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Anti-Topoisomerase I Antibody

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181. <i>Clostridioides difficile</i>: diagnosis and treatments. Full Text available with Trip Pro

<i>Clostridioides difficilei>: diagnosis and treatments. Clostridioides difficile (formerly Clostridium) is a major cause of healthcare associated diarrhea, and is increasingly present in the community. Historically, C difficile infection was considered easy to diagnose and treat. Over the past two decades, however, diagnostic techniques have changed in line with a greater understanding of the physiopathology of C difficile infection and the use of new therapeutic molecules. The evolution (...) , and the challenge is to target the right population with the adapted therapeutic molecule. In multiple recurrences, fecal microbiota transplantation is recommended. New approaches, including antibodies, vaccines, and new molecules are already available or in the pipeline, but more data are needed to support the inclusion of these in practice guidelines. This review aims to provide a baseline for clinicians to understand and stratify their choice in the diagnosis and treatment of C difficile infection based

2019 BMJ

182. Effects of <i>Helicobacter pylori</i> treatment and vitamin and garlic supplementation on gastric cancer incidence and mortality: follow-up of a randomized intervention trial. Full Text available with Trip Pro

Effects of <i>Helicobacter pylorii> treatment and vitamin and garlic supplementation on gastric cancer incidence and mortality: follow-up of a randomized intervention trial. To assess the effects of Helicobacter pylori treatment, vitamin supplementation, and garlic supplementation in the prevention of gastric cancer.Blinded randomized placebo controlled trial.Linqu County, Shandong province, China.3365 residents of a high risk region for gastric cancer. 2258 participants seropositive (...) for antibodies to H pylori were randomly assigned to H pylori treatment, vitamin supplementation, garlic supplementation, or their placebos in a 2×2×2 factorial design, and 1107 H pylori seronegative participants were randomly assigned to vitamin supplementation, garlic supplementation, or their placebos in a 2×2 factorial design.H pylori treatment with amoxicillin and omeprazole for two weeks; vitamin (C, E, and selenium) and garlic (extract and oil) supplementation for 7.3 years (1995-2003).Primary

2019 BMJ

183. Genomic Mismatch at <i>LIMS1</i> Locus and Kidney Allograft Rejection. Full Text available with Trip Pro

Genomic Mismatch at <i>LIMS1i> Locus and Kidney Allograft Rejection. In the context of kidney transplantation, genomic incompatibilities between donor and recipient may lead to allosensitization against new antigens. We hypothesized that recessive inheritance of gene-disrupting variants may represent a risk factor for allograft rejection.We performed a two-stage genetic association study of kidney allograft rejection. In the first stage, we performed a recessive association screen of 50 (...)  = 6.5×10-5). In the combined analysis (discovery cohort plus replication cohorts), the risk genotype was associated with a higher risk of rejection than the nonrisk genotype (hazard ratio, 1.63; 95% CI, 1.37 to 1.95; P = 4.7×10-8). We identified a specific antibody response against LIMS1, a kidney-expressed protein encoded within the collision locus. The response involved predominantly IgG2 and IgG3 antibody subclasses.We found that the LIMS1 locus appeared to encode a minor histocompatibility

2019 NEJM

184. Benralizumab for <i>PDGFRA</i>-Negative Hypereosinophilic Syndrome. Full Text available with Trip Pro

Benralizumab for <i>PDGFRAi>-Negative Hypereosinophilic Syndrome. Hypereosinophilic syndrome is a group of diseases defined by marked eosinophilia in blood or tissue and eosinophil-related clinical manifestations. Benralizumab is a monoclonal antibody against interleukin-5 receptor α, which is expressed on human eosinophils.In this randomized, double-blind, placebo-controlled, phase 2 trial, we administered a series of three monthly subcutaneous injections of either benralizumab (at a dose

2019 NEJM Controlled trial quality: predicted high

185. The prevalence of ANA antibodies, anticentromere antibodies, and anti-cyclic citrullinated peptide antibodies in patients with primary Sjögren’s syndrome compared to patients with dryness symptoms without primary Sjögren’s syndrome confirmation Full Text available with Trip Pro

patients were divided into two groups: I - with diagnosed pSS (N = 75); and II - with dryness without pSS evidence (N = 38). Diagnostics: indirect immunofluorescence (IF; Hep-2 cell line) of antinuclear antibodies (ANA), anti-SS-A anti-SS-B antibodies determined with semi-quantitative method, autoantibody profile (14 antigens, ANA Profil 3 EUROLINE); basic laboratory, ophthalmic examination tests, minor salivary gland biopsy with focus score (FS), joint and lung evaluation, and ESSDAI questionnaire (...) (pSS activity).88% of group I had ANA antibodies (1 : 320 titre), 5.3% at 1 : 160. Anti-SS-A antibodies were present in 88% of group I, including all ANA 1 : 160. Anti-SS-A antibodies positively correlated with greater and moderate activity of ESSDAI 5 (p = 0.046) and FS. The presence of SS-B antibodies significantly affected disease activity. ACPA present: group I - 13% (associated with higher arthritis incidence; p = 0.003); group II - 8%. ACA antibodies present in 4% of group I, but not in group

2017 Reumatologia

186. Alanine scanning mutagenesis of the MEDI4839 (Suvratoxumab) epitope reduces alpha toxin lytic activity <i>in vitro</i> and <i>S. aureus</i> fitness in infection models. Full Text available with Trip Pro

Alanine scanning mutagenesis of the MEDI4839 (Suvratoxumab) epitope reduces alpha toxin lytic activity <i>in vitroi> and <i>S. aureusi> fitness in infection models. Alpha toxin (AT) is a cytolytic pore-forming toxin that plays a key role in Staphylococcus aureus pathogenesis; consequently, extensive research was undertaken to understand the AT mechanism of action and its utility as a target for novel prophylaxis and treatment strategies against S. aureus infections. MEDI4893 (suvratoxumab (...) ) is a human anti-AT IgG1 monoclonal antibody (MAb) that targets AT and is currently in phase 2 clinical development. As shown previously, the MEDI4893-binding epitope on AT is comprised of the highly conserved amino acid regions 177 to 200 and 261 to 271, suggesting these amino acids are important for AT function. To test this hypothesis and gain insight into the effect of mutations in the epitope on AT neutralization by MEDI4893, nine MEDI4893 contact residues in AT were individually mutated to alanine

2018 Antimicrobial Agents and Chemotherapy

187. Genomic <i>ERBB2</i>/<i>ERBB3</i> mutations promote PD-L1-mediated immune escape in gallbladder cancer: a whole-exome sequencing analysis. (Abstract)

Genomic <i>ERBB2i>/<i>ERBB3i> mutations promote PD-L1-mediated immune escape in gallbladder cancer: a whole-exome sequencing analysis. Patients with gallbladder carcinoma (GBC) lack effective treatment methods largely due to the inadequacy of both molecular characterisation and potential therapeutic targets. We previously uncovered a spectrum of genomic alterations and identified recurrent mutations in the ErbB pathway in GBC. Here, we aimed to study recurrent mutations of genes (...) to the growth and progression of GBC in vivo. Treatment with an ERBB2/ERBB3 inhibitor or a PD-L1 monoclonal antibody reversed these immunosuppressive effects, and combined therapy revealed promising therapeutic activities.ERBB2/ERBB3 mutations may serve as useful biomarkers in identifying patients who are sensitive to ERBB2/ERBB3 inhibitors and PD-L1 monoclonal antibody treatment.NCT02442414;Pre-results.© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All

2018 Gut

188. Systematic approach demonstrates enrichment of multiple interactions between non-<i>HLA</i> risk variants and <i>HLA-DRB1</i> risk alleles in rheumatoid arthritis. Full Text available with Trip Pro

Systematic approach demonstrates enrichment of multiple interactions between non-<i>HLAi> risk variants and <i>HLA-DRB1i> risk alleles in rheumatoid arthritis. In anti-citrullinated protein antibody positive rheumatoid arthritis (ACPA-positive RA), a particular subset of HLA-DRB1 alleles, called shared epitope (SE) alleles, is a highly influential genetic risk factor. Here, we investigated whether non-HLA single nucleotide polymorphisms (SNP), conferring low disease risk on their own

2018 Annals of the Rheumatic Diseases

189. Case Report: Misleading Serological Diagnosis of Paracoccidioidomycosis in a Young Patient with the Acute Form Disease: <i>Paracoccidioides brasiliensis</i> or <i>Paracoccidioides lutzii</i>? Full Text available with Trip Pro

Case Report: Misleading Serological Diagnosis of Paracoccidioidomycosis in a Young Patient with the Acute Form Disease: <i>Paracoccidioides brasiliensisi> or <i>Paracoccidioides lutziii>? Negative results in serological routine screening of patients with microbiologically proven Paracoccidioidomycosis (PCM) are occasionally reported. Failure in detecting anti-Paracoccidioides antibodies has been ascribed to factors either related to serological techniques or to the status of the host immune (...) reactivity. Recently, this issue has been renewed by the recognition that the Paracoccidioides genera comprises two species, lutzii and brasiliensis, which have distinct antigenic profiles and, therefore, may elicit different host antibody responses. We describe a patient with the acute form PCM due to Paracoccidioides brasiliensis with negative results on two reference centers' routine screening for P. brasiliensis antibodies, but positive results with Paracoccidioides lutzii antigens. The present case

2018 American Journal of Tropical Medicine & Hygiene

190. <i>Anopheles</i> Salivary Biomarker as a Proxy for Estimating <i>Plasmodium falciparum</i> Malaria Exposure on the Thailand-Myanmar Border. Full Text available with Trip Pro

<i>Anophelesi> Salivary Biomarker as a Proxy for Estimating <i>Plasmodium falciparumi> Malaria Exposure on the Thailand-Myanmar Border. Timely identification and treatment of malaria transmission "hot spots" is essential to achieve malaria elimination. Here we investigate the relevance of using an Anopheles salivary biomarker to estimate Plasmodium falciparum malaria exposure risk along the Thailand-Myanmar border to guide malaria control. Between May 2013 and December 2014, > 9,000 blood (...) samples collected in a cluster randomized control trial were screened with serological assays to measure the antibody responses to Anopheles salivary antigen (gSG6-P1) and P. falciparum malaria antigens (circumsporozoite protein, merozoite surface protein 119 [MSP-119]). Plasmodium falciparum infections were monitored through passive and active case detection. Seroprevalence to gSG6-P1, MSP-119, and CSP were 71.8% (95% Confidence interval [CI]: 70.9, 72.7), 68.6% (95% CI: 67.7, 69.5), and 8.6% (95% CI

2018 American Journal of Tropical Medicine & Hygiene

191. High-resolution antibody array analysis of proteins from primary human keratinocytes and leukocytes. Full Text available with Trip Pro

information about i) subcellular location, ii) size of the intended target, and iii) cell type-dependent variation in protein expression. Similarities in the reactivity patterns of either different antibodies to the same protein or antibodies to similar proteins were used as additional supporting evidence. This approach provided validation of several hundred proteins and identification of monomeric proteins and protein complexes. High-resolution MAP solves many of the problems associated with obtaining (...) High-resolution antibody array analysis of proteins from primary human keratinocytes and leukocytes. Antibody array analysis of labeled proteomes has high throughput and is simple to perform, but validation remains challenging. Here, we used differential detergent fractionation and size exclusion chromatography in sequence for high-resolution separation of biotinylated proteins from human primary keratinocytes and leukocytes. Ninety-six sample fractions from each cell type were analyzed

2018 PLoS ONE

192. Fc engineering of anti-Nectin-2 antibody improved thrombocytopenic adverse event in monkey. Full Text available with Trip Pro

by phagocytosis in the mononuclear phagocytic system. To mitigate the adverse safety profile, we mutated the Fc region of Y-443 to reduce the Fc binding activity to Fcγ receptor I, which is the primary receptor for phagocytosis on macrophages. Moreover, we further engineered the Fc through defucosylation to maintain ADCC activity. The resultant Fc engineered antibody, termed Y-634, demonstrated diminished thrombocytopenia in Cyno toxicological studies and maintained anti-tumor activity in a mouse xenograft (...) Fc engineering of anti-Nectin-2 antibody improved thrombocytopenic adverse event in monkey. Nectin-2 is a transmembrane glycoprotein which is involved in the process of Ca2+-independent cell-cell adhesion. In our previous study, we have demonstrated that Nectin-2 is over-expressed in breast and ovarian cancer tissues by using gene expression analysis and immunohistochemistry. Furthermore, we discovered multiple anti-Nectin-2 fully human monoclonal antibodies which inhibited tumor growth

2018 PLoS ONE

193. Generation of high-affinity, internalizing anti-FGFR2 single-chain variable antibody fragment fused with Fc for targeting gastrointestinal cancers. Full Text available with Trip Pro

cancer types, including gastric, colorectal, endometrial, ovarian, breast and lung cancer. In this paper, we describe application of the phage display technology to produce a panel of high affinity single chain variable antibody fragments (scFvs) against the extracellular ligand-binding domain of FGFR2 (ECD_FGFR2). The binders were selected from the human single chain variable fragment scFv phage display libraries Tomlinson I + J and showed high specificity and binding affinity towards human FGFR2 (...) Generation of high-affinity, internalizing anti-FGFR2 single-chain variable antibody fragment fused with Fc for targeting gastrointestinal cancers. Fibroblast growth factor receptors (FGFRs) are promising targets for antibody-based cancer therapies, as their substantial overexpression has been found in various tumor cells. Aberrant activation of FGF receptor 2 (FGFR2) signaling through overexpression of FGFR2 and/or its ligands, mutations, or receptor amplification has been reported in multiple

2018 PLoS ONE

194. Clinical impact of complement (C1q, C3d) binding De Novo donor-specific HLA antibody in kidney transplant recipients. Full Text available with Trip Pro

at the time of biopsy. C1q/C3d binding activities of dnDSA were assessed using C1qScreen assay (One lambda, USA) and Lifecodes C3d detection assay (Immucor, USA), respectively. Clinical outcomes including biopsy-proven antibody mediated rejection (AMR), C4d detection and post-biopsy graft survival were investigated.De-novo DSAs were detected in fifty-four (33.5%) patients (HLA class I only, n = 19; class II only, n = 29; both class I and II, n = 6). Of them, complement binding activities were detected (...) Clinical impact of complement (C1q, C3d) binding De Novo donor-specific HLA antibody in kidney transplant recipients. Complement binding activity of donor-specific HLA antibodies (DSA) has been suggested as a new tool to stratify immunologic risk in kidney transplantation (KT). The objective of this study was to evaluate the clinical implication of C1q/C3d binding activity of de novo DSA (dnDSA) in KT recipients.A total of 161 pretransplant DSA-negative recipients were monitored for dnDSA

2018 PLoS ONE

195. cGMP production of astatine-211-labeled anti-CD45 antibodies for use in allogeneic hematopoietic cell transplantation for treatment of advanced hematopoietic malignancies. Full Text available with Trip Pro

cGMP production of astatine-211-labeled anti-CD45 antibodies for use in allogeneic hematopoietic cell transplantation for treatment of advanced hematopoietic malignancies. The objective of this study was to translate reaction conditions and quality control methods used for production of an astatine-211(211At)-labeled anti-CD45 monoclonal antibody (MAb) conjugate, 211At-BC8-B10, from the laboratory setting to cGMP production. Five separate materials were produced in the preparation of 211At-BC8 (...) at room temperature. The experiments conducted have defined conditions for translation of 211At-BC8-B10 production from the laboratory to cGMP suite. This study has allowed the initiation of a phase I/II clinical trial using 211At-BC8-B10 (NCT03128034).

2018 PLoS ONE

196. <i>Mycobacterium vaccae</i> nebulization protects Balb/c mice against bronchial asthma through neural mechanisms. (Abstract)

<i>Mycobacterium vaccaei> nebulization protects Balb/c mice against bronchial asthma through neural mechanisms. Objectives: Bronchial asthma can be effectively controlled but not be cured, its etiology and pathogenesis are still unclear, and there are no effective preventive measures. The key characteristic of asthma is chronic airway inflammation, and recent research has found that airway neurogenic inflammation plays an important role in asthma. We previously found that Mycobacterium vaccae (...) the last challenge, mouse airway responsiveness; pulmonary brain-derived neurotropic factor (BDNF), neurofilament-medium length (NF-M, using NF09 antibody), and acetylcholine expression; and nerve growth factor (NGF) mRNA level were determined.Results: We found that the BDNF, NF09, acetylcholine expression, and NGF mRNA level were decreased in the Neb.group compared with levels in the asthma control group.Conclusion:M. vaccae nebulization may protected in Balb/c mice against bronchial asthma through

2020 Journal of Asthma

197. Vasculitides and glomerulonephritis associated with <i>Staphylocococcus aureus</i> infective endocarditis: cases reports and mini-review of the literature. (Abstract)

Vasculitides and glomerulonephritis associated with <i>Staphylocococcus aureusi> infective endocarditis: cases reports and mini-review of the literature. We reported two cases of Staphylococcus aureus Infective Endocarditis associated with vasculitides and glomerulonephritis respectively, before conducting an online search of previously published similar cases reports. Twenty five references were selected: 15 cases of glomerulonephritis; 2 cases of vasculitis and 8 cases involving both (...) glomerulonephritis and vasculitis. Vasculitides and glomerulonephritis associated with Staphylococcus aureus definite Infective Endocarditis have been reported since 1976. All cases except one described clinical symptoms occurring before or during initial antibiotics treatment. Except kidney, organs that were more frequently affected by vasculitis process were skin, gastrointestinal tract and peripheral nerve and the vessels involved were small to medium size vessels. When antineutrophil cytoplasmic antibodies

2020 Annals of medicine

198. Treatment of <i>Clostridioides (Clostridium) difficile</i> infection. (Abstract)

Treatment of <i>Clostridioides (Clostridium) difficilei> infection. Clostridioides (formerly: Clostridium) difficile infection (CDI) is a major cause of diarrhoea for inpatients as well as outpatients. Usually, CDI is healthcare-associated but the number of community-acquired infections is increasing. CDI is generally associated with changes in the normal intestinal microbiota caused by administration of antibiotics. Elderly and immunocompromised patients are at greater risk for CDI and CDI (...) cornerstones for the treatment of CDI are vancomycin and fidaxomicin. Metronidazole should be used only in mild-to-moderate disease in younger patients who have no or only few risk factors for recurrence.In recurrent CDI, bezlotoxumab infusion (a monoclonal antibody against C. difficile toxin B) may be considered as an adjunctive therapeutic strategy in addition to the standard care provided to patients with several risk factors for recurrence.Faecal microbiota transplantation (FMT) should be offered

2020 Annals of medicine

199. Bacterial citrullinated epitopes generated by <i>Porphyromonas gingivalis</i> infection-a missing link for ACPA production. (Abstract)

Bacterial citrullinated epitopes generated by <i>Porphyromonas gingivalisi> infection-a missing link for ACPA production. Porphyromonas gingivalis (P.g.) is discussed to be involved in triggering self-reactive immune responses. The aim of this study was to investigate the autocitrullinated prokaryotic peptidylarginine deiminase (PPAD) from P.g. CH2007 (RACH2007-PPAD) from a rheumatoid arthritis (RA) patient and a synthetic citrullinated PPAD peptide (CPP) containing the main (...) autocitrullination site as potential targets for antibody reactivity in RA and to analyse the possibility of citrullinating native human proteins by PPAD in the context of RA.Recombinant RACH2007-PPAD was cloned and expressed in Escherichia coli. Purified RACH2007-PPAD and its enzymatic activity was analysed using two-dimensional electrophoresis, mass spectrometry, immunoblot and ELISA. Autoantibody response to different modified proteins and peptides was recorded and bioinformatically evaluated.RACH2007-PPAD

2020 Annals of the rheumatic diseases

200. Impact of EGFR-TKI Treatment on the Tumor Immune Microenvironment in <i>EGFR</i> Mutation-Positive Non-Small Cell Lung Cancer. Full Text available with Trip Pro

Impact of EGFR-TKI Treatment on the Tumor Immune Microenvironment in <i>EGFRi> Mutation-Positive Non-Small Cell Lung Cancer. The impact of EGFR tyrosine kinase inhibitors (TKI) on the tumor immune microenvironment (TME) in non-small cell lung cancer (NSCLC) is unclear.We retrospectively identified 138 patients with EGFR-mutated NSCLC who underwent rebiopsy after progression during EGFR-TKI treatment. PD-L1 and CD73 expression in tumor cells and tumor-infiltrating lymphocyte (TIL) density (...) was higher than that before in patients with a high PD-L1 expression level. TMB tended to be higher after EGFR-TKI treatment than before (3.3→4.1 mutations/Mbp, P = 0.0508). Median progression-free survival for subsequent treatment with antibodies to PD-1 was longer for patients with a high than for those with a low PD-L1 expression after EGFR-TKI (7.1 vs. 1.7 months, P = 0.0033), and two of five patients whose PD-L1 expression level changed from low to high after EGFR-TKI treatment achieved a PFS of >6

2020 Clinical Cancer Research

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