tbuckley/cabot-search huggingface dataset:
AB0391 LOW SERUM COMPLEMENT C3 LEVEL AS A RISK FACTOR FOR RELAPSE OF ANTINEUTROPHIL CYTOPLASMIC ANTIBODY-ASSOCIATED VASCULITIS: A RETROSPECTIVE COHORT STUDY
Authors: H. Sakai, H. Yamashita, S. Nakajima, Y. Takahashi, H. Kaneko
Journal: Annals of the Rheumatic Diseases (2021)

Background: The alternative pathway of complement activation has recently been recognized as a key pathogenic event in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Some previous studies have reported that low serum complement C3 level in AAV patients is associated with more severe renal disease, worse renal prognosis, or higher mortality. However, the correlation between low serum C3 level and AAV relapse remains unclear. Objectives: To analyze the clinical characteristics and outcomes of AAV patients with low serum C3 levels at the time of diagnosis. Methods: We conducted a retrospective observational cohort study including 83 consecutive patients diagnosed with AAV in our hospital from January 1999 to December 2020. Serum C3 levels were measured at diagnosis. AAV included microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA); patients with ANCA-negative AAV were excluded. Patients were divided into low- and high-C3 groups (C3 &lt; 100 and ≥ 100 mg/dL, respectively). We compared the clinical characteristics, and relapse-free and overall survival rates, of the two groups, and identified predictors of AAV relapse. Results: Of the 83 patients (MPA, n = 61; GPA, n = 18; EGPA, n = 4), 20 (24%) were in the low-C3 group. We found no significant group difference in sex, body mass index, disease type, ANCA subtype, Birmingham Vasculitis Activity Score (BVAS), or treatment. The low-C3 group patients were older (p=0.01), and had a higher Five Factor Score (FFS) (p=0.01) and a lower remission rate (p=0.02), than the high-C3 group. The generalized Wilcoxon test revealed that the relapse-free survival time was significantly shorter in the low-C3 group (29 months; 95% confidence interval [CI]: 15–49) than in the high-C3 group (82 months; 95% CI: 61–NA; p=0.01) (Figure 1A). The overall survival was also shorter in the low-C3 group (83 months; 95% CI: 8-121) than in the high-C3 group (112 months; 95% CI: 77-NA; p=0.03) (Figure 1B). In the Cox proportional hazards model, a low C3 level (&lt; 100 mg/dL) (hazard ratio [HR], 3.01; 95% CI: 1.29–7.04], p=0.01) and GPA (HR, 3.04; 95% CI: 1.32–7.01; p=0.01) were independent predictors of AAV relapse. Figure 1. Kaplan-Meier estimates of the relapse-free (A) and overall (B) survival rates of AAV patients by baseline serum C3 levels. Eight patients who did not show remission were excluded in the relapse-free survival analysis. Black line: high-C3 group (≥ 100 mg/dL); red line: low-C3 group (&lt; 100 mg/dL). Conclusion: AAV patients with low C3 levels at diagnosis were at higher risk of relapse. Larger prospective studies are required to confirm these findings. Disclosure of Interests: None declared
In vivo gene editing via homology-independent targeted integration for adrenoleukodystrophy treatment
Authors: Sung-Ah Hong, Jung Hwa Seo, Soohyun Wi, Eul Sik Jung, Jihyeon Yu, Gue-Ho Hwang, Ji Hea Yu, Ahreum Baek, Soeon Park, Sangsu Bae, Sung-Rae Cho
Journal: Molecular Therapy (2021)

Adrenoleukodystrophy (ALD) is caused by various pathogenic mutations in the X-linked ABCD1 gene, which lead to metabolically abnormal accumulations of very long-chain fatty acids in many organs. However, curative treatment of ALD has not yet been achieved. To treat ALD, we applied two different gene-editing strategies, base editing and homology-independent targeted integration (HITI), in ALD patient-derived fibroblasts. Next, we performed in vivo HITI-mediated gene editing using AAV9 vectors delivered via intravenous administration in the ALD model mice. We found that the ABCD1 mRNA level was significantly increased in HITI-treated mice, and the plasma levels of C24:0-LysoPC (lysophosphatidylcholine) and C26:0-LysoPC, sensitive diagnostic markers for ALD, were significantly reduced. These results suggest that HITI-mediated mutant gene rescue could be a promising therapeutic strategy for human ALD treatment.
Case 16-2021: A 37-Year-Old Woman with Abdominal Pain and Aortic Dilatation
Authors: Anahita Dua, Patrick D. Sutphin, Mark J. Siedner, Jakob Moran
Journal: New England Journal of Medicine (2021)

A 37-year-old woman with a history of injection-drug use was admitted with 3 weeks of abdominal pain. CT angiography showed aneurysmal dilatation of the infrarenal abdominal aorta (aortic diameter, 3.9 cm). Management decisions were made.
AB0029 THE METABOLIC HIERARCHY OF IMMUNE PROCESSES IN HUMAN MONOCYTES
Authors: P. L. Krauß, F. Buttgereit, T. Gaber, M. Pfeiffenberger, Y. Chen, T. Buttgereit
Journal: Annals of the Rheumatic Diseases (2021)

Background: At sites of inflammation, monocytes carry out specific immunological functions while facing challenging bioenergetic restrictions. Objectives: Here, we investigated the potential of human monocytes to adapt under conditions of reduced energy supply by gradually inhibiting oxidative phosphorylation (OXPHOS) under glucose free conditions. Methods: We modelled this reduced energy supply with myxothiazol, an inhibitor of mitochondrial respiration, at 0, 2 and 4 pmol/10 6 cells to decrease mitochondrial ATP production for 0%, 25% and 66% under glucose free conditions. For the three energy levels, we assessed (i) phagocytosis of FITC-labelled E.coli using flow cytometry, (i) production of reactive oxygen species (ROS) through NADPH oxidase (NOX) as determined by VAS2870-sensitive OCR using a Clark-type electrode, (iii) ATP generation and steady state level using a Clark-type electrode and luminometric assessment (iv) expression of surface activation markers CD16, CD80, CD11b, HLA-DR and (v) production of the inflammatory cytokines IL-1β, IL-6 and TNF-α using flow cytometry in peripheral blood-derived human monocytes with and without LPS-stimulation. Results: As a prerequisite for our study, we demonstrate that human monocytes survived strong inhibition of mitochondrial respiration without any sign of apoptosis as determined by flow cytometry. As a result of the inhibition of OXPHOS, we demonstrate a reduction of VAS2870-sensitive OCR (ROS production through NOX), ATPase-dependent OCR and ATP steady-state levels. Focusing on immune function, we observed that phagocytosis and the production of IL-6 were the least sensitive to reduced energy supply while surface expression of CD11b, HLA-DR, production of TNF-α and IL-1β were most affected by inhibition of OXPHOS. Conclusion: Our data demonstrate an energy-dependent hierarchy of immune functions in monocytes, which may represent a potential therapeutic target in monocyte-mediated inflammatory diseases. Disclosure of Interests: None declared
A randomized trial examining the effect of predictive analytics and tailored interventions on the cost of care
Authors: Mariana Nikolova-Simons, Sara Bersche Golas, Jorn op den Buijs, Ramya S. Palacholla, Gary Garberg, Allison Orenstein, Joseph Kvedar
Journal: npj Digital Medicine (2021)

This two-arm randomized controlled trial evaluated the impact of a Stepped-Care intervention (predictive analytics combined with tailored interventions) on the healthcare costs of older adults using a Personal Emergency Response System (PERS). A total of 370 patients aged 65 and over with healthcare costs in the middle segment of the cost pyramid for the fiscal year prior to their enrollment were enrolled for the study. During a 180-day intervention period, control group (CG) received standard care, while intervention group (IG) received the Stepped-Care intervention. The IG had 31% lower annualized inpatient cost per patient compared with the CG (3.7 K, $8.1 K vs. $11.8 K, p = 0.02). Both groups had similar annualized outpatient costs per patient ($6.1 K vs. $5.8 K, p = 0.10). The annualized total cost reduction per patient in the IG vs. CG was 20% (3.5 K, $17.7 K vs. $14.2 K, p = 0.04). Predictive analytics coupled with tailored interventions has great potential to reduce healthcare costs in older adults, thereby supporting population health management in home or community settings.
Comparing 99mTc-PSMA to 99mTc-MDP in Prostate Cancer Staging of the Skeletal System
Authors: Joseph Kabunda, Lerato Gabela, Chester Kalinda, Colleen Aldous, Venesen Pillay, Nozipho Nyakale
Journal: Clinical Nuclear Medicine (2021)

This prospective study was aimed at assessing the ability of 99mTc-PSMA scan to detect bone metastases in prostate cancer (PCa) against 99mTc-MDP scan as a standard and assess the correlation of these modalities in PCa staging of bone involvement.Forty-one patients (41) with histologically confirmed PCa were scanned using both methods. Planar imaging was performed with additional regional SPECT/CT 3 to 4 hours posttracer injection. Scans were reported as positive, negative, or equivocal. In the case of positive scans, lesions were quantified by each of the 3 reporters separately. Planar and SPECT/CT images were reported together to obtain the final report on each scan.Our preliminary results showed no significant difference in the detection of bone metastases between the 2 scans. 99mTc-PSMA detected 52 of the 55 bone lesions detected on 99mTc-MDP. However, 99mTc-PSMA provided extra information by reporting lymph nodal metastases in 7 patients and residual disease in the prostate in 2 patients with biochemical progression after radical therapy. In 1 patient, the PSMA scan resulted in change in management with patient now on 177Lu-PSMA radioligand therapy. Equivocal findings were reported in 4 patients on 99mTc-MDP and none on 99mTc-PSMA.99mTc-PSMA was comparable to 99mTc-MDP in detection of bone metastases and demonstrated an additional benefit of providing information on visceral disease. 99mTc-PSMA may be a better alternative to 99mTc-MDP in staging, restaging, and assessment of patients with biochemical progression after radical therapy of PCa in a resource-limited setup like ours while also assisting to detect patients eligible for PSMA-labeled radioligand therapy.
GRiNCH: simultaneous smoothing and detection of topological units of genome organization from sparse chromatin contact count matrices with matrix factorization
Authors: Da-Inn Lee, Sushmita Roy
Journal: Genome biology (2021)

High-throughput chromosome conformation capture assays, such as Hi-C, have shown that the genome is organized into organizational units such as topologically associating domains (TADs), which can impact gene regulatory processes. The sparsity of Hi-C matrices poses a challenge for reliable detection of these units. We present GRiNCH, a constrained matrix-factorization-based approach for simultaneous smoothing and discovery of TADs from sparse contact count matrices. GRiNCH shows superior performance against seven TAD-calling methods and three smoothing methods. GRiNCH is applicable to multiple platforms including SPRITE and HiChIP and can predict novel boundary factors with potential roles in genome organization.
Sequential Bilateral Vision Loss in a Woman With Scalp Tenderness and Jaw Claudication
Authors: Aaron R. Kaufman, Peter W. MacIntosh, Brooke T. Johnson
Journal: JAMA Neurology (2021)

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AB0791 THE DIAGNOSIS VALUE OF SYNOVIAL FLUID LYMPHOCYTE IN GOUT PATIENTS
Authors: Q. Huang, Y. Huang, Y. Liu, Z. Zhong, W. Deng, T. W. LI
Journal: Annals of the Rheumatic Diseases (2021)

Background: Synovial fluid cell counts have long been recognised to have utility in the diagnosis and management of arthritis. Few studies have explained the diagnosis value of synovial fluid cell counts in gout patients. Objectives: The study aims to investigate the diagnosis value of synovial fluid cell counts in gout patients. Methods: A total of 185 gout, 64 rheumatoid arthritis(RA), 26 axial spondyloarthritis(axSpA) and 24 osteoarthritis(OA) patients were included into the study. According to serum uric acid(sUA) level on attack, gout patients were divided into normal sUA gout patients and high sUA gout patients. The laboratory data was recorded and ROC curve was performed. Results: The synovial fluid WBC, PBMC, monocyte, PMN and neutrophil in gout patients were higher than OA patients (P&lt;0.05). The synovial fluid PBMC and lymphocyte in gout patients were lower than RA and axSpA patients (P&lt;0.05). Compared with RA, axSpA and OA patients, ROC curve showed that the AUC value of lymphocyte and sUA for gout were 0.728 and 0.881, which were higher than other variables. The optimal cut off value of lymphocyte for gout was 1.362, with sensitivity of 83.3% and specificity of 60.6%. The AUC value of lymphocyte and sUA for normal sUA gout patients were 0.694 and 0.643, which were higher than other variables. The optimal cut off value of lymphocyte for normal sUA gout patients was 1.362, with sensitivity of 81.6% and specificity of 60.6%. Conclusion: Synovial fluid cell counts of gout patients were different from RA, axSpA, and OA patients. Synovial fluid lymphocyte had a higher diagnosis value for gout. References: [1]Scanu A, Oliviero F, Ramonda R, et al. Cytokine levels in human synovial fluid during the different stages of acute gout: role of transforming growth factor β1 in the resolution phase. Ann Rheum Dis. 2012, 71(4): 621-4. Table 1. Basic characteristics of the participants Gout(n=185 ) RA(n=64 ) axSpA (n=26 ) OA(n=24 ) P value Age (years ) 48.58±15.58 56.19±12.39 * 32.96±15.19 *# 69.63±12.43 *#&amp; &lt;0.001 Gender (male/female ) 176/9 11/53 21/5 8/16 &lt;0.001 WBC(×10 9 /L ) 18.58±22.94 22.24±20.87 15.52±15.03 3.03±5.59 *#&amp; 0.002 PBMC(×10 9 /L ) 1.85±1.99 3.68±2.43 * 3.85±3.34 * 0.74±1.01 *#&amp; &lt;0.001 Monocyte(×10 9 /L ) 1.02±1.59 1.24±1.11 1.34±1.52 0.29±0.37 *#&amp; 0.030 PMN(×10 9 /L ) 16.77±21.51 18.57±19.32 15.75±24.17 2.30±5.00 *#&amp; 0.008 Lymphocyte (×10 9 /L ) 0.80±0.83 2.43±1.76* 2.50±2.04* 0.45±0.80 #&amp; &lt;0.001 Eosinophil (×10 9 /L ) 1.32±3.75 0.56±0.93 0.11±0.17 0.49±1.85 0.098 Neutrophil (×10 9 /L ) 16.42±21.16 18.82±20.89 11.13±14.23 2.23±4.87 *# 0.003 UA(μM ) 497.92±132.24 299.31±97.91 * 351.81±118.93 * 333.38±75.19 * &lt;0.001 ESR(mm/h ) 61.02±37.68 82.42±32.87 * 68.12±36.25 42.34±35.91 *#&amp; &lt;0.001 CRP(mg/L ) 56.52±45.64 44.01±35.27 * 65.49±39.85 # 22.11±40.65 *#&amp; &lt;0.001 * P &lt;0.05 vs gout group, # P &lt;0.05 vs RA group, &amp; P &lt;0.05 vs axSpA group Disclosure of Interests: None declared
REST and Stress Resistance in the Aging Kidney
Authors: Sato Magassa, Liviu Aron, Clément Hoguin, Pierre Isnard, Fabiola Terzi, Christophe Legendre, Bruce A. Yankner, Guillaume Canaud
Journal: Journal of the American Society of Nephrology (2021)

CKD is associated with the loss of functional nephr ons, leading to increased mechanical and metabolic stress in the remaining cells, particularly for cells constituting the filtration barrier, such as podocytes. The failure of podocytes to mount an adequate stress response can lead to further nephron loss and disease progression. However, the mechanisms that regulate this degenerative process in the kidney are unknown.We combined in vitro, in vivo, and organ-on-chip approaches to identify the RE1-silencing transcription factor (REST), a repressor of neuronal genes during embryonic development, as a central regulator of podocyte adaptation to injury and aging.Mice with a specific deletion of REST in podocytes exhibit albuminuria, podocyte apoptosis, and glomerulosclerosis during aging, and exhibit increased vulnerability to renal injury. This phenotype is mediated, in part, by the effects of REST on the podocyte cytoskeleton that promote resistance to mechanical stressors and augment podocyte survival. Finally, REST expression is upregulated in human podocytes during aging, consistent with a conserved mechanism of stress resistance.These results suggest REST protects the kidney from injury and degeneration during aging, with potentially important therapeutic implications.
B cell subset composition segments clinically and serologically distinct groups in chronic cutaneous lupus erythematosus
Authors: Scott A Jenks, Chungwen Wei, Regina Bugrovsky, Aisha Hill, Xiaoqian Wang, Francesca M Rossi, Kevin Cashman, Matthew C Woodruff, Laura D Aspey, S. Sam Lim, Gaobin Bao, Cristina Drenkard, Ignacio Sanz
Journal: Annals of the Rheumatic Diseases (2021)

While the contribution of B-cells to SLE is well established, its role in chronic cutaneous lupus erythematosus (CCLE) remains unclear. Here, we compare B-cell and serum auto-antibody profiles between patients with systemic lupus erythematosus (SLE), CCLE, and overlap conditions.
POS1012 HOW IMPORTANT WOULD BE THE IMPACT OF SPONDYLOARTHRITIS ON MILITARY POPULATION’S WORKING LIFE?
Authors: T. Mehmli, R. Dhahri, M. Slouma, E. Hannech, B. Louzir, L. Metoui, I. Gharsallah
Journal: Annals of the Rheumatic Diseases (2021)

Background: Spondyloarthritis is a group of chronic inflammatory diseases involving axial and peripheral joints. It mainly affects young patients typically of working age. Therefore, its impact on work outcomes may be considerable particularly in military patients. Objectives: The aim of this study was to evaluate the impact of spondyloarthritis on work ability and productivity in military patients, and to assess relationship between work productivity loss and disease activity. Methods: Thirty Three patients diagnosed with spondyloarthritis in the militay hospital of Tunis were included in the study. Age, gender and C-reactive protein were recorded. Data related to duration of the disease, Ankylosing Spondylitis Disease Activity Score (ASDAS) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were also recorded. Employed patients completed Work Productivity and Activity Impairment (WPAI) questionnaire witch assesses four subscales: presenteism, absenteism, overall work impairemend and daily activity impairement in the 7 past days. Results: Among the thirty three patients, 63 % were men and 37% were women. The average age was 43,7 ± 13,5. The average duration of disease was 8,5 ± 7,75 years. Mean C-Reactive protein was 27,5 ± 39,3. Mean ASDAS and BASDAI were 3,12 ± 1,39 and 4,26 ± 1,78 respectively. 22 patients (66%) had an active disease and 11 (33%)were in remission. 48,4% of patients were using NSAIDs, 48,4% were under DMARDs and 42% were under biologics (12 patients using TNF-alpha blockers and 2 patients were given IL-17 inhibitors). Among this patients, 27 were employed. Three patients (11%) had a total work disability and were retired from work and two have been outplaced. Employed patients worked an average of 35,6 ± 10,3 hours per week and missed an average of 3,48 ± 6,49 hours per week. The mean rates of absenteeism, presenteeism and work productivity loss were 8,8 ± 16,9 %, 48,4 ± 19,9 % and 48,6 ± 19,7 %. There was a statistically significant correlation between BASDAI and work missed hours (p&lt;0,05, r=0,48), absenteeism (p&lt;0,05, r=0,48), presenteeism (p&lt;0,01, r=0,669), work impairement (p&lt;0,01, r=0,669), activity impairement (p&lt;0,05, r=0,475) and work productivity loss (p&lt;0,05, r=0,475), as well as between ASDAS CRP and presenteeism (p&lt;0,05, r= 0,593), work impairement (p&lt;0,05, r=0,593), activity impairement(p&lt;0,05, r=0,460) and work productivity loss (p&lt;0,05, r=0,460). No relation was found between WPAI indexes and C-reactive protein. Conclusion: This study demonstrates that spondyloarthritis has a major impact on military patients’ work productivity with a significant correlation between WAPI indexes and disease activity scores (ASDAS CRP and BASDAI). No relation was found with C-reactive protein. Disclosure of Interests: None declared.
AB0084 INCREASED LEVEL OF NEUROPILIN-1 IN CD4+ T CELL AND ITS CORRELATION WITH DISEASE ACTIVITY OF SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: Y. J. Choi, E. K. Lee, M. S. Lee, C. H. Lee, C. H. Chung, W. H. Yoo
Journal: Annals of the Rheumatic Diseases (2021)

Background: Semaphorin has been found as a neuronal guidance molecule, but has recently been called “immune semaphorin”, as their critical role in immune cell activation, differentiation and migration has been revealed. In particular, class 4 semaphorin has been shown to contribute to lymphocyte activation and immune homeostasis. Objectives: This study was aimed to investigate the expression of neuropilin-1 (NRP-1), the receptor of class 4 semaphorin, in the murine mouse model of systemic lupus erythematosus (SLE) and the patients with SLE and the correlation between the expression of NRP-1 and disease activity of SLE. Methods: The expression of NRP-1 was measured in T cells in spleen and renal tissue in control mouse and TLR-7 agonist-induced lupus mouse by flow cytometry, PCR, and immunofluorescence (IF). CD4+ T cells from human peripheral blood were isolated to investigate the expression of NRP-1 in healthy control and the patients with SLE (n=40). Results: The frequency of NRP-1 positivity in CD4+ T cells in spleen was significantly higher in lupus mouse group (median [interquartile range]: 15.34 [14.84] %) compared to vehicle mouse group (4.0 [2.77]%). The quantitative analysis of fluorescense intensity in kidney stained for NRP-1 revealed the increased level in lupus group compared to vehicle group. The CD4+ T cells from peripheral blood mononuclear cells in the patients with lupus also showed significantly higher frequency of NRP-1 positive CD4+ T cells than those from healthy controls. Comparing the correlation of the expression of NRP-1 and disease activity with SLEDAI, C3, C4, and anti-DNA antibodies, the significant correlation between NRP-1 and disease activity markers were confirmed. Conclusion: Our results demonstrate that higher expression of NRP-1 in CD4+ T cells and its significant correlation with disease activity of SLE. These results indicate that pathologic contribution of NRP-1 in the pathogenesis of SLE and potential of targeting NRP-1 for the treatment of SLE. References: [1]Nishide M, Kumanogoh A. The role of semaphorins in immune responses and autoimmune rheumatic diseases. Nat Rev Rheumatol. 2018 Jan;14(1):19-31. Disclosure of Interests: None declared