bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mol* Viewer: modern web app for 3D visualization and analysis of large biomolecular structures
Authors: Sehnal David , Bittrich Sebastian , Deshpande Mandar , Svobodová Radka , Berka Karel , Bazgier Václav , Velankar Sameer , Burley Stephen K , Koča Jaroslav , Rose Alexander S 
Published: April 2021

AbstractLarge biomolecular structures are being determined experimentally on a daily basis using established techniques such as crystallography and electron microscopy. In addition, emerging integrative or hybrid methods (I/HM) are producing structural models of huge macromolecular machines and assemblies, sometimes containing 100s of millions of non-hydrogen atoms. The performance requirements for visualization and analysis tools delivering these data are increasing rapidly. Significant progress in developing online, web-native three-dimensional (3D) visualization tools was previously accomplished with the introduction of the LiteMol suite and NGL Viewers. Thereafter, Mol* development was jointly initiated by PDBe and RCSB PDB to combine and build on the strengths of LiteMol (developed by PDBe) and NGL (developed by RCSB PDB). The web-native Mol* Viewer enables 3D visualization and streaming of macromolecular coordinate and experimental data, together with capabilities for displaying structure quality, functional, or biological context annotations. High-performance graphics and data management allows users to simultaneously visualise up to hundreds of (superimposed) protein structures, stream molecular dynamics simulation trajectories, render cell-level models, or display huge I/HM structures. It is the primary 3D structure viewer used by PDBe and RCSB PDB. It can be easily integrated into third-party services. Mol* Viewer is open source and freely available at https://molstar.org/.
DeepGOWeb: fast and accurate protein function prediction on the (Semantic) Web
Authors: Kulmanov Maxat , Zhapa-Camacho Fernando , Hoehndorf Robert 
Published: April 2021

AbstractUnderstanding the functions of proteins is crucial to understand biological processes on a molecular level. Many more protein sequences are available than can be investigated experimentally. DeepGOPlus is a protein function prediction method based on deep learning and sequence similarity. DeepGOWeb makes the prediction model available through a website, an API, and through the SPARQL query language for interoperability with databases that rely on Semantic Web technologies. DeepGOWeb provides accurate and fast predictions and ensures that predicted functions are consistent with the Gene Ontology; it can provide predictions for any protein and any function in Gene Ontology. DeepGOWeb is freely available at https://deepgo.cbrc.kaust.edu.sa/.
The long and the short of it: unlocking nanopore long-read RNA sequencing data with short-read differential expression analysis tools
Authors: Dong Xueyi , Tian Luyi , Gouil Quentin , Kariyawasam Hasaru , Su Shian , De Paoli-Iseppi Ricardo , Prawer Yair David Joseph , Clark Michael B , Breslin Kelsey , Iminitoff Megan , Blewitt Marnie E , Law Charity W , Ritchie Matthew E 
Published: April 2021

Abstract
Application of Oxford Nanopore Technologies’ long-read sequencing platform to transcriptomic analysis is increasing in popularity. However, such analysis can be challenging due to the high sequence error and small library sizes, which decreases quantification accuracy and reduces power for statistical testing. Here, we report the analysis of two nanopore RNA-seq datasets with the goal of obtaining gene- and isoform-level differential expression information. A dataset of synthetic, spliced, spike-in RNAs (‘sequins’) as well as a mouse neural stem cell dataset from samples with a null mutation of the epigenetic regulator Smchd1 was analysed using a mix of long-read specific tools for preprocessing together with established short-read RNA-seq methods for downstream analysis. We used limma-voom to perform differential gene expression analysis, and the novel FLAMES pipeline to perform isoform identification and quantification, followed by DRIMSeq and limma-diffSplice (with stageR) to perform differential transcript usage analysis. We compared results from the sequins dataset to the ground truth, and results of the mouse dataset to a previous short-read study on equivalent samples. Overall, our work shows that transcriptomic analysis of long-read nanopore data using long-read specific preprocessing methods together with short-read differential expression methods and software that are already in wide use can yield meaningful results.
O06 Baseline predictors of methotrexate-related adverse events in methotrexate-naïve patients with RA
Authors: Sherbini Ahmad A , Gwinnutt James M , Hyrich Kimme L , Verstappen Suzanne M M ,   RAMS Co-Investigators
Published: April 2021

Abstract
Background/Aims
Methotrexate (MTX) is the most common treatment for rheumatoid arthritis (RA). The prevalence of adverse events (AEs) associated with MTX treatment for RA have been studied extensively, but there are limited data on the predictors of these AEs. This study aims to summarise the prevalence rates of MTX AEs, including gastrointestinal (GI), neurological, mucocutaneous, and elevated alanine transaminase (ALT) enzyme, and to identify baseline demographic and clinical predictors of these AEs.
Methods
The Rheumatoid Arthritis Medication Study (RAMS) is a UK multi-centre prospective cohort study of patients with RA starting MTX for the first time. Relevant demographic, medication, clinical and disease related data were collected at baseline. AEs were reported at six and twelve months follow-ups. The prevalence rates of AEs were calculated based on the proportions of patients who reported having had an AE within one year of follow-up. The associations between candidate baseline predictors and AEs were assessed using multivariable logistic regression.
Results
A total of 2,089 patients were included with a mean age of 58.4 (standard deviation: 13.5) years, 1390 (66.5%) were women. 1,814 and 1,579 patients completed the 6 and 12 months follow-up visits, respectively. The prevalence rates of the AEs within one year of follow-up were: GI = 777 (40.6%), mucocutaneous = 441 (23.1%), neurological = 487 (25.5%), elevated ALT (&gt; upper limit of normal [ULN]) = 286 (15.5%). Younger age and being a woman were associated with increased risk of GI AEs, (age: OR 0.97 per year increase in age, 95% CI 0.98, 1.00; male sex: OR 0.58 vs female, 95% CI 0.46, 0.74) (Table 1). Higher baseline Health Assessment Questionnaire (HAQ) score was an independent predictor of GI, mucocutaneous, and neurological AEs. Furthermore, having ALT &gt;1xULN at baseline or history of diabetes was associated with increased risk of subsequent ALT elevation during the study follow-up.
Conclusion
In patients with RA starting MTX, GI AEs were the most commonly reported AEs during the first year of follow-up. The identified predictors of AEs may facilitate discussions between clinicians and patients prior to commencing MTX, and may lead to increased adherence and consequently improved effectiveness.
Disclosure
A.A. Sherbini: None. J.M. Gwinnutt: Grants/research support; BMS. K.L. Hyrich: Member of speakers’ bureau; Abbvie. Grants/research support; Pfizer, UCB, BMS. S.M.M. Verstappen: Consultancies; Celltrion. Member of speakers’ bureau; Pfizer. Grants/research support; BMS.
O11 Examining BASDAI by gender: differing scores, but similar patterns of disease
Authors: Maguire Sinead , Gallagher Phil , O'Shea Finbar 
Published: April 2021

Abstract
Background/Aims
Research has shown that females with axial spondyloarthritis (axSpA) score worse on patient reported outcomes (PROs) than males. However, this does not always correlate to worse clinical findings. The purpose of this study was to understand why women with axSpA have worse BASDAI scores than men, by examining how both genders score across the components of the BASDAI. The Ankylosing Spondylitis Registry of Ireland (ARSI) is a national registry on patients with axSpA in Ireland and a source of epidemiological data.
Methods
Analysis of the ASRI was preformed using IBM SPSS version 26. Patients were analysed on the basis of gender. Comparison of baseline characteristics and mean BASMI, BASFI, HAQ and ASQoL were tested for significance using an independent two tailed t-test and a Mann Whitney U test. Mean total BASDAI score and mean score for each component of the BASDAI were compared and tested for significance with the same statistical tests. A chi-squared test for independence was used to determine significance in variation of HLA-B27 status and radiographic findings.
Results
A total of 857 patients were included in the analysis. Patient population was 24.9% (213) female and 75.1% (644) male with a mean age of 45.9 years and mean disease duration of 19.4 years (means: BASDAI 4.02, BASMI 4, BASFI 3.67, HAQ 0.53, ASQoL 6.48). Females had worse BASDAI(4.6 vs 3.83, p &lt; 0.01), HAQ(0.6 vs 0.51, p = 0.03) and ASQoL scores (7.62 vs 6.12, p &lt; 0.01) than males. BASFI scores were worse in females which did not reach significance (3.89 vs 3.63, p = 0.26). However, females had significantly better BASMI scores than males (3.51 vs 4.16, p &lt; 0.01). Within the BASDAI, females scored significantly worse than males across all components (Fatigue: 5.56 vs 4.51, p &lt; 0.01; Spinal pain: 5.51 vs 4.63, p &lt; 0.01; Other pain: 3.82 vs 3.19, p = 0.01; Discomfort: 4.05 vs 3.29, p &lt; 0.01; EMS: 4.55 vs 3.94, p = 0.01), however duration of EMS did not reach significance (3.54 vs 3.12, p = 0.07)(table 1). Within the BASDAI, females recorded highest mean scores for fatigue (5.56), while males recorded highest mean scores for spinal pain(4.63). Lowest mean scores for both genders was for EMS duration (3.54 vs 3.12). Ranking of the BASDAI components by mean scores show similarity in the ranking of discomfort, EMS, other pain and EMS duration.
Conclusion
AxSpA females have consistently worse PROs but have better spinal mobility than males. Despite females recording worse BASDAI scores than males, the pattern of disease activity manifestation is similar in 4 of the 6 components of the BASDAI. However, fatigue is the most problematic symptom in females with active axSpA while spinal pain is the most problematic symptom for males. This variation by gender should be kept in consideration when evaluating a patient with suspected active axSpA.
Disclosure
S. Maguire: None. P. Gallagher: None. F. O'Shea: None.
O15 Using a smartphone app to characterise and quantify skin colour changes in Raynaud's attacks
Authors: Dinsdale Graham , Manning Joanne , Herrick Ariane , Dickinson Mark , Taylor Christopher 
Published: April 2021

Abstract
Background/Aims
The lack of objective outcome measures for Raynaud's phenomenon (RP) has been a major limiting factor in development of effective treatments. At present, the Raynaud's Condition Score (RCS) is the only validated outcome measure, and is highly subjective. Mobile phone technology could provide a way forward. We have developed a smartphone app for RP monitoring that guides the patient through the process of capturing images of their hands during RP episodes, as well as capturing other data through post-attack and daily questionnaires. One of the objectives of our research programme (reported here) was to compare digital image (photographic) parameters to the RCS.
Methods
40 patients with RP (8 with primary RP, 32 with RP secondary to systemic sclerosis) were recruited (40 female, median age (range): 57 years (25-74), median (range) duration of RP symptoms: 17 (0-53) years). Patients were given a smartphone handset with a pre-installed Raynaud’s Monitoring app and were trained on how to use it/take usable photographs. They were then asked to take photographs of RP attacks over a 14 day period and also to record the RCS for each episode. The app specifically prompts the patient to take a picture of their hand every minute during an attack, until confirmation is given that the attack is complete. At a 2nd visit, the handsets, images, and data were collected for analysis. The mean colour change during each RP attack was quantified (semi-automated method) by the Bhattacharyya distance (BD) in colour space between a region of interest (e.g. a section of a digit) and a control region (dorsal hand). BD was then compared to the RCS using ANOVA, after controlling for patient variability in the range of RCS values used by each patient.
Results
A total of 3,030 images were collected, describing 229 RP attacks. The median RCS reported was 6 (inter-quartile range [IQR]: 4), while the median for BD was 5.6 (IQR 3.2). ANOVA showed that measured values of the mean image BD were significantly different when different values of RCS were recorded by the patient (p &lt; 0.001), i.e. attacks where patients selected different values of RCS had significantly different values of BD. Across all attacks/patients the F-value from ANOVA for RCS was 76.2, suggesting that the variation in BD for different values of RCS is much greater than the variation in BD for any one value of RCS.
Conclusion
Patients successfully used a smartphone app to collect photographs and data during episodes of RP. A strong association was found between skin colour change (via BD) and the gold-standard RCS. Mobile phone-documented colour change therefore has potential as an objective measure of RP. Further validation work is now required, as well as studies examining sensitivity to change.
Disclosure
G. Dinsdale: None. J. Manning: None. A. Herrick: None. M. Dickinson: None. C. Taylor: None.
P012 Raynaud's phenomenon: a primary care problem?
Authors: Winstone Katie E , Anderson Marina E , Stickland Anna E 
Published: April 2021

Abstract
Background/Aims
Despite an established awareness of Raynaud’s phenomenon (RP), defined as an episodic vasospasm of the arteries in the extremities, no studies have yet described the way in which the phenomenon is assessed and managed within a primary care setting. The primary aim of this study is to evaluate the way in which Raynaud’s Phenomenon commonly presents, is investigated, and managed within a UK general practice (GP); auditing concordance with the National Institute for Health and Care Excellence (NICE) Clinical Knowledge Summary (CKS) 2020 guidance.
Methods
An audit of 79 patients with a coded diagnosis of RP was completed at Green Lane Medical Centre, a Merseyside General Practice. Patient care was audited against standards within the NICE CKS.
Results
The patient group was comprised of 53 females (67.1%) and 26 males (32.9%). 89.9% (71/79) of patients have a working diagnosis of primary RP. Patient age at the time of audit: 4% aged 0-18; 29% aged 19-45; 30% aged 46-60; 37% aged 60+. 59.5% (47/79) of patients had 2 or more troubling symptoms of RP documented by their GP, with 12.7% (10/79) describing a classic triphasic colour change. Examination findings were documented for 55.7% (44/79) of patients and 27.9% (22/79) received an autoantibody screen. 26.6% (21/79) of patients were referred to secondary care, with 42.9% (9/21) of these referrals specifying an intention to rule out Secondary RP. Documentation available regarding patient management indicated that conservative advice was provided to 62.5% (40/64) of patients, the most common being a patient information sheet (26/64). Medical management was offered to 39.1% (25/64) of patients but was declined by 24.0% (6/25) of those to whom it was offered, with most (16/19) patients who were commenced on medical therapy discontinuing by the time of audit. In secondary care, 81.0% (17/21) of referred patients had further investigations, 57.1% (12/21) received reassurance before or after the investigations and conservative advice was the most common management.
Conclusion
This study suggests that GPs play a major role in the assessment and management of patients with RP; 73.4% (58/79) of patients were not referred to secondary care. Of those that were referred, the majority were due to worsening or severe symptoms, or suspected secondary RP, in line with the CKS guidance. Most patients present with 2 or more of the symptoms described in the NICE CKS guidance and the use of examination and screening blood tests in primary care appears to be the mainstay of assessment. In accordance with the CKS guidance, most patients are provided with information and lifestyle advice. High rates of medical therapy discontinuation suggest that assessment of severity of symptoms and improved patient education of medication side effects may play a role in determining the most appropriate candidates for medical therapy.
Disclosure
K.E. Winstone: None. M.E. Anderson: None. A.E. Stickland: None.
P111 Osteoporosis is a significant predictor of frailty in older community dwelling adults: findings from the Hertfordshire Cohort Study
Authors: Laskou Faidra , Jameson Karen , Dennison Elaine 
Published: April 2021

Abstract
Background/Aims
Frailty is associated with a range of adverse health outcomes, including falls and fractures. Previous work in a Japanese cohort found that the presence of both osteoporosis (OP) and sarcopenia (SP) increased the risk of frailty compared to the presence of OP or SP alone. We examined these relationships in a comparable cohort of community dwelling older people in the UK.
Methods
Our study comprised of 432 participants (216 men and 216 women) of the UK the Hertfordshire Cohort Study (HCS). Participants were assessed at baseline and followed up 5 years later with questionnaires, clinical examination, measures of physical performance and grip strength. Proximal femur bone mineral density (BMD) values were determined using dual-energy X-ray absorptiometry. OP was defined at BMD T- scores &lt; = -2.5 at the femoral neck or use of anti-osteoporosis medication. Cut-offs for low grip strength; &lt;30kg for men and &lt;20kg for women and ALM index &lt; =7.23kg/m2 for men, &lt; =5.67kg/m2 for women, were used to define SP. Frailty was defined using the Fried definition. Logistic regressions were performed to analyse associations of OP/SP as explanatory variables for frailty.
Results
The mean (SD) age of participants was 75.7 (2.6) years. At baseline, the prevalence of frailty and pre-frailty was 12.2% (men, 8%, women, 16.3 %), and 57% (men, 55.7%; women, 58.2%) respectively. Individuals living with frailty were older, tended to drink less alcohol, have lower physical activity, lower walking speed and grip strength (P &lt; 0.001). They were more likely to be female compared to non-frail subjects (P = 0.007). Co-existence of SP, OP and frailty was observed in 0.6% of the population; 0.6% had SP and frailty; 1.6% had OP and frailty and 1.6% of the study population had SP and OP. 71.8% did not have SP, OP or frailty at baseline. SP was significantly associated with frailty at baseline (p &lt; 0.001). The cumulative incidence of frailty during the 5-year period was 2.47% /year (2.13%/year in men, 2.89%/year in women) and that of SP was 2.14%/year (2.84% in men, 1.35%/year in women). The presence of OP at baseline was a significant predictive factor for the occurrence of frailty at follow-up (odds ratio [OR], 3.04; 95% confidence interval [95% CI], 1.11,8.38; P = 0.031), while the risk of developing frailty was also increased in those participants who were both osteoporotic and sarcopenic at baseline; though this was not significant (OR; 10.08, 95% CI,0.55,186.08; P = 0.12).
Conclusion
Our findings demonstrate that the presence of OP is a significant predictive factor for developing frailty and might be used as a trigger for appropriate interventions to reduce or reverse its development in older adults. Our findings are in accordance with the previous reports in Asian populations and warrant further investigation in other national cohorts.
Disclosure
F. Laskou: None. K. Jameson: None. E. Dennison: None.
P113 How has COVID-19 affected the treatment of osteoporosis? The answers from a global survey
Authors: Fuggle Nicholas R , Singer Andrea , Harvey Nicholas , Reginster Jean-Yves , Cooper Cyrus , Greenspan Susan 
Published: April 2021

Abstract
Background/Aims
The COVID-19 pandemic has had profound effects on the health of the global population both directly, via the sequelae of the infection, and indirectly, including the relative neglect of chronic disease management. Together the International Osteoporosis Federation and National Osteoporosis Foundation sought to ascertain the impact on osteoporosis management.
Methods
Questionnaires were electronically circulated to a sample of members of both learned bodies and included information regarding the location and specialty of respondents, current extent of face to face consultations, alterations in osteoporosis risk assessment, telemedicine experience, alterations to medication ascertainment and delivery, and electronic health record (EHR) utilisation. Responses were collected, quantitative data analysed, and qualitative data assessed for recurring themes.
Results
Responses were received from 209 healthcare workers from 53 countries, including 28% from Europe, 24% from North America, 19% from the Asia Pacific region, 17% from the Middle East, and 12% from Latin America. Most respondents were physicians (85%) with physician assistants, physical therapists and nurses/nurse practitioners represented in the sample. The main three specialties represented included rheumatology (40%), endocrinology (22%) and orthopaedics (15%).In terms of the type of patient contact, 33% of respondents conducted telephone consultations and 21% video consultations. Bone mineral density assessment by dual-energy x-ray absorptiometry (DXA) usage was affected with only 29% able to obtain a scan as recommended. The majority of clinicians (60%) had systems in place to identify patients receiving subcutaneous or intravenous medication, and 43% of clinicians reported difficulty in arranging appropriate osteoporosis medications during the COVID-19 crisis.
Conclusion
To conclude through surveying a global sample of osteoporosis healthcare professionals, we have observed an increase in telemedicine consultations, delays in DXA scanning, interrupted supply of medications and reductions in intravenous medication delivery.
Disclosure
N.R. Fuggle: None. A. Singer: None. N. Harvey: None. J. Reginster: None. C. Cooper: None. S. Greenspan: None.
On the Complexity of Resting State Spiking Activity in Monkey Motor Cortex
Authors: Dąbrowska Paulina Anna , Voges Nicole , von Papen Michael , Ito Junji , Dahmen David , Riehle Alexa , Brochier Thomas , Grün Sonja 
Published: April 2021

Abstract
Resting state has been established as a classical paradigm of brain activity studies, mostly based on large-scale measurements such as functional magnetic resonance imaging or magneto- and electroencephalography. This term typically refers to a behavioral state characterized by the absence of any task or stimuli. The corresponding neuronal activity is often called idle or ongoing. Numerous modeling studies on spiking neural networks claim to mimic such idle states, but compare their results with task- or stimulus-driven experiments, or to results from experiments with anesthetized subjects. Both approaches might lead to misleading conclusions. To provide a proper basis for comparing physiological and simulated network dynamics, we characterize simultaneously recorded single neurons’ spiking activity in monkey motor cortex at rest and show the differences from spontaneous and task- or stimulus-induced movement conditions. We also distinguish between rest with open eyes and sleepy rest with eyes closed. The resting state with open eyes shows a significantly higher dimensionality, reduced firing rates, and less balance between population level excitation and inhibition than behavior-related states.