tbuckley/cabot-search huggingface dataset:
RETRACTED ARTICLE: Activation of LncRNA TINCR by H3K27 acetylation promotes Trastuzumab resistance and epithelial-mesenchymal transition by targeting MicroRNA-125b in breast Cancer
Authors: Huaying Dong, Jianguo Hu, Kejian Zou, Mulin Ye, Yuanwen Chen, Chengyi Wu, Xin Chen, Mingli Han
Journal: Molecular Cancer (2019)

Abstract Background Trastuzumab resistance followed by metastasis is a major obstacle for improving the clinical outcome of patients with advanced human epidermal growth factor receptor 2-positive (HER-2+) breast cancer. While long non-coding RNAs (lncRNAs) can modulate cell behavior, the contribution of these RNAs in trastuzumab resistance and metastasis of HER-2+ breast cancer is not well known. In this study, we sought to identify the regulatory role of lncRNA in trastuzumab resistance and accompanied Epithelial-mesenchymal Transition (EMT) process in advanced HER-2+ breast cancer. Methods Trastuzumab-resistant SKBR-3-TR and BT474-TR cell lines were established by grafting SKBR-3 and BT474 cells into mouse models and subjected to trastuzumab treatment. LncRNA microarray followed by quantitative reverse transcription PCR (qRT-PCR) was carried out to verify the differentially expressed lncRNAs. Western blotting, bioinformatics analysis, immunofluorescence assay and immunoprecipitation assays (ChIP and RIP) were performed to identify the involvement and functional interactions between H3K27 acetylation and terminal differentiation-induced non-coding RNA (TINCR) or between TINCR and its downstream genes including miR-125b , HER-2 and Snail-1 . In addition, a series of in vitro and in vivo assays were performed to assess the functions of TINCR. Results An increase in both, IC 50 value of trastuzumab and EMT was observed in the established trastuzumab-resistant cell lines. The expression level of TINCR was significantly increased in trastuzumab-resistant cells when compared with sensitive cells. Knockdown of TINCR reversed the trastuzumab resistance and the acquired EMT in these cells. TINCR was detected in the cytoplasm of breast cancer cells and could sponge miR-125b, thereby releasing HER-2 and inducing trastuzumab resistance. In addition, Snail-1 was found to be the target gene of miR-125b and overexpression of Snail-1 could reverse the suppressed migration, invasion, and EMT caused by TINCR silencing. The upregulation of TINCR in breast cancer was attributed to the CREB-binding protein (CBP)-mediated H3K27 acetylation at the promoter region of TINCR. Clinically, HER-2+ breast cancer patients with high TINCR expression levels were associated with poor response to trastuzumab therapy and shorter survival time. Conclusion TINCR could promote trastuzumab resistance and the accompanied EMT process in breast cancer. Therefore, TINCR might be a potential indicator for prognosis and a therapeutic target to enhance the clinical efficacy of trastuzumab treatment.
Abstract 15825: Inter-reader Concordance and Variations in Interpretation of Post Resuscitation ECG in Abnormal vs Normal Metabolic Milieus Following Out-of-hospital Cardiac Arrest
Authors: Gautam R Shroff, David F Miranda, Bradley A Bart, Yader Sandoval, Holly Rodin, Stephen W Smith
Journal: Circulation (2015)

Background: Among survivors of out of hospital cardiac arrest (OHCA), the post resuscitation 12-lead electrocardiogram (ECG) is a widely used tool to identify acute thrombotic coronary occlusion (ACTO) and for appropriate triage to the catheterization laboratory. It is unknown how a post-resuscitation abnormal metabolic milieu impacts ECG accuracy. We studied inter-reader concordance in ECG interpretation as well as same-patient variation in interpretation between abnormal (A) and normal (N) metabolic milieus (MM). Methods: We performed a retrospective analysis of 125 consecutive patients with OHCA with a shockable rhythm undergoing coronary angiography in a single institution. Patients with AMM were defined as pH &lt;7.1, K &lt;2.8 or &gt;6 mEq/L, vasoactive drug use or lactate &gt;2 ng/ml. All post resuscitation ECGs recorded in both AMM and NMM for each patient prior to any invasive intervention were blindly interpreted by 2 experienced readers, classified into two categories: diagnostic for ATCO (ATCO +) and not diagnostic for ATCO (ATCO -) and compared to angiographic ATCO. The Cohen’s kappa scale was used to measure concordance. Results: Concordance between readers was 0.69 (95% CI 0.56-0.84) in AMM and 0.82 (95% CI 0.64-0.99) in NMM. Of 35 ECGs interpreted as diagnostic for ATCO (+) in AMM, 27 (77%) were reclassified as ATCO (-) after metabolic correction. Among 90 ECGs initially diagnosed as ATCO (-) in AMM, 2 (2%) were reclassified as ATCO (+) whereas 88 (98%) remained as ATCO (-) in NMM. Most ATCO (-) ECGs were in the setting of angiographic ATCO; see table. Conclusions: Despite acceptable inter-reader concordance (moderate in AMM, high in NMM) between experienced ECG readers, a significant proportion of angiographic ATCO was missed on post resuscitation ECGs. A high percentage of patients with angiographic ATCO were reclassified on ECG from ATCO (+) in AMM to ATCO (-) in NMM, suggesting possible interim blunting/resolution of typical diagnostic ECG changes in NMM.
OP0095 Soluble cd163 as a potential biomarker in systemic sclerosis
Authors: C. Frantz, S. Pezet, J. Avouac, Y. Allanore
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Recent accumulating evidences indicate a crucial role of macrophage lineage in the pathogenesis of fibrotic diseases including systemic sclerosis (SSc). CD163 is a surface marker expressed by M2 macrophages that accumulate during the healing phase of acute inflammation. It is actively released from the plasma membrane in response to certain inflammatory stimuli and enters the circulation in its soluble form (sCD163). <h3>Objectives</h3> In this study, we aimed to evaluate the performance of serum and urinary sCD163 concentrations as possible biomarker in SSc. <h3>Methods</h3> Urine and serum samples were obtained from SSc patients, fulfilling the 2013 ACR/EULAR classification criteria for SSc, and age- and sex-matched controls. Serum and urinary sCD163 concentrations were measured by commercially available ELISA kit (R and D systems) and evaluated for their significance as potential biomarkers. Statistical analysis was carried out using Mann-Whitney U test and the relationship between parameters was statistically examined by Spearman's rank test. <h3>Results</h3> Two hundred and three SSc patients were included, 163 (80%) were female, with a mean ±standard deviation (SD) age of 59±13 years and a mean ±SD disease duration of 12±9 years. Eighty-one (41%) patients had diffuse cutaneous SSc and mean ±SD mRSS was 6.6±7.7. Lung fibrosis on imaging was observed in 33% of the patients, 7% had pulmonary arterial hypertension, 44% had history of digital ulcers and 41% were taking immunosuppressive therapy. Control group consisted of 47 age- and sex-matched patients with non-inflammatory diseases, being osteoporosis for the very large majority. Serum sCD163 levels were significantly higher in SSc patients compared with controls (mean ±SD: 529±251 vs 385.1±153 ng/ml; p&lt;0.001). Urinary sCD163 concentrations in SSc patients were also higher than those in controls, but this did not reach significance (236.9±498 vs 176.2±173 ng/mg uCr; p=0.580). When looking at the subsets according to skin disease or disease duration, no difference could be identified. Furthermore, when the organ involvements were investigated, no subpopulation could be identified as having higher concentrations. <h3>Conclusions</h3> To our knowledge this is the first evaluation of both serum and urinary sCD163 levels in SSc. Our results show a significant difference for sera values that should be prioritised for further studies as compared to urinary concentrations conversely to what has been described in lupus. Our results further support that the M2 macrophages/CD163 signalling system may play a role in the pathogenesis of SSc. However, further studies are required to address the exact role of CD163 in the pathogenesis of SSc and to determine whether it could help in the risk-stratification of the patients in this heterogeneous disease. <h3>Disclosure of Interest</h3> None declared
AB1062 Risk factors for mortality after tuberculous arthritis
Authors: Y.-C. Chen
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background:</h3> Tuberculosis arthritis is an emerging international problem despite advances in the methods of diagnosis and treatment; it is still prevalent in developing countries and on the increase in developed ones. <h3>Objectives</h3> Patients with tuberculous (TB) arthritis increase mortality This study investigated to search for the risk factors of mortality in TB arthritis. <h3>Methods</h3> We retrospectively reviewed patients with TB arthritis who admit to Kaohsiung Chang Gang Memorial Hospital Jauary 2001 to December 2015. The long-term outcomes of the patients were analysed. <h3>Results</h3> A total of 281 patients (124 females and 17 males; mean age: 64.86±14.51 years) were enrolled. At the end of the study, 229 patients were alive and 52 had died. The mean follow up period were 8.31±4.52 years. The patients who were old age (p=0.004, HR=1.038, 95% CI 1.012–1.065), liver disease (p=0.036, HR=2.571, 95% CI 1.062–6.224) and underlying cancer (p=0.001, HR=3.640, 95% CI 1.725–7.679) had a significantly higher mortality rate than others. <h3>Conclusions</h3> When we treat TB arthritis, old age and underlying liver and cancer history should paid more attention to decrease the risk of mortality. <h3>Reference</h3> [1] LongQ, LiY, WangYetal(2008)BarrierstoaccessingTBdiagnosis forrural-to-urbanmigrantswithchroniccoughinChongqing, China: a mixed methods study. BMC Health Serv Res8:202 <h3>Acknowledgements</h3> We thank Kaohsiung CGMH for data support <h3>Disclosure of Interest</h3> None declared
AB0377 Are co-morbidities during rheumatoid arthritis different from those in ankylosing spondyloarthritis ?
Authors: M.A. El Achek, M. Jguirim, A. Farhat, M. Braham, I. Bejia, M. Touzi, S. Zrour, N. Bergaoui
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Patients with inflammatory rheumatic diseases are certainly not unscathed from a lot of comorbidities which may be due to the systemic inflammatory activity of rheumatic diseases themselves, immune dysfunction, or iatrogenic, they may also occur independently. Cardiovascular morbidity remains one of the most important to detect and is increased during these diseases. So are there significant differences between co-morbidities associated with rheumatoid arthritis (RA) and those with ankylosing spondyloarthritis (AS)? <h3>Objectives</h3> To highlight the difference between comorbidities in RA and AS. <h3>Methods</h3> This is a retrospective study of 111 patients followed for RA ACR 1987 criteria), and 60 patients followed for AS, compiled between January 2005 and December 2016. <h3>Results</h3> The mean age of patients with RA was 51.04 years [18–80 years] with a sex ratio (M/F) of 0.18. The average duration of disease progression was 6.54 years [0–29 years]. The mean age of patients with AS was 40.4 years [18–61] with a sex ratio (M/F) of 19. The average duration of disease progression was 16.8 years [1–45 years]. About cardiovascular comorbidities, 16.2% of patients with RA and 5.1% with AS were diagnosed with high blood pressure. Dyslipidemia was found in 2.7% of patients with RA and in 0% with AS. 31.5% with RA and 21.7% of AS have overweight and obesity was illustrated in 22.5% of RA and 11.7% of AS. Heart and coronary failure were documented in 5.4% of RA and 1.7% of AS. Likewise renal failure in 3,6% of RA and 3.4% of AS. Diabetes was found in 18% of RA and 10% of AS. Hypothyroidism in 5.4% of RA and 1.7% of AS. Gout attack in 0.9% of RA and 0% with AS and osteoporosis in 21.3% of RA and 40% of AS. <h3>Conclusions</h3> Our study concluded at the frequency of comorbidities and mostly cardiovascular in rheumatoid arthritis compared with AS. Osteoporosis is also more common in our studied population with RA, although not rare with our patients with AS. This can be explained by the prescription of corticosteroid therapy in RA. <h3>Disclosure of Interest</h3> None declared
THU0446 Usefulness of colour doppler ultrasonography in follow up of giant cell arteritis
Authors: H. Mukoyama, K. Nishimura, K. Kadoba, R. Saito, D. Waki, T. Yokota
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Colour doppler ultrasonography (CDU) in temporal arteries (TA) is useful for diagnosis and follow-up of giant cell arteritis (GCA).<sup>1</sup> However, the usefulness of CDU in carotid arteries (CA) for follow-up of GCA is not fully understood.<sup> 2</sup> <h3>Objectives</h3> We investigated retrospectively relationship between clinical features and vessel wall thickness of TA and CA on CDU at baseline and during follow-up. <h3>Methods</h3> We recruited patients with newly diagnosed GCA in our hospital from January in 2004 to July in 2017. Among 35 patients, both of TA and CA were evaluated by CDU before and after treatment in 14 patients (four male and 10 female). Trained ultrasonographers and rheumatologists evaluated the CDU findings. Vessel wall thickness was evaluated at thickest portion of parietal or frontal ramus of TA, where biopsy was often performed. Intima-media thickness (IMT) of CA was also evaluated at thickest portion in each carotid artery. <h3>Results</h3> Average age was 73.2±11.3 years old. Follow-up periods after starting treatment were 244±149 weeks. All patients were diagnosed as GCA according to ACR criteria (1990) or temporal artery biopsy. Twelve patients were complicated with polymyalgia rheumatica (PMR) meeting EULAR/.ACR classification criteria (2012). All patients were treated with oral glucocorticoids (0.2 to 1.0 mg/kg prednisolone, 0.886 mg/kg on average). Immunosuppressants were added in four patients (methotrexate; n=3, tacrolimus; n=1). Aspirin was prescribed in nine patients. Eleven patients (78.6%) had circumferential hypoechoic vessel wall thickness (halo sign) of TA at baseline, and halo signs dissapeared in eight patients during follow-up. Average of vessel wall thickness significantly decreased from 0.665 mm to 0.311 mm (p=0.0016). The vessel wall thickness apparently increased in two patients out of three on clinical relapse, but it didn't increase in those who kept remission. Graphical changes consistent with vasculitis in CA were observed in six patients, who showed hypoechoic thick intima and media on ultrasound or integration of FDG on PET/CT. Average of IMT in CA decreased from 1.167 mm to 0.883 mm (p=0.090) during follow-up in patients with vasculitis on CA. IMT changed little in patients without vasculitis on CA. Improvement rate was significantly higher in CA-involved patients than in CA-non-involved patients (p=0.043). IMT increased during follow-up in two CA-non-involved patients. Difference in B/A between CA involved and non-involved: p=0.043 (Mann-Whitney U test) <h3>Conclusions</h3> CDU of temporal arteries is useful for follow-up of GCA. CDU of carotid arteries has limited usefulness only in CA-involved patients. <h3>References</h3> [1] Suelves AM, et al. Clin Ophthalmol. 2010; Nov 25;4:1383–4. [2] Hafner F, et al. Eur J Clin Invest2014; 44(3):249–256. <h3>Disclosure of Interest</h3> None declared
Reconstruction of full-length circular RNAs enables isoform-level quantification
Authors: Yi Zheng, Peifeng Ji, Shuai Chen, Lingling Hou, Fangqing Zhao
Journal: Genome Medicine (2019)

Currently, circRNA studies are shifting from the identification of circular transcripts to understanding their biological functions. However, such endeavors have been limited by large-scale determination of their full-length sequences and also by the inability of accurate quantification at the isoform level. Here, we propose a new feature, reverse overlap (RO), for circRNA detection, which outperforms back-splice junction (BSJ)-based methods in identifying low-abundance circRNAs. By combining RO and BSJ features, we present a novel approach for effective reconstruction of full-length circRNAs and isoform-level quantification from the transcriptome. We systematically compared the difference between the BSJ-level and isoform-level differential expression analyses using human liver tumor and normal tissues and highlight the necessity of deepening circRNA studies to the isoform-level resolution. The CIRI-full software can be accessed at https://sourceforge.net/projects/ciri .
Efficacy and safety of <scp>PAC</scp> ‐14028 cream – a novel, topical, nonsteroidal, selective <scp>TRPV</scp> 1 antagonist in patients with mild‐to‐moderate atopic dermatitis: a phase <scp>II</scp> b randomized trial
Authors: Y.W. Lee, C.‐H. Won, K. Jung, H.‐J. Nam, G. Choi, Y.‐H. Park, M. Park, B. Kim
Journal: British Journal of Dermatology (2019)

Transient receptor potential vanilloid subfamily, member 1 (TRPV1) may play an important role in pruritus and inflammation induction in atopic dermatitis (AD). The treatment effect of TRPV1 antagonist via topical application in patients with AD remains unknown.To assess the clinical efficacy and safety of PAC-14028, a TRPV1 antagonist, via topical application in patients with AD.In this 8-week, phase IIb, randomized, double-blind, multicentre, vehicle-controlled study, patients with mild-to-moderate AD were randomized to receive PAC-14028 cream 0·1%, 0·3%, 1·0% or vehicle cream twice daily. The primary efficacy end point was the Investigator's Global Assessment (IGA) success rate defined as the percentage of patients with an IGA score of 0 or 1 at week 8. The secondary efficacy end points included the severity Scoring of Atopic Dermatitis (SCORAD) index and Eczema Area and Severity Index (EASI) 75/90.A total of 194 patients were enrolled. IGA success rates at week 8 were 14·58% for vehicle cream, 42·55% for PAC-14028 cream 0·1% (P = 0·0025 vs. vehicle), 38·30% for PAC-14028 cream 0·3% (P = 0·0087 vs. vehicle) and 57·45% for PAC-14028 cream 1·0% (P < 0·001 vs. vehicle). In particular, statistically significant differences were found between the vehicle and treatment groups in the IGA success rates with two-grade improvement. The SCORAD index, EASI 75/90, sleep disturbance score and pruritus visual analogue scale showed a trend towards improvement. No significant safety issues were reported.PAC-14028 cream may be an effective and safe treatment modality for the treatment of patients with mild-to-moderate AD.
Bone marrow transplantation for adolescents and young adults with sickle cell disease: Results of a prospective multicenter pilot study
Authors: Lakshmanan Krishnamurti, Donna S. Neuberg, Keith M. Sullivan, Naynesh R. Kamani, Allistair Abraham, Federico Campigotto, Wandi Zhang, Thabat Dahdoul, Laura De Castro, Suhag Parikh, Nitya Bakshi, Ann Haight, Kathryn L. Hassell, Rebekah Loving, Joseph Rosenthal, Shannon L. Smith, Wally Smith, Marcus Spearman, Kristen Stevenson, Catherine J. Wu, Christina Wiedl, Edmund K. Waller, Mark C. Walters
Journal: American Journal of Hematology (2019)

We conducted a multicenter pilot investigation of the safety and feasibility of bone marrow transplantation (BMT) in adults with severe sickle cell disease (SCD) (NCT 01565616) using a reduced toxicity preparative regimen of busulfan (13.2 mg/kg), fludarabine (175 mg/m 2 ) and thymoglobulin (6 mg/kg) and cyclosporine or tacrolimus and methotrexate for graft‐vs‐host disease (GVHD) prophylaxis. Twenty‐two patients (median age 22 years; range 17‐36) were enrolled at eight centers. Seventeen patients received marrow from an HLA‐identical sibling donor and five patients received marrow from an 8/8 HLA‐allele matched unrelated donor. Before BMT, patients had stroke, acute chest syndrome, recurrent pain events, were receiving regular red blood cell transfusions, or had an elevated tricuspid regurgitant jet (TRJ) velocity, which fulfilled eligibility criteria. Four patients developed grades II‐III acute GVHD (18%) and six developed chronic GVHD (27%) that was moderate in two and severe in one patient. One patient died of intracranial hemorrhage and one of GVHD. Nineteen patients had stable donor chimerism, 1‐year post‐transplant. One patient who developed secondary graft failure survives disease‐free after a second BMT. The one‐year overall survival and event‐free survival (EFS) are 91% (95% CI 68%‐98%) and 86% (95% CI, 63%‐95%), respectively, and 3‐year EFS is 82%. Statistically significant improvements in the pain interference and physical function domains of health‐related quality of life were observed. The study satisfied the primary endpoint of 1‐year EFS ≥70%. This regimen is being studied in a prospective clinical trial comparing HLA‐matched donor BMT with standard of care in adults with severe SCD (NCT02766465).
AB1055 Brucellar spondylodiscitis: do mri signs of severity influence the duration of the treatment
Authors: O. Saidane, I. Oueslati, R. Tekaya, A. Ben Tekaya, I. Mahmoud, L. Abdelmoula
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Brucellar spondylodiscitis is rarely associated with neurological involvement. Magnetic resonance imaging has high sensitivity for detecting the paravertebral and epidural extension <h3>Objectives</h3> The purpose of this study was to determine the influence of the MRI severity signs on the treatment duration <h3>Methods</h3> A retrospective study of 27 patients with Brucellar spondylodiscitis during a period of 17 years [2000–2016] was performed. Diagnosis was made on clinical presentation, laboratory findings, radiographic evidence and Brucellar seroagglutination tests. Three patients underwent CT scans and a spinal MRI was carried out for 24 patients. All of them received antibiotic treatment based on a combination of Rifampicin and Doxycycline of varying duration <h3>Results</h3> Ten women and 17 men were included. The mean age was 54 years. Twenty-six patients suffered from spinal pain (96.3%) and 12 patients had radiculalgia (44.4%). The lumbar spine was the most frequently involved region (59,3%), followed by the dorsal spine (18.5%) and the cervical spine (11.1%). The neurological examination showed no abnormalities. Spinal MRI showed paravertebral abscess in 56.5% of cases. Seventeen patients (73,9%) had epiduritis and 9 patients (39,9%) had spinal cord compression on the MRI. An abnormal signal of the spinal cord was observed in 2 cases (8,7%). All patients received a combination of Rifampicin and Doxycycline. The mean duration of the antimicrobial treatment was 8 months. There was no statistically significant association between the occurrence of abscesses, epiduritis, spinal cord compression, abnormal signal of the spinal cord on the MRI and the duration of treatment (p=0.935, p=0.929, p=0.379, p=0.889 respectively). <h3>Conclusions</h3> MRI of the spine frequently revealed signs of severity in brucellar spondylodiscitis patients, although without clinical expression. Despite their severity these signs did not result in a longer period of antibiotic therapy <h3>Disclosure of Interest</h3> None declared