tbuckley/cabot-search huggingface dataset:
Pan-genomic analyses identify key <i>Helicobacter pylori</i> pathogenic loci modified by carcinogenic host microenvironments
Authors: Jennifer M Noto, Abha Chopra, John T Loh, Judith Romero-Gallo, M Blanca Piazuelo, Mark Watson, Shay Leary, Amber C Beckett, Keith T Wilson, Timothy L Cover, Simon Mallal, Dawn A Israel, Richard M Peek
Journal: Gut (2017)

Objective Helicobacter pylori is the strongest risk factor for gastric cancer; however, the majority of infected individuals do not develop disease. Pathological outcomes are mediated by complex interactions among bacterial, host and environmental constituents, and two dietary factors linked with gastric cancer risk are iron deficiency and high salt. We hypothesised that prolonged adaptation of H. pylori to in vivo carcinogenic microenvironments results in genetic modification important for disease. Design Whole genome sequencing of genetically related H. pylori strains that differ in virulence and targeted H. pylori sequencing following prolonged exposure of bacteria to in vitro carcinogenic conditions were performed. Results A total of 180 unique single nucleotide polymorphisms (SNPs) were identified among the collective genomes when compared with a reference H. pylori genome. Importantly, common SNPs were identified in isolates harvested from iron-depleted and high salt carcinogenic microenvironments, including an SNP within fur (FurR88H). To investigate the direct role of low iron and/or high salt, H. pylori was continuously cultured in vitro under low iron or high salt conditions to assess fur genetic variation. Exposure to low iron or high salt selected for the FurR88H variant after only 5 days. To extend these results, fur was sequenced in 339 clinical H. pylori strains. Among the isolates examined, 17% (40/232) of strains isolated from patients with premalignant lesions harboured the FurR88H variant, compared with only 6% (6/107) of strains from patients with non-atrophic gastritis alone (p=0.0034). Conclusion These results indicate that specific genetic variation arises within H. pylori strains during in vivo adaptation to conditions conducive for gastric carcinogenesis.
Opening the Black Box of Cognitive-Behavioural Case Management in Clients with Ultra-High Risk for Psychosis
Authors: Jessica A. Hartmann, Patrick D. McGorry, Stefanie J. Schmidt, G. Paul Amminger, Hok Pan Yuen, Connie Markulev, Gregor E. Berger, Eric Y.H. Chen, Lieuwe de Haan, Ian B. Hickie, Suzie Lavoie, Meredith J. McHugh, Nilufar Mossaheb, Dorien H. Nieman, Merete Nordentoft, Anita Riecher-Rössler, Miriam R. Schäfer, Monika Schlögelhofer, Stefan Smesny, Andrew Thompson, Swapna Kamal Verma, Alison R. Yung, Barnaby Nelson
Journal: Psychotherapy and Psychosomatics (2017)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Cognitive-behavioural therapy (CBT) is the first-choice treatment in clients with ultra-high risk (UHR) for psychosis. However, CBT is an umbrella term for a plethora of different strategies, and little is known about the association between the intensity and content of CBT and the severity of symptomatic outcome. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; A sample of 268 UHR participants received 6 months of CBT with case management (CBCM) in the context of the multi-centre NEURAPRO trial with monthly assessments of attenuated psychotic symptoms (APS). Using multilevel regressions and controlling for the initial severity of APS, the associations between (1) number of CBCM sessions received and severity of APS and (2) specific CBCM components and severity of APS were investigated. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; In month 1, a higher number of sessions and more assessment of symptoms predicted an increase in APS, while in month 3, a higher number of sessions and more monitoring predicted a decrease in the level of APS. More therapeutic focus on APS predicted an overall increase in APS. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Our findings indicate that the association between intensity/content of CBCM and severity of APS in a sample of UHR participants depends on the length of time in treatment. CBCM may positively impact the severity of APS later in the course of treatment. Therefore, it would seem important to keep UHR young people engaged in treatment beyond this initial period. Regarding the specific content of CBCM, a therapeutic focus on APS may not necessarily be beneficial in reducing the severity of APS, a possibility in need of further investigation.
AB0913 Agreement study and expert consensus for the clinical picture of chikv infection
Authors: JC Rueda, J-I Angarita, C Pinzon, AM Santos, E-L Saldarriaga, JM Rueda, DL Saaibi, E Forero, I Pelaez-Ballestas, PX Pavía, J Londono
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> World Health Organization suggested case definitions to suspect and diagnose chikungunya virus infection which are: possible case, probable case and confirmed case. Although useful, when applied in practice, its lack definition for specific joint involvement and absence of other systemic symptoms apart from fever, leads to a broad clinical spectrum which increases the need for laboratory tests. <h3>Objectives</h3> To establish agreement on clinical criteria of CHIKV infection based on clinical expertise of specialists from affected areas of Colombia and to develop a set of clinical criteria. <h3>Methods</h3> A group of specialists in rheumatology, epidemiology and bacteriology from different parts of Colombia with experience in diagnosis and treatment of CHIKV patients from the epidemic of 2014–2015 met to reach agreements on clinical characteristics of CHIKV infection. A series of questions were formulated and agreement in percentage was calculated on the following answers: totally agree, agree, not in agree or disagree, disagree and totally disagree. Agreement was set when the sum to the answers totally agree and agree or disagree and totally disagree of was ≥50%. When agreement was not reached, the moderator performed a discussion with the opinions of the confronting members of the group and after that reformulated the question. This procedure was made until agreement was reached. With the results a set of clinical criteria was proposed. <h3>Results</h3> The agreement percentage to the formulated questions are depicted in table 1. Disagreement was achieved with mucosal imvolvement (100%), G/I involvement (88%), and arthralgia and arthritis in shoulders (63% and 100%) and in elbows (100%). <h3>Conclusions</h3> Agreement was achieved in abrupt onset of symptoms, and the presence of fever, rash, myalgia, fatigue, and symmetrical arthritis or arthralgia of wrists, hands, knees, ankles and feet. A set of clinical criteria was proposed (figure 1). <h3>Disclosure of Interest</h3> None declared
Angiotensin II Type 1 receptor antibodies are associated with inflammatory cytokines and poor clinical outcomes in pediatric kidney transplantation
Authors: Meghan H. Pearl, Qiuheng Zhang, Miguel Fernando Palma Diaz, Jonathan Grotts, Maura Rossetti, David Elashoff, David W. Gjertson, Patricia Weng, Elaine F. Reed, Eileen Tsai Chambers
Journal: Kidney International (2017)
Abstract 13533: Delta-like 4/Notch Signaling Promotes Fatty Liver Disease in Mice
Authors: Tomiharu Niida, Ling Ling Lok, Chunyu Zheng, Jun-ichiro Koga, Daiju Fukuda, Alexander Banks, Masanori Aikawa
Journal: Circulation (2013)

Background:  Fatty liver disease is associated with inflammation and cardiometabolic syndrome. We previously demonstrated that the administration of a neutralizing antibody for Delta-like 4 (Dll4), the ligand of Notch signaling, improves key features of cardiometabolic disorders including macrophage activation, atherosclerosis, insulin resistance and hepatic lipid accumulation in mice. The present study has explored the mechanisms through which Dll4/Notch signaling promotes fatty liver.   Methods and Results:  We administered Dll4 antibody or control IgG (250 μg, i.p.,twice per week) in high-fat/high-cholesterol fed LDL receptor-deficient mice. Dll4 antibody suppressed prototypical Notch target genes (e.g., Hey1). While body weight and plasma lipid profile did not differ between groups, the livers of mice treated with Dll4 antibody for 4 weeks contained fewer lipids than those of control mice. Dll4 blockade reduced macrophage accumulation in the liver. Dll4 blockade tended to decrease hepatic expression of interleukin-1β (IL-1β), tumor necrosis factor-α, IL-6 and monocyte chemoattractant protein-1 (MCP-1), markers of pro-inflammatory M1 macrophages. Dll4 antibody inhibited expression of diacylglycerol acyltransferase 2, a gene involved in triglyceride synthesis. To further address the role of Dll4 in hepatic inflammation, we performed co-culture experiments of macrophages and hepatocytes. When we exposed the mouse hepatocyte cell line AML12 to conditioned media from Dll4-overexpressing RAW264.7 macrophage cells, mRNA levels of IL-6 and MCP-1 increased.   Conclusion:  Dll4/Notch signaling induces hepatocyte inflammation, offering a new therapeutic target for fatty liver.
Update on the Europrevall food allergen library: requirements for high quality allergens to improve in vitro diagnosis
Authors: K Hoffmann-Sommergruber, A Sancho, T Holzhauser, J Lidholm, Da Marknell, P Skov, S Alessandri, A Lovegrove, J Marsh, A Neubauer, I Lauer, G Hofstetter, C Radauer, G Reese, M Fernandez-Rivas, S Vieths, P Shewry, C Mills
Journal: Allergy (2009)
FRI0241 The effect of abatacept on cytokine profile in patients with rheumatoid arthritis
Authors: MA Borisova, GV Lukina, Y Sigidin, EL Luchihina, DE Karateev, A Novikov, E Alexandrova, E Aronova, S Glukhova, E Nasonov
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Pathological activation of T-cells with the overproduction of pro-inflammatory cytokines is playing a major role in the pathogenesis of rheumathoid arthritis (RA). The influence of the selective co-stimulation modulator abatacept (ABA) on the dynamics of cytokine profile in patients with RA is not fully understood. <h3>Objectives</h3> To assess the changes in cytokine profile in patients treated with ABA. <h3>Methods</h3> 44 patients with RA and an inadequate response to synthetic DMARDs or biologics were enrolled in the study. Most of them were middle aged females (46,9±13,9 years) with median RA duration 2 years (1,4–3), high disease activity (DAS28=5,2±0,8), RF-positive (80%) and ACPA-positive (79,5%). 16 healthy individuals were included in the study as control. The serum levels of IL-1, IL-6, IL-17, TNF-α, VEGF, IP-10 (pg/ml) were measured by ELISA immunoassay, YKL-40 by MicroVue immunoassay at baseline and 24 weeks. Disease activity was measured by DAS28, results were assessed every 12 weeks by EULAR criteria. ABA was administered intravenously every 4 weeks. <h3>Results</h3> Levels of IL-6 (2.4 (1,1–6,4) vs 0.7 (0,62–1,0), p=0,0002), YKL-40 (97 (68,4–97, 9) vs. 64 (52,4–107,5), p=0,03), IP-10 (21 (12,9–49,8) vs 14 (9,2–15,2), p=0,005) were significantly higher in patients with RA compared to control. ABA significant reduced disease activity already after 12 weeks of therapy (p&lt;0,05). After 24 weeks of ABA therapy good and moderate response by EULAR criteria was achieved in 86%, low disease activity by DAS28 in 52%. By the 6-th month ABA significant decreased levels of IL-6 (1,29 (0,9–2,2, p=0,0006), IP-10 (14 (7,5–28), p=0.007) as well as MMP3: before 30.1 (13–82), after 24 weeks 10 (7.4–55), p=0.0003 and RF: before 218 (9.6–187), after 24 weeks 159 (9.7–155), p=0.02. Lowering of the IL-6 (r=0,5) and IP-10 (r=0,32) levels were significantly (p&lt;0.05) associated with a decrease of DAS28. <h3>Conclusions</h3> ABA therapy leads to a significant reduction in serum levels of IL-6, IP-10, MMP3 and RF. The serum levels of IL-6 and IP-10 correlate with decrease activity of RA. <h3>Disclosure of Interest</h3> None declared
AB0754 Comparison of composite indices tailored for psoriatic arthritis treated with csdmards and bdmards: a longitudinal observational study
Authors: FM Perrotta, A De Socio, E Lubrano
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Remission or low disease activity should be the target of therapy in chronic inflammatory arthritis as well as in Psoariatic arthritis (PsA). In a complex disease such as PsA, several methods are available to define remission that comprise the assessment of different clinical features. <h3>Objectives</h3> The aim of this study was to compare the composite indices tailored for PsA in both patients treated with csDMARDs and bDMARDs. <h3>Methods</h3> Adult PsA patients classified with CASPAR criteria and with &gt;6 months follow up treated with first csDMARDs and bDMARDs were consecutively enrolled in our outpatient clinic. To assess disease activity, composite indices tailored for PsA namely DAPSA, cDAPSA, PASDAS, MDA (5/7) and MDA (7/7) were used. DAPSA and cDAPSA score ≤4, MDA 7/7 and PASDAS ≤1.9 identified remission while MDA 5/7and PASDAS &lt;3.2 the minimal disease activity and inactive disease criterion<sup>1–5</sup>. <h3>Results</h3> One hundred nine PsA patients were enrolled. Of this, 79 patients were in stable treatment with bDMARDs and 30 with csDMARDs. Overall, 28 (25.6%), 23 (21.1%), 19 (17.4%), 54 (49.5%), 13 (11.9%) and 35 (32.1%) PsA patients were in cDAPSA remission, DAPSA remission, MDA 7/7, MDA 5/7, PASDAS ≤1.9 and PASDAS &lt;3.2. Patients in bDMARDs had a significantly low median DAPSA, cDAPSA and PASDAS score than patients treated with csDMARDs (table 1). Overall, the concordance between the indices ranging from slight to good. <h3>Conclusions</h3> PsA patients in bDMARD are more likely to reach a status of MDA and remission in respect to csDMARDs. PASDAS ≤1.9 and MDA 7/7 seem to be stringent remission criteria. <h3>References</h3> Coates LC et al. Defining disease activity in psoriatic arthritis: a proposed objective target for treatment. Ann Rheum Dis 2010;69:48–53. Coates LC et al. Defining low disease activity states in psoriatic arthritis using novel composite disease instruments. J Rheumatol 2016;43:371–5. Helliwell PS et al. The development of candidate composite disease activity and responder indices for psoriatic arthritis (GRACE project). Ann Rheum Dis 2013;72:986–91. Schoels MM et al. Disease activity in psoriatic arthritis (PsA): defining remission and treatment success using the DAPSA score. Ann Rheum Dis 2016;75:811–8. Nell-Duxneuner VP et al. Evaluation of the appropriateness of composite disease activity measures for assessment of psoriatic arthritis. Ann Rheum Dis 2010;69:546–49. <h3>Disclosure of Interest</h3> None declared
FRI0032 Curative effect of camellia sinensis (CS) against opportunistic infection in vulnerable animal model of rheumatoid arthritis
Authors: A Tanwar, R Chawla, M Basu, R Arora, HA Khan
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rheumatoid arthritis (RA) is an autoimmune disease characterised by chronic inflammation of pro-inflammatory cytokines. Opportunistic infection plays a significant role in loss of tolerance to citrullinated proteins along with inflammatory progression of RA. Due to the immunosuppressive property of anti-rheumatic drugs, the patients of RA become highly vulnerable to microbial infections [1]. Thus, the present study employed an <i>in vivo</i> animal model to explore the holistic remedies for the effective treatment of RA. <h3>Objectives</h3> To study the immunomodulatory effect of <i>Camellia sinensis (Cs)</i> against inflammatory disorder <h3>Methods</h3> Study utilized collagen induced arthritis (CIA) rat model with <i>Salmonella typhimurium</i> (10<sup>8</sup> CFU/ml, p.o) as an opportunistic infectious agent which was introduced to enhance disease severity (on 21st day)[2]. Treatment with Cs at oral dose 400 mg/kg/body wt. (p.o) was started from 21st day for 14 days to explore its curative, anti-edematogenic effect and quantitation of oxidative stress markers. To validate biochemical changes, the histopathologiy and level of cytokines were also studied in joint tissue followed by 7 Tesla Magnetic Resonance Imaging (7T MRI). <h3>Results</h3> Treatment groups significantly restored the level of oxidative stress markers (Table-1). Furthermore, there was significant reduction in the number of bacterial colonies in blood and fecal matter in the treatment group as compared to infected group, while pro-inflammatory cytokine level of TNF-α, IL-1, IL-6 was significantly lower in joint tissue. Histological &amp; 7T-MRI changes in the treatment group included significant reduction of cartilage erosion &amp; pannus formation and there were no signs of inflammation in the small intestine as compared to arthritic and infected group (Figure 1). <h3>Conclusions</h3> The present study demonstrated that Cs has anti-inflammatory effect and could also be used as potent immunomodulator to manage RA. <h3>References</h3> R. Fleischmann, et al, Efficacy and safety of tofacitinib in patients with active rheumatoid arthritis: review of key Phase 2 studies, Int. J. Rheum. Dis. (2016). doi:10.1111/1756–185X.12901. D.D. Brand, et al Rosloniec, Collagen-induced arthritis, Nat. Protoc. 2 (2007) 1269–1275. doi:10.1038/nprot.2007.173. <h3>Acknowledgements</h3> Authors are greatful to VC, Jamia Hamdard and Director, INMAS for providing research facility and support. <h3>Disclosure of Interest</h3> None declared
THU0257 Enhanced activation of NLRP3 inflammasomes in patients with SJÖGREN's syndrome
Authors: JN Kim, S-K Kim, J-Y Choe
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> There has been data about pathogenic role of NLRP3 inflammasome in Sjögren9s syndrome. However, linkage between their clinical features and NLRP3 inflammasome has not been clearly defined. <h3>Objectives</h3> The aim of this study is to identify the association of NLRP3 inflammasome with clinical features in patients with primary Sjögren9s syndrome. <h3>Methods</h3> A total 25 female patients with Sjögren9s syndrome and gender-matched 25 healthy controls were consecutively enrolled. The mRNA expression for target genes including NLRP3, ASC, caspase-1, IL-1b, and IL-18 in peripheral blood mononuclear cells (PBMCs) were measured using real-time polymerase chain reaction. Serum IL-1b and IL-18 expression were also measured by ELISA method. Clinical information and disease activity and damage for Sjogren9s syndrome such as EULAR Sjögren9s Syndrome Disease Activity Index (ESSDAI) and Sjögren9s Syndrome Disease Damage Index (SSDDI) were collected at the time of enrollment. Statistical analysis were applied including Spearman9s correlation coefficient and Mann-Whitney t-test. <h3>Results</h3> Patients with Sjögren9s syndrome was found to be highly expressed in mRNA IL-1b and its protein, compared to controls (p&lt;0.001 and p=0.001, respectively). The mRNA levels of caspase-1 and ASC were significantly higher than those in controls (p=0.021 and p=0.008, respectively), but not mRNA level of NLRP3. The mRNA level of IL-1b is closely related with mRNA level of NLRP3 and ESR (r =0.549, p&lt;0.001 and r =0.577, p=0.003, respectively). Serum IL-1b protein expression in Sjögren9s syndrome was found to be associated with mRNA level of caspase-1. Based on SSDDI, patients with SSDDI ≥1 was older and higher IL-1b and NLRP3 mRNA expression, compared to those with SSDDI =0 (p=0.035, p=0.005, and p=0.016, respectively). <h3>Conclusions</h3> This study confirmed that activation of NLRP3 inflammasome might implicated the pathogenesis of Sjögren9s syndrome. <h3>Disclosure of Interest</h3> None declared
Photophobia in neurologic disorders
Authors: Yiwen Wu, Mark Hallett
Journal: Translational Neurodegeneration (2017)

Photophobia is a common symptom seen in many neurologic disorders, however, its pathophysiology remains unclear. Even the term is ambiguous. In this paper, we review the epidemiology and clinical manifestations of photophobia in neurological disorders, including primary headache, blepharospasm, progressive supranuclear palsy, and traumatic brain injury, discuss the definition, etiology and pathogenesis, and summarize practical methods of diagnosis and treatment.
CheckMate 649: A randomized, multicenter, open-label, phase III study of nivolumab (NIVO) + ipilimumab (IPI) or nivo + chemotherapy (CTX) versus CTX alone in patients with previously untreated advanced (Adv) gastric (G) or gastroesophageal junction (GEJ) cancer.
Authors: Markus H. Moehler, Yelena Yuriy Janjigian, Antoine Adenis, Jean-Sebastien Aucoin, Narikazu Boku, Ian Chau, James M. Cleary, Kynan Feeney, Fabio A. Franke, Guillermo Ariel Mendez, Michael Schenker, Mingshun Li, Erika Hitre, Felix Couture, Michalis Karamouzis, Pierre-Luc Etienne, Jaffer A. Ajani
Journal: Journal of Clinical Oncology (2018)

TPS192 Background: Pts with adv G/GEJ cancer have an OS of ≈ 1 y, indicating an unmet medical need for new first-line treatments. Expression of PD-L1 is observed in up to 40% of pts with G/GEJ cancer and is associated with poor prognosis. In the randomized phase 3 ATTRACTION-2 study, NIVO demonstrated superior overall survival vs placebo with a 38% reduction of the risk of death (median OS, 5.3 vs 4.1 mo; HR, 0.62 P&lt; 0.0001) and increased the OS rate at 12 mo (27% vs 12%; Boku N et al ESMO 2017) in pts with adv CTX-R (≥ 2 lines) G/GEJ cancer. In the phase 1/2 CheckMate-032 study in pts with CTX-R G/GEJ/esophageal cancer (79% ≥ 2 prior Tx lines), NIVO 1 mg/kg + IPI 3 mg/kg had a manageable safety profile and resulted in 24% ORR (40% ORR in pts with PD-L1 + tumors), a median OS of 6.9 mo, and a 35% OS rate at 12 mo (Janjigian Y et al ASCO 2017). In the phase 1 CheckMate-012 trial, NIVO + CTX had clinical activity and manageable safety in pts with NSCLC (Rizvi NA et al J Clin Oncol 2016). These positive results support investigation of NIVO, NIVO + IPI, and NIVO + CTX in earlier lines of treatment for G/GEJ cancer. The open-label, phase 3 CheckMate 649 trial will evaluate NIVO + IPI and NIVO + CTX vs CTX alone as first-line treatment for pts with adv G/GEJ cancer (NCT02872116). Methods: 1266 pts aged ≥ 18 y with untreated, inoperable adv/metastatic G/GEJ cancer (histologically confirmed adenocarcinoma) regardless of PD-L1 status will be randomized to receive either NIVO + IPI, NIVO + CTX (capecitabine/oxaliplatin [XELOX] or fluorouracil/leucovorin/oxaliplatin [FOLFOX]), or investigator choice of XELOX or FOLFOX. Tumor tissue for determination of PD-L1 status (Dako assay) must be provided from ≤ 6 mo before study treatment. No prior systemic treatment, including HER2 inhibitors, are allowed. Pts with known HER2 + status, suspected autoimmune disease, grade &gt; 1 peripheral neuropathy, or active infection are excluded. Primary endpoint is OS in pts with PD-L1 + (≥ 1%) tumors. Other endpoints include OS in all pts; PFS and time to symptom deterioration in all pts and in pts with PD-L1 + tumors; and safety. Clinical trial information: NCT02872116.