bluuebunny/crossref_metadata_2025_split huggingface dataset:
MecA in
Streptococcus mutans
is a multi-functional protein
Authors: Ellepola Kassapa , Shields Robert C. , Kajfasz Jessica K. , Zhang Hua , Lemos Jose A. , Wu Hui , Wen Zezhang T. 
Published: November 2024

ABSTRACT

Our recent studies have shown that deficiency of MecA in
Streptococcus mutans
significantly affects cell division, growth, and biofilm formation. In this study, an
in vitro
mixed-species model, proteomics, and affinity pull-down assays were used to further characterize the MecA-mediated regulation in
S. mutans
. The results showed that compared with the wild type, UA159, the
mecA
mutant significantly reduced its production of glucans and weakened its ability to facilitate mixed-species biofilm formation. Relative to the wild type, the
mecA
mutant also displayed unique characteristics, including colony morphology, growth rate, and biofilm formation that did not fully resemble any of the
clpP, clpX, clpE, clpCE,
and
clpC
individual or combinational mutants. Deletion of
mecA
was shown to result in alteration of >337 proteins, including down expression of GtfBC&D and adhesin P1. More than 277 proteins were differentially expressed in response to
clpP
deletion, including increased expression of GtfB. By cross-referencing the two proteomes, a distinctive set of proteins was found to be altered in the
mecA
mutant, indicating a ClpP-independent role of MecA in the regulation of
S. mutans
. When analyzed using affinity pull-down, ClpC, ClpX, ClpE, and CcpA were among the members identified in the MecA-associated complex. Further analysis using a bacterial two-hybrid system confirmed CcpA, ClpX, and ClpE as members of the MecA interactome. These results further suggest that MecA in
S. mutans
is more than an adapter of the Clp-proteolytic machinery, although the mechanism that underlies the Clp-independent regulation and its impact on
S. mutans
pathophysiology await further investigation.

IMPORTANCE

MecA is known as an adaptor protein that works in concerto with ATPase ClpC and protease ClpP in the regulated proteolysis machinery. The results presented here provide further evidence that MecA in
S. mutans
, a keystone cariogenic bacterium, plays a significant role in its ability to facilitate mixed-species biofilm formation, a trait critical to its cariogenicity. Proteomics analysis, along with affinity pull-down and bacterial two-hybrid system, further confirm that MecA can also regulate
S. mutans
physiology and biofilm formation through pathways independent of the Clp proteolytic machinery, although how it functions independently of Clp awaits further investigation.
Remission Possible: New Era of SLE Treatment with Biologics Involvement
Authors: Aringer Martin 
Published: November 2024

Treat-to-target (T2T) is a therapeutic approach used in several rheumatologic disorders such as rheumatoid arthritis, gout, axial spondylarthritis, and other inflammatory diseases such as inflammatory bowel disease. Developing a T2T strategy for systemic lupus erythematosus (SLE) has been difficult due to the complexity of the disease. The 2019 EULAR recommendations for the management of SLE, reestablished in the 2023 EULAR guideline, specified that the primary treatment goal should be remission or the lowest possible disease activity. In SLE, remission is associated with reduced organ damage, fewer flares, reduced hospitalisation, reduced mortality, and improved health-related quality of life. Previously remission in SLE was seen as an unattainable goal; however, the treatment landscape for SLE has evolved, and recent advancements, particularly the use of biologics, have emerged as promising therapeutic options to improve patient outcomes. A new post-hoc analysis of the TULIP Phase III programme provides evidence across four years that remission is an achievable goal with anifrolumab, a type I interferon (IFN) receptor antagonist for adult patients with moderate to severe (SLE) who are receiving standard therapy. At Week 208, 30.3% (n=58/194) of patients treated with anifrolumab were in remission compared with 18.3% (n=12/65) of those in the standard therapy alone group. This was an increase from 19.7% (n=49/251) of patients treated with anifrolumab who achieved remission at the first LTE visit (Week 64) compared with 9.9% (n=10/104) of those in the standard therapy alone group. Treatment with anifrolumab was also associated with more frequent, prolonged, and sustained DORIS remission attainment compared with placebo during the 4-year TULIP+LTE period. Real-world case studies have also illustrated the effectiveness of biologics in controlling disease activity, enhancing quality of life, and establishing long-term safety profiles. In conclusion, biologic therapies have emerged as a valuable treatment option for achieving remission or lupus low disease activity state. Biologics has opened a new era revolutionizing the management of SLE, offering renewed hope for patients living with this challenging autoimmune disease.
How Do We Identify and Manage Progressive CTD-ILD?-Update in Treatment and Guideline
Authors: Distler Oliver , Maher Toby 
Published: November 2024

The lung is a frequent target of autoimmune-mediated injury in patients with rheumatic diseases. Not infrequently, respiratory involvement may be the presenting manifestation of connective tissue diseases (CTDs). The prevalence of interstitial lung disease (ILD) in rheumatoid arthritis is about 20 to 30% of patients, while ILD may occur in 20 to 50% of patients with idiopathic inflammatory myositis, 40-50% or more of patients with systemic sclerosis, 2 to 5% of patients with systemic lupus erythematosus, 20 to 60% of patients with mixed connective tissue disease, and up to 25% of patients with Sjögren’s syndrome. Rheumatic disease-associated lung involvement is a major cause of morbidity and mortality in these patients. It shows a considerable heterogeneity in incidence and prevalence, clinical course, and the involved lung structure depending on the underlying rheumatic disease. Each rheumatic disease is associated with a characteristic pattern of their lung disease. The standard therapy has traditionally been immunosuppressant. With the evolvement of treatment, anti-fibrotic is now indicated for chronic fibrosing ILDs with a progressive phenotype, including autoimmune disease-associated ILD. By targeting the underlying mechanism of pulmonary fibrosis, it is shown that the annual rate of FVC decline can be reduced by more than 50%. In this lecture, Prof. Oliver Distler and Prof. Toby Maher will review the importance of timely treatment, the management practices and treatment guidelines for CTD-ILD.
Screening for PAH - How to Reduce Delay in CTD-PAH Diagnosis
Authors: Lee Yeon-Ah 
Published: November 2024

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a diverse clinical presentation, including pulmonary involvement. While pulmonary complications are common in SLE, a subset of patients develop pulmonary arterial hypertension (PAH), a life-threatening condition characterized by elevated pulmonary vascular resistance and right ventricular dysfunction. Early detection and timely management are crucial for improving outcomes in this vulnerable patient population. This lecture will focus on the importance of PAH screening in SLE, highlighting the clinical insights and management strategies for this challenging condition. The lecture will begin by reviewing the epidemiology and pathophysiology of PAH in SLE, emphasizing the role of autoimmunity, inflammation, and microvascular dysfunction. The clinical manifestations of PAH in SLE, including dyspnea, fatigue, chest pain, and syncope will be discussed. These symptoms may be subtle and often overlap with other SLE manifestations, making early recognition challenging. The lecture will then delve into the importance of PAH screening in SLE. We will discuss the current recommendations for screening, including the use of blood markers to evaluate the PAH risk factors, echocardiography to assess right ventricular function and pulmonary artery pressure. We will also explore the role of other diagnostic tools, such as NT-proBNP test, pulmonary function tests and right heart catheterization, in confirming the diagnosis of PAH. The management strategies for PAH in SLE will then be focused, emphasizing the importance of multidisciplinary care involving rheumatologists, pulmonologists, cardiologists, and other specialists. We will explore the current evidence-based guidelines for pharmacotherapy, including the role of vasodilators, endothelin receptor antagonists, and phosphodiesterase type 5 inhibitors. Finally, the lecture will end with real-world cases, highlighting the heterogeneity of the disease, the need of identifying the disease early, and the need for personalized medicine approaches to improve outcomes for this vulnerable patient population. This lecture aims to equip clinicians with the knowledge and tools to effectively identify PAH in SLE, facilitating early diagnosis and timely initiation of appropriate management strategies, ultimately improving patient outcomes.
Axial Spondyloarthritis Unresponsive to Secukinumab, an IL-17A Inhibitor Therapy, a Case Report
Authors: Danasasmita Gantira , Ariane Anna , Hidayat Rudy 
Published: November 2024

Introduction Axial spondyloarthritis (axSpA) is a group of autoinflammatory disease that hypothetically caused by tumor necrosis factor (TNF) axis and interleukin (IL)-23/IL-17 axis. Based on algorithm of treatment from ASAS/EULAR 2022, biologic agent is indicated if patient did not response to NSAIDs, the first line treatment. TNF inhibitor and IL-17 inhibitor are two biologic agent that has been approved and gave significant result in improving disease activity. Case Description A 47 years old woman who has been diagnosed with axSpA since 2022. At first she was given medication with NSAIDs. She has also been given conventional DMARD, sulfasalazine an methotrexate, until maximum dose but still no response in controlling the disease activity. After about one year of treatment, she finally tried using the biologic agent, Secukinumab. She was given 150 milligram weekly initial dose for a month, followed by monthly administration. After administering the eight dose, she achieved inactive disease activity. However, after the fourteenth dose, symptoms began to reappear and disease activity became very high like the first time of diagnosis. Discussion IL-17A inhibitor (IL-17Ai) has been widely used for treating axSpA since ASAS20/40 and partial response at 16 week was reached 61,36 and 14%. IL-17Ai seem more effective in ameliorating entheseal inflammation and new bone formation, in accordance with role of IL-23/IL-17 axis in stimulating osteoclast. ASAS/EULAR recommend patients who fail therapy with one biological agent in 12 weeks to switch to another type of biological agent. However there’s still no publication data for efficacy to give TNF inhibitor after IL-17Ai or JAK inhibitor failure. Conclusion The effectiveness of biological agents in axSpA is quite similar. In cases where therapy fails, it is still an open question whether the optimal therapy choice is to change the type of drug or a combination of two types of biological agents.
Unveiling Predictive Parameters for Rheumatoid Arthritis Development in Arthralgia Patients: Insights from a Prospective Longitudinal Study
Authors: Tam Cheuk Yin , Cheng Tsz Ho , Tam Lai Shan , So Ho 
Published: November 2024

Background: Early diagnosis of rheumatoid arthritis (RA) is crucial for timely intervention and improved outcomes. Although research on the preclinical phase of RA is a prominent topic, there remains an unmet need to effectively stratify patients at risk of developing RA based on basic clinical assessment and laboratory investigations. This prospective longitudinal study aimed to identify risk factors for RA development in individuals experiencing arthralgia. Method: Two hundred consecutive adults with arthralgia were enrolled from new referrals to our rheumatology clinic. Patients with synovitis or a known arthritis diagnosis were excluded. Follow-up assessments were conducted every 6 months, or sooner if symptoms worsened, for a maximum of 2 years. The study endpoint was the development of RA, according to the 2010 ACR/EULAR classification criteria. Baseline demographic characteristics, clinical parameters, serology, and acute phase reactant levels were compared between patients who developed RA and those who did not. In addition, the classification score based on the 2010 ACR/EULAR classification criteria was utilised as a composite weighted score summarising the clinical presentation in the cohort, although the patients were deemed not fulfilling the mandatory criteria of having synovitis at baseline. Results: By May 2024, 104 patients had been followed up for at least one year, with a median duration of 78 weeks (IQR: 58-97). The baseline symptom duration was 51 weeks (IQR: 29 – 97). Among these patients, 23 (22.1%) developed RA after a median follow-up duration of 41 weeks (IQR: 25 – 52). Patients who developed RA had a significantly higher proportion of joint symptoms <1 year, difficulty making a fist, positive rheumatoid factor (RF), anti-CCP antibodies, and elevated ESR and CRP levels at baseline. Multivariate logistic regression identified difficulty making a fist (OR: 4.87, 95% CI: 1.40 – 17.04, p = 0.013) and positive anti-CCP antibodies (OR: 13.04, 95% CI: 3.74 – 45.44, p < 0.001) as independent predictors for RA development. Meanwhile, patients who developed RA had significantly higher baseline scores extrapolating from the 2010 ACR/EULAR classification criteria compared to the non-RA group. Conclusion: Difficulty making a fist and positive anti-CCP antibodies are independent predictors of RA development. Additionally, patients who developed RA exhibited significantly higher baseline scores on the 2010 ACR/EULAR classification criteria. Early recognition of these variables and taking reference from the score of classification criteria may aid in RA risk stratification. Further research is needed to validate these findings and explore additional predictive markers.
The Neutrophil-to-C3 Ratio: Unveiling Diagnostic Efficacy for Lupus Nephritis and Association with Reduced Retinal Vascular Density in Systemic Lupus Erythematosus
Authors: Maitiyaer Maierhaba , Li Peiyi , Li Huangdong , Jiang Dingwen , Zhang Jingyu , Yang Chuwei , Yang Xiaobin , Chen Chengmei , Huang Wenhui , Liu Zhiping , Yu Shuilian 
Published: November 2024

Background: Lupus nephritis (LN) frequently manifests as a significant complication in systemic lupus erythematosus (SLE) patients, with emerging research indicating a plausible correlation between subclinical retinal involvement and renal manifestations. This study aims to investigate the relationship between the neutrophil-to-C3 ratio (NC3R) and both LN as well as retinal microvasculature damage among SLE patients. Methods: In this cross-sectional study, a cohort of 220 participants was recruited, consisting of 78 LN patients and 142 patients without LN. We assessed clinical indicators and organ involvement and conducted correlation analyses between NC3R and markers of lupus activity. Additionally, we analyzed the diagnostic performance of NC3R in diagnosing LN and constructing ROC curves. Logistic regression analysis was performed to investigate the impact of NC3R on LN. We further examined the influence of NC3R on retinal vasculature density based on its cutoff value and conducted correlation analyses accordingly. Results: The LN group exhibited a significant increase in NC3R compared to the group without LN (5.9 vs 4.5, P=0.007). NC3R demonstrated positive correlations with 24-hour proteinuria (R=0.329, P<0.001) and systemic lupus erythematosus disease activity index (SLEDAI) score (R=0.268, P<0.001). Multiple regression analysis revealed NC3R as an independent risk factor for LN (OR: 2.01, P=0.035). NC3R was proven valuable in distinguishing LN patients (AUC: 0.613), with an optimal cutoff value of 6.40 (sensitivity: 48.1%, specificity: 72%). Our results indicated that the lower NC3R group (NC3R<6.40) exhibited reduced vascular density, particularly within the macular region. Furthermore, we observed a positive correlation between NC3R levels and vascular density. Conclusions: NC3R demonstrated promising potential as a reliable indicator for predicting both LN and retinal microvasculature involvement. Consequently, the pre-treatment evaluation of NC3R had the potential to assist clinicians in identifying potential organ involvement among SLE patients.
Performance of the ASAS-proposed Cut-offs for Positive MRI Typical of Axial Spondyloarthritis for Discriminating Axial Involvement in Patients with Psoriatic Arthritis
Authors: Yan Xianfeng , Cheng Isaac T , So Jacqueline , So Ho , Lee Ryan Ka Lok , Griffith James Francis , Tam Lai-Shan 
Published: November 2024

Background: Unlike axial spondyloarthritis (axSpA), no classification criteria are currently available for axial psoriatic arthritis (axPsA). This study aimed to evaluate the performance of the proposed cut-offs from the Assessment of Spondyloarthritis International Society (ASAS) data-driven definitions for active and structural magnetic resonance imaging (MRI) lesions typical of axSpA in distinguishing axial involvement in patients with psoriatic arthritis (PsA). Methods: Seventy-two consecutive PsA patients (67% male, aged 45± 14 years) meeting the CASPAR classification criteria, regardless of the presence of back pain, were included. All patients underwent radiography of the pelvis and spine, as well as sacroiliac joint (SIJ) MRI, while 52 (72%) of 72 patients also underwent whole-spine MRI. The final diagnosis of axPsA was ascertained by two experienced rheumatologists. One rheumatologist with expertise in imaging and one trained reader evaluated the radiography and MRI images. Results: AxPsA was diagnosed in 27/72 (38%) patients. The proposed cut-offs for active sacroiliitis demonstrated high specificity (95.6%) but relatively low sensitivity (51.9%) in distinguishing patients with and without axPsA. When structural lesions of the SIJ were included in addition to active lesions, the sensitivity significantly improved (96.3% vs. 51.9%) with a modest decrease in specificity (86.7% vs. 95.6%). Incorporating MRI spine lesions (using the proposed cut-offs for positive spine MRI from the SPACE cohort) alongside SIJ lesions did not further change sensitivity or specificity compared with assessing SIJ alone. Conclusion: The ASAS-proposed cut-offs for identifying active and structural lesions of SIJ demonstrated satisfactory performance in discriminating axial involvement in PsA patients.
How Early Should We Use b/tsDMARDs in Active PsA? - Data from a 1-year Prospective Cohort in Hong Kong
Authors: Shek Wai Kit , Cheng Tsz Ho , So Ho , Tam Lai Shan 
Published: November 2024

Background Despite the wide availability of biologic/targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) for treating psoriatic arthritis (PsA), there remain controversies regarding the positioning of b/tsDMARDs in the management algorithm for patients with active peripheral disease. While the European League Against Rheumatism (EULAR) recommends conventional synthetic DMARDs (csDMARDs) as the first-line treatment (1), the American College of Rheumatology (ACR) guideline takes a more aggressive approach, and suggests upfront use of b/tsDMARDs (2). The study aimed to evaluate whether earlier use of b/tsDMARDs might increase the likelihood of achieving minimal disease activity (MDA) in patients with PsA under the treat-to-target framework. Method Consecutive patients with PsA who fulfilled the CASPSA criteria with active peripheral disease were recruited in this prospective cohort study. The analysis included patients who were (1) given b/tsDMARDs during the study period and (2) completed 1-year follow-up. A standardized treat-to-target strategy was adopted. Patients were categorized into csDMARDs-naïve group, single-csDMARD-inadequate response (IR) group and multiple-csDMARDs-IR group. The rate of achieving MDA at the end of one year was compared. Result A total of 100 PsA patients were recruited and 27 patients (mean age: 51± 13, 15 [68%] male, disease duration: 5.6± 6.9 years) were included in the analysis. At baseline, all patients exhibited moderate to high disease activity. Prior to initiating b/tsDMARDs, 4 patients were csDMARDs-naïve, 10 patients had failed 1 csDMARD and 13 patients had failed 2 or more csDMARDs. There was no significant difference between clinical features and disease activity among the 3 groups at baseline (Table 1). Within the study period, 3 (11%) and 24 (89%) patients were given anti-TNF and anti-IL-17 agents respectively. After 1-year, there was substantial improvement in disease activity in the whole cohort (Disease Activity in Psoriatic Arthritis [DAPSA]: 22.7 at baseline vs 9.0 at 1-year, p=0.039), and 17(63%) patients achieved MDA. A differential MDA achievement rate was observed across different groups. All csDMARDs-naïve patients achieved MDA, compared to 70% in the single-csDMARD-IR and 46.2% in the multiple-csDMARDs-IR groups (p=0.046) (Figure 1). There was also a trend of better DAPSA response at one-year in the csDMARDs-naïve group (4.9± 1.6 vs 10.2± 11.8 [single-csDMARD-IR] and 9.4± 8.1 [multiple-csDMARDs-IR]). Conclusion A lower MDA achievement rate was observed in b/tsDMARDs users with prior csDMARD exposure. Earlier initiation of b/tsDMARDs might improve treatment outcome in PsA.
Establishment of Prediction Model for Psoriatic Arthritis Based on Logistic Regression
Authors: GUO Qing , Luan Hong , Zhao Xi , Min Xue , Zhen Ying Zhang 
Published: November 2024

Background: Psoriatic arthritis (PsA) is an inflammatory musculoskeletal disease associated with psoriasis (PsO) that appears approximately 7-8 years after psoriasis and remains undiagnosed in most of patients, which is disabled and difficult to treat. So early risk assessment is particularly important. However, at present, the risk assessment of the status quo is not optimistic. The aim of this study was to establish and validate a prediction model for assessing the risk of PsA in psoriasis patients. Methods: Ambispective cohort study was conducted. Demographic and clinical records were collected and followed up and blindly reviewed. Single and multiple factors analysis were used to analyze the factors influencing PsA, and Logistic regression equation models were developed to verify their predictive value. Results: Among 1141 Pso patients, 221 patients had PsA. Logistic regression equation model showed that Arthralgia (OR= 438.079; 95% CI: 175.154-1095.682), nail dystrophy (OR= 7.453; 95% CI: 4.116-13.498), scalp lesions (OR= 3.047; 95% CI: 1.297-7.159), Inverse (intertriginous) lesions (OR= 2.45; 95% CI: 1.382-4.342) and BMI (OR= 0.909; 95% CI: 0.846-0.977) were identified as potential predictors affecting the risk of transition from PsO to PsA. And the receiver operating characteristic (ROC) curve of PsA was drawn, the area under the curve (AUC) was 0.974 (95% CI 0.963 - 0.985), the prediction sensitivity was 96.40%, the specificity was 92.10%, the calibration curve showed that the predicted results was in good agreement with the observed results. Conclusion: The independent predictors of PsA involve Arthralgia, nail dystrophy, scalp lesions, Inverse (intertriginous) lesions, BMI. The Logistic prediction model based on these predictors has reliable predictive value and can help early clinical assessment and treatment.