclosure
M. Abdullah: None. N. Heng: None. S. Noor: None. U. Ahmed: None. C. Lavery: None. S. Bawa: None.
P099 Risk of obstructive sleep apnoea in patients with rheumatic disease: a prospective cohort study
Authors: Ng Wan Lin , Kamarudin Nurasyikin , Anjum Aqeel , Devlin Joe , O'Brien Aidan , Fraser Alexander 
Published: April 2021

Abstract
Background/Aims
Sleep plays an important component in our lives and sleep abnormalities have been known to be linked with various rheumatic conditions. Obstructive sleep apnoea (OSA) could potentially affect the severity of rheumatic symptoms such as pain, fatigue and also influence the disease activity. This study aims to evaluate the risk of OSA in patients with rheumatic diseases in an Irish cohort.
Methods
Patients with a diagnosis of a rheumatic disease were recruited from rheumatology outpatients. These patients were asked to complete the Berlin Sleep Questionnaire (BSQ) to evaluate their level of risk for OSA. The Health Assessment Questionnaire (HAQ), Patient Global Assessment (PtGA) and the Physician Global Assessment (PhGA) were also completed.
Results
These patients were asked to complete the Berlin Sleep Questionnaire (BSQ) to evaluate their level of risk for OSA. The Health Assessment Questionnaire (HAQ), Patient Global Assessment (PtGA) and the Physician Global Assessment (PhGA) 111 patients were recruited. Mean age was 52 years and 22 (19.8%) were males. The most common diagnosis in our cohort was rheumatoid arthritis 54 (45.4%), followed by spondyloarthritis 12 (10.1%), psoriatic arthritis 11 (9.2%), systemic lupus erythematosus 9 (7.6%), Behçet’s disease 7 (5.9%), scleroderma 6 (5.0%) and others 20 (16.8%); with 8 patients having two diagnoses. Our cohort also completed the HAQ which demonstrated 98 (88.3%) having mild to moderate disability and 13 (11.7%) having moderate to severe disability. 39 out of 111 were noted to have a high risk for OSA based on the BSQ. In the high risk cohort, the mean PtGA score was 46.5 while PhGA score was 30.3, compared to the low risk cohort which was 36.7 for PtGA and 24.9 for PhGA. 33 (84.6%) patients in the high risk cohort had mild to moderate disability and 6 (15.4%) had moderate to severe disability as compared to 64 (88.9%) with mild to moderate disability and 8 (11.1%) with moderate to severe disability in the low risk cohort.were also completed.
Conclusion
This is the first prospective study in Ireland to evaluate the risk of OSA in patients with rheumatic diseases. 35.1% from our cohort were found to be at high risk for OSA and are due to undergo overnight pulse oximetry and polysomnography to objectively assess the presence or absence of OSA. The disease activity reported by both patient and physician along with the level of disability were greater in the high risk cohort. This suggests that OSA increases the likelihood of exacerbating rheumatic activities.
Disclosure
W. Ng: None. N. Kamarudin: None. A. Anjum: None. J. Devlin: None. A. O'Brien: None. A. Fraser: None.
P130 The relationship between antinuclear antibodies and erosive disease in patients with rheumatoid arthritis
Authors: Guruparan Thushyanthan , Hutchinson Matthew , Hayward Rhys , Penn Henry , Kalia Parul 
Published: April 2021

Abstract
Background/Aims
The effects of antinuclear antibodies (ANA) in rheumatoid arthritis (RA) are not fully characterised. Studies investigating the effect of ANA on disease activity in RA have yielded mixed results. The presence of ANA has been correlated with higher levels of CRP and joint inflammation in RA. Evidence suggests that ANA positivity at baseline may predict poor response to both traditional disease modifying agents and biologic therapy. ANA may also be associated with higher incidences of ocular disease, Felty’s syndrome, vasculitis and subjective pain in RA patients. On the other hand, other studies showed a lack of correlation between ANA status and joint inflammation in RA. Our study investigates the relationship between ANA positivity and joint erosions in rheumatoid patients.
Methods
This is a cross-sectional study of patients attending the early arthritis clinic at Northwick Park Hospital in London over a five year period (2014-2019). A total of 631 patients were identified of whom 261 had RA. We collected data on the age, gender, ANA positivity, the presence of anti-CCP (anti cyclic-citrullinated peptide) antibodies and rheumatoid factor (RF) at presentation as well as the presence of erosive disease on radiological reports of hand X-rays. Positive ANA was defined as having a titre of 1:80 or greater. Patients with missing ANA result or hand X-ray reports were excluded, leaving 228 patients. Two-tailed Chi-square tests for categorical data and two-tailed student’s t-tests for continuous data were performed to determine the statistical significance of comparisons made between the ANA positive and negative groups.
Results
Of the 228 patients, 49 (21.5%) were male and 179 (78.5%) were female. The mean age was 58 years. 84 (36.8%) patients were ANA positive (group 1) and 144 (63.2%) were ANA negative (group 2). In group 1, 23/84 (27.4%) patients had erosive disease. In group 2, erosions were found in 25/144 patients (17.4%). This difference was not statistically significant (p = 0.073). The number of patients who were RF positive in groups 1 and 2 were 79.5% and 73.6% respectively (p = 0.317); 75/84 (89.3%) patients in group 1 and 113/143 (79.0%) in group 2 were anti-CCP antibody positive (p = 0.048). The means of the age of patients were 53 and 62 years in group 1 and group 2 respectively (p &lt; 0.0001); the ANA positive group was significantly younger. The male:female ratio was 13:71 in group 1 and 36:108 in group 2 (p = 0.091).
Conclusion
Our study showed no significant association between ANA status and erosive disease in RA, although a greater proportion of patients had erosions in the ANA positive group. Larger observational studies may better study this relationship.
Disclosure
T. Guruparan: None. M. Hutchinson: None. R. Hayward: None. H. Penn: None. P. Kalia: None.
Individual Alpha Frequency Determines the Impact of Bottom-Up Drive on Visual Processing
Authors: Nelli Stephanie , Malpani Aayushi , Boonjindasup Max , Serences John T 
Published: April 2021

Abstract
Endogenous alpha oscillations propagate from higher-order to early visual cortical regions, consistent with the observed modulation of these oscillations by top-down factors. However, bottom-up manipulations also influence alpha oscillations, and little is known about how these top-down and bottom-up processes interact to impact behavior. To address this, participants performed a detection task while viewing a stimulus flickering at multiple alpha band frequencies. Bottom-up drive at a participant’s endogenous alpha frequency either impaired or enhanced perception, depending on the frequency, but not amplitude, of their endogenous alpha oscillation. Fast alpha drive impaired perceptual performance in participants with faster endogenous alpha oscillations, while participants with slower oscillations displayed enhanced performance. This interaction was reflected in slower endogenous oscillatory dynamics in participants with fast alpha oscillations and more rapid dynamics in participants with slow endogenous oscillations when receiving high-frequency bottom-up drive. This central tendency may suggest that driving visual circuits at alpha band frequencies that are away from the peak alpha frequency improves perception through dynamical interactions with the endogenous oscillation. As such, studies that causally manipulate neural oscillations via exogenous stimulation should carefully consider interacting effects of bottom-up drive and endogenous oscillations on behavior.
Two distant helicases in one mycovirus: evidence of horizontal gene transfer between mycoviruses, coronaviruses and other nidoviruses
Authors: Abdoulaye Assane Hamidou , Hai Du , Tang Qing , Jiang Daohong , Fu Yanping , Cheng Jiasen , Lin Yang , Li Bo , Kotta-Loizou Ioly , Xie Jiatao 
Published: April 2021

Abstract
Nidovirales, which accommodates viruses with the largest RNA genomes, includes the notorious coronaviruses; however, the evolutionary route for nidoviruses is not well understood. We have characterized a positive-sense (+) single-stranded (ss) RNA mycovirus, Rhizoctonia solani hypovirus 2 (RsHV2), from the phytopathogenic fungus Rhizoctonia solani. RsHV2 has the largest RNA genome size of 22,219 nucleotides, excluding the poly(A) tail, in all known mycoviruses, and contains two open reading frames (ORF1 and ORF2). ORF1 encodes a protein of 2,009 amino acid (aa) that includes a conserved helicase domain belonging to helicase superfamily I (SFI). In contrast, ORF2 encodes a polyprotein of 4459 aa containing the hallmark genes of hypoviruses. The latter includes a helicase belonging to SFII. Following phylogenetic analysis, the ORF1-encoded helicase (Hel1) unexpectedly clustered in an independent evolutionary branch together with nidovirus helicases, including coronaviruses, and bacteria helicases. Thus, Hel1 presence indicates the occurrence of horizontal gene transfer between viruses and bacteria. These findings also suggest that RsHV2 is most likely a recombinant arising between hypoviruses and nidoviruses.