tbuckley/cabot-search huggingface dataset:
Safety and Efficacy of Intravenous Golimumab in Patients With Active Psoriatic Arthritis
Authors: Arthur Kavanaugh, M. Elaine Husni, Diane D. Harrison, Lilianne Kim, Kim Hung Lo, Jocelyn H. Leu, Elizabeth C. Hsia
Journal: Arthritis & Rheumatology (2017)

Objective To evaluate the safety and efficacy of intravenous ( IV ) golimumab treatment in psoriatic arthritis (PsA). Methods In this phase III , randomized, double‐blind, placebo‐controlled trial, patients were randomly assigned to receive IV placebo (n = 239) or golimumab at 2 mg/kg (n = 241) at weeks 0, 4, 12, and 20. The primary end point was the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR 20 response) at week 14. Controlled secondary end points included change from baseline in Health Assessment Questionnaire disability index ( HAQ DI ) score at week 14, proportions of patients with ACR 50 and ACR 70 responses and ≥75% improvement on the Psoriasis Area and Severity Index (a PASI 75 response) at week 14, and change from baseline at week 24 in the total modified Sharp/van der Heijde score ( SHS ) with modifications for patients with PsA. Results At week 14, an ACR 20 response was achieved by 75.1% of patients in the golimumab group compared with 21.8% of patients in the placebo group ( P &lt; 0.001). Greater proportions of golimumab‐treated patients had an ACR 50 response (43.6% versus 6.3%), an ACR 70 response (24.5% versus 2.1%), and a PASI 75 response (59.2% versus 13.6%) at week 14 ( P &lt; 0.001 for all). Patients in the golimumab group had greater mean changes at week 14 in HAQ DI score (–0.60 versus –0.12; P &lt; 0.001). At week 24, the mean change in total PsA‐modified SHS was –0.4 in the golimumab group and 2.0 in the placebo group ( P &lt; 0.001). Through week 24, 40.6% of patients in the placebo group and 46.3% of patients in the golimumab group had ≥1 adverse event ( AE ); infections were the most common type. Conclusion Patients receiving IV golimumab at 2 mg/kg had significantly greater improvements in the signs and symptoms of PsA and less radiographic progression through week 24. AE s were consistent with those seen with other anti–tumor necrosis factor agents.
08.41 cloning of gingival tissue b cells from an acpa+ ra patient with periodontitis
Authors: Natalia Sherina, Khaled Amara, Natalie Sippl, Daniel RamsköLd, Johanna Steen, Lena Israelsson, Monika Hansson, Annika van Vollenhoven, Kaja Eriksson, Tulay Yucel-Lindberg, Vivianne Malmström, Karin Lundberg
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rheumatoid arthritis (RA) is characterised by autoantibodies to citrullinated proteins (ACPA). Smoking and specific HLA alleles are well-established risk factors for ACPA+RA, and more recently <i>Porphyromonas gingivalis</i>, a major cause of periodontitis (PD), has been linked to ACPA+RA. Our ambition with this study is to clone ACPA-specific B-cells from gingival tissue of patients suffering from both PD and RA, in order to demonstrate that citrulline-specific B-cells, previously only detected in RA joints and circulation, may also reside in gingival tissue. <h3>Materials and methods</h3> Gingival tissue-derived single CD19+ B-cells from an ACPA+RA patient with PD were sorted by flow cytometry. Immunoglobulin (Ig) variable region genes were sequenced and expressed to generate recombinant monoclonal antibodies (mAbs). These mAbs will subsequently be screened for reactivity towards citrullinated antigens by ELISA and an antigen multiplex assay. <h3>Results</h3> We successfully isolated 480 CD19+ B-cells from the gingival tissue, and to this date, we have analysed 110 variable heavy chain Ig genes (<i>IGHV</i>). Ig gene sequences analysis demonstrated that the B-cell repertoire was predominantly polyclonal, although two clonally related B-cell populations (approximately 2%) were detected. Compared to healthy controls, RA/PD B-cells showed decrease in VH3 and JH5 genes, and increase in VH4, JH4 and JH6. By individual VH gene segments, IGHV4–31 was overrepresented compared to controls (p&lt;0.0001). Conversely, IGHV1-2, IGHV3-23, and IGHV4-34 were under-represented (p&lt;0.0001). Interestingly, antibodies with positively charged IGHV CDR3 regions, a feature associated with auto-reactivity, were enriched in gingival tissue. Alignment of VH sequences to their closest germline counterparts revealed that RA/PD B-cells exhibited extensive mutations in the <i>IGH</i> CDR regions and higher levels of somatic mutations in the V gene segments compared to controls (p&lt;0001). These observations suggest that the B-cell response in the gingival tissue was antigen-driven. We have so far expressed 47 mAbs, and we are currently screening these for citrulline-reactivity. <h3>Conclusions</h3> We have been able to successfully isolate and clone a number of gingival-tissue-derived B-cells. Based on the hypothesis that the ACPA-response may be initiated at mucosal surfaces such as gingival tissue, we now have the tools available to more directly address this etiological question.
Effect of non-monetary incentives on uptake of couples' counselling and testing among clients attending mobile HIV services in rural Zimbabwe: a cluster-randomised trial
Authors: Euphemia L Sibanda, Mary Tumushime, Juliet Mufuka, Sue Napierala Mavedzenge, Stephano Gudukeya, Sergio Bautista-Arredondo, Karin Hatzold, Harsha Thirumurthy, Sandra I McCoy, Nancy Padian, Andrew Copas, Frances M Cowan
Journal: The Lancet Global Health (2017)

Couples' HIV testing and counselling (CHTC) is associated with greater engagement with HIV prevention and care than individual testing and is cost-effective, but uptake remains suboptimal. Initiating discussion of CHTC might result in distrust between partners. Offering incentives for CHTC could change the focus of the pre-test discussion. We aimed to determine the impact of incentives for CHTC on uptake of couples testing and HIV case diagnosis in rural Zimbabwe.In this cluster-randomised trial, 68 rural communities (the clusters) in four districts receiving mobile HIV testing services were randomly assigned (1:1) to incentives for CHTC or not. Allocation was not masked to participants and researchers. Randomisation was stratified by district and proximity to a health facility. Within each stratum random permutation was done to allocate clusters to the study groups. In intervention communities, residents were informed that couples who tested together could select one of three grocery items worth US$1·50. Standard mobilisation for testing was done in comparison communities. The primary outcome was the proportion of individuals testing with a partner. Analysis was by intention to treat. 3 months after CHTC, couple-testers from four communities per group individually completed a telephone survey to evaluate any social harms resulting from incentives or CHTC. The effect of incentives on CHTC was estimated using logistic regression with random effects adjusting for clustering. The trial was registered with the Pan African Clinical Trial Registry, number PACTR201606001630356.From May 26, 2015, to Jan 29, 2016, of 24 679 participants counselled with data recorded, 14 099 (57·1%) were in the intervention group and 10 580 (42·9%) in the comparison group. 7852 (55·7%) testers in the intervention group versus 1062 (10·0%) in the comparison group tested with a partner (adjusted odds ratio 13·5 [95% CI 10·5-17·4]). Among 427 (83·7%) of 510 eligible participants who completed the telephone survey, 11 (2·6%) reported that they were pressured or themselves pressured their partner to test together; none regretted couples' testing. Relationship unrest was reported by eight individuals (1·9%), although none attributed this to incentives.Small non-monetary incentives, which are potentially scalable, were associated with significantly increased CHTC and HIV case diagnosis. Incentives did not increase social harms beyond the few typically encountered with CHTC without incentives. The intervention could help achieve UNAIDS 90-90-90 targets.The study was funded by the UK Department for International Development, Irish AID, and Swedish SIDA, through Population Services International Zimbabwe under the Integrated Support Program.
Researchers need access to NHS data for effective redesign of clinical pathways
Authors: Ruth Gilbert, Peter Dutey-Magni
Journal: BMJ (2017)

Sood and colleagues argue for clinical informatics leaders in NHS organisations to accelerate the development of digitally enhanced models of care.1 We think that safe and effective redesign of clinical pathways and better use of health data requires not just digital leadership but also academic involvement. 

Researchers are needed to generate and publish robust evidence on the benefits and …
Addendum to “Subgroups of Castration-resistant Prostate Cancer Bone Metastases Defined Through an Inverse Relationship Between Androgen Receptor Activity and Immune Response” [Eur Urol 2017;71:776–87]
Authors: Erik Bovinder Ylitalo, Elin Thysell, Emma Jernberg, Marie Lundholm, Sead Crnalic, Lars Egevad, Pär Stattin, Anders Widmark, Anders Bergh, Pernilla Wikström
Journal: European Urology (2017)
Effect of Diethylstilbestrol on Mammary Tumor Formation in Strain C3H Mice Fed a Low Cystine Diet
Authors: White, Florence R., White, Julius
Journal: JNCI Journal of the National Cancer Institute (1944)

Journal Article Effect of Diethylstilbestrol on Mammary Tumor Formation in Strain C3H Mice Fed a Low Cystine Diet Get access Florence R. White, Florence R. White assistant biochemist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar Julius White Julius White senior biochemist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 4, Issue 4, February 1944, Pages 413–415, https://doi.org/10.1093/jnci/4.4.413 Published: 01 February 1944
03.22 Vitamin d utilises different pathways to inhibit th17 differentiation dependent on the maturation stage of the cd4<sup>+</sup> t cell
Authors: Wendy Dankers, Jan Piet van Hamburg, Wida Razawy, Nadine Davelaar, Anne-Marie Mus, Patrick Asmawidjaja, Johannes van Leeuwen, Louis Boon, Edgar Colin, Erik Lubberts
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> In many human autoimmune diseases, including rheumatoid arthritis (RA), vitamin D is associated with disease suppression. Furthermore, experimental collagen-induced arthritis (CIA) is prevented by 1,25(OH)<sub>2</sub>D<sub>3</sub> supplementation, the active form of vitamin D. Since high doses of 1,25(OH)<sub>2</sub>D<sub>3</sub> in humans can cause serious side effects, understanding the mechanism behind the suppression may lead to new therapeutic targets. Although currently this mechanism is not known, it is hypothesised that Th17 cells play an important role in the immunomodulatory effect of vitamin D. Here we study the effect of 1,25(OH)<sub>2</sub>D<sub>3</sub> on the differentiation of Th17 cells and the underlying mechanism in the context of the autoimmune-mediated CIA model. <h3>Materials and methods</h3> DBA/1 mice were immunised with type II collagen (CII) in complete Freund's adjuvant. 10 days after immunisation the mice were sacrificed and spleens were harvested. Total CD4+, naïve CD4+ or effector CD4+ T cells were isolated and cultured for 3–7 days under Th17 polarising conditions with or without 1,25(OH)<sub>2</sub>D<sub>3</sub>. <h3>Results</h3> 1,25(OH)<sub>2</sub>D<sub>3</sub> inhibits Th17 differentiation in total CD4+ T cells in CII-immunised mice. Interestingly, 1,25(OH)<sub>2</sub>D<sub>3</sub> induces IL-4 and IL-10 in these cells. Therefore we investigated whether the effect of 1,25(OH)<sub>2</sub>D<sub>3</sub> on Th17 differentiation was dependent on IL-4 or IL-10. In both naïve and effector CD4+ T cells from CII-immunised mice, 1,25(OH)<sub>2</sub>D<sub>3</sub> inhibited Th17 differentiation as demonstrated by decreased IL-17A, IL-17F and IL-22. Blocking IL-10 did not prevent this effect in either subsets. However, in the effector cells, but not the naïve cells, blocking IL-4 partially reduced the effect of 1,25(OH)<sub>2</sub>D<sub>3</sub> on Th17 differentiation. <h3>Conclusions</h3> 1,25(OH)<sub>2</sub>D<sub>3</sub> similarly inhibits Th17 differentiation of naïve and effector CD4+ T cells from CII-immunised mice. However, only the inhibition in effector cells, not in naïve cells, is partially dependent on IL-4. These data show that 1,25(OH)<sub>2</sub>D<sub>3</sub>utilises different pathways to inhibit Th17 differentiation, depending on the maturation stage of the CD4+ T cell.
Measurement tools for mental health problems and mental well-being in people with severe or profound intellectual disabilities: A systematic review
Authors: Samantha Flynn, Leen Vereenooghe, Richard P. Hastings, Dawn Adams, Sally-Ann Cooper, Nick Gore, Chris Hatton, Kerry Hood, Andrew Jahoda, Peter E. Langdon, Rachel McNamara, Chris Oliver, Ashok Roy, Vasiliki Totsika, Jane Waite
Journal: Clinical Psychology Review (2017)
Evaluation of Integrated CLL Scoring System (ICSS) in 420 Patients with Chronic Lymphocytic Leukemia
Authors: Andrea Visentin, Federica Frezzato, Silvia Imbergamo, Valentina Trimarco, Veronica Martini, Filippo Severin, Flavia Raggi, Laura Bonaldi, Edoardo Scomazzon, Leonardo Martinello, Francesco Piazza, Monica Facco, Gianpietro Semenzato, Livio Trentin
Journal: Blood (2016)
MicroRNA-150 controls differentiation of intraepithelial lymphocytes through TGF-β receptor II regulation
Authors: Sang-Hwan Seo, Min Seong Jang, Doo-Jin Kim, Seok-Min Kim, Se-Chan Oh, Cho-Rok Jung, Yunji Park, Sang-Jun Ha, Haiyoung Jung, Young-Jun Park, Suk Ran Yoon, Inpyo Choi, Tae-Don Kim
Journal: Journal of Allergy and Clinical Immunology (2017)
02.43 Role of anti-peptide citrullinated antibodies in cardiovascular disease in rheumatoid arthritis
Authors: Raquel Hernández, Julia Uceda, Sergio A Rodriguez, Carmen V Almeida, Jose L Marenco
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rheumatoid arthritis (RA) is a systemic autoimmune disease of unknown and multifactorial aetiology, whose prevalence is around 1% of the adult population. It most commonly affects women between the 4th and 6th decade. Patients with RA have an increased cardiovascular morbidity and mortality (CV) being the main cause of death. "Systematic Coronary Risk Evaluation" (SCORE) allows us to estimate the risk of death from cardiovascular disease as 10 years. <h3>Objectives</h3> To evaluate whether the presence of anti-peptide citrullinated (ACPA) antibodies is associated with increased frequency of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA) or with greater SCORE. <h3>Methods</h3> observational, analytical case-control study nested in a cohort of patients diagnosed with AR follow-up in the Valme hospital area. Cases were considered the patients who have developed a myocardial infarction or cerebrovascular or ischaemic heart disease and controls RA patients without CVD. They all determined ACPA levels, the classic cardiovascular <h3>Results</h3> A total of 260 patients were included from a database of 327 patients with AR. In 67 of these, we coudn't get the main variables of the sutdy, and were excluded. <h3>Conclusions</h3> In our sample, unlike other published studies, we found no differences in the occurrence of cardiovascular events, or the SCORE in patients ACPA (+) v ACPA (-). While subgroups of patients with ACPA + have a greater tendency to be treated with biological therapy. This lack of differences could also be explained by the early implantation of both primary and secondary prevention of cardiovascular disease in patients with RA. <h3>References</h3> Results from systematic screening for cardiovascular risk in outpatients with rheumatoid arthritis in accordance with the EULAR recommendations; ARD Online First, published on July 12, 2013 as 10.1136/annrheumdis-2013-20368
08.31 Unravelling the role of il33/st2l axis on sustained ifn-a production in systemic lupus erythematosus
Authors: Spiridon Georgakis, Garyfallia Papadaki, Irene Gergianaki, Prodromos Sidiropoulos, Panagiotis Verginis, Aikaterini Gkirtzimanaki, George Bertsias
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> In Systemic Lupus Erythematosous (SLE), extracellular DNA (as in extracellular chromatin traps or immune complexes) combined with alarmins/danger- associated molecular patterns promote the production of IFNa by plasmatocytoid dendritic cells (pDCs).<sup>123</sup> IL-33 is a cell necrosis-derived alarmin with immunostimulatory properties which depend on the context of immune cells and inflammatory milieu.<sup>4</sup> We hypothesised that IL-33 might augment the interferogenic potential of extracellular DNA in SLE. <h3>Materials and methods</h3> Human peripheral blood pDCs were isolated from SLE patients and healthy individuals and IL-33 receptor (ST2L) expression was determined by flow cytometry and RT-PCR. Oligonucleotides (CpG ODNs) were administered with/without recombinant IL-33 and IFN-a production was measured by RT-PCR and ELISA. IL-33 decoration of neutrophil extracellular traps (NETs) was examined using immunofluorescence and confocal microscopy. pDCs were stimulated with NETs-containing supernatants with/without recombinant IL-33 and IFN-a production was measured. <h3>Results</h3> Spontaneous-released NETs from peripheral blood neutrophils of active SLE patients were decorated with IL-33 to larger extent compared to healthy-derived NETs. Circulating CD303<sup>+</sup>/CD123<sup>+</sup> pDCs from active SLE patients exhibited membrane expression of ST2L albeit at lower levels compared to healthy pDCs (p&lt;0,05). Combined CpG/IL-33 activation of pDCs promoted enhanced IFN-a mRNa and protein levels compared to CpG alone (p&lt;0,05). Moreover, co-administration of IL-33 and NET-containing supernatants on pDCs significantly enhanced IFN-a protein and mRNA levels (p&lt;0,05). <h3>Conclusions</h3> The alarmin IL-33 produced by SLE NETing neutrophils promotes IFN-a production by pDCs therefore contributing to autoimmune inflammatory responses. <h3>Topic</h3> Autoimmune inflammation <h3>References</h3> Garcia-Romo, G. S., S. Caielli, B. Vega, <i>et al</i>. "Netting Neutrophils Are Major Inducers of Type I IFN Production in Paediatric Systemic Lupus Erythematosus."<i>Science Translational Medicine</i> 2011;3:73. Lande R., Gregorio J., Facchineti V., <i>et al.</i> ''Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide.''<i>Nature</i>2007;<b>449.</b> Tian, Jane, Ana Maria Avalos, Su-Yau Mao, <i>et al</i>. "Toll-like Receptor 9–dependent Activation by DNA-containing Immune Complexes Is Mediated by HMGB1 and RAGE."<i>Nature Immunology</i> 2007;<b>8.5</b>:487–96 Duan, Lihua, Jie Chen, Feili Gong, <i>et al</i>. "The Role of IL-33 in Rheumatic Diseases." <i>Clinical and Developmental Immunology</i>2013:1–5.
Consolidation with high-dose chemotherapy for responding patients to standard chemotherapy in advanced, metastatic soft tissue sarcoma (STS): A randomized trial from FNCLCC-French Sarcoma Group
Authors: N. N. Binh, C. Chevreau, N. Penel, J. Bay, J. Coindre, S. Mathoulin-Pelissier, I. Ray-Coquard, A. Italiano, J. Genève, J. Blay
Journal: Journal of Clinical Oncology (2009)

10505 Background: Whether high dose (HD) chemotherapy improves disease-free (DFS) or overall (OS) survival has been suggested in phase II trial, but never explored in a randomized setting. This randomized, open, phase III study was designed to assess whether or not an HD chemotherapy with peripheral blood stem cells (PBSC) would improve OS in patients with advanced or metastatic STS responding to MAID chemotherapy. Methods: Pts aged 18 to 65 and with advanced STS were enrolled. After 4 courses of MAID, patients in PR or CR, or in whom complete surgical removal of all lesions was performed, were proposed for randomisation between 2 more cycles of MAID (control arm) vs 1 MAID followed by an intensification with MICE, ie: mesna (3.6g/m2, d1–5), ifosfamide (4g/m2, d1–4), carboplatin (UCA5, d2–4) and etoposide (300mg/m2, d1–4), followed by PBSC (HD arm). The primary endpoint was OS and the study was designed to detect by logrank test a 25% difference between the arms. Results: From 03/00 to 06/08, 266 patients were included and 87 were randomised (15 centres); low accrual and new treatment concepts lead to an IDMC in 11/08 who analysed 45 treated in the control arm (41 with full treatment) and 40 in the HD arm [only 21 received MICE, because consent withdrawal (6), insufficient PBSC harvest (5), tumor reprogression (4)]. Baseline characteristics (pts and tumors) were similar between treatment arms. With a 39 months follow-up, 25 pts were alive in the control arm, and 19 in the HD arm. The 3 years OS was 45.5% for control arm versus 35.8 for HD arm (HR = 1.12; 95% CI 0.58, 2.14; p = 0.72 Intention to treat analysis); PFS was 29.9% and 12.1 respectively (HR = 1.48; 95% CI 0.87, 2.53; p = 0.14). Higher rate of grade 3 - 4 hematologic (87% vs 46%), and digestive toxicity (33% vs 0%) were observed in the HD arm. Two treatment-related deaths occurred, both in the HD arm. Conclusions: In this study, HD chemotherapy for STS patients didn't improve OS and DFS. Consolidations with new concepts have to be explored. [Table: see text]
Randomized Comparison of Adjunctive Cilostazol Versus High Maintenance Dose Clopidogrel in Patients With High Post-Treatment Platelet Reactivity
Authors: Young-Hoon Jeong, Seung-Whan Lee, Bong-Ryong Choi, In-Suk Kim, Myung-Ki Seo, Choong Hwan Kwak, Jin-Yong Hwang, Seong-Wook Park
Journal: Journal of the American College of Cardiology (2009)