tbuckley/cabot-search huggingface dataset:
The pathological effects of naturally occurring antibodies on human breast cancer
Authors: Yue-Jin Wen, Anne T. Mancino, Thomas Kieber-Emmons
Journal: Cancer Research (2004)

4704  Introduction: Despite the activation of lymphocytes by tumor antigens, the immune system is often inefficient in eliminating tumor cells and preventing progressive tumor growth. It has been reported that naturally occurring antibodies against over-expressed or mutant proteins in tumor cells occur at high frequency in the serum of breast cancer patients. However, spontaneous regression of breast cancer is rare and in contrast, the presence of the antibody in patient serum may correlate with poor prognosis. The purpose of this research was to study the role of naturally occurring human antibody in controlling human breast cancer cell survival. Methods: Total RNA isolated from the PBMC of a patient with breast cancer was used for RT-PCR and the positive PCR products were ligated into a pComb3 display phage for constructing a recombinant cDNA expression library of human IgG Fab. Primary breast cancer cell lysate was used to screen the antibody library. The tumor antigen binding ability of antibodies was tested by ELISA analysis. Breast cancer cell lines were treated with antibodies at various concentrations. The cancer cell growth was measured by 3H-Thymidine uptake assay and the cell apoptosis measured by FACS with FITC annexin V. Results: A cDNA expression library containing 1.2 x 105 primary human IgG Fab clones has been successfully constructed. Twenty clones were screened from the library; which represented 14 different transcripts by sequence homology search from the GenBank data bases. ELISA was performed on three clones; all showed stronger binding to antigens from primary breast cancer and breast cancer cell lines than to one from normal breast tissue. Functional studies showed that antibodies exhibited different biological effects on breast cancer cell survival in vitro when used at various concentrations. At low level (2 μg/ml) some clones stimulated growth of MDA-MB-231 breast cancer cell line but had no effect on MCF-7 and SK-BR-3 cell growth in vitro, indicating that these antibodies can promote breast cancer cell growth by binding to some tumor antigen that expressed in various levels among different cell lines. Treatment with high level of these clones (20 μg/ml) had no effect to promote cancer cell growth of above three cell lines. However, two tested antibody clones showed strong effect to block etoposide-induced cell apoptosis in all three above cell lines, which occurred with a Fab concentration as low as 2 μg/ml and reached to a complete blocking with a high level at 20 μg/ml. Conclusions: Our studies provide evidence to explain why naturally occurring immune response is often inefficient in eliminating tumor cells and preventing progressive growth. These findings suggest that serum auto-antibodies to tumor-associated antigens may initially contribute to cancer promotion when immune response developed at a low level and finally involve in tumor immune escaping with a high level of immune response.
AB0387 Is rheumatoid arthritis a risk factor for dementia ?
Authors: O. Saidane, M. Sellami, I. Mahmoud, A. Ben Tekaya, H. Ajlani, R. Tekaya, L. Abdelmoula
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> A direct link between chronic inflammation and dementia was well established by different epidemiological studies. Nevertheless, data on impaired cognitive function during rheumatoid arthritis (RA) are still controversial and doubtful. <h3>Objectives</h3> To assess the association of RA and impaired cognitive function. <h3>Methods</h3> This is a case-control study involving patients with RA according to ACR/EULAR criteria 2010 and randomly-chosen controls by matching on age and gender during 4 months. The Mini Mental State Examination (MMSE) was used to evaluate cognitive functions. Cognitive impairment was defined by a MMSE score lower than 24 (or 26 in patients with primary education). The activity of RA was evaluated using Disease activity score (DAS28). <h3>Results</h3> A total of 20 RA patients (12 women and 8 men) with a mean age of 52.6 years [31–72] and 20 healthy controls (15 women and 5 men) with a mean age of 55.8 years [50–77] were included. No significant differences for age or gender between RA patients and controls were observed. Rheumatoid factor was positive in 95% of cases. Mean disease duration was 3.2 years [2–6]. Thirteen RA patients had active disease with mean DAS28 of 4.73. Three-quarters of RA patients had been treated with methotrexate and only 8 patients received biotherapy: 5 anti TNF alpha and 3 Rituximab. Forty percent of RA group were illiterate versus 49% in control group. Eleven RA patients (55%) had a normal cognitive function versus 15 (75%) in control group. A moderate cognitive impairment (mean MMSE of 18.62) was found in 8 RA patients (40%) and 2 controls (10%) primarily affecting constructional apraxia. No severe cognitive impairment was found in the 2 groups. Significant positive association was found between cognitive impairment and RA (p=0.001). Patients with RA using methotrexate had higher risk for cognitive impairment comparing to patients using biotherapy (p=0.02). <h3>Conclusions</h3> Our study highlighted a serious psychological expression of RA which was early onset of cognitive impairment and dementia. This is a possible effect of inflammation and vascular disease caused by RA. <h3>Disclosure of Interest</h3> None declared
Accounting for Disparities in the Evaluation of Medicare Alternative Payment Plans
Authors: Cheryl K. Zogg, Gezzer Ortega, Adil H. Haider
Journal: JAMA Surgery (2019)

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Cholemic Nephropathy Causes Acute Kidney Injury and Is Accompanied by Loss of Aquaporin 2 in Collecting Ducts
Authors: Jan Hinrich Bräsen, Young‐Seon Mederacke, Jessica Schmitz, Kateryna Diahovets, Abedalrazag Khalifa, Björn Hartleben, Fermín Person, Thorsten Wiech, Eric Steenbergen, Anika Großhennig, Michael P. Manns, Roland Schmitt, Ingmar Mederacke
Journal: Hepatology (2019)

Impairment of renal function often occurs in patients with liver disease. Hepatorenal syndrome is a significant cause of acute kidney injury (AKI) in patients with cirrhosis (HRS-AKI, type 1). Causes of non-HRS-AKI include cholemic nephropathy (CN), a disease that is characterized by intratubular bile casts and tubular injury. As data on patients with CN are obtained primarily from case reports or autopsy studies, we aimed to investigate the frequency and clinical course of CN. We identified 149 patients who underwent kidney biopsy between 2000 and 2016 at the Department of Gastroenterology, Hepatology and Endocrinology at Hannover Medical School. Of these, 79 had a history of liver disease and deterioration of renal function. When applying recent European Association for the Study of the Liver criteria, 45 of 79 patients (57%) presented with AKI, whereas 34 patients (43%) had chronic kidney disease (CKD). Renal biopsy revealed the diagnosis of CN in 8 of 45 patients with AKI (17.8%), whereas none of the patients with CKD was diagnosed with CN. Univariate analysis identified serum bilirubin, alkaline phosphatase, and urinary bilirubin and urobilinogen as predictive factors for the diagnosis of CN. Histological analysis of AKI patients with normal bilirubin, elevated bilirubin, and the diagnosis of CN revealed loss of aquaporin 2 (AQP2) expression in collecting ducts in patients with elevated bilirubin and CN. Biopsy-related complications requiring medical intervention occurred in 4 of 79 patients (5.1%). Conclusion: CN is a common finding in patients with liver disease, AKI, and highly elevated bilirubin. Loss of AQP2 in AKI patients with elevated bilirubin and CN might be the result of toxic effects of cholestasis and in part be responsible for the impairment of renal function.
Disentangling a complex nationwide Salmonella Dublin outbreak associated with raw-milk cheese consumption, France, 2015 to 2016
Authors: Aymeric Ung, Amrish Y. Baidjoe, Dieter Van Cauteren, Nizar Fawal, Laetitia Fabre, Caroline Guerrisi, Kostas Danis, Anne Morand, Marie-Pierre Donguy, Etienne Lucas, Louise Rossignol, Sophie Lefèvre, Marie-Léone Vignaud, Sabrina Cadel-Six, Renaud Lailler, Nathalie Jourdan-Da Silva, Simon Le Hello
Journal: Eurosurveillance (2019)

On 18 January 2016, the French National Reference Centre for Salmonella reported to Santé publique France an excess of Salmonella enterica serotype Dublin (S. Dublin) infections. We investigated to identify the source of infection and implement control measures. Whole genome sequencing (WGS) and multilocus variable-number tandem repeat analysis (MLVA) were performed to identify microbiological clusters and links among cases, animal and food sources. Clusters were defined as isolates with less than 15 single nucleotide polymorphisms determined by WGS and/or with identical MLVA pattern. We compared different clusters of cases with other cases (case-case study) and controls recruited from a web-based cohort (case-control study) in terms of food consumption. We interviewed 63/83 (76%) cases; 2,914 controls completed a questionnaire. Both studies' findings indicated that successive S. Dublin outbreaks from different sources had occurred between November 2015 and March 2016. In the case-control study, cases of distinct WGS clusters were more likely to have consumed Morbier (adjusted odds ratio (aOR): 14; 95% confidence interval (CI): 4.8-42) or Vacherin Mont d'Or (aOR: 27; 95% CI: 6.8-105), two bovine raw-milk cheeses. Based on these results, the Ministry of Agriculture launched a reinforced control plan for processing plants of raw-milk cheeses in the production region, to prevent future outbreaks.
Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases
Authors: Yana Vinogradova, Carol Coupland, Julia Hippisley-Cox
Journal: BMJ (2019)

Abstract Objective To assess the association between risk of venous thromboembolism and use of different types of hormone replacement therapy. Design Two nested case-control studies. Setting UK general practices contributing to the QResearch or Clinical Practice Research Datalink (CPRD) databases, and linked to hospital, mortality, and social deprivation data. Participants 80 396 women aged 40-79 with a primary diagnosis of venous thromboembolism between 1998 and 2017, matched by age, general practice, and index date to 391 494 female controls. Main outcome measures Venous thromboembolism recorded on general practice, mortality, or hospital records. Odds ratios were adjusted for demographics, smoking status, alcohol consumption, comorbidities, recent medical events, and other prescribed drugs. Results Overall, 5795 (7.2%) women who had venous thromboembolism and 21 670 (5.5%) controls had been exposed to hormone replacement therapy within 90 days before the index date. Of these two groups, 4915 (85%) and 16 938 (78%) women used oral therapy, respectively, which was associated with a significantly increased risk of venous thromboembolism compared with no exposure (adjusted odds ratio 1.58, 95% confidence interval 1.52 to 1.64), for both oestrogen only preparations (1.40, 1.32 to 1.48) and combined preparations (1.73, 1.65 to 1.81). Estradiol had a lower risk than conjugated equine oestrogen for oestrogen only preparations (0.85, 0.76 to 0.95) and combined preparations (0.83, 0.76 to 0.91). Compared with no exposure, conjugated equine oestrogen with medroxyprogesterone acetate had the highest risk (2.10, 1.92 to 2.31), and estradiol with dydrogesterone had the lowest risk (1.18, 0.98 to 1.42). Transdermal preparations were not associated with risk of venous thromboembolism, which was consistent for different regimens (overall adjusted odds ratio 0.93, 95% confidence interval 0.87 to 1.01). Conclusions In the present study, transdermal treatment was the safest type of hormone replacement therapy when risk of venous thromboembolism was assessed. Transdermal treatment appears to be underused, with the overwhelming preference still for oral preparations.
Abstract P099: A Methylome- and Transcriptome-Wide Study of Dietary Fructose Intake in Humans
Authors: Stella Aslibekyan, Anh N Do, Marguerite R Irvin, Bertha A Hidalgo, Degui Zhi, Hemant K Tiwari, Devin M Absher, Jose M Ordovas, Donna K Arnett
Journal: Circulation (2017)

Background: Animal model studies reported robust associations between fructose intake, a known determinant of metabolic health across species, and DNA methylation/ gene expression patterns. To date, these associations have not been comprehensively investigated in humans. Methods: Using DNA methylation data on ~470,000 cytosine-phosphate-guanine (CpG) sites in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN, n=991) quantified in CD4+ T-cells, we have interrogated the cross-sectional relationships between fructose intake (ascertained using a validated food frequency questionnaire) and epigenome-wide methylation. We fit linear mixed models adjusted for age, sex, study site, technical covariates (fixed effects) and family relatedness (random effect). We have supplemented the methylation analyses with a transcriptome-wide scan on 98 unrelated GOLDN participants with available RNASeq data in whole blood. For the RNASeq data analysis, we used negative binomial models of read counts as a function of fructose intake, adjusted for age, sex, study site, technical covariates (including differential white blood cell counts). Results and Conclusions: The top loci differentially methylated with respect to fructose intake mapped to SNED1 (regression coefficient +/- SE= 0.002 +/- 0.0005, P=5x10-6) and FARSB (regression coefficient +/- SE= 0.002 +/- 0.0004, P=5x10-6) on chromosome 2. SNED1 is an insulin responsive transcription factor that has previously been shown to be downregulated in the setting of metabolic syndrome. FARSB encodes an aminoacyl-tRNA synethetase implicated in cell growth. Additionally, two genes reached transcriptome-wide significance in the RNASeq analysis: MTATP8P1 (P=1x10-7) and PDXDC1 (P=6x10-7). Sequence variation in PDXDC1 (pyridoxal-dependent decarboxylase isoform) has previously been linked to lipid metabolism, while MTATP8P1 is a pseudogene for a mitochondrially encoded ATP synthase. Upon future replication and functional validation, our preliminary findings offer promising insights into the link between fructose intake and metabolic health.
THU0710-HPR Qualities of participation as described by people with early ra in working age
Authors: A. Sverker, I. Thyberg, E. Valtersson, M. Björk, G. Östlund, S. Hjalmarsson
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Early diagnosis and medication has been effective but impairments, activity limitations, and participation restrictions are still evident in RA. To be able to participate despite RA is a recurrent goal for persons with early RA as well as in standards of care. Nevertheless, patients' perceptions of what kind of situations constitute an experience of participation are seldom explored in research. Though, participation ladders illustrating people's influence on matters that concern them have earlier been described in social sciences in relation to citizens' rights, and children's rights. <h3>Objectives</h3> To describe when and how people with early RA describe a positive sense of participation in everyday life, including to categorise the qualities of these experiences. <h3>Methods</h3> This study is part of the Swedish early RA project "TIRA". Critical incidents technique was used in the design of the semi structured interviews. In all, 59 patients (age 18–63 years) were interviewed; 25 men and 34 women. The study has been approved by the local ethics committee and has followed the ethical standards of the Helsinki Declaration. Content analysis was used to identify meaning units with descriptions related to the aim, which were sorted based on type of situations described, and later on categories based of quality aspects of participation were developed. <h3>Results</h3> The qualities of participation as described by people with RA were arranged as a ladder with the following steps; 1. Being part of a group, 2. Carry out activities in company, 3. Share everyday chores and responsibilities, 4. Have influence on actions, 5. Give direction of goals, 6. Share decision making. Participation was experienced with others at specific moments when the positive feeling described was <i>being part of a group</i> in relations with family, friends, in working life and in recreation and social life. For instance, both women and men described the experience of participation in the work group, especially when given the possibility to<i> have influence on actions,</i> or the possibility to <i>give direction of goals</i> in the management of work or in organised activities. They described a positive feeling of participation if <i>sharing everyday chores and responsibilities</i> with someone and when just <i>carrying out activities</i> in company with others at work, in domestic life, and in sports and leisure activities. The interviewees also described how the sense of participation was particular intensive when <i>sharing decision making</i>. <h3>Conclusions</h3> Participation from an individual's perspective is about belonging and having influence that mediates a positive feeling of being included and that you matter as a person. The results are important when using participation as a goal in the clinical care. <h3>Disclosure of Interest</h3> None declared
Cancer Theranosis: Multimodal Cancer Theranosis Using Hyaluronate‐Conjugated Molybdenum Disulfide (Adv. Healthcare Mater. 1/2019)
Authors: Myeong‐Hwan Shin, Eun‐Yeong Park, Seulgi Han, Ho Sang Jung, Do Hee Keum, Geon‐Hui Lee, Taeyeon Kim, Chulhong Kim, Ki Su Kim, Seok Hyun Yun, Sei Kwang Hahn
Journal: Advanced Healthcare Materials (2019)

In article number 1801036, Ki Su Kim, Sei Kwang Hahn, and co-workers develop hyaluronate conjugated molybdenum disulfide (HA-MoS2 conjugate) for targeted cancer theranosis. The HA-MoS2 conjugate can be successfully used for both photoacoustic and fluorescence imaging. In addition, upon NIR light illumination, HA-MoS2 conjugate enables highly effective target-specific photothermal cancer therapy. Taken together, HA-MoS2 conjugate appears to show a great potential for various theranostic applications.
FRI0068 Ultrasonographic subclinical cardiovascular findings in hispanic ra patients: a case-control study
Authors: J.R. Azpiri-López, D.A. Galarza-Delgado, I.J. Colunga-Pedraza, A.H. Guillén-Lozoya, J.A. Dávila-Jiménez, E.E. Abundis-Márquez
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Patients with RA have a 1.5–2.0 fold increased risk of developing coronary artery disease (CAD) compared with the general population. Patients with RA are typically managed by several physicians, and coordination of care may be suboptimal.<sup>1</sup> The leading cause of death in RA-patients is atherosclerotic cardiovascular disease (ASCVD).<sup>2</sup> Carotid artery and heart evaluation by ultrasound is a useful tool for detection of cardiovascular conditions. <h3>Objectives</h3> To compare the presence of subclinical cardiovascular conditions among Mexican-mestizo RA patients and matched controls. <h3>Methods</h3> Design: Observational, cross-sectional, case-control study. Patients of 40 to 75 years old who fulfilled the 2010 ACR/EULAR and/or the 1987 ACR classification criteria for RA were consecutively enrolled. Patients with previous ASCVD or any other rheumatic disease were excluded. Two board-certified radiologist performed and assessed all carotid ultrasounds (cUS) and two board- certified cardiologist performed and assessed transthoracic echocardiography (TTE) according to guidelines of the American Society of Echocardiography. ASE, 2016 <h3>Results</h3> The RA patients showed higher prevalence of cardiovascular risk conditions with respect to control population, such as concentric remodelling/hypertrophy, diastolic dysfunction, valve regurgitation and Carotid intima media thickness (CIMT) (See table 1). <h3>Conclusions</h3> This study reinforces the usefulness of cUS and TTE as a tool in the evaluation of cardiovascular conditions in RA patients. A systematic search of extra-articular and cardiovascular comorbidities should be mandatory in all RA patients. <h3>References</h3> [1] Crowson CS, Liao KP, Davis JM, Solomon DH, Matteson EL, Knutson KL, Gabriel SE. Rheumatoid arthritis and cardiovascular disease. American heart journal2013;166(4):622–628. [2] Avina-Zubieta JA, Thomas J, Sadatsafavi M, Lehman AJ, Lacaille D. Risk of incident cardiovascular events in patients with rheumatoid arthritis: a meta-analysis of observational studies. Annals of the rheumatic diseases2012;71(9):1524–9. <h3>Acknowledgements</h3> None <h3>Disclosure of Interest</h3> None declared
SP0181 Highlights from the health professionals in rheumatology sessions
Authors: F. Estevez-Lopez
Journal: Annals of the Rheumatic Diseases (2018)

The EULAR congress is one of the biggest events in the world of rheumatology. In order to accommodate all the diversity of topics, several sessions take place at the same time in different rooms. It is very hard to be in all the sessions, poster tours, social meetings, and other interesting learning events. Indeed, it is common to have the feeling of wanting to be at several places simultaneously, which unfortunately is impossible. The purpose of this session is to summarize the information presented and discussed during the Health Professionals in Rheumatology programme at the 2018 EULAR Congress celebrated in Amsterdam (The Netherlands). Attending to this "Highlights" session is a second opportunity to do not miss the most relevant works presented in the Health Professionals in Rheumatology programme. <h3>Disclosure of Interest</h3> None declared