bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of Vismodegib Derivatives as Potential Smo Agonist: A Case of Undergraduate Experimental Teaching
Authors: Bao X. F. , Zhong M. Y. , Wu Z. X. , Zhang Q. Y. , Wang L. L. , Chen G. L.
Published: November 2023

The activation of Hh pathway demonstrates therapeutic potential for many diseases. Smo is the main target for the development of Hh pathway modulators. However, compared with Smo antagonist, the development of Smo agonists is lagging behind. Based on our previous work, a series of vismodegib derivatives were designed and synthesized, and their potential to activate the Hh pathway were evaluated via determining the up-regulation of known pathway target genes Gli1, whcih revealed that many target compounds could activate the Hh pathway. XH-16 and XH-17, with the strongest agonistic effect, could upregulate the expression of Gli1 by more than 50% at a concentration of 10 μM. In vitro cytotoxicity against A549 and the MDA-MB-231 cells was evaluated and the results revealed that XH-16 and XH-17 did not exhibit cytotoxicity at a concentration of 50 μM. Molecular docking results confirmed that XH-16 and XH-17 could bind to Smo indicating that their agonistic effect on the Hh pathway may be due to the activation of Smo. XH-16 and XH-17 with novel molecular scaffold could be used as a lead compound for the development of Smo agonists. Moreover, the research process was introduced in a medicinal chemistry experimental course to assist undergraduates in understanding the core of medicinal chemistry and building capabilities for independently carrying out a medicinal chemistry project. And the teaching practice experiences were summed up to provide suggestions for the development of exploratory experimental course.
Multifocal primary intrapulmonary thymoma successfully resected via robotic-assisted thoracoscopic surgery
Authors: Shell Daniel , Malone James , Kho Jane , Yap Cheng-Hon
Published: November 2023

Primary intrapulmonary thymoma (PIT) represents a rare subset of ectopic thymoma that arises solely from inside the pulmonary parenchyma. Multifocal PIT, where multiple isolated PIT origins coexist in the lungs, has only been confirmed in one previous case report, in which the patient died before surgical resection. These tumours are difficult to diagnose as imaging findings are non-specific, and non-invasive biopsy often yields inaccurate results. We present the case of a man in his 70s who was referred to thoracic surgery for resection of a presumptive endobronchial pulmonary carcinoid tumour. Only after surgical resection did we identify that the patient had multifocal PIT. In this report, we describe our diagnostic and management process for this patient and review the current literature on PIT.
Experiences of adolescents using sexual health services on Reunion Island: protocol for a qualitative phenomenological study
Authors: Reynaud Danielle , Laboureur Estelle , Marimoutou Catherine , Cartron Emmanuelle
Published: November 2023

Introduction

Adolescence and early adulthood are often critical periods of sexual development. The discovery of sexual intercourse can lead to sexual risk-taking which may impact the incidence of sexually transmitted infections (STIs) and unwanted pregnancies. Despite available sexual health services on Reunion Island, sexual health indicators for adolescents are very poor showing a high number of teenage pregnancies and abortions, low use of contraception and an upsurge of STIs. In contrast, this French region is equipped with many services and resources that enable young adults to make informed sexual health choices. This study protocol describes the methodology to describe adolescent experiences of using sexual health services on Reunion Island.

Methods and analysis

A monocentric descriptive qualitative study using a phenomenological approach will be conducted from December 2022 to August 2023 and will be based on face-to-face semistructured interviews with participants aged 15–19 years and residing on Reunion Island. Recruitment will be distributed at various educational institutions and sexual health centres and will be facilitated by the ‘snowball’ and ‘word-of-mouth’ effect. Data analysis will be independently carried out by three investigators to increase reliability. An interpretative phenomenological analysis will be performed.

Ethics and dissemination

Ethics approval was obtained from the Ethics Committee of the Hospital Center University De Bordeaux (CER-BDX-2022-55). Data generated do not fall within the field of biological or medical knowledge nor into the category of Research Involving the Human Person as defined in Articles L. 1121-1 and R. 1121-1 of the Public Health Code in France. All participants will receive information about the study in verbal and written forms and will give their oral consent before enrolment. Results will be published in a peer-reviewed journal as well as presented and disseminated at the Regional Health Agency of Reunion Island, conferences and in meetings with school directors.
Non-pharmacological interventions for patients with psoriasis: a scoping review
Authors: Zhang Xiu-jie , Lin Jingrong , Feng Li , Ou Minxing , Gong Fu-qing
Published: November 2023

Objectives

Healthcare ultimately aims to eradicate diseases and restore normality to people’s lives. However, until this is achieved for every person, there is a need to support and assist patients with psoriasis using non-pharmacological interventions. These ‘adjuvant’ approaches have received little attention, whereas dermatologists and researchers strive for better pharmacological therapy. Here, we aimed to perform a scoping review to identify and catalogue non-pharmacological interventions for patients with psoriasis.

Design

A scoping review.

Setting

All healthcare settings.

Search strategy

EMBASE, PubMed, CINAHL, PsycINFO and Scopus databases were searched from their inception to June 2022. Irrespective of the study type, the studies included non-pharmacological interventions for patients with psoriasis. This theme was extracted from the included articles. Two reviewers independently screened and analysed the data.

Results

From 1322 initial records, 71 studies were identified and analysed. Non-pharmacological interventions for patients with psoriasis include two levels: organisational and individual. The organisational non-pharmacological interventions included the nationwide healthcare model (PsPSP, ProvenCare, German PsoHealth and Psoriasis Network, IMPROVE model and PsoWell clinic), innovative teledermatology models (mHealth app, electronic Targeted Intervention for Psoriasis study and therapist-guided internet-based cognitive and behavioural treatments) and multidisciplinary interventions. The individual non-pharmacological interventions included educational interventions (therapeutic patient education, psychoeducational intervention and self-management education), psychosocial interventions (cognitive and behavioural treatments, self-help and peer-to-peer support programmes) and others (happify and motivational interviewing-based training).

Conclusions

Based on previous literature, a nationwide healthcare model protocol was constructed for patients with psoriasis. This provided the direction for developing a new psoriasis healthcare model and a basis for summarising the non-pharmacological interventions for patients with psoriasis, which helps them adjust to changes in the skin disease.
IC3 protocol: a longitudinal observational study of cognition after stroke using novel digital health technology
Authors: Gruia Dragos-Cristian , Trender William , Hellyer Peter , Banerjee Soma , Kwan Joseph , Zetterberg Henrik , Hampshire Adam , Geranmayeh Fatemeh
Published: November 2023

Introduction

Stroke is a major cause of death and disability worldwide, frequently resulting in persistent cognitive deficits among survivors. These deficits negatively impact recovery and therapy engagement, and their treatment is consistently rated as high priority by stakeholders and clinicians. Although clinical guidelines endorse cognitive screening for poststroke management, there is currently no gold-standard approach for identifying cognitive deficits after stroke, and clinical stroke services lack the capacity for long-term cognitive monitoring and care. Currently, available assessment tools are either not stroke-specific, not in-depth or lack scalability, leading to heterogeneity in patient assessments.

Methods and analysis

To address these challenges, a cost-effective, scalable and comprehensive screening tool is needed to provide a stroke-specific assessment of cognition. The current study presents such a novel digital tool, the Imperial Comprehensive Cognitive Assessment in Cerebrovascular Disease (IC3), designed to detect both domain-general and domain-specific cognitive deficits in patients after stroke with minimal input from a health professional. To ensure its reliability, we will use multiple validation approaches, and aim to recruit a large normative sample of age-matched, gender-matched and education-matched UK-based controls. Moreover, the IC3 assessment will be integrated within a larger prospective observational longitudinal clinical trial, where poststroke cognition will be examined in tandem with brain imaging and blood biomarkers to identify novel multimodal biomarkers of recovery after stroke. This study will enable deeper cognitive phenotyping of patients at a large scale, while identifying those with highest risk of progressive cognitive decline, as well as those with greatest potential for recovery.

Ethics and dissemination

This study has been approved by South West—Frenchay Research Ethics Committee (IRAS 299333) and authorised by the UK’s Health Research Authority. Results from the study will be disseminated at conferences and within peer-reviewed journals.

Trial registration number

NCT05885295. Stage: Pre-results.
Solutions to Enhance Health with Alternative Treatments (SEHAT) protocol: a double-blinded randomised controlled trial for gut microbiota-targeted treatment of severe acute malnutrition using rice bran in ready-to-use therapeutic foods in Indonesia
Authors: Weber Annika M , Barbazza Silvia , Fauzi Moretta D , Rachmadewi Asrinisa , Zuhrina Ririh , Putri Fildzah K , Campos Ponce Maiza , Hoeven Marinka van der , Rimbawan Rimbawan , Nasution Zuraidah , Giriwono Puspo E , Wieringa Frank T , Soekarjo Damayanti D , Ryan Elizabeth P
Published: November 2023

Introduction

Current formulations of ready-to-use therapeutic foods (RUTFs) to treat severe acute malnutrition (SAM) in children focus on nutrient density and quantity. Less attention is given to foods targeting gut microbiota metabolism and mucosal barrier functions. Heat-stabilised rice bran contains essential nutrients, prebiotics, vitamins and unique phytochemicals that have demonstrated favourable bioactivity to modulate gut microbiota composition and mucosal immunity. This study seeks to examine the impact of RUTF with rice bran on the microbiota during SAM treatment, recovery and post-treatment growth outcomes in Jember, Indonesia. Findings are expected to provide insights into rice bran as a novel food ingredient to improve SAM treatment outcomes.

Methods and analysis

A total of 200 children aged 6–59 months with uncomplicated SAM (weight-for-height z-scores (WHZ) <−3, or mid-upper arm circumference (MUAC) <115 mm or having bilateral pitting oedema +/++) or approaching SAM (WHZ<−2.5) will be enrolled in a double-blinded, randomised controlled trial. Children in the active control arm will receive a locally produced RUTF; those in the intervention arm will receive the local RUTF with 5% rice bran. Children will receive daily RUTF treatment for 8 weeks and be monitored for 8 weeks of follow-up. Primary outcomes include the effectiveness of RUTF as measured by changes in weight, WHO growth z-scores, MUAC and morbidity. Secondary outcomes include modulation of the gut microbiome and dried blood spot metabolome, the percentage of children recovered at weeks 8 and 12, and malnutrition relapse at week 16. An intention-to-treat analysis will be conducted for each outcome.

Ethics and dissemination

The findings of this trial will be submitted to peer-reviewed journals and will be presented at relevant conferences. Ethics approval obtained from the Medical and Health Research Ethical Committee at the Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Madain Yogyakarta Ref. No.: KE/FK/0546/EC/2022 and KE/FK/0703/EC/2023 and from Colorado State University IRB#1823, OHRP FWA00000647.

Trial registration number

NCT05319717.
School health professionals’ understanding of culture: a scoping review protocol
Authors: Wahlström Emmie , Landerdahl Stridsberg Sara , Larsson Camilla , Stier Jonas
Published: November 2023

Introduction

Culture is highlighted in previous research as important in encounters where health professionals and children do not share a language or culture. In these encounters, culture is described as mainly related to the child, whereas the health professionals’ understanding of their own culture as impacting the encounter tends to be left out. To clarify how culture is understood and conceptualised among professionals, it is of relevance to collate previous research on health professionals’ understanding of culture. In the scoping review that this protocol describes, we aim to focus on the context of the school health services, being a context accessible to many children in their everyday life. The aim of the review will be to identify, describe and analyse previous research concerning school health professionals’ (ie, school nurses, school social workers, school doctors and school psychologists) understanding of culture.

Methods and analysis

This scoping review will be guided by the methodology described by Peterset aland Khalilet al. Searches will be conducted in Scopus, PubMed, Cinahl Plus, SocIndex, Sociological Abstracts, Social Services Abstracts, APA PsycInfo, APA PsycArticles, Web of Science and Applied Social Sciences Index & Abstracts (ASSIA). Any published scientific papers focusing on school health professionals’ understanding of culture (conceptualised through a variety of related terms) and school health services conducted within the last 10 years (2013–2023) will be included. Two reviewers will independently screen all titles and abstracts for inclusion. Two reviewers will conduct the screening of full-text documents and the extraction of information. Qualitative content analysis as well as discourse analysis will be employed.

Ethics and dissemination

Ethical approval is not required for this study. The findings will be disseminated through peer review publication as well as presentation at conferences and to relevant stakeholders.
Paediatric hospitalisation related to medications administration errors of non-opioid analgesics, antipyretics and antirheumatics in England and Wales: a longitudinal ecological study
Authors: Naser Abdallah Y , Al-shehri Hassan
Published: November 2023

Objective

This study aimed to explore paediatric hospitalisation related to medication administration errors (MAEs) of non-opioid analgesics, antipyretics and antirheumatics in England and Wales.

Design

An ecological study.

Setting

A population-based study on hospitalised patients in England and Wales. Hospital admission data were extracted from the Hospital Episode Statistics database in England and the Patient Episode Database for Wales for the period between April 1999 and April 2020. Admissions cause was confirmed using the diagnostic codes T39.0–T39.9.

Participants

Paediatric patients aged 15 years and below who were hospitalised at all National Health Service (NHS) trusts and any independent sector funded by NHS trusts.

Primary outcome measure

Hospitalisation rates related to MAEs of non-opioid analgesics, antipyretics and antirheumatics.

Results

The yearly number of admissions for MAEs associated with non-opioid analgesics, antipyretics and antirheumatics experienced a notable growth of 21.7% over the span of two decades, rising from 4574 cases in 1999 to 5568 cases in 2020. The observed increase demonstrates a significant upward trend in hospital admissions rate, with a 12.3% growth from 46.16 per 100 000 individuals in 1999 to 51.83 per 100 000 individuals in 2020 (95% CIs 44.83 to 47.50 and 50.47 to53.19, respectively, trend test, p<0.05). The therapeutic categories that exhibited the highest frequency of MAEs were ‘4-aminophenol derivatives’ and ‘other non-steroidal anti-inflammatory drugs’, accounting for 79.3% and 16.0% of cases, respectively. It is worth noting that there was a significant increase of 28.9% in hospitalisations linked to MAEs specifically associated with ‘4-aminophenol derivatives.’

Conclusion

The research revealed a notable rise in the overall yearly number of hospital admissions associated with MAEs within the paediatric population. This study emphasises the necessity for additional research aimed at mitigating the potential hazards associated with the ingestion of these medications, particularly within susceptible demographics, such as young children.
Understanding a community’s needs for an emergency department-based childhood injury prevention programme: a mixed-methods study
Authors: Yusuf Hamzah Majid , Rosenthal Efrat , Kornblith Aaron , Sowar Christine , Del Toro Rigoberto , Chen Carol C
Published: November 2023

Objective

Unintentional injuries are the most common cause of childhood death in the USA and are preventable. We developed a framework for an injury prevention programme using local injury data and understanding stakeholder perspectives.

Methods

We used a mixed-methods approach. We performed a retrospective cross-sectional analysis of children presenting to an academic hospital system between January 2019 and December 2020 with an injury-related diagnosis. The primary outcome was encounters with an injury-related ICD-10 code. We conducted a thematic analysis by interviewing caregivers and emergency department (ED) providers.

Results

There were 10 193 unique injury-related encounters. Most common injuries were natural/environmental (22.9%), falls (20.0%) and striking an object (5.1%). Highest rates of injury were seen in children who identified as Native Hawaiian or Pacific Islander (154 injuries per 10 000 children per year), followed by Hispanic or Latino (148). Three out of 20 zip code areas represented 43.4% of all injuries and correlated with lower household income. Twenty-five caregivers and eight ED providers participated in interviews that resulted in four major themes: perceptions of injury risk, caregiver receipt of injury prevention information, barriers and provider counselling.

Conclusion

Clear differences exist within the injury burden in San Francisco by demographics, geography and type of injury. The findings from the study will guide the first steps in designing a strategic paediatric injury prevention centre. The methods may guide future investigations into the dynamic needs of clinicians and caregivers regarding injury. A strategic programme focused on the community’s unique needs and barriers may effectively reduce injury rates.
Exploring the global health and defence engagement interface
Authors: Whitaker John , Rickard R , Leather A , Davies J
Published: November 2023

Militaries have an important and inevitable role in global health and will interface with existing health systems on deployments. While the primary concern of militaries is not global health, there are clear, and increasingly frequent, circumstances when global health activities align with the interests of defence. Recognising this link between global health and security warrants thoughtful consideration and action where concerns affecting both intersect. In addition to providing medical support to military personnel on operations, advantageous effects can be achieved directly from military medical activities as part of Defence Engagement. While there are limitations and ethical boundaries to the role of militaries in global health, further training, research and conceptual development are warranted to optimise military medical activity at the intersection of security and global health to deliver advantageous effects. This paper forms part of a special issue ofBMJ Military Healthdedicated to Defence Engagement.
Cancer patients’ awareness of extent of disease: anxiety, depression, quality of life
Authors: Manalo Maria Fidelis Coronel , Yang Grace Meijuan , Reandelar Macario , Ozdemir Van Dyk Semra , Malhotra Chetna , Finkelstein Eric A.
Published: November 2023

Objective

In Asian cultures, the belief that full disclosure would harm the patient’s health would lead to non-disclosure. The study aimed to determine whether making patients aware of the extent of their disease will lead to psychological morbidity and poor quality of life (QOL).

Methods

This was a cross-sectional study among 195 patients with stage 4 cancer who were aware of their cancer diagnosis at the medical oncology, radiation oncology and palliative care units at an academic cancer centre. Participants were asked about their cancer stage, treatment goal and if they prefer to know their life expectancy. They answered the 14-item Hospital Anxiety and Depression Scale and 27-item validated Functional Assessment of Cancer Therapy-General questionnaires. Determination of the association of patients’ awareness of the extent of the disease with psychological status and QOL was analysed using univariate and multivariate statistics.

Results

About three-fourths of patients with cancer knew they had an advanced disease, but very few were aware that the current treatments they were taking for their cancer would not cure them. No association between awareness of the extent of the disease and psychological morbidity was found. Still, those aware of the advanced disease had significantly higher QOL scores for social well-being.

Conclusions

This study revealed that physicians should not hesitate to communicate the cancer diagnosis and prognosis to patients, as the disclosure was not associated with psychological morbidity. Open communication between physicians, patients and their families on the extent of the disease could empower patients to make informed decisions about their treatment, engage in advance care planning and seek the necessary support.
Feature selection and framework design toward data-driven predictive sustainability assessment and optimization for additive manufacturing
Authors: Naser Ahmed Z. , Defersha Fantahun , Yang Sheng
Published: November 2023

Additive manufacturing (AM) is considered an innovative technology to fabricate goods with green characteristics. In comparison to conventional manufacturing approaches, AM technologies have shown promising results in enhancing sustainability in production systems. Various research has been conducted to assess the environmental impacts of AM based on the well-known life cycle assessment (LCA) framework. However, this approach requires intensive domain knowledge to build the environmental impact model and interpret the findings. This knowledge barrier may cause delays and challenges in the selection of the optimal design and process parameters for additively manufactured parts. Such challenges can be particularly prevalent during the early product design and planning stages. As such, the research community demands an automated LCA tool to support AM toward elevated sustainability. To achieve this ambitious goal, this paper particularly investigates the fundamental question—“What are the key influential parameters that pose an impact on the environmental sustainability of AM?” Thus, this paper proposes a methodological framework for identifying the key influential parameters for AM. The framework was demonstrated by taking the fused filament fabrication process as a case study. Through instantiating various parts within the proposed framework and conducting LCA on over 200 AM instances, followed by correlation analysis, the key influential parameters were identified. Consequently, a data-driven predictive sustainability assessment and optimization framework was developed by integrating the identified influential features.
Lie Group-Based Neural Networks for Nonlinear Dynamics
Authors: Wen Ying , Chaolu Temuer
Published: November 2023

This paper introduces a novel neural network approach based on Lie groups to effectively solve initial value problems of differential equations for nonlinear dynamical systems. Our method utilizes a priori knowledge inherent in the system, i.e. Lie group expressions, and employs a single-layer network structure with the essence of a multilayer perceptron (MLP). To validate the effectiveness of our approach, we conducted an extensive empirical study using various examples representing complex nonlinear dynamical systems. The research results demonstrate the outstanding performance and efficacy of our method, outperforming Neural Ordinary Differential Equations in terms of accuracy, convergence speed, and stability.
Bifurcation Analysis of a Planar Piecewise Linear System of Focus–Focus Type
Authors: Wu Fang , Wang Jiafu , Huang Lihong
Published: November 2023

This paper is devoted to discussing the sliding bifurcation phenomena of a planar piecewise linear system with two zones separated by a straight line. We consider those systems for which in each zone there is precisely one real focus. By introducing Poincaré map and defining proper displacement function, some results on the existence of crossing periodic orbits, sliding periodic orbits, sliding-crossing periodic orbits and sliding homoclinic connections are obtained. Moreover, we establish some conditions for the simultaneous occurrence of crossing and sliding periodic orbits and show a concrete example.
Integrability and Global Dynamics of Two Chaotic Systems
Authors: Hussein Sarbast , Amen Azad Ibrahim
Published: November 2023

In this paper, integrability and the global dynamics of two chaotic systems, Coullet and Malasoma systems, are studied. We mainly use the contradiction technique to show that both systems have no polynomial, Darboux and rational first integrals. Moreover, it is proved that the Cullet system has no analytic first integrals if some conditions on the parameters are satisfied. We also give a complete description of the dynamics at infinity by Poincaré compactification technique for both aforementioned systems.
Hong Kong Guangdong Rheumatology Meeting
Authors: HONG Mukeng
Published: November 2023

Rheumatoid arthritis (RA) is an autoimmune disorder that has been associated with the gut microbiota. However, whether and how the gut microbiota plays a pathogenic role in RA remains unexplored. Here, we observed that Fusobacterium nucleatum is enriched in RA patients and positively associated with RA severity. F. nucleatum similarly aggravates arthritis in a mouse model of collagen-induced arthritis (CIA). F. nucleatum outer membrane vesicles (OMVs) containing the virulence determinant FadA translocate into the joints, triggering local inflammatory responses. Specifically, FadA acts on synovial macrophages, resulting in the activation of the Rab5a GTPase involved in vesicle trafficking and inflammatory pathways and YB-1, a key regulator of inflammatory mediators. OMVs containing FadA and heightened Rab5a-YB-1 expression were observed in RA patients compared with controls. These findings suggest causal role of F. nucleatum in aggravating RA and provide promising therapeutic targets for clinically ameliorating RA.
Opening Lecture
Authors: BARALIAKOS Xenofon
Published: November 2023

Ankylosing spondylitis (AS), also referred to as radiographic axial spondyloarthritis (r-axSpA), is a challenging, inflammatory rheumatic condition primarily impacting the sacroiliac joints and often extending to the spine. The prevalence of axSpA, encompassing both radiographic AS and non-radiographic axSpA, is estimated to vary between 0.2% and 0.5% among Chinese adults, depending on the classification criteria employed.

Treatment objectives for AS focus on improving the patient’s quality of life, function, and social involvement by managing inflammation and other disease symptoms. To achieve these goals, the American College of Rheumatology (ACR), the Spondylitis Association of America (SAA), and the Spondyloarthritis Research and Treatment Network (SPARTAN) advocate the use of non-steroidal anti-inflammatory drugs (NSAIDs) as the first-line treatment for AS, followed by biologic disease-modifying anti-rheumatic drugs (bDMARDs) like TNF inhibitors. While it has been common practice to initiate treatment with a TNF inhibitor or IL-17 inhibitor, the updated recommendations from the Assessment of SpondyloArthritis International Society (ASAS) and the European League Against Rheumatism (EULAR) now suggest the consideration of Janus kinase (JAK) inhibitors for patients with persistent high disease activity despite conventional therapy. Furthermore, the updated guidelines propose switching to another biologic DMARD (TNF inhibitor or IL-17 inhibitor) or JAK inhibitor if the first biologic DMARD proves ineffective.

Despite recent advancement, there remains an unmet need for effective therapies in the treatment of AS. Across various biologic studies, only 40-50% of patients achieve an ASAS40 response. Moreover, approximately one-third of patients fail to attain low disease activity according to the Ankylosing Spondylitis Disease Activity Score (ASDAS), and 65% do not achieve inactive disease status on ASDAS after one year of bDMARD therapy. There is a lack of oral treatment options for AS beyond NSAIDs, as all current biologics are administered via injection or infusion. Targeting JAK-mediated pathways with an oral option holds promise as a potential approach for treating adult AS patients.
Symposium 6
Authors: MOK Chi Chiu
Published: November 2023

The ultimate goal of treatment of systemic lupus erythematosus (SLE) is to prolong survival without compromising the quality of life. The survival rates of SLE have plateaued since the 2000s’ and morbidities related to disease activity and treatment are still problematic. A big unmet need for SLE therapy is to develop strategies that can enhance efficacy, reduce disease flares and drug related complications. Cocktail immunosuppressive therapies for the synergistic effect of individual drugs may enhance efficacy and enable dosage reduction. However, risk of infective complications, adoption of a step-up or step-down approach and the choice of agents are still controversial, partly because of the issue of cost-effectiveness. Belimumab is the first biological agent licensed for pediatric and adult patients with renal and non-renal SLE, based on several pivotal randomized controlled trials (BLISS-52, BLISS-76, BLISS-NEA, BLISS-SC, BLISS-LN). The continuous use of belimumab enables reduction of disease flares, glucocorticoid doses and organ damage. Anifrolumab, a monoclonal antibody against type I interferon receptors, has shown efficacy for non-renal SLE in the TULIP studies. It is recently licensed for moderate to severe SLE patients who are receiving standard therapies. Although rituximab did not show benefit in renal and non-renal SLE, it is commonly used off-label to treat refractory lupus manifestations. The newer generation anti-CD20 biologic, obinutuzumab, shows promising preliminary results in a phase 2 lupus nephritis (LN) trial. Combination of anti-CD20 and anti-BAFF is being studied in LN but the results are conflicting hitherto. Ianalumab, a monoclonal antibody against BAFF receptor that exhibits dual mechanisms of action (BAFF inhibition and B cell depletion), is being studied in LN. The updated 2023 EULAR recommendations for SLE have included the role of biological agents in the treatment algorithm. Belimumab and anifrolumab may be considered in non-major organ SLE, including skin disease, that is refractory to hydroxychloroquine with or without other immunosuppressive agents. Initial combination therapy of glucocorticoids, mycophenolate mofetil or low dose cyclophosphamide, with belimumab is an option for the treatment of severe LN, and belimumab may be used as long-term maintenance therapy of SLE/LN. In this talk, the evidence and the role of the older and newer biologic and targeted agents in SLE/LN will be reviewed.
Symposium 7
Authors: FONSECA João Eurico
Published: November 2023

Pre-clinical rheumatoid arthritis (RA) is a phase of the disease that occurs before the characteristic symptoms and clinical manifestations of RA become evident.

One key aspect of pre-clinical RA research has been the identification of biomarkers that can predict the development of RA in individuals who are at risk. Rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs) are often detectable in the pre-clinical phase, sometimes years before clinical onset. These biomarkers, along with genetic and environmental factors contribute to the risk profile for RA development.

Synovial biopsy, serum and peripheral blood cell characterization, magnetic resonance imaging (MRI) and ultrasound, have allowed researchers to capture subclinical joint inflammation in individuals who do not yet exhibit clinical symptoms. This has provided valuable insights into the progression of RA, as well as the potential for early intervention to prevent irreversible joint damage.

Understanding the pathogenesis of pre-clinical RA has revealed the role of several initial pathways that are relevant for the onset of the disease, paving the way for new treatment intervention and new very early diagnostic strategies.

Ongoing research will continue to refine our understanding of this phase of the disease and optimize strategies for its management.
Symposium 11
Authors: WONG Jane
Published: November 2023

Autoimmune diseases are conditions of immune dysfunction, leading to inappropriate hyperactivation of the adaptive immunity and subsequent damage to various tissues of the host. Autoimmune conditions presenting in the rheumatology clinics (rheumatoid arthritis, systemic lupus erythematosus or immune mediated myositis) are often treated by immunosuppression, which are almost invariably associated with increased susceptibility to infections. However, immunosuppression can sometimes be used to conversely treat susceptibility to infections.

An emerging group of autoimmune diseases which target the host’s own immune system (or associated cytokines) are becoming increasing recognized which phenotypically mimics various immunodeficiency syndromes – known as “phenocopies of PID”. One particular phenocopy of a PID known as Mendelian Susceptibility to Mycobacterial Disease (MSMD) has been increasingly recognized in our locality. This “acquired MSMD” is due to autoantibodies against anti-IFN[Formula: see text], leading to increased susceptibility to mycobacterial and other “IFN-[Formula: see text] dependent” infections. Alike other autoimmune diseases, appropriate and targeted immunosuppression can alleviate the effect of anti-IFN-[Formula: see text] antibodies and aid treatment of associated infections.

During this talk, our experience in the diagnosis and management toward acquired MSMD in our locality will be discussed. We will also share findings from our novel diagnostic and functional tests, as well as outcomes of acquired MSMD patients treated with B-cell depleting therapies.
Abstract 7 — Deep Learning Differentiation of Inflammatory Lesions in Sacroiliac Joint MRI Based on Spondyloarthritis Research Consortium of Canada (SPARCC) System
Authors: Chung Ho Yin , Chan Shirley Chiu Wai , Lin Yingying , Cao Peng
Published: November 2023

Objective

To develop a deep learning algorithm for grading sacroiliitis based on SPARCC in magnetic resonance imaging (MRI).

Method

A total of 996 images with inflammatory lesions from 210 participants with MRI sacroiliitis were used for training and validation. The testing cohort consisted of 18 participants with and 19 without MRI sacroiliitis. One hundred and fifty four images from the testing cohort had inflammatory lesions identified by a pre-trained algorithm from our previous study[1]. The ground truth was defined by manually outlined regions of interests (ROIs) consisting of bone marrow edema (BME) at the sacroiliac joint. The performance of the deep learning pipeline in predicting the SPARCC score was compared to manual interpretation by two experienced readers.

Result

The intra-observer reliability and the Pearson coefficient between the SPARCC scores from two experienced readers and the deep learning pipeline were 0.83 and 0.86, respectively. The sensitivities in identifying all inflammatory lesions, deep lesions, and intense lesions were 0.83, 0.79 and 0.81, respectively. The Dice coefficients of the sacrum and ilium segmentation were 0.82 and 0.80, respectively. The accuracies of identifying the SI joint and reference vessel were 0.90 and 0.88, respectively.

Conclusion

The performance of AI algorithms in SPARCC scoring was compatible with manual scoring by experienced readers. This proposed deep learning pipeline could be the first demonstration of a complete and SPARCC-informed deep-learning approach in scoring STIR images in SpA.
Abstract 8 — Risk of Liver Injury in Psoriasis and Rheumatoid Arthritis is Associated with Metabolic Risk Factors Rather than Methotrexate and Leflunomide
Authors: Chung Ho Yin , Chan Shirley Chiu Wai , Wong Christina Sze Man
Published: November 2023

Objectives

To assess the associations of hepatic injury and fibrosis in patients with psoriasis (PsO) and rheumatoid arthritis (RA).

Methods

A total of 318 patients attending dermatology and/or rheumatology out-patient clinics in Queen Mary Hospital, with clinical diagnosis of PsO, psoriatic arthritis (PsA) or RA were consecutively recruited from July 2020 to August 2022. Demographic data, comorbidities, and medications were recorded. Body mass index (BMI) was measured. Serum biomarkers for hepatic injury including autotaxin, matrix metalloproteinase (MMP) 3, MMP 8, and MMP 9 were determined. Transient elastography (TE) was performed to determine liver stiffness measure (LSM) and controlled attenuation parameter (CAP). Regression models were built to determine the association between methotrexate and leflunomide cumulative dosage, serum biomarkers and TE scores.

Results

A total of 67 (20.4%) patients had LSM>7.1 kPa. Multivariate linear regression showed methotrexate cumulative dosage was associated with autotaxin level (B=4.77, 95% CI 1.39; 8.15, p=0.001). There was no association between methotrexate cumulative dosage and MMP 3, MMP 8, MMP 9, LSM, CAP. There was also no association between leflunomide cumulative dosage and autotaxin, MMP 3, MMP 8, MMP 9, LSM, CAP. BMI (B=6.18, 95% CI 4.95; 7.41, p<0.001), hypertension (B=18.98, 95% CI 4.15; 31.82, p=0.01), hyperlipidaemia (B=20.21, 95% CI 3.50; 36.92, p=0.02) were associated with CAP.

Conclusion

Methotrexate and leflunomide have minimal hepatic risk in patient with PsO and RA. Metabolic risk factors had strong associations with hepatic injury.
Abstract 10 — Enhancing Dissolution Efficiency of Ketoprofen, A Rheumatoid Arthritis Pain Management Drug, through Solid Dispersion Formulation
Authors: Yadav Pankajkumar
Published: November 2023

Background

Ketoprofen (KPN) is commonly prescribed drug to alleviate pain related with rheumatoid arthritis (RA). However, KETO belongs to the BCS class-II category, characterized by poor water solubility, resulting in less dissolution capability leading to limited systemic absorption. Purpose of this study was to increase aqueous solubility as well as rate of dissolution of KPN using solid-dispersion technique.

Methods

Two different hydrophilic carriers, D-mannitol and polyvinylpyrrolidone K30 (PVP K30) and, were utilized, in varying ratios with the drug, to formulate solid dispersions. Kneading and solvent evaporation techniques were employed for preparing KPN solid dispersions with PVP K30, while kneading and melting methods were utilized for solid dispersions containing D-mannitol. The liquid state of the formulations was characterized through phase-solubility studies, while Scanning Electron Microscopy (SEM), Fourier Transform Infrared (FTIR) spectroscopy, Differential Scanning Calorimetry (DSC) and X-ray diffraction (XRD) analysis were performed to examine the solid state.

Results

Both carriers demonstrated a favorable impact on the aqueous solubility of KPN. Solid state examination of D-mannitol solid dispersions revealed that KPN existed as fine particles, while it was entrapped within the polymer matrix in solid dispersions with PVP K30. Compared to poor rate of dissolution of pure drug KPN, the drug dispersions in both carriers showed a significantly improved dissolution rate. Improvement of dissolution rate can be ascribed to enhanced wetting behavior and dispersion of fine particles along with reduced crystalline fraction and an increase in the amorphous nature of KPN.

Conclusion

PVP K30 solid dispersions of KPN exhibited a noteworthy enhancement in the dissolution efficacy of KPN. Moreover, physical mixtures of KPN exhibited better dissolution profiles with D-mannitol and PVP K30 in comparison to pure KPN.
Abstract 22 — Derivation and Internal Validation of a Multi-Biomarker-Based Disease Activity Prediction Score for Psoriatic Arthritis Patients
Authors: Jin Yingzhao , Cheng Isaac T , So Ho , Yip Terry Cheuk Fung , Wong CK , Tam Lai-shan
Published: November 2023

Background

While C-reactive protein (CRP) is commonly used to monitor disease activity in Psoriatic Arthritis (PsA), over half of the patients with moderate-to-high disease activity had normal CRP level. Our study aims to investigate the correlation of serum protein biomarkers and disease activity in patients with PsA.

Methods

176 patients fulfilled the CASPAR (ClASsification criteria for Psoriatic ARthritis) were recruited in this cross-sectional study. Disease activity was measured by the clinical Disease Activity in Psoriatic Arthritis (cDAPSA). 45 protein biomarkers, cartilage and bone turn-over markers level were assessed (Table 1). The patients were randomly divided into a derivation-cohort and a validation-cohort at a ratio of 7:3. Least absolute shrinkage and selection operator (LASSO) was used to select biomarkers which were associated with moderate/high disease activity in the derivation cohort. Receiver operating characteristic (ROC) curve, GiViTI calibration belt were used to assess the performance of the model in both cohorts.

Results

The cohort [age: 55.5 (44.0-62.75) years, male: 80 (45.5%)] had moderate disease activity [DAPSA: 15.9 (8.3-26.9); PASI: 3.2 (0.5-6.8)]. 101 PsA patients (57.4%) had moderate/high disease activity. Biomarker levels associated with moderate/high disease activity included SAA (Serum amyloid A), IL8 (Interleukin 8), IP10 (Interferon gamma-induced protein 10), M-CSF (Macrophage colony-stimulating factor), SCGF-[Formula: see text] (Stem cell growth factor), SDF-1[Formula: see text] (Stromal cell-derived factor 1[Formula: see text]) (Figure 1A, B). The model’s equation including the 6 biomarker levels was applied to the validation-cohort. The area under the ROC curve (AUC) for discriminating moderate/high disease activity was 0.802 and 0.835 for the derivation-and-validation-cohorts, respectively (Figure 1C, D). The multi-biomarkers panel model had higher-AUC when compared with that of CRP (AUC=0.727, p=0.022). The P-values of calibration charts in the two sets were 0.902 and 0.123 (Figure 1E, F).

Conclusions

The multi-biomarkers panel had excellent performance in discriminating patients with moderate/high disease activity from those with low disease activity/remission.
Abstract 23 — Ameliorative Effect of Biogenic Silver Nanoparticles Mediated with Naringin Against Collagen Induced Rheumatoid Arthritis in Rodents by Acting on Inflammation and Gut Microbiota
Authors: Yadav Ekta
Published: November 2023

Background

Rheumatoid arthritis (RA) hallmarked by functional impairment in joints due to inflammation, destruction and erosion of cartilages and bones. RA accounts as a major healthcare burden globally, hence there is a requirement of a novel therapeutic approach. Naringin is a flavanone glycoside possessing a variety of pharmacological activities in addition to anti-inflammatory and antioxidant properties. Among various metal oxide nanoparticles, silver nanoparticle drawing the attention of researchers as it possesses anti-inflammatory activity and utilized widely as a delivery vehicle for various natural anti-inflammatory drugs against RA. The study was designed to explore the effect of biogenic silver nanoparticles mediated with naringin (NAgNP) against RA induced by type II collagen, inflammation and gut microbiota in wistar rats.

Methods

NAgNPs were synthesized by co-precipitation method and characterized by various characterization techniques. Rats were employed for the study and randomized into five groups. Except control group, each group was treated with bovine type-II collagen (intradermal injection, 100 [Formula: see text] g) suspended in Freund’s complete adjuvant. On day 21 of the study, bovine type-II collagen and booster incomplete Freund’s adjuvant were again provided. Vehicle (Con), Methotrexate (Std, 3 mg/kg) and Test drugs, i.e., NAgNP, at three different dose levels (2, 4 and 8 mg/kg) were given in respective groups for consecutive 21 days. On the last day of study, various biochemical parameters including pro-inflammatory cytokine level in serum and the status of gut microbiome population were assessed with Illumina HiSeq.

Results

Characterization techniques confirmed the formation of spherical NAgNP with a size range of 80-100 nm. Data revealed that the groups administered with NAgNP exhibited a statistically significant decrease in (p < 0.01) rat paw swelling as well as arthritis scores than the control group. Different inflammatory markers such as IL-1[Formula: see text], IL-6, IL-7 and TNF-[Formula: see text] were found to be significantly reduced as compared to the control group. Significant improvement in the gut microbial population by alleviating the relative level of various microbes associated with inflammation was also observed.

Conclusion

NAgNP can be utilized as a beneficial candidate in the management of RA by the mechanism of amelioration of inflammation and gut microbiota.