tbuckley/cabot-search huggingface dataset:
AB1058 Is hepatitis b surface antigen (HBSAG) enough alone as a screening test for hbv infection in rheumatic disease patients before starting immunosuppressive therapies?
Authors: R.A. Abdel Noor, M. Watany, S. Abd-Elsalam, W. Elkhalawany, S. Soliman, R. Badawi
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Prevalence of hepatitis B virus in patients with rheumatic diseases has been reported differently among studies. The loss of immune control in these patients may result in the reactivation of HBV replication within hepatocytes. Considering the lifelong use of multiple anti-rheumatic drugs, screening for HBV is recommended before starting immunosuppressive or immunomodulatory therapy. <h3>Objectives</h3> The aim of this study was to select the best and simplest test for screening of HBV in rheumatic patients in Egypt. <h3>Methods</h3> This cross sectional study was carried out on 102 patients with different rheumatic diseases. Screening to all patients by hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) and human immune deficiency virus antibodies (HIV) were done. HBV core antibodies and real time PCR to detect HBV DNA were done. <h3>Results</h3> The mean age of the patients was 37.18%±12.37. 3.9% of them were males and 96.1% were females. We found that HBsAg was positive in two patients (2%) and negative in 100 patients (98%). HBcAb was positive in 24 patients (23.5%) and negative in 78 patients. however PCR for hepatitis B DNA was positive in 2 patients (2.0%) only who were positive for both HBsAg and HBC Ab. HBsAg had 100% Sensitivity, 100% Specificity, 100% PPV, 100% NPV and 99.0% accuracy. While antiHBc had 100% Sensitivity, 78% Specificity, 8% PPV, 100% NPV and 78% accuracy in screening of HBV. <h3>Conclusions</h3> We can conclude that screening for hepatitis B virus is essential for all patients with rheumatic diseases before starting therapies either steroids, immunosuppressive therapies or biologics. For financial issues especially in developing countries screening by HBsAg may be enough as an initial test especially if non biological therapies are used as it is superior to anti HBc for screening for HBV infection. <h3>References</h3> [1] Raimondo G, Allain J-P, Brunetto MR, Buendia M-A, Chen D-S, Colombo M, et al. Statements from the Taormina expert meeting on occult hepatitis B virus infection. Journal of hepatology. 2008;49(4):652–7. [2] Harigai M, Mochida S, Mimura T, Koike T, Miyasaka N. A proposal for management of rheumatic disease patients with hepatitis B virus infection receiving immunosuppressive therapy. Modern rheumatology. 2014;24(1):1–7. [3] Karadağ Ö, Kaşifoğlu T, Özer B, Kaymakoğlu S, Kuş Y, İnanç M, et al. Viral hepatitis screening guideline before biological drug use in rheumatic patients. European Journal of Rheumatology. 2016;3(1):25. <h3>Disclosure of Interest</h3> None declared
Abstract P270: Long-Term Benefits of Blood Pressure Lowering in Young Adulthood: A Computer Simulation Study
Authors: Ciaran N Kohli-Lynch, Anusorn Thanataveerat, Eric Vittinghoff, Mark J Pletcher, Andrew E Moran
Journal: Circulation (2017)

Introduction: Extended periods of exposure to elevated blood pressure (BP) in early adult life contribute independently to later life coronary heart disease (CHD) risk. Currently, there are significant gaps in hypertension awareness, treatment, and control in young adults. The long-term health benefits of controlling high BP in young adults have not previously been quantified. Objective: This study aimed to project CHD prevention benefits from controlling raised blood pressure starting in early adulthood compared with control at age 40 or older. Method: A state-transition microsimulation model estimated individual-level CHD outcomes, dependent on risk factors exposures and accounting for competing risk of stroke or non-cardiovascular death. Risk for first CHD event after age 40 was conditioned both on time-weighted average of early adult (ages 20-39) diastolic blood pressure (DBP), and raised DBP or systolic blood pressure (SBP) at age ≥ 40. We simulated CHD outcomes in a cohort of US adults with DBP ≥ 85 mmHg any time in young adulthood in 3 scenarios: no treatment, later life SBP control alone, or early DBP control plus later life BP control. Results: By age 39, 2.2% of the CVD-free young adult U.S. population was estimated to have early elevated DBP and was eligible for treatment. With follow up until age 69 years, early BP control prevented twice the number of primary CHD events (Table). Conclusion: This study quantifies the opportunity cost of failing to control hypertension identified in young adulthood. It is unclear whether early blood pressure control should be achieved by lifestyle or pharmacological intervention.
Targeting of cathepsin S reduces cystic fibrosis-like lung disease
Authors: Donna M. Small, Ryan R. Brown, Declan F. Doherty, Anthony Abladey, Zhe Zhou-Suckow, Rebecca J. Delaney, Lauren Kerrigan, Caoifa M. Dougan, Keren S. Borensztajn, Leslie Holsinger, Robert Booth, Christopher J. Scott, Guillermo López-Campos, J. Stuart Elborn, Marcus A. Mall, Sinéad Weldon, Clifford C. Taggart
Journal: European Respiratory Journal (2019)

Cathepsin S (CatS) is upregulated in the lungs of patients with cystic fibrosis (CF). However, its role in CF lung disease pathogenesis remains unclear. In this study, β-epithelial Na + channel-overexpressing transgenic (βENaC-Tg) mice, a model of CF-like lung disease, were crossed with CatS null (CatS −/− ) mice or treated with the CatS inhibitor VBY-999. Levels of active CatS were elevated in the lungs of βENaC-Tg mice compared with wild-type (WT) littermates. CatS −/− βENaC-Tg mice exhibited decreased pulmonary inflammation, mucus obstruction and structural lung damage compared with βENaC-Tg mice. Pharmacological inhibition of CatS resulted in a significant decrease in pulmonary inflammation, lung damage and mucus plugging in the lungs of βENaC-Tg mice. In addition, instillation of CatS into the lungs of WT mice resulted in inflammation, lung remodelling and upregulation of mucin expression. Inhibition of the CatS target, protease-activated receptor 2 (PAR2), in βENaC-Tg mice resulted in a reduction in airway inflammation and mucin expression, indicating a role for this receptor in CatS-induced lung pathology. Our data indicate an important role for CatS in the pathogenesis of CF-like lung disease mediated in part by PAR2 and highlight CatS as a therapeutic target.
AB0762 Relationship of the six minute walking test and quality of life in patients with systemic sclerosis
Authors: G. Cuomo, K. GJELOSHI, F. Masini, F. Danzo, C. Romano, L.E. Adinolfi
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The six minute walking test (6MWT) is a standardised measure of submaximal exercise capacity. It is a surrogate measure of heart and lung involvement. There are no studies on relationship between 6MWT and quality of life evaluated by Short form 36. <h3>Objectives</h3> To evaluate the relationships between of the 6 min walking distance (6MWD) and each items of SF36 <h3>Methods</h3> Fifty consecutive SSc patients were investigated. They underwent 6MWT and complete the SF-36 (assessed the 8 domains of the questionnaire as well as the physical component score-PCS and mental component score-MCS). <h3>Results</h3> 6MWD ranged from 253 to 582 (median 420); we listed the correlations from 6MWT and only the statistically significant features of SSc and the items of SF36 Age: median 48 (range 20–72); Rho −0.51; p&lt;0.00001 EScSG Activity Index: median 0.5 (range 0–5); Rho −0.33; p0.009 HAQ-DI: median 0.375 (range 0–2.275); Rho −0.26; p 0.048 mRSS: median 2 (range 0–17); Rho-0.35; p0.007 Pulmonary hypertension (echocardiography): median 30 (range 13–80); Rho −0.26; p 0.048 SF36: PCS: median 43 (range 20–65); Rho 0.41; p 0.0016 PF: median 75 (Range 0–100); Rho 0.40; p 0.002 GH: median 50 (range 10–92); Rho 0.43; p 0.0007 <h3>Conclusions</h3> Our study first demonstrates that 6MWT is correlated to some aspects of quality of life as measured by SF36 in the SSc patients. This results must been considered when assessing 6MWT in SSc. <h3>References</h3> [1] Schoindre Yet al, J Rheumatol2009. [2] Flahertyet al, Am J Respir Crit Care Med2006 [3] Casanova C. et al, Eur respire J2007 <h3>Disclosure of Interest</h3> None declared
Extracellular vesicles from human umbilical cord blood ameliorate bone loss in senile osteoporotic mice
Authors: Yin Hu, Ran Xu, Chun-Yuan Chen, Shan-Shan Rao, Kun Xia, Jie Huang, Hao Yin, Zhen-Xing Wang, Jia Cao, Zheng-Zhao Liu, Yi-Juan Tan, Juan Luo, Hui Xie
Journal: Metabolism (2019)
SAT0640 Whole body-mri in axial spondyloarthritis (AXSPA): diffusion weighted imaging (DWI) outperforms the stir sequence
Authors: A. Nzeusseu Toukap, N. Vander Maren, L. Collette, N. Michoux, P. Triqueneaux, M.S. Stoenoiu, F. Houssiau, J. Malghem, F.E. Lecouvet
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> None <h3>Objectives</h3> To compare the diagnostic value of DWI and STIR sequences as part of WB-MRI studies in AxSpA patients. <h3>Methods</h3> 20 consecutive patients (P) with confirmed diagnosis of active AxSpA and 20 controls (C) referred for metastatic cancer screening were investigated with identical WB-MRI protocols including DWI and STIR images. Two independent observers recorded the presence of "lesions" (high signal intensity foci on STIR and high b-value DWI images) in 17 anatomic areas; making a 17-point "area score") and a calculated 40-point "lesion score". Both were tested for correlation with clinical and biological parameters. <h3>Results</h3> In P, the "lesion score" was significantly higher with DWI than with STIR (p&lt;0.025). The most experienced observer had higher DWI lesion scores, suggesting a learning effect. The lesion score and some anatomic areas could discriminate P from C. For this purpose, DWI had a higher AUC than STIR (AUC=99.9, CI: 99.5–1.00 vs AUC=95.8, CI: 90.9–1.00). For a trained MRI observer using DWI, a lesion score threshold of &gt;4 had 100% sensitivity and 95% specificity. With STIR, a threshold of &gt;3 had 85% sensitivity and 90% specificity. The area score AUC was significantly lower with STIR than with DWI (p=0.0233), but no satisfactory area score threshold was identified. The most frequently involved areas were the spine and hip entheses in C, the spine and SIJ in P. Manubrio- and chondro-sternal joint involvement was specific for AxSpA. The lesion score was positively correlated with ASDAS-CRP and (log) CRP. <h3>Conclusions</h3> DWI is a promising alternative to STIR in WB-MRI studies for the detection of active lesions in AxSpA. Training may be necessary. The involvement of specific anatomic areas could distinguish P from C. <h3>Acknowledgements</h3> None <h3>Disclosure of Interest</h3> None declared
Abstract 15630: Novel Mitochondrial Protein D-glutamate Cyclase Decreases During the Progression of Heart Failure
Authors: Shuhei Tateishi, Makoto Ariyoshi, Masumi Katane, Kenji Hamase, Yurika Miyoshi, Maiko Nakane, Atsushi Hoshino, Yoshifumi Okawa, Yuichiro Mita, Satoshi Kaimoto, Motoki Uchihashi, Kuniyoshi Fukai, Kazunori Ono, Daichi Hato, Ryoetsu Yamanaka, Sakiko Honda, Yohei Fushimura, Eri Kwai-Kanai, Naotada Ishihara, Masashi Mita, Hiroshi Homma, Satoaki Matoba
Journal: Circulation (2017)

Introduction: Recently, importance of D-amino acids in mammals has been drawing attention. D-Amino acids are enantiomers of L-amino acids and have been recognized as biomarkers and bioactive substa...
THU0073 A subset of neutrophil highly expressing cd49d and vegfr1 can enhance pannus formation via increase fls migration and invasion ability by up-regulating mmp3 and 13
Authors: H.Y. Li, Y.L. Cao, X. cao, C.L. su, Q.P. yang, Q.P. yang, Y. liu, B.Y. luo, Y. zhao, T.N. Marion
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Neutrophil is known to play an important role in the progression of rheumatoid arthritis (RA). Pannus formation requires hypoxia microenvironment<sup> (1,2)</sup> and a small population of neutrophil highly expressing CD49d, VEGFR1 and CXCR4 is reported to induce angiogenesis at the sites of hypoxia<sup>(3)</sup>. <h3>Objectives</h3> In the current study, we aim to identify this subset of neutrophil and investigate its function and role during the pannus formation. <h3>Methods</h3> Collagen-induced arthritis (CIA) model was applied in this study and CD49d<sup>+</sup>VEGFR1<sup>+</sup>Ly6G<sup>+</sup> neutrophil was monitored at the onset and remission of arthritis. The levels of IL-17, IL-4, IL-6, IL-10, TNF-a and IFN-g in CIA model sera were tested by ELISA at day 30, 36 and 42, respectively. mRNA expressions of cytokines including TNF-α, VEGF, IL18 and MMP9 were detected by RT-PCR. Meanwhile, chemokines genes of CXCL10, CXCL9, CLL3 and CLL4 expressed in CD49d<sup>+</sup>VEGFR1<sup>+</sup>neutrophil were also measured. <i>In vitro</i>, synovial fibroblast-like cells (FLS) was co-cultured with MHL60, expressing CD49d and VEGFR1, and the migration and erosion was measured. <h3>Results</h3> CD49d<sup>+</sup>VEGFR1<sup>+</sup> neutrophil was detected in the peripheral blood and ankle at various time points with the peak on day 30. The gene expression of TNFα, VEGF, IL-18 as well as CXCL10, CXCL9, CLL3 andCLL4 was significantly increased in CD49d<sup>+</sup>VEGFR1<sup>+</sup> neutrophil. Pre-coculture with MHL60 was able to increase FLS migration and erosion. Meanwhile, the expression of MMP13, MMP3 was robustly enhanced at the mRNA and protein level. <h3>Conclusions</h3> A subset of neutrophil highly expressing CD49d and VEGFR1 was detected for the first time in CIA mice. CD49d<sup>+</sup>VEGFR1<sup>+</sup> neutrophil is able to secrete various chemokine and cytokines. Meanwhile, it can enhance FLS migration and invasion ability via up-regulating MMP3 and 13. <h3>References</h3> [1] Ng CT, et al. Synovial tissue hypoxia and inflammation in vivo. Ann. Rheum. Dis. 2010;69:1389–1395. [2] Kennedy A, et al. Angiogenesis and blood vessel stability in inflammatory arthritis. Arthritis Rheum2010;62:711–721. [3] Massena S, et al. Identification and characterization of VEGF-A responsive neutrophils expressing CD49d, VEGFR1, and CXCR4 in mice and humans. Blood. 2015;126(17):2016–26.. <h3>Acknowledgements</h3> no <h3>Disclosure of Interest</h3> None declared
Patient groups fail to declare financial interests during NICE assessments
Authors: Harriet Pike
Journal: BMJ (2019)

Patients’ groups involved in assessing treatments for the NHS often fail to disclose their financial interests, a review published in The BMJ shows.1

More than two thirds of patient groups involved in NICE technology appraisals received funding from the manufacturer of the treatment being assessed or from a competitor, the review found. NICE decision makers were not aware of most of these competing interests.

Researchers led by Kate Mandeville at the London School of Hygiene and Tropical Medicine assessed 53 patient organisations that contributed to 41 NICE technology appraisals published in 2015 and 2016. Drug industry funding was determined from manufacturers’ disclosures and from patient organisations’ accounts, annual reports, websites, declarations of interests, and responses.

Patient organisations contributed to the appraisal of a technology on 117 separate occasions. The researchers found that 38 of 53 patient organisations (72%) had received funding from the manufacturer of a technology or competitor product in the same or preceding year that the group contributed to the appraisal of that technology. NICE’s committees were aware of less …
Partial Reconstitution of Humoral and Cellular Immunity in Patients with Chronic Lymphocytic Leukemia Treated with Acalabrutinib
Authors: Christopher Pleyer, Clare C. Sun, Pia Niermann, Xin Tian, Inhye E. Ahn, Janet Valdez, Jennifer Lotter, Raquel Izumi, Ahmed Hamdy, Adrian Wiestner
Journal: Blood (2018)
AB0711 Tocilizumab for severe/refractory vascular behÇet’s disease
Authors: W. Zheng, Y. Ding, J. Liu, J. Shi, C. Li, Y. Zhao, X. Zeng
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Vascular Behçet's Disease (BD) is a common yet severe complication of BD. Despite aggressive conventional therapy, vascular BD remains as one of the leading causes of morbidity of BD. Tocilizumab (TCZ), an IL-6 receptor antagonist, is an emerging biological agents for neurologic BD or ocular BD, however, the efficacy of TCZ for vascular BD is unknown. <h3>Objectives</h3> To elucidate the efficacy and safety of TCZ for severe/refractory vascular BD. <h3>Methods</h3> We retrospectively analysed the clinical data of vascular BD patients treated with TCZ in our centre between 2014 and 2017. <h3>Results</h3> Seven patients (6 males and 1 female) were enrolled, with a mean age and median course of 32.9±9.1 years old and 72 months (range 54 to 138), respectively. Multiple arterial lesions were documented in all patients, including arterial aneurysm (n=5), stenosis (n=4), occlusion (n=3), and multiple venous thrombosis were documented in two patients. Recurrent aneurysms together with graft occlusion or endoleak occurred in two out of 3 aneurysms patients who underwent endovascular stent placements. As for concomitant medical conditions, one patient complicated with hepatitis B infection, and three complicated with latent tuberculosis infection and received anti-tuberculosis prophylaxis. Prior to TCZ therapy, all patients experienced disease progression despite high-dose glucocorticosteroid in combination with multiple immunosuppressants. All patients received TCZ, 8 mg/kg iv every 4 weeks for a median of 7 (range 3 to 15) doses, and baseline medium-to-low dose corticosteroid and immunosuppressants, After a median follow-up of 16 months (range 4 to 29), all patients achieved both clinical and serological improvements. Radiologic improvement of artery stenosis was demonstrated in one patient. The condition of one patient with endoleak after the stent placement remained stable without surgical intervention. No newly-onset arterial lesions or venous thrombosis were observed. The median ESR (18 vs 7 mm/h, p&lt;0.05) and hsCRP level (30.6 vs 2.0 mg/L, p&lt;0.05) were also significantly decreased. Furthermore, corticosteroids dose was tapered from 27.1±6.3 mg to 8.9±1.2 mg (p&lt;0.05), and immunosuppressants were tapered in number and dosage in 3 (42.9%) and 3 patients (42.9%), respectively. No serious adverse event or TB reactivation was observed. <h3>Conclusions</h3> TCZ, in combination with corticosteroids and immunosuppressants, was effective and well tolerated in severe/refractory vascular BD, with a favourable steroid- and immunosuppressant-sparing effect. <h3>Disclosure of Interest</h3> None declared
Abstract B29: Dissecting the effects of Brd4 short isoform on breast cancer progression
Authors: Xinyi Zhu, Kent W. Hunter
Journal: Cancer Research (2016)

Abstract Breast cancer is one of the most common female malignancies in the United States with metastatic disease being the main contributor to breast cancer morbidity and mortality. Our lab previously identified BRD4, a member of the bromodomain family, as a regulator of breast cancer progression. Brd4 is a chromatin-modifying factor that regulates the expression of a large set of genes. Brd4 is normally expressed as two isoforms. The long isoform (Brd4-LF) contains two bromodomains in the N-terminus, an ET domain, a serine-rich SEED domain, and a proline-rich C-terminus. The short isoform (Brd4-SF) differs from the long isoform by a deletion of the proline-rich C-terminus and a three amino acid difference on the N-terminal domain. Previous studies in our laboratory indicate that these two isoforms have opposing effects on breast cancer progression. Highly metastatic mouse mammary tumor cells overexpressing Brd4-LF suppressed tumor growth and dissemination, whereas overexpression of Brd4-SF increased metastatic outgrowth in lungs. We have shown that these two isoforms are found in different compartments within the cell nucleus, leading to altered interaction with nuclear proteins. Brd4-LF is localized in the nuclear matrix while Brd4-SF is found in the nuclear envelope where it interacted with the LINC complex and known metastasis susceptibility proteins RRP1B and SIPA1. Given that these two isoforms reside in different subnuclear locations, we hypothesize that the isoforms bind to different sets of genes. To test this hypothesis we are utilizing the chromatin-immunoprecipitation sequencing (ChIP-seq) assay to characterize the genetic interactions associated with Brd4-SF. Identification of the Brd4-SF interacting genes will provide us with mechanistic insight into the underlying causes of the different metastatic outcomes promoted by the two isoforms, highlighting potential targets for future targeted therapies. Citation Format: Xinyi Zhu, Kent W. Hunter. Dissecting the effects of Brd4 short isoform on breast cancer progression. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr B29.
A Chemical Category-Based Prioritization Approach for Selecting 75 Per- and Polyfluoroalkyl Substances (PFAS) for Tiered Toxicity and Toxicokinetic Testing
Authors: Grace Patlewicz, Ann M. Richard, Antony J. Williams, Christopher M. Grulke, Reeder Sams, Jason Lambert, Pamela D. Noyes, Michael J. DeVito, Ronald N. Hines, Mark Strynar, Annette Guiseppi-Elie, Russell S. Thomas
Journal: Environmental Health Perspectives (2019)

Summary: Per- and polyfluoroalkyl substances (PFASs) are a group of fluorinated substances of interest to researchers, regulators, and the public due to their widespread presence in the environment. A few PFASs have comparatively extensive amounts of human epidemiological, exposure, and experimental animal toxicity data (e.g., perfluorooctanoic acid), whereas little toxicity and exposure information exists for much of the broader set of PFASs. Given that traditional approaches to generate toxicity information are resource intensive, new approach methods, including in vitro high-throughput toxicity (HTT) testing, are being employed to inform PFAS hazard characterization and further (in vivo) testing. The U.S. Environmental Protection Agency (EPA) and the National Toxicology Program (NTP) are collaborating to develop a risk-based approach for conducting PFAS toxicity testing to facilitate PFAS human health assessments. This article describes the construction of a PFAS screening library and the process by which a targeted subset of 75 PFASs were selected. Multiple factors were considered, including interest to the U.S. EPA, compounds within targeted categories, structural diversity, exposure considerations, procurability and testability, and availability of existing toxicity data. Generating targeted HTT data for PFASs represents a new frontier for informing priority setting. https://doi.org/10.1289/EHP4555