tbuckley/cabot-search huggingface dataset:
AB0831 FREQUENCY OF RENAL CRISIS IN PATIENTS WITH SYSTEMIC SCLEROSIS: NEW DATA FROM A CHINESE COHORT AND A SYSTEMIC REVIEW WITH META-ANALYSIS
Authors: D. Xu, J. He, T. LI, R. Mu
Journal: Annals of the Rheumatic Diseases (2021)

Background: Scleroderma renal crisis (SRC) is a rare but life-threatening complication in SSc, which defined as malignant hypertension and progressive renal failure [1] . Previous reports of the prevalence for scleroderma renal crisis (SRC) show variable outcomes. Objectives: We aim to find out the prevalence for SRC in Chinese, and conduct a meta-analysis to assess the prevalence of SRC in worldwide and investigate possible factors of variability. Methods: We evaluated the prevalence for SRC and compared the clinical characteristics in SSc patients with or without SRC. A systematic review on the prevalence of SRC was carried out in PubMed, Embase and Cochrane. Meta-analysis was performed using available data on the prevalence for SRC. Results: 302 patients were enrolled in PKUPH-SSc cohort and the prevalence of SRC was 4.97%. In our cohort, SRC was found in 3.60% limited cutaneous SSc (lcSSc) and 7.75% diffused cutaneous SSc (dcSSc) patients. Twenty-nine studies including a total population of 22686 SSc patients were analyzed in the meta-analysis. The overall pooled prevalence of SRC was 4.0%, but heterogeneity among the studies was substantial (I 2 =86.1%, P &lt;0.00001). Meta-regression revealed that subtype of SSc and geographic factors partially explained this heterogeneity. Sub-group analyses demonstrated that the prevalence of SRC in dcSSc and lcSSc were 9.0% and 2.0%. The SRC prevalence in SSc was 3.0% in Asia, 5.0% in Europe, and 3.0% in North America, respectively. Conclusion: Data on our new cohort showed the prevalence of SRC was around 5% in China, and meta-analysis confirmed that the prevalence of SRC varies among centers. The marked heterogeneity of SRC prevalence was partially explained by subtype of SSc and geographic origin of patients. References: [1]Woodworth TG, Suliman YA, Li W, Furst DE, Clements P (2016) Scleroderma renal crisis and renal involvement in systemic sclerosis. Nat Rev Nephrol 12 (11):678-91. Disclosure of Interests: None declared
Genome-wide DNA mutations in Arabidopsis plants after multigenerational exposure to high temperatures
Authors: Zhaogeng Lu, Jiawen Cui, Li Wang, Nianjun Teng, Shoudong Zhang, Hon-Ming Lam, Yingfang Zhu, Siwei Xiao, Wensi Ke, Jinxing Lin, Chenwu Xu, Biao Jin
Journal: Genome biology (2021)

Elevated temperatures can cause physiological, biochemical, and molecular responses in plants that can greatly affect their growth and development. Mutations are the most fundamental force driving biological evolution. However, how long-term elevations in temperature influence the accumulation of mutations in plants remains unknown.
POS1058 SUBCLINICAL DACTYLITIS: COMPARATIVE STUDY OF THERAPEUTIC RESPONSE WITH TNF INHIBITORS, SECUKINUMAB AND USTEKINUMAB
Authors: C. Guillén-Astete, Á. Andreu-Suárez, V. García García
Journal: Annals of the Rheumatic Diseases (2021)

Background: Non tender dactylitis has been recently associated with synovitis, tenosynovitis and enthesitis without fat tissue hyperemia. Dactylitis is a remarkable hallmark of spondyloarthritis and particularly in psoriatic arthritis. Also, dactylitis has been recognized as one of the most difficult musculoskeletal feature of the disease to treat. It has been of interest to compare the effectiveness of available therapies in cases of clinical dactylitis, however, the efficacy on subclinical dactylitis has not studied yet. Objectives: To determine the effectiveness of three different biological therapy approaches in subclinical (non-tender) dactylitis in patients diagnosed by psoriatic arthritis in terms of changes detected by ultrasound scan. Methods: A retrospective ultrasound record-based study was conducted to compare the findings of ultrasonographic studies performed before and 6 months after the start of one of the following biologic therapies in patients diagnosed by psoriatic arthritis: TNF-inhibitors, secukinumab and ustekinumab. We included patients with a complete before-after ultrasound scan of the hands from three different rheumatology clinics. To be considered as a subclinical dactylitis two conditions were had to be achieved: non tender finger and absence of fat tissue hyperemia. Results: Patients included: 22 on TNF-inhibitors (28 subclinical dactylitis), 14 on secukinumab (17 subclinical dactylitis) and 13 on ustekinumab (16 subclinical dactylitis). Median of line of treatment of each biologic therapy: 1, 3 and 3, respectively. In the TNF-inhibtors group, 14/28 achieved synovitis resolution, 12/26 achieved tenosynovitis resolution and 2/28 achieved enthesitis resolution. In the secukinumab group, 11/17 achieved synovitis resolution, 11/17 achieved tenosynovitis resolution and 13/17 achieved enthesitis resolution. In the ustekinumab group, 10/16 achieved synovitis resolution, 10/15 achieved tenosynovitis resolution and 13/16 achieved enthesitis resolution. Complete dactylitis resolution was achieved in 12/28, 11/17 and 10/16 patients, respectively. Differences on independent success ratio of secukinumab and ustekinumab were not statistically significative, however both groups had higher rates of independent success compared to TNF-inhibitors group (P&lt;0.05, both cases). The line of treatment did not affect the resolution rate of non-TNF-inhibitors group. Conclusion: This is –as far as our knowledge know- the first study comparing the effect of different therapies on subclinical dactylitis. Besides the inherit limitations of a retrospective study, it seems to point that both secukinumab and ustekinumab are better therapeutic options than TNF-inhibitors. Of course, prospective further studies are needed. Disclosure of Interests: None declared.
Clonal expansion of T memory stem cells determines early anti-leukemic responses and long-term CAR T cell persistence in patients
Authors: Luca Biasco, Natalia Izotova, Christine Rivat, Sara Ghorashian, Rachel Richardson, Aleks Guvenel, Rachael Hough, Robert Wynn, Bilyana Popova, Andre Lopes, Martin Pule, Adrian J. Thrasher, Persis J. Amrolia
Journal: Nature Cancer (2021)
Evolution, Emotion, and Episodic Engagement
Authors: Daniel S. Pine, Steven P. Wise, Elisabeth A. Murray
Journal: American Journal of Psychiatry (2021)

Although rodent research provides important insights into neural correlates of human psychology, new cortical areas, connections, and cognitive abilities emerged during primate evolution, including human evolution. Comparison of human brains with those of nonhuman primates reveals two aspects of human brain evolution particularly relevant to emotional disorders: expansion of homotypical association areas and expansion of the hippocampus. Two uniquely human cognitive capacities link these phylogenetic developments with emotion: a subjective sense of participating in and reexperiencing remembered events and a limitless capacity to imagine details of future events. These abilities provided evolving humans with selective advantages, but they also created proclivities for emotional problems. The first capacity evokes the "reliving" of past events in the "here-and-now," accompanied by emotional responses that occurred during memory encoding. It contributes to risk for stress-related syndromes, such as posttraumatic stress disorder. The second capacity, an ability to imagine future events without temporal limitations, facilitates flexible, goal-related behavior by drawing on and creating a uniquely rich array of mental representations. It promotes goal achievement and reduces errors, but the mental construction of future events also contributes to developmental aspects of anxiety and mood disorders. With maturation of homotypical association areas, the concrete concerns of childhood expand to encompass the abstract apprehensions of adolescence and adulthood. These cognitive capacities and their dysfunction are amenable to a research agenda that melds experimental therapeutic interventions, cognitive neuropsychology, and developmental psychology in both humans and nonhuman primates.
Bruceine D inhibits HIF-1α-mediated glucose metabolism in hepatocellular carcinoma by blocking ICAT/β-catenin interaction
Authors: Rui Huang, Lijun Zhang, Jinmei Jin, Yudong Zhou, Hongwei Zhang, Chao Lv, Dong Lu, Ye Wu, Hong Zhang, Sanhong Liu, Hongzhuan Chen, Xin Luan, Weidong Zhang
Journal: Acta Pharmaceutica Sinica B (2021)

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths, characterized by highly hypoxic tumor microenvironment. Hypoxia-inducible factor-1α (HIF-1α) is a major regulator involved in cellular response to changes of oxygen levels, supporting the adaptation of tumor cells to hypoxia. Bruceine D (BD) is an isolated natural quassinoid with multiple anti-cancer effects. Here, we identified BD could significantly inhibit the HIF-1α expression and its subsequently mediated HCC cell metabolism. Using biophysical proteomics approaches, we identified inhibitor of β-catenin and T-cell factor (ICAT) as the functional target of BD. By targeting ICAT, BD disrupted the interaction of β-catenin and ICAT, and promoted β-catenin degradation, which in turn induced the decrease of HIF-1α expression. Furthermore, BD could inhibit HCC cells proliferation and tumor growth in vivo, and knockdown of ICAT substantially increased resistance to BD treatment in vitro. Our data highlight the potential of BD as a modulator of β-catenin/HIF-1α axis mediated HCC metabolism.
Pembrolizumab Plus Concurrent Chemoradiation Therapy in Patients With Unresectable, Locally Advanced, Stage III Non–Small Cell Lung Cancer
Authors: Salma K. Jabbour, Ki Hyeong Lee, Nikolaj Frost, Valeriy Breder, Dariusz M. Kowalski, Theodore Pollock, Evgeny Levchenko, Noemi Reguart, Alex Martinez-Marti, Baerin Houghton, Jean-Baptiste Paoli, Sufia Safina, Keunchil Park, Takefumi Komiya, Amy Sanford, Vishal Boolell, Hong Liu, Ayman Samkari, Steven M. Keller, Martin Reck
Journal: JAMA Oncology (2021)

Administration of pembrolizumab plus concurrent chemoradiation therapy (cCRT) may provide treatment benefit to patients with locally advanced, stage III non-small cell lung cancer (NSCLC).
AB0777 A RARE CASE OF A SOLITARY PLASMOCYTOMA OF A LUMBAR VERTEBRA
Authors: D. Khalifa, H. Hachfi, N. Ben Chekaya, M. Brahem, M. Younes
Journal: Annals of the Rheumatic Diseases (2021)

Background: Solitary plasmocytoma is a rare tumour that represents around 2 to 5% of all plasma cell dyscrasias. It normally affects soft tissu but rarely the bone. Diagnosis is based on histology, the absence of bone marrow involvement. Objectives: To drag attention to think of solitary plasmocytoma of bone when dealing with a vertebral fracture in the absence of the CRAB criteria of multiple myeloma. Methods: We report a rare case of a vertebral fracture of the 4th lumbar vertebra (L4) revealing a solitary plasmocytoma of bone. Results: A 67-year-old female patient presented to our rheumatology department with back and left radicular pain of brutal onset, 15 days prior to her visit. Pain was severe and awakened her at nights. On examination, mobilities of the spine were unchanged but on palpation she had exquisite pain of L4. Laboratory tests showed a normal sedimentation rate of 15mm the first hour, a negative c-reactive protein, normal calcemia and kidney tests. X-rays of lumbar spine showed a vertebral fracture with a destruction over 50% of the vertebral size and cortical rupture. MRI of the spine showed the absence of other lytic lesions or other fractures or spinal cord compression and showed the total destruction oft he anterior vertebral body of L4 (Figure 1). Protein electrophoresis was in normal range and 24h urinary proteinuria was negative. Other tests rules out gynecological, thyroid, and renal neoplasms. Sternal puncture showed a rich bone marrow of normal cells without further infiltration. Bone biopsy of the detected lesion showed tumour cells made of mature plasmocytes confirming the diagnosis of solitary plasmocytoma of the bone. The patient was treated with radiation therapy. The evolution after 24 months showed a stabalised lesion and the absence of progression to multiple myeloma. Figure 1. T2 weighted MRI showing the vertebral fracture of L4 Conclusion: It is important to keep in mind the diagnosis of solitary plasmocytoma of bone when facing a solitary lesion or vertebral fracture despite relatively non agressive radiological signs. It is also important to note the possible evolution to multiple myeloma and keep a hawk-eyed guard. References: [1]Masmoudi K, Elleuch E, Akrout R, et al. Le plasmocytome solitaire osseux: à propos de 3 cas et revue de la littérature. Pan Afr Med J ; 25. Epub ahead of print 6 December 2016. DOI: 10.11604/pamj.2016.25.219.10933. Disclosure of Interests: None declared
AB0078 LIPID IMMOBILIZATION AS A METHOD TO OBTAIN ANTIGENIC NANO-OBJECTS
Authors: O. Rusanova, O. Emelyanova, N. Emelyanov
Journal: Annals of the Rheumatic Diseases (2021)

Objectives: Objective of the study is to research the effect of emulsion polymerization on active sites of cardiolipin antigen determinant in antiphospholipid syndrome (APS) in patients with systemic lupus erythematosus (SLE). Methods: Having integrated antigen nanoobjects we developed immobilized magnetocontrollable antigen nanosystems and put them to an evaluation test. The nanosystems are polyacrylamide granules with a built in antigen. To obtain stable immobilized multi–use biopharmaceuticals with targeted properties (shape, particle diameter, pore size, density) we used a modified version of emulsion polymerization method using polyacrylamide carrier gel. This method permitted a greater sorptive capacity, preserving the antigen in maximum native state, and opened up the possibility of controllable modification of nanoobjects. Cardiolipin was used as the antigen in question. Results: Following the method described above we performed sorption of anticardiolipin antibodies from blood plasma of SLE patients who showed clinical presentations of antiphospholipid syndrome. Blood serum from 10 apparently healthy individuals served as control. The level of cardiolipin antibodies was determined before and after sorption by indirect solid phase immunoenzyme method. In the eluate we estimated total protein by Lowry method. In vitro testing showed that the obtained antigen nanosystems based on immobilized cardiolipin could effectively remove cardiolipin antibodies from whole blood of SLE patients with clinical presentations of APS to achieve the values of healthy individuals (before sorption cardiolipin antibodies 0.328 ± 0.028; after sorption 0.059 ± 0.017; p&lt;0.001; sorption capacity 8.00 ± 0.390 mg/ml). Conclusion: The method of emulsion polymerization with consideration to hydrophobic and hydrophilic properties of lipid molecules permits obtaining and modifying biomolecules with certain properties, in a controlled fashion. Disclosure of Interests: None declared
POS0950 ARE THERE GENDER DIFFERENCES IN AXIAL SPONDYLOARTHRITIS: DATA FROM A PORTUGUESE SPONDYLOARTHRITIS COHORT
Authors: A. R. Cunha, R. Aguiar, M. J. Santos, V. Afreixo, A. Barcelos
Journal: Annals of the Rheumatic Diseases (2021)

Background: Historically, axial spondyloarthritis (particularly ankylosing spondylitis) was considered a men’s disease and has been under-recognized in women. Emerging evidence reveals gender differences in patophysiology, disease presentation and therapeutic efficacy. Objectives: To determine if there are differences between genders in a Portuguese cohort of patients with axSpA as regards clinical manifestations, disease activity, functional capacity, patient related outcomes and radiographic findings. Methods: Patients with ≥18 years fulfilling the ASAS- Assessment of Spondyloarthritis International Society classification criteria for axSpA and registered in the electronic national database- Reuma.pt were included in a multicentric cross-sectional study. Sociodemographic data, clinical features and radiographic findings were collected from the first record in Reuma.pt. These variables were compared between genders using Mann-Whitney test and Chi-Square test. Variables with a significant association with group variable (gender) were considered in the multiple variable analysis to adjust the gender effect on the outcome variables. Results: A total of 1995 patients were included, 1114 (55.9%) men and 881 (44.1%) women. Men had a lower median age at onset of disease (25.1 vs 28.4, p=0.000) and median age at diagnosis (26.9 vs 30.4, p=0.000) and were more frequently smokers (32.1% vs 15.7%, p=0.000). Comparing to women, men had worse BASMI scores (4.0 vs 3.4, p=0.000), higher levels of CPR (10.5 vs 6.9, p=0.000) and were more often HLA-B27 positive (67.8% vs 54%, p=0.000). In univariable analysis, sacroiliitis on radiograph or/and MRI (95.5% vs 91.7%, p=0.04) was more common in men, however that wasn’t confirmed in multivariable analysis. In contrast, women more frequently had more inflammatory bowel disease (8.8% vs 4.9%, p=0,004), higher levels of ESR (25.0 vs 21.0, p=0.003) and worse PROs- BASDAI (5.7 vs 4.5, p=0.000), PGA (60.0 vs 55.0, p=0.000) and fatigue (6.2 vs 5.4, p=0,000). Conclusion: Physicians must be aware of differences between genders in axial spondyloarthritis because this can result in less underdiagnosis and misdiagnosis, allow optimization of treatment strategies, and decrease overall disease burden in women with axSpA patients. References: [1]Rusman T, van Vollenhoven RF, van der Horst-Bruinsma IE. Gender Differences in Axial Spondyloarthritis: Women Are Not So Lucky. Curr Rheumatol Rep. 2018;20(6):35. [2]Tournadre A, Pereira B, Lhoste A, Dubost JJ, Ristori JM, Claudepierre P, et al. Differences between women and men with recent-onset axial spondyloarthritis: results from a prospective multicenter French cohort. Arthritis Care Res (Hoboken). 2013;65(9):1482-9. Disclosure of Interests: None declared
POS0363 IDENTIFICATION OF MOLECULAR PHENOTYPES AND IMMUNE CELL INFILTRATION IN PSORIATIC ARTHRITIS PATIENTS’ SKIN TISSUES BY INTEGRATED BIOINFORMATICS ANALYSIS
Authors: T. Cheng, S. X. Zhang, J. Qiao, R. Zhao, S. Song, Y. Zhang, P. Zhao, G. Y. Liu, P. F. He, X. Li
Journal: Annals of the Rheumatic Diseases (2021)

Background: Psoriatic arthritis (PsA) is an inflammatory musculoskeletal disease associated with cutaneous psoriasis 1 . Heterogeneity of clinical manifestation often makes differential diagnosis difficult 2 . Thus, the underlying molecular pathogenesis of PsA need to be further studied to diagnose early and ensure optimal management of arthritis and key comorbidities. Objectives: This research was conducted to identify molecular phenotypes and immune infiltration in the skin tissues of psoriatic arthritis patients according to bioinformatics analysis. Methods: The mRNA expression profiles of GSE13355 (116 samples), GSE14905 (56 samples) and GSE30999 (162 samples) were obtained from the publicly GEO databases. Non-negative matrix factorization (NMF), functional enrichment and cibersort algorithm were applied to illustrate the conditions of PsA patients’ skin tissues for classification after screening the differentially expressed genes (DEGs) between lesion biopsy and non-lesion biopsy. Results: Two subsets (Sub1 and Sub2) were identified and validated by NMF typing of 612 detected DEGs (Figure 1a). A total of 54 signature genes (18 in Sub1 and 36 in Sub2) were obtained (Figure 1b). GO and KEGG enrichment analysis showed the signature genes in Sub1 were mainly involved in proliferation and differentiation of immune cells, whereas genes in Sub2 were related to humoral immune response mediated by antimicrobial peptide (Figure 1c.1d). Further, immune cell infiltration results revealed Sub2 had higher levels of resting NK cells ( P &lt;0.001), macrophages M1( P &lt;0.001), resting mast cells ( P &lt;0.001) and regulatory T cells ( P &lt;0.001) but lower concentrations of activated CD4 + memory T cells ( P &lt;0.001), activated NK cells ( P &lt;0.05), activated dendritric cells( P &lt;0.001), eosinophils ( P &lt;0.05) and neutrophil ( P &lt;0.001) (Figure 1e). Conclusion: The pathogenesis of psoriatic arthritis is related to both cellular immunity and humoral immunity. It is indispensable to adjust the treatment strategies according to patient’s immune status. References: [1]Ritchlin CT, Colbert RA, Gladman DD. Psoriatic Arthritis. The New England journal of medicine 2017;376(10):957-70. doi: 10.1056/NEJMra1505557 [published Online First: 2017/03/09]. [2]Veale DJ, Fearon U. The pathogenesis of psoriatic arthritis. Lancet (London, England) 2018;391(10136):2273-84. doi: 10.1016/s0140-6736(18)30830-4 [published Online First: 2018/06/13]. Acknowledgements: This project was supported by National Science Foundation of China (82001740), Open Fund from the Key Laboratory of Cellular Physiology (Shanxi Medical University) (KLCP2019) and Innovation Plan for Postgraduate Education in Shanxi Province (2020BY078). Disclosure of Interests: None declared
AB0606 IMPACT OF ABDOMINAL AORTIC CALCIFICATION AND SERUM CREATININE-TO-CYSTATIN C RATIO TO BONE FRAGILITY FRACTURE
Authors: I. Yoshii
Journal: Annals of the Rheumatic Diseases (2021)

Background: Relationship between bone fragility fracture (BFF) and abdominal aortic calcification (AAC) has been discussed in recent decade. Objectives: Now we investigated the relationship between the two and a new factor of BFF: serum creatinine-to cystatin C ratio (Cr/CysC). Methods: A total of nine-hundred and thirty one osteoporotic patients were recruited. Diagnosis of osteoporosis was indexed by the criteria of Japanese Primary Osteoporosis Diagnostic Criteria. Patient’s lumbar spine X-ray pictures were taken and dual-energy X-ray absorptiometry (DXA) of lumbar spine and hip joint were tested at the same time, and all of them were followed us for more than one year up to nine years with at least an administration of vitamin D. Anti-osteoporotic drugs were administrated for 660 patients. Vertebral compression fracture (VF) and AAC were evaluated with lateral view of X-ray picture. VF was classified in accordance with Semi-quantified method (SQ), and AAC was classified as follows: Grade0; No calcification, Grade1; Partial calcification not continued over one vertebral height, Grade2; Calcification continuous over one vertebral height. BFF history of the patients except of VF was harvested from the medical record and with interview. Patients’ background at first measurement were measured and Cr/CysC was calculated as well. Prevalence of BFF at the baseline for each grade with SQ was compared according to the grade of AAC. Background factors including bone mineral densities (BMD) of the lumbar spine and hip joint measured using DXA were compared for each AAC grade. Occurrence of BFF was picked up during following up (BFF_F/U) of the patients. Prevalence of BFF_F/U for each ACC grade was statistically compared, and relationship between BFF_F/U and factors at the baseline was statistically evaluated. Results: A total of 219 of Grade0, 428 of Grade1, and 278 of Grade2 were recruited. Prevalence of BFF at baseline for each VF group was 182, 16, 9, and 12 for Grade0, 138, 98, 122, and 70 for Grade1, and 53, 45, 82, and 144 for Grade2, with Grade-0, Grade-1, Grade-2, and Grade-3 by SQ, respectively ( p &lt;0.01). Factors that demonstrated significant correlation with occurrence of BFF were sex, age, BMD of the lumbar spine and the hip joint, and Cr/CysC with univariate mode binary logistic regression anaysis. However, Cr/CysC did not demonstrate significant correlation using multivariate model. Occurrence of BFF_F/U for each AAC group was 26, 90, and 82 for Grade0, Grade1, and Grade2, respectively ( p &lt;0.01). The only factor that demonstrated significantly correlated with occurrence of BFF_F/U was Cr/CysC in the Grade1 and the Grade2 of the AAC classification. Conclusion: ACC grade significantly correlates with occurrence of BFF. Cr/CysC also significantly correlates with occurrence of BFF after follow up under presence of AAC. Disclosure of Interests: None declared.