bluuebunny/crossref_metadata_2025_split huggingface dataset:
De-objectifying Animals
Authors: Lostal Marina 
Published: April 2021

Abstract
The legal framework of the International Criminal Court does not contain any provision concerning animals. This stands in contrast with the frequency with which they appear in both trial and reparations proceedings. The silence of the legal framework is problematic insofar as the ‘animal turn movement’, which questions the classical understanding and treatment of animals as objects, has permeated into both the international and domestic legal spheres. This article wishes to initiate a discussion on the treatment of animals before the Court by examining whether they could qualify as victims under Rule 85(a) of the Rules of Procedure and Evidence. While the short answer to this question is an unequivocal ‘no’, the conclusion reached is not the purpose of the analysis. The analysis shows that animals cannot qualify as ‘victims’ because they are not human beings. Yet, they comfortably meet the other two criteria, namely, (a) suffering harm, which (b) results from the commission of crimes within the Court’s jurisdiction. Thus, this article argues that — at least — granting animals the same treatment as human beings is no more objectionable as a matter of legal principle than granting them the status of ‘things’. This calls for a prompt discussion of the regulation of animals within the Court.
Combined statistical modeling enables accurate mining of circadian transcription
Authors: Rubio-Ponce Andrea , Ballesteros Iván , Quintana Juan A , Solanas Guiomar , Benitah Salvador A , Hidalgo Andrés , Sánchez-Cabo Fátima 
Published: April 2021

AbstractCircadian-regulated genes are essential for tissue homeostasis and organismal function, and are therefore common targets of scrutiny. Detection of rhythmic genes using current analytical tools requires exhaustive sampling, a demand that is costly and raises ethical concerns, making it unfeasible in certain mammalian systems. Several non-parametric methods have been commonly used to analyze short-term (24 h) circadian data, such as JTK_cycle and MetaCycle. However, algorithm performance varies greatly depending on various biological and technical factors. Here, we present CircaN, an ad-hoc implementation of a non-linear mixed model for the identification of circadian genes in all types of omics data. Based on the variable but complementary results obtained through several biological and in silico datasets, we propose a combined approach of CircaN and non-parametric models to dramatically improve the number of circadian genes detected, without affecting accuracy. We also introduce an R package to make this approach available to the community.
Printing strategies for scaling-up perovskite solar cells
Authors: Wang Yulong , Duan Changyu , Lv Pin , Ku Zhiliang , Lu Jianfeng , Huang Fuzhi , Cheng Yi-Bing 
Published: April 2021

Abstract
Photovoltaic technology offers a sustainable solution to the problem of soaring global energy demands. Recently, metal halide perovskite solar cells (PSCs) have attracted worldwide interest because of their high power conversion efficiency of 25.5% and great potential in becoming a disruptive technology in the photovoltaic industry. The transition from research to commercialization requires advancements of scalable deposition methods for both perovskite and charge transporting thin films. Herein, we share our view regarding the current challenges to fabrication of PSCs by printing techniques. We focus particularly on ink technologies, and summarize the strategies for printing uniform, pinhole-free perovskite films with good crystallinity. Moreover, the stability of perovskite solar modules is discussed and analyzed. We believe this review will be advantageous in the area of printable electronic devices.
Integrated Surveillance for Antimicrobial Resistance in Salmonella From Clinical and Retail Meat Sources Reveals Genetically Related Isolates Harboring Quinolone- and Ceftriaxone-Resistant Determinants
Authors: M’ikanatha Nkuchia M , Yin Xin , Boktor Sameh W , Dettinger Lisa A , Tewari Deepanker 
Published: April 2021

Abstract

Background
Antimicrobial resistance in foodborne pathogens, including nontyphoidal Salmonella (NTS), is a public health concern. Pennsylvania conducts integrated surveillance for antimicrobial resistance in NTS from human and animal sources.

Methods
During 2015–2017, clinical laboratories submitted 4478 NTS isolates from humans and 96 isolates were found in 2520 retail meat samples. One hundred nine clinical isolates that shared pulsed-field gel electrophoresis patterns with meat isolates and all strains from meat samples were tested for susceptibility to antimicrobial agents. Six clinical and 96 NTS isolates from meat sources (total 102) were analyzed by whole-genome sequencing (WGS).

Results
Twenty-eight (25.7%) of the 109 clinical NTS and 21 (21.9%) of strains from meat sources had resistance to ≥3 antimicrobial drug classes (multidrug resistance). Sixteen of the 102 (15.7%) isolates analyzed by WGS had resistance mechanisms that confer resistance to expanded-spectrum cephalosporins, such as ceftriaxone. We identified blaCTX-M-65 in 2 S. Infantis isolates from clinical and 3 S. Infantis isolates from meat sources. These 5 blaCTX-M-65–positive S. Infantis strains carried ≥5 additional resistance genes plus a D87Y mutation in gyrA that encodes fluoroquinolone resistance. WGS showed that isolates from patients and meat samples were within ≤10 and ≤5 alleles for S. Infantis and S. Reading, respectively.

Conclusions
A significant proportion of NTS isolates from human and animal sources were multidrug resistant and 16% had genetic mechanisms that confer resistant to ceftriaxone. These results emphasize need for integrated surveillance in healthcare and agricultural settings.
P033 Scleroderma-like fibrotic disorder associated with a gastro-intestinal stromal tumour which responded only to imatinib
Authors: Butt Zaran A , NG Wan Lin , Howard Donough , Osman Kamal 
Published: April 2021

Abstract
Background/Aims
Gastro-intestinal stromal tumour (GIST) is recognised as the most prevalent mesenchymal tumour of the gastro-intestinal (GI) tract. The vast majority of GIST display activating mutations in receptor tyrosine kinases, such as platelet-derived growth factor receptor alpha (PDGFRA) and c-kit. This characteristic has lead to the development and approval of targeted therapies such as Imatinib for metastatic GIST. Scleroderma is an idiopathic fibrotic syndrome which involves excess collagen deposition in multiple tissues and organs. There is emerging evidence that dysfunctional fibroblasts are central to the underlying pathogenesis of this disease. An increasing awareness of the complex interplay of these fibroblasts with other cells and inflammatory mediators, such as platelet-derived growth factor (PDGF), is being recognised. This novel case serves to further develop our understanding of these pathological interactions, and to highlight a prospective role for Imatinib in disrupting them.
Methods
We present a case report below.
Results
A 54-year-old Caucasian male was referred to our rheumatology clinic due to worsening Raynaud's syndrome, arthralgia, and dry cough. He subsequently developed weight loss, pyrosis and skin thickening. This clinical picture was suggestive of a new diagnosis of systemic sclerosis. However, fibrotic skin changes did not extend to the distal finger, and anti-nuclear antibody (ANA) was negative. Symptoms were also refractory to various vasodilator and immunosuppressive therapies, including nifedipine, repeated iloprost infusions, azathioprine, mycophenolic acid, prednisolone, and sildenafil. Computed tomography (CT) imaging revealed interstitial pulmonary fibrosis and a mass within the gastric fundus. Histopathologic features and immunological staining of this mass were consistent with a GIST. Resection of the tumour did not improve fibrotic symptoms. Surveillance imaging one-year later was highly concerning for metastatic recurrence, which was later confirmed with tissue biopsy. He was subsequently initiated on Imatinib therapy, which led to a rapid improvement in fibrotic changes within weeks.
Conclusion
While there have been previous descriptions of para-neoplastic fibrotic syndromes, this is the first reported case of a scleroderma-mimicking disorder associated with GIST. It hints at an important potential overlap in the pathogenesis of these disease processes, and a potential role for tyrosine-kinase inhibitors in the treatment of scleroderma-like fibrotic disorders.
Disclosure
Z.A. Butt: None. W. Ng: None. D. Howard: None. K. Osman: None.
P037 DMARDs & hepatitis E: the hidden culprit
Authors: Brown Geraint A , Kearney Louise , Warner Elizabeth , Ellis Spencer 
Published: April 2021

Abstract
Background/Aims
Disease-modifying anti-rheumatic drugs (DMARDs) require blood monitoring as recommended by the British Society for Rheumatology guidelines. Deranged liver function tests are a common abnormality, and when a significant transaminitis occurs further investigations are required. We wish to present three cases where a transaminitis was caused by acute hepatitis E. Hepatitis E rarely causes illness in the general population. Transmission can occur via sewage-contaminated food and water, undercooked or raw pig and game meat, or processed pork and shellfish. Blood transfusion and solid organ transplantation is very rare. There is an estimated 60,000 cases of Hepatitis E per year in England. Those who are immunosuppressed are more likely to develop chronic liver disease.
Methods
.
Results
Case 1 is 55 year old male with a seronegative inflammatory arthritis treated with methotrexate and sulfasalazine whose ALT rose to 2043 U/l. After a negative liver screen including autoantibodies, Hepatitis E IgM was detected. Case 2 is a 71 year old male with seropositive rheumatoid arthritis prescribed Methotrexate and Sulfasalazine who developed a transaminitis following a holiday to Spain. Hepatitis E serology was positive. Case 3 is a 65 year old male with seropositive rheumatoid arthritis on Abatacept and Methotrexate who also developed deranged liver function tests following a trip to Spain. Alcohol excess was initially suspected due to the consumption of &gt; 20 units per week. However, on cessation of all medications the ALT continued to rise to 1087 U/l. He was found to be Hepatitis E IgM positive with viral PCR also detected. In all three cases contaminated food was likely to be the source of infection and DMARDs were successfully restarted in all patients following normalisation of liver function tests.
Conclusion
This case series highlights an important differential for transaminitis with very little published literature. Hepatitis E is under reported and not routinely requested in practice as part of a liver screen. Failure to check Hepatitis E serology may lead to DMARDs being discontinued inappropriately. All patients should be educated about the risks of Hepatitis E from food products.We recommend that DMARDs are suspended once Hepatitis E infection has been diagnosed in order to allow the immune system combat the infection. Treatment is usually self limiting, though in severe cases Ribavirin has been used with good effect. DMARDs should be restarted once liver markers normalise, and two serum Hepatitis E RNA results and two stool samples are negative. The presence of persistent Hepatitis E RNA (viral shedding) is highly suspicious for chronic infection, which would warrant hepatology input.
Disclosure
G.A. Brown: None. L. Kearney: None. E. Warner: None. S. Ellis: None.
P045 Nothing is too 'cagey' for the rheumatologist
Authors: Kazmi Muhammad F 
Published: April 2021

Abstract
Background/Aims
Rheumatological conditions can present with a number of non-specific features like arthralgia, fever, fatigue, weight loss along with raised inflammatory markers and positive antibodies. Due to this, when similar symptoms are referred for input it is very important to consider other ‘mimics’. We report a case of Pigeon fancier’s lung presenting with these symptoms which was referred as likely connective tissue disease.
Methods
A 52-year-old lady of South Asian origin was referred by her GP with six month history of 3kg weight loss, arthralgia, fatigue, low grade fever and persistently raised inflammatory markers (ESR ranging from 50-64 mm/hr, CRP 10-14 mg/L, normal BMI). On further questioning there was history of mouth ulcers, non-specific rash, occasional cough but no Raynaud’s or joint swelling. Blood investigations showed weakly positive ANA and RF but negative ENA, DNA, antiCCP , CK, C3,C4. C-ANCA was positive but PR3 negative. CXR was clear and tests for chronic infections including TB were negative. Due to lack of objective CTD signs, plan was to take a careful monitoring approach to see if clinical features evolved. A month later due to worsening cough, a CT chest/abdomen arranged by GP showed ground-glass changes consistent with pneumonitis and hence her rheumatology appointment was expedited to see if there was an autoimmune unifying diagnosis. She was also referred by her GP to the chest clinic in view of CT report and mild shortness of breath.
Results
On further review, again there were no objective CTD signs. On direct questioning there was history of travelling before worsening chest symptoms to South Asia. Also around a year before her symptoms started she was given an African grey parrot. Based on this, serology for Avian precipitin was checked which showed strongly positive IgG antibodies to avian antigens (Budgerigar droppings and feathers, Pigeon feathers IgG Abs) confirming the diagnosis of pigeon fanciers lung. She fulfilled the diagnostic criteria and was asked to avoid the trigger. Urgent respiratory input was arranged where diagnosis was agreed with and disease was deemed sub-acute in presentation. Due to PFTs showing low transfer factor of 38%, Prednisolone was started with significant improvement within few days. Review of CT chest only showed inflammatory changes and no established fibrosis predicting excellent prognosis as delay in treatment can cause irreversible pulmonary fibrosis.
Conclusion
A number of conditions can mimic rheumatological conditions which usually turn out to be either infectious or malignant in origin. This case highlights the importance of considering other differentials and along with taking a travel history also asking for other possible triggers like pets. In similar scenarios the diagnosis may be ‘cagey’ but as rheumatologists we are expected to answers questions which others can’t.
Disclosure
M.F. Kazmi: None.
P048 Cytomegalovirus retinitis in a patient with rheumatoid arthritis on tofacitinib
Authors: Beharry Karen , Kaur Simerdip , Papagiannuli Efrosini , Moses Samuel , Lord Denise De 
Published: April 2021

Abstract
Background/Aims
Cytomegalovirus (CMV) retinitis is one of the most common opportunistic ocular infections and has traditionally been associated with immunocompromised individuals. We present a case of CMV retinitis following 3 months of treatment with tofacitinib in conjunction with methotrexate (MTX) for rheumatoid arthritis (RA) in an elderly lady with no other co-morbidities.
Methods
The case is presented below.
Results
69-year-old lady with long standing seronegative, anti-cyclic citrullinated peptide negative, erosive RA since 2016. She was intolerant of sulphasalazine, leflunamide, methotrexate and etanercept. Hydroxychloroquine was avoided due to idiopathic cystoid macular oedema in the right eye with a baseline visual acuity of 6/18. Baseline fundus fluorescein angiogram (FFA) was negative for any vascular, inflammatory or occlusive disease. She was escalated to tofacitinib in August 2019. Approximately 3 months later, she noticed significantly reduced vision in her right eye from 6/18 down to 6/60. She had an FFA and Indocyanine Green Angiography, which showed quite extensive retinal ischaemia and vasculitis. Her bloods revealed a raised serum ACE and a T-spot test from 2018 was reactive followed by a repeat in 2019 which was equivocal. Tofacitinib was discontinued. She was commenced on rifampicin and isoniazid as 3 months prophylaxis for latent tuberculosis (LTBI). Additionally, she was started on oral prednisolone 60mg daily for presumed sarcoid related retinal vasculitis. She failed to improve despite a week’s treatment and subsequently had a vitreous aspirate which was strongly positive for CMV PCR. Her CMV viral load was 267copies/ml. The aspirate was negative for other infectious agents. She was commenced on valganciclovir for CMV retinitis. Unfortunately, her vision remained unchanged despite the viral load becoming undetectable a few weeks later. Despite having LTBI, there was no reactivation of this with her immunosuppressive therapy.
Conclusion
CMV retinitis is usually associated with immunocompromised individuals and is rarely encountered related to tofacitinib therapy for rheumatoid arthritis. Tofacitinib suppresses T cell function by inhibiting STAT signalling pathways, modulating T cell activation and cytokine production. Our case highlights the preferential development of CMV retinitis over active TB in the presence of LTBI, which is a recognised risk with the use of JAK kinase inhibitors. TB risk has been associated with genetic mutations in IL-12, IFN-γ and STAT1 pathways while CMV activation may be influenced by mutations in HLA ,Toll-like receptors, immunoglobulin light chain antibodies, IFN lambda region as well as alternative transcripts of the CMV viral major immediate early genes.
Disclosure
K. Beharry: None. S. Kaur: None. E. Papagiannuli: None. S. Moses: None. D. De Lord: None.
P064 The impact of the COVID-19 pandemic on outpatient services: an analysis of patient feedback of virtual outpatient clinics in a tertiary teaching centre with a focus on musculoskeletal and rheumatology services
Authors: Byravan Swetha , Sunmboye Kehinde 
Published: April 2021

Abstract
Background/Aims
Due to the COVID-19 pandemic there have been changes to NHS services to limit unnecessary patient hospital visits and comply with new social restriction rules. One of these changes has been the introduction of virtual consultations in outpatient clinics to replace traditional face to face appointments.
Methods
A retrospective analysis of patient feedback from adult outpatient virtual appointments in a 4-month period was collated and reviewed (May-September 2020). After an appointment, patients were sent a text message asking for feedback. The text consisted of one main question asking patients to rate their experience and a comment section. The data from this brief patient survey was obtained for all rheumatology patient responses. At the end of the text there was a link for a more comprehensive online survey which patients could fill out if they wish to provide more detailed feedback. Responses to this survey encompasses all adult outpatient specialities including musculoskeletal services.
Results
There were 269 responses to the detailed patient survey from various adult outpatient clinics. The most common type of virtual consultation was telephone which was the case in 79%, of which 91% of patients stated the caller was polite and 89% felt they had an opportunity to ask questions. When asked what their overall view 43% of patients stated they would not mind conducting all future appointments via telephone, 23.5% felt that in the current situation a telephone consultation was acceptable but would have preferred a face to face and 7% were completely unsatisfied. From the musculoskeletal group there were 36 responses (20 orthopaedic, 15 rheumatology and 1 musculoskeletal). 92% of patients stated they were given the opportunity to ask questions and 86% were satisfied with the advice given to them. 33% (n = 12) stated they would not mind having virtual consultations in the future even after the pandemic, but 28% stated they would have preferred a face to face consultation. There were 784 responses to the shorter patient survey via text message from rheumatology patients. When asked to rate their experience 94% (n = 739) of patients stated it was either good or very good, and only 1% said it was poor or very poor. There were largely positive comments in the feedback. Most frequent points were patients felt listened to, communication was good and virtual consultations were less stressful.
Conclusion
At present the use of virtual clinics seems to be well received by patients and most importantly their quality of care is not compromised. From a patient’s perspective there are many benefits and cumulative feedback so far suggests that majority of the patients are willing to adapt to this new approach to outpatient appointments both now and post-COVID-19.
Disclosure
S. Byravan: None. K. Sunmboye: None.
P093 Sleep characteristics and frailty in men: the influence of testosterone
Authors: Sharma Seema D , Cook Michael J , Vanderschueren Dirk , Antoniou Leen , Gielen Evelien , Wu Frederick C , O’Neill Terence W 
Published: April 2021

Abstract
Background/Aims
Previous studies have suggested an association between sleep disturbance and frailty. The mechanism is unknown, though it has been suggested that hormonal factors may play a role. The aim of this analysis was to determine the association between sleep duration, sleep quality and frailty in middle age and older European men and the influence of testosterone on these associations.
Methods
Men aged 40-79 years were recruited from population samples in eight European centres for participation in the European Male Age Study. Participants were interviewed and asked also to complete a questionnaire about sleep which included a question about average number of hours sleep per night and questions about sleep quality. Sleep quality was scored 0-20 with higher score indicating poor quality. A frailty index (FI) was constructed. Participants also had a single fasting morning venous blood sample taken and total testosterone measured using gas chromatography mass spectrometry. Using negative binomial regression we looked at the association between sleep duration, sleep quality and frailty (outcome; range 0-100) with the results adjusted for putative confounders and also testosterone level.
Results
2,369 participants contributed data to the analysis. Mean sleep duration was 7.01 hours. 256 (10.7%) participants had sleep quality scores between 10 -14 and 101 (4.2%) participants’ scores were between 15 and 20. Mean (standard deviation) testosterone level was 16.4 (6.2) pmol/l and 14.7% of subjects had a low testosterone level (&lt;10.5pmol/l). After adjustment for age, centre, body mass index, depression, pain, alcohol intake and smoking, compared to those with a sleep score of 0-4, those with scores of 10-14 and 15-20 were more likely to have a higher frailty index (RR = 1.37; 95% CI 1.25,1.49) and (RR = 1.57; 95% CI 1.38, 1.78) respectively. Further adjustment for testosterone did not influence the strength of these associations. Compared to those with sleep 6-8 hours, those with less than 5 hours had a significantly higher FI (RR = 1.16; 95% CI 1.06, 1.28) and also those with a longer sleep duration (9 hours or more) had a significantly increased FI (RR = 1.11; 95% CI 1.00, 1.23). Further adjustment for testosterone did not influence the strength of these associations.
Conclusion
Frailty is associated with impaired sleep quality and also sleep duration. The mechanism is unknown though cannot be explained by testosterone level.
Disclosure
S.D. Sharma: None. M.J. Cook: None. D. Vanderschueren: None. L. Antoniou: None. E. Gielen: None. F.C. Wu: None. T.W. O’Neill: None.