bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution of antiviral resistance captures a transient interdomain functional interaction between chikungunya virus envelope glycoproteins
Authors: Battini Leandro , Thannickal Sara A , Cibello Malena Tejerina , Bollini Mariela , Stapleford Kenneth A , Álvarez Diego E
Published: November 2024

Envelope proteins drive virus and host-cell membrane fusion to achieve virus entry. Fusogenic proteins are classified into structural classes that function with remarkable mechanistic similarities. Fusion proceeds through coordinated movements of protein domains in a sequence of orchestrated steps. Structures for the initial and final conformations are available for several fusogens, but folding intermediates have largely remained unresolved and interdependency between regions that drive conformational rearrangements is not well understood. Chikungunya virus (CHIKV) particles display heterodimers of envelope proteins E1 and E2 associated as trimeric spikes that respond to acidic pH to trigger fusion. We have followed experimental evolution of CHIKV under the selective pressure of a novel small-molecule entry inhibitor. Mutations arising from selection mapped to two residues located in distal domains of E2 and E1 heterodimer and spikes. Here, we pinpointed the antiviral mode of action to inhibition of fusion. Phenotypic characterization of recombinant viruses indicated that the selected mutations confer a fitness advantage under antiviral pressure, and that the double-mutant virus overcame antiviral inhibition of fusion while single-mutants were sensitive. Further supporting a functional connection between residues, the double-mutant virus displayed a higher pH-threshold for fusion than single-mutant viruses. Finally, mutations implied distinct outcomes of replication and spreading in mice, and infection rates in mosquitoes underscoring the fine-tuning of envelope protein function as a determinant for establishment of infection. Together with molecular dynamics simulations that indicate a link between these two residues in the modulation of the heterodimer conformational rearrangement, our approach captured an otherwise unresolved interaction.

Importance

CHIKV is a reemergent pathogen that has caused large outbreaks in the twenty years. There are no available antiviral therapies and a vaccine has only recently been approved. Here, we describe the mode of action of a novel inhibitor designed against CHIKV envelope proteins heterodimer that blocks entry at the stage of fusion between virus and host membranes. Fusion is common to the entry of enveloped viruses. Virus envelope proteins drive fusion undergoing a series of transitions from an initial metastable conformational state to a more stable post-fusion state. Intermediate conformations are transient and have mostly remained inaccessible to structure determination. In this study, directed evolution of resistance to antiviral inhibition of fusion uncovered a functional interaction between two residues residing in domains that are apart in both the pre-fusion and post-fusion states. Thus, our approach allowed gaining insight into the molecular detail of the inner working of virus fusion machinery.
The effect of social media engagement on telemedicine adoption: an empirical study
Authors: Dass Jhanvi , Yeravdekar Rajiv , Singh Ankit
Published: November 2024

Purpose

This study aims to assess the collective impact of social media engagement and anxiety due to COVID-19 on telemedicine adoption intentions with other constructs of the Technology Acceptance Model (TAM) concerning anxiety linked to COVID-19 and the influence of privacy concerns on TAM constructs. These constructs encompass the perception of ease of use, perceived usefulness, one’s attitude toward telemedicine and the intention to utilize telemedicine.

Design/methodology/approach

A total of 178 comprehensive responses were gathered over a six-month period from residents in Mumbai, India, to examine the proposed model. The data was analyzed using software tools, including SPSS version 23 and IBM AMOS 21, to compute factor loadings, assess model fit, estimate path relationships and conduct hypothesis testing.

Findings

Privacy concerns with telemedicine usage had a significant negative impact on behavioral engagement (B = −0.20, SE = 0.08, p < 0.05) and positively impacted affective engagement (B = 0.25, SE = 0.06, p < 0.01). Similarly, anxiety due to COVID-19 had a negative impact on the perceived usefulness of telemedicine (B = −0.10, SE = 0.03, p < 0.05).

Research limitations/implications

This research addresses a void in the existing literature by merging the TAM and the Social Media engagement theory. This study reaffirms the impact of past and relevant experiences, privacy concerns and COVID-19-induced anxiety on various components of TAM, thus expanding and enriching the TAM model.

Practical implications

Healthcare administrators should implement strategies to alleviate privacy-related apprehensions associated with telemedicine platforms. Additionally, they should promote existing users to create and disseminate positive content to mitigate COVID-19-induced anxiety and foster meaningful engagement, thereby enhancing the willingness to adopt telemedicine.

Social implications

Providers and promoters of telemedicine platforms and services may lean toward employing digital marketing campaigns that rely on emotional persuasion, including tapping into the fear factor to boost subscription and service sales. Such practices raise ethical questions, underscoring the need for well-defined advertising standards to govern the marketing of these products.

Originality/value

This article is among the relatively rare studies that document the favorable influence of emotional engagement on the intention to utilize telemedicine, underscoring the significant role of emotions in shaping telemedicine adoption Intentions.
Subjective well-being and mental health during the COVID-19 pandemic in Hungary
Authors: Xu Feifei
Published: November 2024

Purpose

This study aims to examine the impact of COVID-19 pandemics on subjective well-being (SWB) and mental health in Hungary, with a particular focus on the roles of socioeconomic and COVID-19-related factors in shaping these outcomes.

Design/methodology/approach

A cross-sectional online survey was conducted among 2,000 Hungarian adults from May 25 to June 8, 2021. The data was collected using standardized questionnaires, including the SWLS, GAD-7 and PHQ-9. Correlation analysis, one-way ANOVA and linear regression were used.

Findings

The study found significant anxiety (41.5%), depression (48.1%) and life dissatisfaction (41.9%) among 2,000 participants. Females reported higher anxiety and depression than males. Single individuals had the lowest life satisfaction. Higher income levels are correlated with greater life satisfaction. Quarantine and vaccination were linked to higher life satisfaction and lower psychological distress. The regression showed that older age, being married and higher income were linked to lower depression and anxiety. Severity of infection and quarantine increased both depression and anxiety. Infection reduced life satisfaction, but severe cases showed a slight improvement in satisfaction, highlighting complex health and well-being relationships.

Practical implications

The findings reveal complex relationships, including unexpected resilience in severe COVID-19 cases.

Originality/value

This study offers insights into the impact of the COVID-19 pandemic on SWB and mental health in Hungary. By analyzing socioeconomic, demographic and pandemic-related factors in a large sample, it highlights complex relationships between quarantine, infection severity, vaccination and well-being. The findings contribute to understanding how these factors influence mental health, informing targeted interventions during health crises.
Investigating young consumers’ acceptance of hemp fiber textiles and apparel: an analysis of Partial Least Squares Structural Equation Modeling
Authors: Zhang Yanbo , Liu Chuanlan , Xia Sibei
Published: November 2024

Purpose

Concerns over environmental degradation, alongside the global legalization of hemp cultivation, have prompted applications of hemp-derived textile products. However, research examining consumers’ acceptance of such products is lacking. It is critical to understand how young consumers adopt these products as they prioritize sustainability and lead the future purchasing power. Thus, this study aims to investigate young consumers’ perceptions, attitudes, and purchase intentions regarding hemp fiber textiles and clothing based on the Theory of Consumption Value and the Spiral of Silence Theory.

Design/methodology/approach

A US-based research company was hired to recruit survey participants, yielding 314 valid data. Data analysis, including Exploratory Factor Analysis and Partial Least Squares Structural Equation Modeling, was conducted using the R programming language and RStudio software.

Findings

Purchase intentions of hemp-based clothing and textiles among young consumers are influenced by attitude, perceived social value and future trend perception. Perceived social value also impacts attitude and future trend perception. High environmental involvement correlates with positive attitudes. Consumers’ subjective knowledge of hemp and objective knowledge regarding hemp fiber impact their perceptions of future trends in such products.

Originality/value

This research represents a seminal consumer study focusing on the resurgence of industrial hemp fiber textiles and clothing. This study empirically validates the significant role of social factors in young consumer acceptance of such products at both personal and societal levels. This study expands current knowledge and provides actionable insights for practitioners.
Aligning the new work environment with OECD Goal 8: a design case of a global automobile brand from Turkey
Authors: Sunar Bukulmez Pınar , Girginkaya Akdag Suzan , Ekin Gamze
Published: November 2024

Purpose

This paper aims to investigate the economic sustainability of new work environments by exploring how interior design strategies can contribute to the Organization for Economic Co-operation and Development (OECD)’s Sustainable Development Goal (SDG) 8, which focuses on decent work and economic growth. SDG 8 aims to foster sustained, inclusive and sustainable economic development, as well as full and productive employment.

Design/methodology/approach

The pilot study was conducted at a global automobile brand’s largest facility in Kocaeli/Turkey, where 102 employees participated in stakeholder meetings divided into 18 groups. Additionally, 46 employees were interviewed through focus groups and one-on-one sessions across nine encounters. The collected data were analyzed using deductive thematic analysis, interpreting codes and themes related to spatial politics, timing politics and hybrid working culture in the new work environment.

Findings

Identified themes include individually focused tasks, virtual collaboration, agile working, socialization and urban interaction. These themes are then traced through the conceptual design proposal developed by the interior design team and discussed in relation to their alignment with SDG 8.2 (diversify, innovate and upgrade for economic productivity), SDG 8.4 (improve resource efficiency in consumption and production) and SDG 8.8 (protect labor rights and promote safe and secure working environments for all workers).

Research limitations/implications

These three targets (for inclusivity and innovation, for environmentally sustainable and for employee well-being) were selected for their relevance in shaping the physical work environment.

Originality/value

The key finding of this paper is the need for a deeper understanding of economic sustainability in interior design and the contribution of SDG 8 targets on the spatial, temporal and cultural dimensions of new work environments. Brands committed to sustainability must adopt new work models and reimagine their work environments to enhance employee satisfaction and performance, through comprehensive user research and design solutions aligned with SDG 8.
Prediction of electroconvulsive therapy outcome: A network analysis approach
Authors: Blanken Tessa F. , Kok Rob , Obbels Jasmien , Lambrichts Simon , Sienaert Pascal , Verwijk Esmée
Published: November 2024

Objective

While electroconvulsive therapy (ECT) for the treatment of major depressive disorder is effective, individual response is variable and difficult to predict. These difficulties may in part result from heterogeneity at the symptom level. We aim to predict remission using baseline depression symptoms, taking the associations among symptoms into account, by using a network analysis approach.

Method

We combined individual patient data from two randomized controlled trials (total N = 161) and estimated a Mixed Graphical Model to estimate which baseline depression symptoms (corresponding to HRSD‐17 items) uniquely predicted remission (defined as either HRSD≤7 or MADRS<10). We included study as moderator to evaluate study heterogeneity. For symptoms directly predictive of remission we computed odds ratios.

Results

Three baseline symptoms were uniquely predictive of remission: suicidality negatively predicted remission (OR = 0.75; bootstrapped confidence interval (bCI) = 0.44–1.00) whereas retardation (OR = 1.21; bCI = 1.00–2.02) and hypochondriasis (OR = 1.31; bCI = 1.00–2.25) positively predicted remission. The estimated effects did not differ across trials as no moderation effects were found.

Conclusion

By using a network analysis approach this study identified that the presence of suicidal ideation predicts an overall worse treatment outcome. Psychomotor retardation and hypochondriasis, on the other hand, seem to be associated with a better outcome.
Effectiveness of protected areas in the Caucasus Mountains in preventing rangeland degradation
Authors: Ghoddousi Arash , Pratzer Marie , Lewinska Katarzyna E. , Eggers Juliana , Bleyhl Benjamin , Ambarli Hüseyin , Arakelyan Marine , Askerov Elshad , Butsic Van , Ghazaryan Astghik , Lortkipanidze Bejan , Radeloff Volker C. , Kuemmerle Tobias
Published: November 2024

As land use intensifies globally, it increasingly exerts pressure on protected areas. Despite open, nonforested landscapes comprising up to 40% of protected areas globally, assessments have predominately focused on forests, overlooking the major pressures on rangelands from livestock overgrazing and land conversion. Across the southern Caucasus, a biodiversity hotspot extending over 5 countries, we conducted a broadscale assessment of the extent to which protected areas mitigate land‐use pressure on rangelands in them. Using satellite‐based indicators of rangeland vegetation greenness from 1988 to 2019, we assessed the effectiveness of 52 protected areas. This period encompassed the collapse of the Soviet Union, economic crises, armed conflicts, and a major expansion of the protected area network. We applied matching statistics combined with fixed‐effects panel regressions to quantify the effectiveness of protected areas in curbing degradation as indicated by green vegetation loss. Protected areas were, overall, largely ineffective. Green vegetation loss was higher inside than outside protected areas in most countries, except for Georgia and Turkey. Multiple‐use protected areas (IUCN categories IV–VI) were even more ineffective in reducing vegetation loss than strictly protected areas (I & II), highlighting the need for better aligning conservation and development targets in these areas. Mapping >10,000 livestock corrals from satellite images showed that protected areas with a relatively high density of livestock corrals had markedly high green vegetation loss. Ineffectiveness appeared driven by livestock overgrazing. Our key finding was that protected areas did not curb rangeland degradation in the Caucasus. This situation is likely emblematic of many regions worldwide, which highlights the need to incorporate degradation and nonforest ecosystems into effectiveness assessments.
Are Risky Banks Disciplined by Large Corporate Depositors?
Authors: IMBIEROWICZ BJÖRN , SAUNDERS ANTHONY , STEFFEN SASCHA
Published: November 2024

We analyze depositor discipline using auctions of unsecured money market deposits of firms to banks. In each auction, only the firm observes the banks and their interest rate bids. We observe that deposit interest rate bids increase with bank risk. Conditional on the same interest rate bid and firm–bank relationship, depositors select less risky banks. Banks reduce their risk after their deposit offers are less often selected. Risky banks eventually exit the market, and reenter when they become safer. This has important implications for banks’ access to unsecured corporate funding, financial stability, and our understanding of market discipline more broadly.
Mapping microfinance research to sustainable development goals: Insights from Scientometrics and BERTopic analysis
Authors: Pattnaik Debidutta , Hassan M. Kabir
Published: November 2024

Microfinance research plays a pivotal role in addressing global development challenges, yet comprehensive assessments of its alignment with sustainable development goals (SDGs) remain scarce. This study fills this gap by systematically mapping the landscape of microfinance literature to its corresponding SDG contributions. Leveraging data from Scopus and SCIval, we analyzed 1004 microfinance articles spanning between 2014 and 2023. Our findings reveal a substantial body of research focused on poverty alleviation (SDG 1) and economic empowerment (SDG 8), with notable attention to gender equality (SDG 5) and reduced inequalities (SDG 10). Key thematic clusters include the performance and impact of microfinance institutions (MFIs), microinsurance innovations, and Islamic microfinance. Notably, top‐cited articles underscored the sector's commitment to poverty alleviation and economic growth, with a nuanced exploration of gender dynamics and rural household impacts. Furthermore, our BERTopic analysis unveils the multidimensional nature of microfinance research, highlighting prevalent themes such as MFI performance and rural household impact. Geographically, research efforts are concentrated in the United States, India, and France, reflecting a global commitment to SDG‐aligned microfinance interventions. The paper's theoretical contributions lie in its framework development, interdisciplinary engagement, nuanced understanding of microfinance themes, global perspective, and methodological advancements, all of which enhance the scholarly discourse on microfinance's role in achieving SDGs.
Accuracy of different maxillomandibular relationship recording techniques in the edentulous maxillary arch
Authors: Pletkus Justinas , Auškalnis Liudas , Gendvilienė Ieva , Pletkus Rolandas , Eyüboğlu Tan Fırat , Özcan Mutlu , Akulauskas Mykolas , Rutkūnas Vygandas
Published: November 2024

Purpose

This study investigated the effect of three digital bite registration techniques on the accuracy of intraoral scanning in maxillary edentulous and mandibular dentate arches.

Materials and Methods

Maxillary edentulous and mandible fully dentate models were created. Four dental implants were placed in the maxilla, fitted with scan bodies, and reference scans were obtained using a Nikon Altera 10.7.6 scanner. Digital impressions were acquired 10 times for each model using a Trios 4 intraoral scanner. Three different digital bite records were collected for each pair of mandible and maxilla scans. The first one was a bite record without additional material (WSB), the second utilized a silicone index between the models (WSB silicone), and the third followed a pre‐preparation scanning protocol (Pre‐PREP). The data was exported in standard tessellation language (STL) format, which was assessed for trueness and precision using statistical analysis.

Results

According to mean trueness values, WSB exhibited the lowest value, 173 µm, followed by WSB silicone 242 µm and Pre‐PREP 620 µm. The differences were significant only when comparing Pre‐PREP to WSB and Pre‐PREP to WSB silicone (p < 0.05). Regarding precision, WSB demonstrated a mean value of 171.5 µm, followed by WSB silicone with 213.8 µm, and Pre‐PREP with 222.2 µm with no significant difference between the groups.

Conclusion

The presence of interarch bite registration material adversely affected interocclusal record accuracy, while WSB silicone presented a suitable substitute for WSB.
Kaposiform Hemangioendothelioma With Features of Congenital Hemangioma Treated With Sirolimus
Authors: Lee Danny , Sui Jennifer , Al‐Nabti Alreem , Schiff Deborah , Matiz Catalina , Naheedy John , Eichenfield Dawn Z.
Published: November 2024

Kaposiform hemangioendothelioma (KHE) is a vascular neoplasm characterized by abnormal angiogenesis and lymphangiogenesis. Here, we present a case of a 19‐month‐old male with KHE of the right leg with bony involvement who was initially misdiagnosed with infantile hemangioma. Due to its heterogeneous presentation and frequent occurrence of comorbidities such as Kasabach‐Merritt phenomenon, clinical and pathological correlation is essential for diagnosis of KHE.
Cholesterol sensing goes vegetarian
Authors: Foley John F.
Published: November 2024

The cholesterol-sensing protein LYCHOS is a hybrid of a GPCR and a plantlike transport protein.
More on the Descriptional Complexity of Products of Finite Automata
Authors: Holzer Markus , Rauch Christian
Published: November 2024

We investigate the descriptional complexity of the [Formula: see text]- and [Formula: see text]-products with [Formula: see text] of two automata, for reset, permutation, permutation-reset, and finite automata in general. This is a continuation of the recent studies on the state complexity of the well-known cascade product undertaken in [7, 8]. Here we show that in almost all cases, except for the direct product ([Formula: see text]) and the cascade product ([Formula: see text]) for certain types of automata operands, the whole range of state complexities, namely the interval [Formula: see text], where [Formula: see text] is the state complexity of the left operand and [Formula: see text] that of the right one, is attainable. To this end we prove a simulation result on products of automata that allows us to reduce the products of automata in question to the [Formula: see text], [Formula: see text], and a double sided [Formula: see text]-product.
Clinical Implications of Catabolic and Anabolic Bone Changes in Psoriatic Arthritis
Authors: Schett Georg
Published: November 2024

Psoriatic arthritis (PsA) is a complex inflammatory condition characterized by both catabolic and anabolic changes that significantly impact patient outcomes.

Catabolic processes in PsA primarily manifest as bone erosions and joint destruction. These changes result from the inflammation triggered by cytokines, which promotes osteoclast activation and increased bone resorption.

On the other hand, anabolic changes are observed through the formation of enthesiophytes, bony projections that develop at the sites where tendons and ligaments attach to bone. This process is often seen as compensatory response to chronic inflammation and mechanical stress.

Clinicians should adopt a holistic approach that not only focuses on alleviating symptoms but also considers the long-term implications of these bone changes.

Understanding the dynamics of catabolic and anabolic changes in PsA is essential for developing effective treatment strategies and improving patient outcomes. By recognizing the significance of both bone erosions and enthesiophyte formation, healthcare providers can better tailor their interventions, ensuring a comprehensive management plan that addresses both inflammation and structural integrity.
Efficient Management of Multiple Domains in Psoriatic Arthritis: Target Treatment Goals and Streamlined Clinical Assessment in a Short Session
Authors: Sewerin Philipp
Published: November 2024

Psoriatic arthritis (PsA) is a chronic, immune-mediated, inflammatory arthropathy that presents with inflammation of the joints and entheses, including those of the axial skeleton, and is associated with increased mortality from cardiovascular diseases. Diagnosis is primarily based on clinical phenotype because of the diversity of the associated features, which can include skin and nail disease, dactylitis, uveitis, and arthritis. Early detection and timely management are crucial for improving clinical outcomes and patients’ quality of life. This lecture will focus on the management of the multiple domains in psoriatic arthritis and clinical insights on incorporating insights from clinical trials into daily clinical practice by streamlining clinical assessment in a short session.

The lecture will begin by reviewing the epidemiology and pathophysiology of PsA, emphasizing the inflammatory nature of PsA. The clinical domains of PsA including skin psoriasis, arthritis, dactylitis, enthesitis and axial involvement will be discussed, highlighting the importance of targeting multiple PsA domains to improve PsA patient’s physical functions and quality of life.

The lecture will then delve into the clinical management of PsA. We will discuss the current recommendations for PsA assessment, including measurement of different clinical domains of PsA. We will explore the PsA assessment in clinical trials and the streamlining strategies of assessment in real-life setting.

The management strategies for PsA will then be focused, emphasizing the importance of targeting improvement in multiple clinical disease domains of PsA. We will explore the current evidence-based guidelines for pharmacological treatments, including the role of different biological disease-modifying antirheumatic drugs.

Finally, the lecture will end with a real-world case sharing session, highlighting the importance of targeting multiple PsA domain by individualized treatment approaches to improve patient’s health outcomes and quality of life.

This lecture aims to equip clinicians by overseas medical expertise on optimizing routine clinical management of multiple disease domains in PsA, ultimately facilitating individualized care to PsA patient to improve their overall clinical outcomes.
Unlocking JAKi Potential: Redefining Axial Spondyloarthritis Treatment Paradigms
Authors: Östör Andrew
Published: November 2024

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that primarily affects the axial skeleton, encompassing both radiographic and non-radiographic forms. The disease is characterized by chronic back pain and spinal stiffness, which are the most common symptoms. However, it often includes peripheral manifestations and extra-musculoskeletal symptoms as well, making the clinical presentation quite diverse.

JAK inhibitors work by blocking the intracellular signaling pathways of several proinflammatory cytokines, which play a crucial role in the pathogenesis of inflammatory diseases. Given their proven efficacy in managing rheumatoid arthritis and their ability to mediate the signaling of cytokines involved in the pathogenesis of axSpA, JAK inhibitors have been the subject of numerous clinical trials in this context.

The Assessment of SpondyloArthritis international Society and the European Alliance of Associations for Rheumatology (ASAS-EULAR) joint recommendations provide comprehensive guidance for the management of axSpA in 2022. The guideline introduced the use of Janus kinase inhibitors (JAKi), as a completely new drug class in the treatment landscape, with efficacy demonstrated in radiographic axSpA. JAKi was recommended, as a means to treatment intensification, in axSpA patients with persistently high disease activity despite conventional treatment. Since then, more trial data results have been released, showing efficacy in non-radiographic axSpA population as well.

In this lecture, Professor Östör will delve into the critical role of shared decision-making in the management of axial spondyloarthritis. He will emphasize the importance of tailoring treatment plans to individual patient preferences and clinical profiles, a practice that is increasingly recognized as vital in achieving optimal outcomes. By examining current international guidelines and the latest study data, Professor Östör will provide a comprehensive overview of the benefit-risk profile of Upadacitinib in the treatment of axSpA. Professor Östör will also share his clinical experience with Upadacitinib, discussing various case studies to illustrate its application in real-world settings. This will include an exploration of how patient preferences and clinical profiles can influence treatment decisions, ensuring a personalized approach to managing this complex disease.
Pain in Inflammatory and Degenerative Joint Diseases
Authors: Hammer Hilde Berner
Published: November 2024

The International Association for the Study of Pain (IASP) agreed in 2020 on a revised definition of pain: “An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage”.

Patients with rheumatic diseases frequently report pain as a primary symptom. However, rheumatology healthcare providers often lack the training to adequately differentiate between different causes of pain, which are mandatory for optimal treatment.

IASP classifies pain into 3 descriptive categories: nociceptive, neuropathic, and nociplastic pain. A recent review (Murphy AE et al, Arthritis Care & Research, 2023) gives a nice overview of these different forms of pain. Nociceptive pain derives from tissue injury, with subsequent sensation of pain by nociceptors. It is usually well-localized and can be precisely described by patients (i.e. rheumatoid arthritis, primary osteoarthritis) and there are localized pathologies that explain the pain symptoms. Neuropathic pain occurs with injury or insult to a peripheral or central nerve. There may be pressure on the nerve as in carpal tunnel syndrome, or changes in nerves caused by diabetes or other causes of nerve pathologies like mononeuritis multiplex. The pain and paresthesia typically follow the distribution of peripheral nerves in a dermatomal distribution. Nociplastic pain describes pain characterized by altered nociceptive processing (e.g., hypersensitivity), suggestive of dysregulation of CNS pain processing pathways. Nociplastic pain likely encompasses many different CNS pathways that lead to amplified processing of pain signals, decreased inhibition of pain, or both. Prototypical nociplastic pain conditions include both widespread (e.g., fibromyalgia) and localized conditions (e.g., chronic temporomandibular pain disorders and irritable bowel syndrome).

Patients with inflammatory or degenerative joint diseases may have one, two or three of the presently described forms of pain, and an important objective for the rheumatologists is to understand which types of pain our patients are suffering from. About one-quarter of the patients with inflammatory rheumatic joint diseases have additional fibromyalgia causing increased scores of patient-reported outcomes like patient’s global VAS and number of tender joints, and this results in elevated composite scores independent on the degree of inflammation. Thus, rheumatologists must try to differentiate between nociceptive pain caused by inflammatory or degenerative pathologies which may be treated by different ant-inflammatory treatments, neuropathic pain which may need operative of medical treatment, or nociplastic pain which should be non-medically treated.
Thoracic Vertebral Fracture in a Female Case of Ankylosing Spondylitis Complicated with Turner Syndrome and Insufficient Response to Adalimumab
Authors: Wen Lin , Huang Jinxian
Published: November 2024

Background:

Ankylosing spondylitis (AS) is a chronic disease characterized by inflammatory back pain, with osteoporosis prevalence ranging from 18.7% to 62%

1. Vertebral fractures are four times more likely to occur

2. Turner syndrome (TS) is the most common sex chromosome abnormality in females, with a 1.4- to 2.2-fold increased likelihood of osteoporosis-related fractures

3. Seven cases of AS combined with TS with HLA-B27 positivity have been reported4.

Methods:

We report a case of a female patient with AS and TS who exhibited an inadequate response to adalimumab (ADA) and suffered a thoracic vertebral fracture.

Results:

A 41-year-old woman with HLA-B27 negative was diagnosed with AS in 2012 because of low back pain, and began ADA treatment in 2018. The patient had a past history of TS (45X/47XXX) with ultrasound revealing smaller than normal ovaries and uterus. Body weight was 54kg and height was 145cm (BMI25.68). She had primary amenorrhea, a wrist fracture at a young age, and a thoracic spine fracture in 2018. Bone mineral density (BMD) values for orthotopic lumbar vertebrae L1-L4 were 0.74 g/cm2, with Z-score of -2.7, and 0.564 g/cm2 at the left femoral neck with Z-score of -2.4. The FRAX tool predicted a 10-year fracture risk of 2.4% for the occurrence of major osteoporotic fracture (MOF), and a fracture risk of 0.9% for hip fracture. She initiated hormone replacement therapy (HRT). In November 2022, she discontinued ADA due to COVID-19 infection. Laboratory tests identified slightly elevated inflammatory markers (Fig. 1), low trough drug level of 0.31ug/ml and positive anti-drug antibody. In February 2023, she slipped in a snowdrift and experienced increased back pain. Spinal MRI revealed osteoporosis with a T7 compression fracture and a new T9 fracture (Figure 2 A,B). Sacroiliac (SI) joints MRI showed significant improvement of inflammation (Fig. 2 C,D). Spine surgery consultation suspected fracture attributed to obvious kyphosis deformity and stress concentration during falls, resulting in buckling compression. Repeated test determined a BMD value of 0.920 g/cm2 for orthotopic L3-L4 with a Z-score of -1.4, and a BMD value of 0.775 g/cm2 for the left total hip with a Z-score of -1.2, the 10-year probability of MOF was 3.2%, and that of hip fracture was 0.5%. She was diagnosed with severe osteoporosis due to recurrent fracture despite of BMD improvement and anti-osteoporosis medications were postponed.

Conclusion:

This case further proved the dominant role of disease co-morbidity and insufficient treatment in the unfavorable outcome regardless of genetic predisposition.
Contrasting Risk Profile in Idiopathic Inflammatory Myopathy (IIM) Patients with Cancer Before and After IIM Diagnosis
Authors: Tang Yan Ki Iris , Luk Lucas , Chan Dennis , Lai Billy , Ho Roy , Tang Vivian , Lee Patrick , So Ho
Published: November 2024

Background:

Patients with adult-onset idiopathic inflammatory myopathy (IIM) were at risk of cancer. While the recently published international guideline on cancer screening suggested cancer risk stratification in patients with newly diagnosed IIM, the difference in clinical and serological risk profile among patients with cancer diagnosed before and after IIM diagnosis remained uncertain.

Methods:

MyoHK was a longitudinal observational cohort that collected data from patients with rheumatologist diagnosis of IIM from 8 rheumatology centres in Hong Kong. Data were reviewed from 2004-2023 for this study. Patients with unavailable myositis specific antibody (MSA) were excluded from analysis. Occurrence of cancer 3 years before to 3 years after the diagnosis of IIM were documented. Patients with active cancer 3 years before diagnosis of IIM were classified to “Prior cancer” group and patients with cancer diagnosed at or within 3 years after IIM diagnosis were classified to “subsequent cancer” group. Patients were stratified to high, intermediate and standard cancer risks. Risk profile between the “prior cancer” and “subsequent cancer” groups were compared.

Results:

501 patients were included in analysis. 82 patients had cancer within 3 years, in which 21 patients (25.6%) had cancer within 3 years preceding IIM diagnosis and 61 patients (74.4%) developed cancer at or within 3 years after IIM diagnosis. Nasopharyngeal, lung and breast cancers accounted for the top 3 cancers in both groups. In the “Prior cancer” group, patients were more likely to be female (85.7% vs 55.7%, p = 0.014) and were MSA-negative (33.3% vs 9.8%, p = 0.011). No patient in the “Prior cancer” group developed interstitial lung disease (0% vs 18.0%, p = 0.037) or fulfilled criteria for anti-synthetase syndrome (0% vs 13.1%, p = 0.062). Anti-TIF1g antibody was the most identified MSA in the two groups (42.9% vs 54.1%, p = 374). Myositis-associated-antibody (14.3% vs 42.6%, p = 0.019) and anti-Ro52 antibody (14.3% vs 37.7%, p = 0.047) were more common in the “subsequent cancer” group. In the overall cohort, 228 (45.5%), 246 (49.1%) and 27 (5.4%) of IIM patients were stratified into high, intermediate and standard cancer risk. Two-thirds of the “Prior cancer” group were stratified into high-risk while the remaining one-third being intermediate-risk, compared to 73.8% (p = 0.532) and 26.2% (p = 0.532) in the “subsequent cancer” group. Mortality between the two groups were comparable (38.1% vs 42.6%, p = 0.716).

Conclusion:

Compared to IIM patients with cancer detected at or after IIM diagnosis, patients with prior cancer were more likely to be female, negative for MSA and absence for ILD.
Biologics Therapy in Paediatric Rheumatic Diseases in Hong Kong
Authors: Chan Winnie KY , Ho Assunta CH , Chiang GPK , Yeung RHM , Kuok MCI , Chan AOM , Lam MHC , Kwong EYL
Published: November 2024

Background: There is a substantial expansion in the number of biologics available for the treatment of JIA and childhood rheumatic disease over the past decades. However, there is no report on their use and safety profile in the local paediatric population.

Method of study:

This is a multi-centred retrospective cohort study, recruiting patients followed up in three Paediatric departments in Hong Kong. Subjects who were followed up for childhood-onset rheumatic diseases and was treated with any of the biologic DMARs on or before the 31st December 2022, were reviewed.

Results:

A total of 96 patients who received biologic DMARs in the studied period were reviewed. Sixty patients were diagnosed to have JIA, cSLE (10), uveitis (8), refractory KD (7), JDM (2), COVID-MISC (3), and others (6). Concerning the JIA group, male: female is 1.4:1. 38% of the patients had polyarticular JIA and 50% had ERA who failed conventional treatment with various cDMARS. Concerning the nature of biologics, 85% of JIA patients used different types of TNF-blockers, including etanercept (38.3%), adalimumab (40%), golimumab (5%) and infliximab (3.3%). Six JIA patients used tocilizumab and one used abatacept as second-line treatment after fail response to TNF-blockers. One JIA patient was on tofacitinib to avoid subcutaneous injection. For other biologics, infliximab for refractory KD (8), rituximab for cSLE and JDM (7 and 1), belimumab in cSLE (2) and anakinra in COVID-MISC (4). One JIA-ERA patient developed lymphoma six months after stopping adalimumab and recovered after chemotherapy. One cSLE patient received rituximab and developed EBV-related CNS lymphoma with repeated infections that required hospitalization. Most patients tolerated the biologic DMARs well without complications. There was no tuberculosis infection or activation. Two cSLE patients developed herpes zoster after rituximab infusion and required hospital treatment. Two patients on adalimumab developed recurrent folliculitis and one had to stop treatment. One patient developed bacteria endophthalmitis while on adalimumab. Four patients on adalimumab developed injection site reactions and one patient need to change to another biologic. One patient on adalimumab developed positive lupus serology without clinical features.

Conclusion:

A broad spectrum of biologics has been used in children with various rheumatic diseases without major complications. Although rare, 2 patients developed lymphoma during the study period. Although there is no causal relationship identified with the use of biologics, continuous monitoring of the long-term safety of these drugs in the paediatric cohort is recommended.
Incidence of ANA Positivity After the Administration of Biologicals
Authors: Gopal Manikandan , Mathew John
Published: November 2024

Background:

Antinuclear antibodies (ANA) are often used in diagnosing autoimmune rheumatological diseases, but their behavior in response to biological therapies, particularly in Asian patients, is not well-documented. The impact of these therapies on ANA status is crucial for understanding disease management and treatment efficacy.

This study aims to evaluate the prevalence and significance of ANA positivity following the administration of biological agents in patients with autoimmune rheumatological diseases.

Methods:

This pilot study was a prospective cohort study involving 100 patients with autoimmune rheumatological diseases who were initially ANA negative at baseline. Predominantly included patients were axial spondyloarthritis (AxSpA) (n=95) and ANCA vasculitis (n=5). Patients with AxSpA were diagnosed according to the 2009 ASAS criteria, and treated with biological agents (e.g., TNF inhibitors such as adalimumab, etanercept, or IL-17 inhibitors such as secukinumab) and followed at a tertiary care center in India from January 2021 to December 2023. ANA levels were measured before and after 3, 6, 9, or 12 months of biological therapy. Changes in ANA positivity, clinical outcomes, and correlations with disease activity were analyzed.

Results:

Out of the 100 patients enrolled, 67 (67%) completed the study. All participants were ANA negative at baseline. After biological therapy, ANA positivity developed in 4 patients (5.9%). Despite this increase in Ana positivity, there was no significant correlation between ANA positivity and clinical disease activity, as measured by the Ankylosing Spondylitis Disease Activity Score (ASDAS) and the visual analog scale (VAS) for pain, BVAS suggesting effective therapeutic response despite changes in ANA status. Additionally, 30 patients were lost to follow-up, highlighting challenges related to the financial sustainability of biological therapy in the resource limited countries.

Conclusion:

Biological therapies for AxSpA are associated with an increase in ANA positivity although this change does not appear to impact clinical disease activity. The rise in ANA titres may reflect disease-related changes or treatment effects rather than a direct correlation with therapeutic efficacy. Further longitudinal studies are needed to understand the clinical significance of these findings and to refine the interpretation of ANA results during biological therapy.
Global Burden of Inflammatory Bowel Disease Among Adolescents and Young Adults in 204 Countries and Territories, from 1990 to 2021: Results from the Global Burden of Disease Study 2021
Authors: Wang Song , Zhao Xiangyun , Wan Xinjian
Published: November 2024

Background

Inflammatory bowel disease (IBD) is a significant component of the global disease burden, particularly among adolescents and young adults. This study aimed to investigate the patterns and trends of IBD among adolescents from 1990 to 2021.

Methods

We retrieved data on the incidence and disability-adjusted life years (DALYs) of IBD in adolescents (aged 15-39 years) from the Global Burden of Disease (GBD) 2021 study, Temporal trends of incidence and DALYs were calculated using the average annual percent change (AAPC). The correlation between age-specific incidence rates and DALYs rates with the Sociodemographic Index (SDI) was performed using Spearman’s correlation analysis.

Results

From 1990 to 2021, age-specific incidence rates significantly increased while age-specific DALYs rates declined [AAPC: 0.22vs-0.16]. All SDI regions saw a decline in age-specific incidence rates while age-specific DALYs rates in adolescent showed an increasing trend in low and middle SDI regions but a-decrease in high, high-middle and low-middle SDI regions. Incidence rates rose from 1990 to 2021 in 21-GBD regions except for high-income North America. In contrast, DALYs rates increased in regions such as Western Sub-Saharan Africa, Central Latin America, Tropical Latin America, Australasia, Eastern Sub-Saharan Africa, Central Sub-Saharan Africa, Central Asia, and North Africa and the Middle East, while they declined in the remaining 21-GBD regions. Among the 204-countries, China exhibited the fastest-growing age-specific incidence rate among adolescents [AAPC: 2.60], followed by Libya (AAPC: 2.59) and Oman (AAPC: 1.56), while Italy showed the fastest decline [AAPC: -0.76] (Figure-1A). Mauritius experienced the fastest growth in age-specific DALYs rates among adolescents (AAPC: 1.93), followed by Libya (AAPC: 1.79) and Mexico (AAPC: 1.45), while Northern Mariana Islands saw the fastest decline (AAPC: -3.28) (Figure-1B). Moreover, the AAPC of age-specific incidence rates for adolescent IBD exhibited a slight decreasing trend with increasing SDI (Figure-1C), and the AAPC of DALYs rates significantly declined with increasing SDI (Figure-1D).

Conclusion

The regional disparities in the incidence and DALYs rates of adolescent IBD highlight the urgent need for innovative prevention and healthcare strategies to alleviate the global burden of IBD among adolescents. Early screening could be crucial in mitigating the impact of IBD on adolescents.
An Observational Cohort Study to Estimate the Durability of Humoral Immune Responses to Vaccination with ChAdOx1 nCoV-19 and the BBV152 in Adult Patients with Autoimmune Rheumatic Diseases (AIRD)
Authors: Kumar Ravi , Madhavan Ramya , Mathew John , Mathew Ashish , Goel Ruchika
Published: November 2024

Background

The durability of immune responses after vaccination against SARS CoV-2 in patients with autoimmune rheumatic diseases (AIRD) is not well studied.

Objective

We aimed to determine the longevity of humoral immune response to homologous vaccination with 2 doses of ChAdOx1 nCoV-19 and BBV152 in adult patients with AIRD.

Methods

In this prospective observational study, patients aged 18 to 60 years, diagnosed with SLE, primary systemic vasculitis and inflammatory arthritis (IA) who were scheduled to or had received vaccination with either ChAdOx1 nCoV-19 or BBV152 were recruited between June 2021 to March 2023. IgG antibodies against SARS CoV-2 spike protein (anti-S) were estimated in serum or plasma of patients prior to vaccination if feasible (T0), 15 to 28 days (T1), 75-100 days (T2), 170-190 days (T3), 240-290 days (T4), 340-370 days (T5) after receiving Vx2 by Diasorin chemiluminescence assay. The association of antibody titers with baseline parameters is estimated using chi-square or Mann Whitney tests using SPSS 16.

Results

Overall, 118 patients (93 females; age: 37.1, IQR: 28- 45 years; disease duration: 60 ((IQR) 29-103) months) with AIRD (SLE:48(40.6%), IA:53(44.9%), systemic vasculitis:7(5.9%) and spondyloarthropathy: 9(7.6%)) were recruited. Baseline demographic data has been depicted in (Table 1). The median antibody titer did not differ significantly between the two vaccines at T1 while the titers at T2, T3 and T4 were significantly lower for those vaccinated with BBV 152 (Table 2). The steroid dose prior to T1 and T2, intake of DMARDs in peri-vaccination period, type of AIRD (IA vs CTD) was not associated with significant difference in antibody titers at T1 and T2.

Conclusion

The anti-S humoral immune response persisted beyond 1 year for most of our patients with AIRD. After 3 months of vaccination, these responses were higher for ChAdOx1 nCoV-19 as compared with BBV152 in our patients with AIRD.