bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Fundamental Role of H2O in the Generation of Coeval Sodic and Potassic Granitoids at Continental Arcs: An Example from the Yangtze Block, South China
Authors: Qi Han , Zhao Jun-Hong , Johnson Tim E 
Published: April 2023

AbstractThe bulk rock composition of granitoids reflects the composition of their source and the conditions of partial melting, which are functions of the geodynamic setting in which they formed. Granitoids in active continental margins (continental arcs) are dominated by calc-alkaline rocks with subordinate alkaline compositions, although how these different magma compositions formed is not well understood. Neoproterozoic magmatic rocks are widely distributed along the western margin of the Yangtze Block in South China to form the &gt;1000-km long Panxi continental arc system, which is dominated by granitoids with minor mafic–ultramafic and intermediate plutons. The granitoids are subdivided into sodic and potassic variants that occur as belts along the western and eastern sides of the continental arc, respectively. Sodic granitoids from the western part consist of tonalite, granodiorite, and monzogranite with crystallisation ages ranging from 870 Ma to 740 Ma. They have low K2O/Na2O ratios (0.1–1.0) and high Na2O contents (3.5–6.7 wt%), high but variable SiO2 (61–75 wt%) concentrations, and negative to positive whole-rock εNd(t) values (−1.7 to +2.9). Zircon grains from the sodic granitoids have εHf(t) values ranging from +0.3 to +9.6 and δ18O from 3.90‰ to 7.71‰. The potassic granitoids from the eastern side consist of monzogranite and syenogranite with crystallisation ages from 820 Ma to 790 Ma. They have high K2O/Na2O ratios (0.6–2.2), K2O (2.6–5.9 wt%) and SiO2 contents (69–78 wt%), but whole-rock εNd(t) (−0.9 to +2.9) and zircon εHf(t) (+1.8 to +12.9), and δ18O values (2.98‰ to 6.41‰) similar to those of the sodic granitoids. The isotopic compositions of both the sodic and potassic granitoids are similar to those of spatially- and temporally-related mantle-derived (mafic to ultramafic) rocks, and are considered to have been derived from juvenile mafic continental crust. Phase equilibrium modelling shows that the H2O content of the granitoid source rocks played a key role in their petrogenesis, both in lowering solidus temperatures and in controlling the compositions of the derived partial melts. Our results indicate that calc-alkaline sodic granitoids can be formed by water-fluxed melting of juvenile mafic crust at 750–900°C and 9–12 kbar in which the required H2O was derived from the dewatering of underplating mafic arc magmas. By contrast, the potassic granitoids were generated by fluid-absent (H2O-undersaturated) partial melting of a similar juvenile mafic source at 725–900°C and 6–9 kbar. We conclude that the sodic granitoids were derived from partial melting of the newly-formed mafic lower crust in the continental arc, whereas the potassic granitoids were likely generated in the back-arc setting induced by upwelling of asthenospheric mantle.
Solitons in openN= 2 string theory
Authors: Hamanaka Masashi , Huang Shan-Chi , Kanno Hiroaki 
Published: April 2023

AbstractThe open N = 2 string theory is defined on the 4D space-time with the split signature (+, +, −, −). The string field theory action of the open N = 2 string theory is described by the 4D Wess–Zumino–Witten (WZW4) model. The equation of motion of the WZW4 model is the Yang equation, which is equivalent to the anti-self-dual Yang–Mills equation. In this paper, we study soliton-type classical solutions of the WZW4 model in the split signature by calculating the action density of the WZW4 model. We find that the action density of the one-soliton solutions is localized on a 3D hyperplane. This shows that there would be codimension-one-solitonic objects, or equivalently some kind of three-branes in the open N = 2 string theory. We also prove that, in the asymptotic region of the space-time, the action density of the n-soliton solutions is a “non-linear superposition” of n one-solitons. This suggests the existence of n intersecting three-branes in the N = 2 strings. Finally we make a reduction to a (1 + 2)D real space-time to calculate the energy densities of the soliton solutions. We can successfully evaluate the energy distribution for the two-soliton solutions and find that there is no singularity in the interacting region. This implies the existence of smooth intersecting codimension-one branes in the whole region. Soliton solutions in the Euclidean signature are also discussed.
Application of photocrosslinkable hydrogels based on photolithography 3D bioprinting technology in bone tissue engineering
Authors: Gao Jianpeng , Liu Xiao , Cheng Junyao , Deng Junhao , Han Zhenchuan , Li Ming , Wang Xiumei , Liu Jianheng , Zhang Licheng 
Published: April 2023

AbstractBone tissue engineering (BTE) has been proven to be an effective method for the treatment of bone defects caused by different musculoskeletal disorders. Photocrosslinkable hydrogels (PCHs) with good biocompatibility and biodegradability can significantly promote the migration, proliferation and differentiation of cells and have been widely used in BTE. Moreover, photolithography 3D bioprinting technology can notably help PCHs-based scaffolds possess a biomimetic structure of natural bone, meeting the structural requirements of bone regeneration. Nanomaterials, cells, drugs and cytokines added into bioinks can enable different functionalization strategies for scaffolds to achieve the desired properties required for BTE. In this review, we demonstrate a brief introduction of the advantages of PCHs and photolithography-based 3D bioprinting technology and summarize their applications in BTE. Finally, the challenges and potential future approaches for bone defects are outlined.
P207 External validation of the Southend giant cell arteritis pre-test probability score in a Dorset fast-track clinic
Authors: Carroll James , Griffith Flynn , Fox Christine , Khurshid Muhammad 
Published: April 2023

Abstract

Background/Aims
Giant cell arteritis (GCA) is a common referral to rheumatology departments and timely and accurate diagnosis is important to prevent ischaemic complications. The current BSR and EULAR guidelines support the use of temporal and axillary artery ultrasound for ruling out GCA in low-probability cases or for confirming GCA in high-probability cases. The Southend GCA pre-test probability score (PTPS) is a tool that can be used to risk-stratify patients and guide the need for additional investigations. Previous publications have categorised patients as low-risk (PTPS &lt;9), intermediate-risk (PTPS 9-12) and high-risk (PTPS &gt;12). We aimed to provide external validation of the Southend PTPS by assessing its performance in patients attending the fast-track GCA clinic at Poole Hospital.

Methods
Between 5th January 2018 and 17th June 2022, 576 patients were seen in the GCA fast-track clinic at Poole Hospital and 506 (87.8%) had a calculated PTPS. Patients were diagnosed with ‘confirmed GCA’, ‘possible GCA’, ‘probable GCA’, ‘presumed GCA’, ‘not GCA’, or ‘large vessel vasculitis’ based on clinical, laboratory, ultrasound, biopsy or additional imaging. For the purpose of this analysis, we included only those patients who were diagnosed with ‘confirmed GCA’ (86 patients) or ‘not GCA’ (319 patients). A PTPS ≥9 was used to calculate the sensitivity, specificity, positive and negative predictive values for a diagnosis of GCA.

Results
The mean age of patients with ‘confirmed GCA’ in our cohort was 78.8 years and the percentage who were female was 72.1%. A PTPS ≥9 had a sensitivity of 97.7% and specificity of 63% for a diagnosis of GCA. The positive predictive value was 41.6% and negative predictive value was 99%.

Conclusion
Our results show that the Southend PTPS can be used to risk stratify patients into high- and low-risk groups and validates the PTPS outside the centre in which it was developed. Our results are comparable to those published by other external centres. The high negative predictive value of the test suggests it is particularly helpful in ruling out GCA and could conceivably have a role in screening referrals to the fast-track clinic; however, further work would be needed to determine the optimal cut-off score.
Disclosure
J. Carroll: None. F. Griffith: None. C. Fox: None. M. Khurshid: None.
E007 Is there an urgent need to change the methotrexate monitoring guidelines to incorporate fibroscan?
Authors: Ramalingam Satheekshan , Sayed Mostafa , Alam Syed , Makkuni Damodar 
Published: April 2023

Abstract

Background/Aims
Methotrexate (MTX) is a widely used DMARD for which routine blood monitoring is required to identify hepatotoxicity and bone marrow suppression. Despite routine monitoring and normal liver function tests some patients develop hepatic fibrosis. Transient elastography (fibroscan) offers an excellent non-invasive approach to measure the stiffness of the liver as a form of assessing hepatic fibrosis and would prove extremely useful to monitor the effects of MTX in our patient groups.

Methods
A retrospective study was conducted between January 2021 and August 2022. Inflammatory arthritis patients who have been on MTX for more than five years were selected for the study. Their fibroscan results were obtained and their median value (kilopascals), if they had an ultrasound in the past showing cirrhosis, metabolic risk factors such as obesity (BMI&gt;30), presence of type 2 diabetes and alcohol consumption (&gt;14 units/week) were recorded from their clinic letters.

Results
Of the 56 patients, there were 18 males and 38 females. 29% of the patients had a median fibroscan value of more than 7 kpa (n = 16). Of these 16 patients, 50% of the patients had a metavir score of F2 (n = 8), 25% of the patients had a metavir score of F3 (n = 4) and 25% of the patients had a metavir score of F4 (n = 4). Of the 16 patients (11 RA and 5 PSA) with high median value, 46% had a BMI &gt; 30 kg/m2 (n = 7), 13% had a diagnosis of type 2 diabetes mellitus (n = 2) and none of the patients had consumed more than 14 units/week of alcohol. Of the 16 patients with high median value, 12% (n = 2) had a diagnosis of cirrhosis on ultrasound. One patient had extremely high median value of 26 had underlying ILD, right heart failure and possible cardiac cirrhosis. 1 patient had developed frank cirrhosis and the high fibroscan results were noted subsequently. For all the patients with high metavir score of F4 and above, MTX therapy was discontinued.

Conclusion
A significant percentage of the cohort (29%) had a high median value above 7 of which 25% of the patients had F4 fibrosis despite having normal liver function tests. The study illustrates the need for a different modality in addition to the routine blood monitoring for the patients on MTX with metabolic risk factors. Therefore, it is vital to obtain a baseline fibroscan in high-risk patient group with preexisting metabolic risk factors prior to initiating MTX therapy and monitor every 5 years thereafter. This will help the clinician to safely continue MTX in this group of patients without the fear of worsening liver fibrosis.
Disclosure
S. Ramalingam: None. M. Sayed: None. S. Alam: None. D. Makkuni: None.
E019 A case of RS3PE triggered by immune check point inhibitor
Authors: Ramachandran Deepak , Mushtaq Warda , Makkuni Damodar 
Published: April 2023

Abstract

Background/Aims
Immune checkpoint inhibitors (ICIs) are increasingly being used in oncology and there is growing evidence of rheumatological problems arising in these group of patients. ICIs have been approved for the treatment of several cancers including non-small cell lung cancer, renal cell carcinoma, Hodgkin lymphoma and other malignancies. Pembrolizumab, an anti-PD1, is known to cause inflammatory arthritis in some patients, and we report a case of relapsing-remitting synovitis with pedal oedema (RS3PE) in a patient with lung cancer.

Methods
A 67-year-old lady was diagnosed with adenocarcinoma in her left lung with pleural and pulmonary metastasis. She was commenced on carboplatin, pemetrexed and pembrolizumab initially for 4 cycles followed by pembrolizumab maintenance therapy for another 2 years. However, while on pembrolizumab therapy, she started to develop intermittent pain and swelling in her small joints of the hands and feet. There was marked pitting pedal oedema extending up to the knee along with swelling of the dorsum of the hand. She had intermittent swelling in the knee joints as well.

Results
The blood tests were negative for rheumatoid factor, anti-CCP and ANA. The CRP was markedly raised (120) from her previous values since she started developing joint symptoms. The kidney and liver function tests were within normal limits. A CT chest, abdomen pelvis was done which did not reveal any metastasis or progression of lung cancer.
At the time of the review she was started on prednisolone 20mg once daily. Following this, the joint pain and swelling started to resolve, and the patient was advised to taper the steroids gradually. The pembrolizumab therapy was stopped few months later. The pedal oedema resolved within a few weeks of starting steroids and the joint inflammation settled after stopping the treatment.

Conclusion
ICI therapy has been known to trigger inflammatory arthropathy like RA. Psoriatic arthritis, undifferentiated monoarthritis and oligoarthritis, RS3PE and tenosynovitis have also been reported. Most published cases are mild to moderate in severity often responding to corticosteroids. Several patients have been treated with traditional DMARDs and biologics. RS3PE syndrome could be part of the paraneoplastic process but the onset of symptoms after starting pembrolizumab and rapid resolution after stopping the treatment indicates that this is likely a drug-induced adverse effect.
Disclosure
D. Ramachandran: None. W. Mushtaq: None. D. Makkuni: None.
E035 An evaluation of the causes and outcomes of haemophagocytic lymphohistiocytosis in Sheffield Teaching Hospitals: 2016 to 2021
Authors: Awdas Bethany , Nadin Thomas , Tattersall Rachel 
Published: April 2023

Abstract

Background/Aims
Haemophagocytic lymphiohistiocytosis (HLH) is a rare, underrecognised hyperinflammatory syndrome, characterised by immune dysregulation. Without treatment, the ensuing cytokine storm leads to high mortality. Secondary HLH (sHLH) is triggered by malignancy, infection, autoimmunity and medicines; treatment with immunosuppression is consensus- rather than evidence-based and extrapolated from primary HLH. Sheffield hosts a mature HLH multidisciplinary advisory group (MDAG). Here we evaluate the cause, treatment, requirement for critical care and mortality of people with HLH managed through the MDAG in a period including the coronavirus pandemic but prior to NHS England approval of anakinra (IL-1 antagonist) for HLH.

Methods
This retrospective evaluation (approved locally STH 10850) identified patients from MDAG records 1st October 2016 to 30th September 2021. Data from electronic/paper records was analysed using Microsoft Excel.

Results
HLH triggers were infection (viral 34%, bacterial 10%), haematological (35%), rheumatological (13%) and other (8%). Rheumatological causes were Still’s disease (n = 5); antiphospholipid syndrome (n = 2); JO1 dermatomyositis (n = 1); SLE (n = 1); and rheumatoid arthritis (n = 1). Other causes included unknown (n = 3); combined systemic JIA and sickle cell crisis (n = 1); medication (alemtuzumab) (n = 1); and primary HLH (n = 1). Overall mortality was 53% and highest in HLH with a haematological malignancy trigger (82%) Prior to the COVID19 pandemic (pre-March 2020), the commonest trigger of HLH was haematological malignancy (47%); after March 2020, the commonest trigger was infection (64%); COVID-19 explained 42% of cases. Mortality fell from 72% to 31%.

Conclusion
In this real-world series of people with HLH, mortality and critical care requirement was high. HLH triggers reflect published evidence as does poor prognosis in haematological malignancy-associated HLH. No-HLH associated with non-haematological malignancy was identified; we may need to improve MDAG reach into oncology. Seeming reduction in mortality following the COVID-19 pandemic may reflect increased recognition of COVID-19 induced hyperinflammation along with locally-agreed access to anakinra for COVID-19-induced HLH. The increase in infection related HLH cases since March 2020 is explained largely by COVID-19 cases. This has led to a relative reduction in cases related to haematological malignancy. HLH requires multidisciplinary management and better research to improve treatment.
Disclosure
B. Awdas: None. T. Nadin: None. R. Tattersall: None.
Which extra-renal flare is ‘difficult to treat’ in systemic lupus erythematosus? A one-year longitudinal study comparing traditional and machine learning approaches
Authors: Maffi Michele , Tani Chiara , Cascarano Giancarlo , Scagnellato Laura , Elefante Elena , Stagnaro Chiara , Carli Linda , Ferro Francesco , Signorini Viola , Zucchi Dina , Cardelli Chiara , Trentin Francesca , Collesei Antonio , Mosca Marta 
Published: April 2023

Abstract

Objectives
To describe phenotypes and outcomes of extra-renal flares in SLE, to identify clusters of extra-renal flares based on baseline features, and to develop a machine learning (ML) tool capable of predicting ‘difficult to treat’ (D2T) flares.

Methods
Extra-renal flares that occurred in our cohort over the last five years with at least one year of follow-up were included. Baseline clinical variables were described and flares assigned to clusters. Attainment of remission and low disease activity state (LLDAS) at 12 months were compared. Flares were then considered ‘D2T’ in case of non-attainment of LLDAS at 6 and 12 months. Baseline features were used to train a ML model able to predict future D2T-flares, at admission. Traditional approaches were then compared with informatic techniques.

Results
Among 420 SLE patients of the cohort, 114 flares occurred between 2015 and 2021; 79 extra-renal flares, predominantly mucocutaneous (24.1%) and musculoskeletal (45.6%), were considered. After 12 months, 79.4% and 49.4% were in LLDAS and in remission, respectively, while 17 flares were classified as D2T (21.5%); D2T flares received a higher cumulative and daily dose of glucocorticoids. Among the clusters, cluster ‘D’ (mild-moderate flares with mucocutaneous manifestations in patients with history of skin involvement) was associated with the lowest rate of remission. Among clinical data, not being on LLDAS at 3 months was the unique independent predictor of D2T flares.

Conclusions
Our clusterization well separates extra-renal flares according to their baseline features and may propose a new identification standard. D2T flares, especially refractory skin manifestations, are frequent in SLE and represent an unmet need in the management of the disease as they are associated with higher glucocorticoid (GC) dosage and risk of damage accrual. Our ML model could help in the early identification of D2T flares, flagging them to elevate the attention threshold at admission.
The diagnostic value of sST2 for myocardial fibrosis in idiopathic inflammatory myopathies in subclinical stage of cardiac involvement
Authors: Sun Jianhong , Xu Yuanwei , Wu Yang , Sun Jiayu , Yin Geng , Chen Yucheng , Xie Qibing 
Published: April 2023

Abstract

Objective
Myocardial fibrosis occurs in the early subclinical stage of cardiac involvement in idiopathic inflammatory myopathies (IIMs). Soluble suppression of tumorigenicity 2 (sST2) is known to have an immunomodulatory impact during autoimmune disease development. The current study investigated the diagnostic value of sST2 for myocardial fibrosis during early stage of cardiac involvement in IIM.

Methods
A total of 44 IIM patients with normal heart function and 32 age- and gender-matched healthy controls (HCs) were enrolled. Serum sST2 levels were measured by ELISA and cardiac magnetic resonance (CMR) parameters for myocardial fibrosis [native T1, extracellular volume (ECV), late-gadolinium enhancement (LGE)] and oedema (T2 values) were analysed.

Results
IIM patients had significantly higher sST2 levels than HCs [67.5 ng/ml (s.d. 30.4)] vs 14.4 (5.5), P &lt; 0.001] and levels correlated positively with diffuse myocardial fibrosis parameters, native T1 (r = 0.531, P = 0.000), ECV (r = 0.371, P = 0.013) and focal myocardial fibrosis index and LGE (r = 0.339, P = 0.024) by Spearman’s correlation analysis. sST2 was an independent predictive factor for diffuse and focal myocardial fibrosis after adjustment for age, gender, BMI and ESR. Risk increased ≈15.4% for diffuse [odds ratio (OR) 1.154 (95% CI 1.021, 1.305), P = 0.022] and 3.8% for focal [OR 1.038 (95% CI 1.006, 1.072), P = 0.020] myocardial fibrosis per unit increase of sST2. Cut-off values for diagnosing diffuse and focal myocardial fibrosis were sST2 ≥51.3 ng/ml [area under the curve (AUC) = 0.942, sensitivity = 85.7%, specificity = 98.9%, P &lt; 0.001] and 53.3 ng/ml (AUC = 0.753, sensitivity = 87.5%, specificity = 58.3%, P &lt; 0.01), respectively.

Conclusion
sST2 showed a marked elevation during the subclinical stage of cardiac involvement in IIM and has potential as a biomarker for predicting diffuse and focal myocardial fibrosis in IIM.
Ten Questions to Guide Learners Seeking Equitable Global Health Experiences Abroad
Authors: Reynolds Christopher W. , Kolars Joseph C. , Bekele Abebe 
Published: April 2023

“Global health experiences,” clinical and research learning opportunities where learners from high-income country (HIC) institutions travel to low- and middle-income countries (LMICs), are becoming increasingly popular and prolific in the health sciences. Increased interest has been well documented among medical, pharmacy, and nursing learners who are driving these agendas at their institutions. Although such opportunities have potential to mutually benefit the learner and host, in practice they can be exploitative, benefiting HIC learners without reciprocity for LMIC hosts. Given these and other pervasive ethical concerns in global health, efforts to decolonize global health and emphasize equity are being made at the institutional level. Despite progress toward global health equity from institutions, most learners lack the resources and education needed to critically evaluate the numerous global health opportunities or equitably codesign these experiences for themselves.
This article offers 10 guiding questions that learners should answer before selecting or codesigning a global health opportunity through a lens of global health equity. These prompts encompass values including motivations, reciprocity, accountability, sustainability, financial implications, self-reflection, bidirectional communication, and mitigating burden and power dynamics. The authors provide tips, pitfalls to avoid, and pragmatic examples for learners working to actualize partnerships and opportunities aligned with the movement of global health equity. With these guiding questions and accompanying reflection tool, learners, faculty members, and their LMIC partners should be better equipped to engage in mutually beneficial partnership through the framework of global health equity.