bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytochrome b5 diversity in green lineages preceded the evolution of syringyl lignin biosynthesis
Authors: Zhao Xianhai , Zhao Yunjun , Zeng Qing-yin , Liu Chang-Jun 
Published: April 2024

Abstract
Lignin production marked a milestone in vascular plant evolution, and the emergence of syringyl (S) lignin is lineage specific. S-lignin biosynthesis in angiosperms, mediated by ferulate 5-hydroxylase (F5H, CYP84A1), has been considered a recent evolutionary event. F5H uniquely requires the cytochrome b5 protein CB5D as an obligatory redox partner for catalysis. However, it remains unclear how CB5D functionality originated and whether it coevolved with F5H. We reveal here the ancient evolution of CB5D-type function supporting F5H-catalyzed S-lignin biosynthesis. CB5D emerged in charophyte algae, the closest relatives of land plants, and is conserved and proliferated in embryophytes, especially in angiosperms, suggesting functional diversification of the CB5 family before terrestrialization. A sequence motif containing acidic amino residues in Helix 5 of the CB5 heme-binding domain contributes to the retention of CB5D function in land plants but not in algae. Notably, CB5s in the S-lignin–producing lycophyte Selaginella lack these residues, resulting in no CB5D-type function. An independently evolved S-lignin biosynthetic F5H (CYP788A1) in Selaginella relies on NADPH-dependent cytochrome P450 reductase as sole redox partner, distinct from angiosperms. These results suggest that angiosperm F5Hs coopted the ancient CB5D, forming a modern cytochrome P450 monooxygenase system for aromatic ring meta-hydroxylation, enabling the reemergence of S-lignin biosynthesis in angiosperms.
Vacuolar degradation of plant organelles
Authors: Otegui Marisa S , Steelheart Charlotte , Ma Wenlong , Ma Juncai , Kang Byung-Ho , De Medina Hernandez Victor Sanchez , Dagdas Yasin , Gao Caiji , Goto-Yamada Shino , Oikawa Kazusato , Nishimura Mikio 
Published: April 2024

Abstract
Plants continuously remodel and degrade their organelles due to damage from their metabolic activities and environmental stressors, as well as an integral part of their cell differentiation programs. Whereas certain organelles use local hydrolytic enzymes for limited remodeling, most of the pathways that control the partial or complete dismantling of organelles rely on vacuolar degradation. Specifically, selective autophagic pathways play a crucial role in recognizing and sorting plant organelle cargo for vacuolar clearance, especially under cellular stress conditions induced by factors like heat, drought, and damaging light. In these short reviews, we discuss the mechanisms that control the vacuolar degradation of chloroplasts, mitochondria, endoplasmic reticulum, Golgi, and peroxisomes, with an emphasis on autophagy, recently discovered selective autophagy receptors for plant organelles, and crosstalk with other catabolic pathways.
Development of a cloud-based flow rate tool for eNAMPT biomarker detection
Authors: Buchanan Bailey C , Tang Yisha , Lopez Hannah , Casanova Nancy G , Garcia Joe G N , Yoon Jeong-Yeol 
Published: April 2024

Abstract
Increased levels of extracellular nicotinamide phosphoribosyltransferase (eNAMPT) are increasingly recognized as a highly useful biomarker of inflammatory disease and disease severity. In preclinical animal studies, a monoclonal antibody that neutralizes eNAMPT has been generated to successfully reduce the extent of inflammatory cascade activation. Thus, the rapid detection of eNAMPT concentration in plasma samples at the point of care (POC) would be of great utility in assessing the benefit of administering an anti-eNAMPT therapeutic. To determine the feasibility of this POC test, we conducted a particle immunoagglutination assay on a paper microfluidic platform and quantified its extent with a flow rate measurement in less than 1 min. A smartphone and cloud-based Google Colab were used to analyze the flow rates automatically. A horizontal flow model and an immunoagglutination binding model were evaluated to optimize the detection time, sample dilution, and particle concentration. This assay successfully detected eNAMPT in both human whole blood and plasma samples (diluted to 10 and 1%), with the limit of detection of 1–20 pg/mL (equivalent to 0.1–0.2 ng/mL in undiluted blood and plasma) and a linear range of 5–40 pg/mL. Furthermore, the smartphone POC assay distinguished clinical samples with low, mid, and high eNAMPT concentrations. Together, these results indicate this POC assay, which utilizes low-cost materials, time-effective methods, and a straightforward immunoassay (without surface immobilization), may reliably allow rapid determination of eNAMPT blood/plasma levels to advantage patient stratification in clinical trials and guide ALT-100 mAb therapeutic decision-making.
Efficient Solver of Relativistic Hydrodynamics with an Implicit Runge–Kutta Method
Authors: Touroux Nathan , Kitazawa Masakiyo , Murase Koichi , Nahrgang Marlene 
Published: April 2024

Abstract
We propose a new method to solve the relativistic hydrodynamic equations based on implicit Runge–Kutta methods with a locally optimized fixed-point iterative solver. For numerical demonstration, we implement our idea for ideal hydrodynamics using the one-stage Gauss–Legendre method as an implicit method. The accuracy and computational cost of our new method are compared with those of explicit ones for the (1+1)D Riemann problem, as well as the (2+1)D Gubser flow and event-by-event initial conditions for heavy-ion collisions generated by TRENTo. We demonstrate that the solver converges with only one iteration in most cases, and as a result, the implicit method requires a smaller computational cost than the explicit one at the same accuracy in these cases, while it may not converge with an unrealistically large Δt. By showing a relationship between the one-stage Gauss–Legendre method with the iterative solver and the two-step Adams–Bashforth method, we argue that our method benefits from both the stability of the former and the efficiency of the latter.
OA35 Amplifying young voices: the crucial role of young people living with rheumatic conditions in shaping information, advice and guidance
Authors: Woolley Lynne , Bovey-Pilkington Dawn 
Published: April 2024

Abstract

Background/Aims
In 2021, Versus Arthritis launched Young Experts - a project to improve the quality and availability of information for young people aged 11-16 living with rheumatic conditions. The adolescent years are a distinct and formative period in life and a lack of youth accessible information had been identified.

Methods
Firstly, we completed an audit of current resources, research, and standards. This helped us identify best practice as well as gaps, including a lack of accessible developmentally appropriate resources and resources for families/professionals supporting young people. Secondly, we gathered insight through UK-wide surveys, focus groups and interviews with young people and parents. This helped us prioritise topics (school was selected as the initial priority topic) and identify key messages. Thirdly, we ran an online co-production project with over 30 young people. Creative activities were facilitated by youth workers and content creators over the course of several weeks on school based topics. Each week built on the last - building on themes, checking understanding, and prioritising. As themes emerged the team also engaged with healthcare professionals, health-based youth workers and education staff to explore key areas and professional perspectives.

Results
A wealth of insight has been gathered on supporting young people living with a rheumatic condition to thrive at school. The initial focus was on support development, but the insight has also had the added benefit of influencing campaigning and awareness raising work. Young people flagged a greater focus on creating films featuring young people and retaining hard copy resources, which fundamentally shaped the new resource development plan. Resources must be in accessible, engaging formats for all young people. Youth feedback led to a greater focus on resources that change their community and society (e.g. actions of school leaders and staff), alongside resources for young people. Prioritisation of messaging to include more content on ‘quality communication’, ‘school engagement’, ‘mental health and wellbeing’ and ‘relationships of trust between school and young people’. Impact on young participants included new friendships, self-management support, and a focus on youth social action to improve things for the next generation of young people. New resources included a series of films co-designed with young people, and school staff resources.

Conclusion
Engaging young people in shaping information should challenge assumptions on content, key messaging and approaches. To design without the involvement young people could lead to new resources that fail to lever their full potential - in both challenging communities to be more inclusive and/or meeting the needs of young people and their families. With thanks to the young people involved in the project and continuing to support this vital work.

Disclosure
L. Woolley: None. D. Bovey-Pilkington: None.
P034 Lessons and feedback from a patient event: Salford Scleroderma Open Day 2023
Authors: Corotana Monisha , Samaranayaka Muditha , Dinsdale Graham , Hughes Michael , Johnson Lily , Wragg Elizabeth 
Published: April 2024

Abstract

Background/Aims
The 2023 Scleroderma Open Day at Salford Royal Hospital coincided with World Scleroderma Day on June 29, and was organised by the hospital's dedicated Scleroderma team. The Open Day featured a rich program; informative expert talks, a first-hand account from a scleroderma patient, and an array of stalls offering invaluable tips, information, and important contacts. Attendees, comprising patients and their friends and family, actively engaged in the event and provided feedback through forms distributed during the event.

Methods
The feedback forms employed in this study encompassed a wide spectrum of vital information, including demographic details of attendees, their holistic evaluations of the event, preferences for event duration, assessments of lecture quality, convenience, and reflections on the efficacy of face-to-face event delivery. Moreover, attendees were encouraged to share their perspectives on potential themes for future Open Days and express their willingness to participate in forthcoming research initiatives.

Results
The assessment of different facets of the Open Day on a scale from 1 (poor) to 5 (very good) revealed remarkable attendee satisfaction (Table 1). Lectures received an admirable mean rating of 4.3 (SD = 0.57). The venue itself was highly appreciated, with an impressive mean rating of 4.7 (SD = 0.57), indicating the success of the hospital as a welcoming host. The choice of face-to-face delivery over online alternatives was favourably endorsed, earning a mean rating of 4.4 (SD = 0.55). It is noteworthy that more than half (60%) of attendees rated the Open Day as ‘good’ (4/5), while a remarkable 40% rated the Open Day as ‘exceptional’ (5/5).

Conclusion
The Scleroderma Open Day at Salford Royal Hospital proved highly successful in providing valuable information on scleroderma, management, and access to additional resources for patients and their loved ones. A significant proportion of attendees expressed interest in participating in future research endeavours, promising a brighter outlook for scleroderma research and care. Potential topics for upcoming events, including the effects of scleroderma on organs, oral and dental health, and medication side effects, were also identified, offering a roadmap for addressing the evolving needs of the scleroderma community.

Disclosure
M. Corotana: None. M. Samaranayaka: None. G. Dinsdale: None. M. Hughes: None. L. Johnson: None. E. Wragg: None.
P113 Rheumatoid arthritis modifies the relationship between depression and overall mortality among African Americans
Authors: Banerjee Sri , Khubchandani Jagdish , Mesidor Maica , Lane Pilar , Gonzales-Lagos Rafael 
Published: April 2024

Abstract

Background/Aims
Rheumatoid arthritis (RA) has been known to be connected with many comorbidities and vascular diseases. Depression is two times more common in the RA population versus the general population. In this research, we will demonstrate the effect of depression on overall mortality and how the connection is influenced by rheumatoid arthritis among African Americans.

Methods
The National Health and Nutrition Examination Survey (NHANES) is a survey completed by non-institutionalized population of the United States. All respondents from the NHANES survey, who were 20 years or older and African American between the years 2005-2010 were included in the analysis with follow-up through December 31, 2019. Healthcare diagnosed self-reported information was used for the determination of RA. We determined depression by Patient Health Questionnaire (PHQ-9) with score ≥ 10. Analysis was performed using complex samples Cox regression to determine the relationship of depression on all-cause mortality and how rheumatoid arthritis influences this.

Results
Percent mortality among African American individuals with rheumatoid arthritis was 23.34% (CI 17.18%-29.34%) among males and 20.83% (CI 15.8-25.8) among females with mean follow-up of 10.1 years. For overall mortality, the age and sex-adjusted hazard ratio (HR) for depression was 2.52 (95% confidence interval [CI], 1.34-4.74 p = 0.01). The adjusted HR was elevated, 3.82 (CI 1.07-13.58, p = 0.04), among people with depression who also had rheumatoid arthritis but close to 1.0 (1.79 CI 0.47-6.88, p = 0.37) among individuals with depression who had no rheumatoid arthritis, after adjusting for medical (tobacco use, hypertension, and obesity) and demographic risk factors (poverty-income-ratio, age, and gender).

Conclusion
Among African Americans, we found that not only does depression lead to 2.5 times higher overall mortality but also rheumatoid arthritis occurrence affects this relationship even after controlling for potential confounders. As for treatment, African Americans are treated less with Disease-Modifying Anti-Rheumatic Drugs (DMARDS) than Caucasians according to previous research. Prevention and treatment programs for rheumatoid arthritis and screening for depression are especially important to treat comorbidities and to implement social change.

Disclosure
S. Banerjee: None. J. Khubchandani: None. M. Mesidor: None. P. Lane: None. R. Gonzales-Lagos: None.
P132 Longitudinal changes in the Scleroderma Health Assessment Questionnaire visual analogue scales in patients with systemic sclerosis: a retrospective cohort study
Authors: Hughes Michael , Sylvestre Yvonne , Manning Joanne , Mandzuk Melissa , Samaranayaka Muditha , Dinsdale Graham , Herrick Ariane 
Published: April 2024

Abstract

Background/Aims
The aim was to examine the course, impact of baseline predictors, and relationship with functional ability, of the six Scleroderma Health Assessment Questionnaire (SHAQ) visual analogue scales (VAS) over time in patients with SSc.

Methods
A retrospective analysis of patients attending annual review visits at a tertiary SSc center between 2005 and February 2020. Linear Mixed-effect models were used to assess longitudinal trajectories and effect of potential prognostic factors on the six different SHAQ VAS, except finger ulcers where the VAS scale was dichotomised (presence/absence) and analysed using a random intercept logistic regression model. To assess whether longitudinal changes in SHAQ VAS correlated with the HAQ-DI/11-point scleroderma functional index, we obtained the gradients of individual linear regression models, overall and by disease type.

Results
537 patients (75% lcSSc) with at ≥ 2 available time-points were included. Mean follow-up time and number of review visits were 6.8 (SD = ±4.2) years 6.4 (SD = ±3.7) visits, respectively. The mean (SD) RP and disease duration (defined as the first non-RP symptom) were 7.6 (11.9) and 8.0 (8.2) years, respectively. Time-in-study (Table 1) was associated with increase in VAS intestinal (p = 0.004), overall disease (p = 0.001) and presence of ulcers (p = 0.013). There was a trend observed concerning RP VAS (p = 0.068) and VAS breathing (p = 0.074), and no difference with VAS pain (p = 0.183). Time since RP onset showed a significant negative association with VAS pain (b=-0.01, [95%CI= -0.01 to 0.00], p = 0.032). Age had a significant negative effect on intestinal VAS (b=-0.01 [95%CI= -0.01 to -0.00], p = 0.040). Presence of ulcers increased with disease duration (OR = 0.97 [95%Cl= 0.94 to 1.00], p = 0.026), and in those with diffuse disease (OR = 0.54 [95%CI= 0.31 to 0.95], p = 0.033). For patients who were anti-RNP positive (compared to negative), the overall disease score VAS was higher (b = 0.23, 95%Cl= 0.00 to 0.45, p = 0.048) higher. All correlations between SHAQ VAS scales and function (HAQ-DI and 11-point scleroderma functional index) were positive (Table 2), and were almost exclusively stronger in patients with diffuse disease.

Conclusion
Longitudinal assessment of the SHAQ VAS scales provides important insights into disease trajectory. We have identified baseline factors associated with VAS outcomes, and associations with function over time.

Disclosure
M. Hughes: None. Y. Sylvestre: None. J. Manning: None. M. Mandzuk: None. M. Samaranayaka: None. G. Dinsdale: None. A. Herrick: None.
E039 Multiple myeloma and neurological complications: prevalence and risk factors
Authors: Dhifallah Malek , Fenniche Insaf , Feki Afef , Djemaa Samar Ben , Kallel Med Hedi , Fourat Hela , Akrout Rim , Baklouti Sofien 
Published: April 2024

Abstract

Background/Aims
Multiple myeloma (MM) is a malignant haematological disorder with a highly variable clinical presentation. Few studies have explored the neurological complications (CN) associated with MM. The objectives of this study were to describe the neurological manifestations observed in MM and to determine predictive factors for neurological complications.

Methods
We collected data from 126 cases of symptomatic multiple myeloma patients followed in our department over a 30-year period (1993 - 2023). We gathered sociodemographic, clinical, and laboratory data. Neurological complications were diagnosed based on clinical findings and magnetic resonance imaging data.

Results
Our study included 126 patients with an average age of 65.23 ± 11.63 years [36-92], and a male-to-female sex ratio of 3.8. Bone pain was present in 92.1% (116 cases) with an average duration of 4 months. The mean erythrocyte sedimentation rate and C-reactive protein levels were 99.08 mm at H1 [3-190] and 27.74 [0-196], respectively. Hemoglobin levels were less than 10g/dl in 51.2% of cases, with an average of 9.902 ± 2.22 g/dl [5-13.9]. Calcium levels exceeded 2.75 mmol/l in 20% of cases, with an average of 2.49 ± 0.33 mmol/l. The mean creatinine level was 88.28 ± 77.9 μmol/l [36-587], with levels above 177 μmol/l observed in 15 cases (10.4%). The Durie and Salmon prognostic classification categorized our patients as follows: Stage IA (3.2%), Stage IIA (4%), Stage IIB (0.8%), Stage IIIA (72.2%), and Stage IIIB (18.3%). Neurological complications were present in 22.2% of patients (n = 28). Sixteen patients (12.7%) had spinal cord compression, with nine having dorsal involvement, six having conus medullaris involvement, and one having cervical involvement. Radicular pain affected 14 patients, with eight experiencing sciatalgia and four having cruralgia. Two patients (1.8%) had carpal tunnel syndrome. No cerebral involvement was observed in our series. In our study, only creatinine levels were significantly lower in patients who developed neurological complications (64.35 vs. 95.19, p = 0.004). However, the occurrence of neurological complications was independent of age (p = 0.696), duration of evolution (p = 0.669), erythrocyte sedimentation rate (p = 0.541), C-reactive protein (p = 0.963), hemoglobin (p = 0.076), or calcium levels (p = 0.274). No association was found between neurological complications and gender (p = 0.849) or prognostic stage (p = 0.119)

Conclusion
Neurological manifestations in MM are diverse and often underestimated. The diagnosis of MM should be considered in the presence of spinal or radicular compression, especially when the laboratory findings suggest it.

Disclosure
M. Dhifallah: None. I. Fenniche: None. A. Feki: None. S. Ben Djemaa: None. M. Kallel: None. H. Fourat: None. R. Akrout: None. S. Baklouti: None.
Marginal and Obsolete? Rural Hospitals in Early Modern Europe: A Case Study of Catalonia
Authors: Marfany Julie 
Published: April 2024

Summary
Small local hospitals have been neglected by historians, and frequently assumed to have been marginal to their communities and largely obsolete by the eighteenth century. This paper questions such assumptions via a case study of Catalonia. It provides the first comprehensive estimates for the number of hospitals over the course of the eighteenth century, and then examines a sample of surviving accounts and other documentation to analyse the extent and nature of care provided. While the quality of care varied and most hospitals were restricted by their income, particularly against a background of war and rising prices, many nevertheless provided considerable care both to transient populations of foundlings and migrants and to their local communities. The paper calls for a re-evaluation of these forms of care in line with the re-evaluation of women’s caring work.
Cortactin controls bone homeostasis through regulating the differentiation of osteoblasts and osteoclasts
Authors: Yang Xiaoli , Chen Meng , Wang Shuang , Hu Xingli , Zhou Jie , Yuan Hairui , Zhu Endong , Wang Baoli 
Published: April 2024

Abstract
Cortactin (CTTN), a cytoskeletal protein and substrate of Src kinase, is implicated in tumor aggressiveness. However, its role in bone cell differentiation remains unknown. The current study revealed that CTTN was upregulated during osteoblast and adipocyte differentiation. Functional experiments demonstrated that CTTN promoted the in vitro differentiation of mesenchymal stem/progenitor cells into osteogenic and adipogenic lineages. Mechanistically, CTTN was able to stabilize the protein level of mechanistic target of rapamycin kinase (mTOR), leading to the activation of mTOR signaling. In-depth investigation revealed that CTTN could bind with casitas B lineage lymphoma-c (c-CBL) and counteract the function of c-CBL, a known E3 ubiquitin ligase responsible for the proteasomal degradation of mTOR. Silencing c-Cbl alleviated the impaired differentiation of osteoblasts and adipocytes caused by CTTN siRNA, while silencing mTOR mitigated the stimulation of osteoblast and adipocyte differentiation induced by CTTN overexpression. Notably, transplantation of CTTN-silenced bone marrow stromal cells (BMSCs) into the marrow of mice led to a reduction in trabecular bone mass, accompanied by a decrease in osteoblasts and an increase in osteoclasts. Furthermore, CTTN-silenced BMSCs expressed higher levels of receptor activator of nuclear factor κB ligand (RANKL) than control BMSCs did and promoted osteoclast differentiation when cocultured with bone marrow-derived osteoclast precursor cells. This study provides evidence that CTTN favors osteoblast differentiation by counteracting the c-CBL-induced degradation of mTOR and inhibits osteoclast differentiation by downregulating the expression of RANKL. It also suggests that maintaining an appropriate level of CTTN expression may be advantageous for maintaining bone homeostasis.