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Wyszukujesz frazę "Wu, David" wg kryterium: Autor


Tytuł:
Structural and biochemical characterisation of $Co^{2+}$-binding sites on serum albumins and their interplay with fatty acids
Autorzy:
Schwarz-Linek, Ulrich
Gucwa, Michał
Blindauer, Claudia A.
Fritzen, Remi
Shabalin, Ivan G.
Cooper, David R.
Stewart, Alan J.
Arya, Swati
Wu, Dongmei
Minor, Wladek
Czub, Mateusz P.
Opis:
Serum albumin–$Co^{2+}$ interactions are of clinical importance. They play a role in mediating the physiological effects associated with cobalt toxicity and are central to the albumin cobalt binding (ACB) assay for diagnosis of myocardial ischemia. To further understand these processes{,} a deeper understanding of albumin–$Co^{2+}$ interactions is required. Here{,} we present the first crystallographic structures of human serum albumin (HSA; three structures) and equine serum albumin (ESA; one structure) in complex with $Co^{2+}$. Amongst a total of sixteen sites bearing a cobalt ion across the structures{,} two locations were prominent{,} and they relate to metal-binding sites A and B. Site-directed mutagenesis and isothermal titration calorimetry (ITC) were employed to characterise sites on HSA. The results indicate that His9 and His67 contribute to the primary (putatively corresponding to site B) and secondary $Co^{2+}$-binding sites (site A){,} respectively. The presence of additional multiple weak-affinity $Co^{2+}$ binding sites on HSA was also supported by ITC studies. Furthermore{,} addition of 5 molar equivalents of the non-esterified fatty acid palmitate (C16:0) reduced the $Co^{2+}$-binding affinity at both sites A and B. The presence of bound myristate (C14:0) in the HSA crystal structures provided insight into the fatty acid-mediated structural changes that diminish the affinity of the protein toward $Co^{2+}$. Together{,} these data provide further support for the idea that ischemia-modified albumin corresponds to albumin with excessive fatty-acid loading. Collectively{,} our findings provide a comprehensive understanding of the molecular underpinnings governing $Co^{2+}$ binding to serum albumin.
Dostawca treści:
Repozytorium Uniwersytetu Jagiellońskiego
Artykuł
Tytuł:
How do network meta-analyses address intransitivity when assessing certainty of evidence : a systematic survey
Autorzy:
Xia, Ruyu
Siemieniuk, Reed Alexander
Wu, Michael
Guyatt, Gordon
Bekkering, Gertruda Elsiena
Brignardello-Petersen, Romina
Pericic, Tina Poklepovic
Hou, Liangying
Rochwerg, Bram
Fei, Yutong
Bała, Małgorzata
Gao, Ya
Gloss, David
Wang, Ying
Opis:
Objectives To describe how systematic reviews with network meta-analyses (NMAs) that used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) NMA approach addressed intransitivity when assessing certainty of evidence. Design Systematic survey. Data sources Medline, Embase and Cochrane Database of Systematic Reviews from September 2014 to October 2022. Eligibility criteria Systematic reviews of randomised controlled trials with aggregate data NMAs that used the GRADE NMA approach for assessing certainty of evidence. Data extraction and synthesis We documented how reviewers described methods for addressing intransitivity when assessing certainty of evidence, how often they rated down for intransitivity and their explanations for rating down. Results Of the 268 eligible systematic reviews, 44.8% (120/268) mentioned intransitivity when describing methods for assessing the certainty of evidence. Of these, 28.3% (34/120) considered effect modifiers and from this subset, 67.6% (23/34) specified the effect modifiers; however, no systematic review noted how they chose the effect modifiers. 15.0% (18/120) mentioned looking for differences between the direct comparisons that inform the indirect estimate. No review specified a threshold for difference in effect modifiers between the direct comparisons that would lead to rating down for intransitivity. Reviewers noted rating down indirect evidence for intransitivity in 33.1% of systematic reviews, and noted intransitivity for network estimates in 23.0% of reviews. Authors provided an explanation for rating down for intransitivity in 59.6% (31/52) of the cases in which they rated down. Of the 31 in which they provided an explanation, 74.2% (23/31) noted they detected differences in effect modifiers and 67.7% (21/31) specified in what effect modifiers they detected differences. Conclusions A third of systematic reviews with NMAs using the GRADE approach rated down for intransitivity. Limitations in reporting of methods to address intransitivity proved considerable. Whether the problem is that reviewers neglected to address rating down for transitivity at all, or whether they did consider but not report, is not clear. At minimum systematic reviews with NMAs need to improve their reporting practices regarding intransitivity; it may well be that they need to improve their practice in transitivity assessment. How to best address intransitivity may remain unclear for many reviewers thus additional GRADE guidance providing practical instructions for addressing intransitivity may be desirable.
Dostawca treści:
Repozytorium Uniwersytetu Jagiellońskiego
Artykuł
Tytuł:
A randomised phase IIb study of mavrilimumab, a novel GM-CSF receptor alpha monoclonal antibody, in the treatment of rheumatoid arthritis
Autorzy:
White, Wendy I.
Korkosz, Mariusz
McInnes, Iain B.
Mysler, Eduardo
Sleeman, Matthew A.
Rubbert-Roth, Andrea
Godwood, Alex
Wang, Bing
Close, David
Wu, Chi-Yuan
Vencovsky, Jiri
Ryan, Patricia C.
Weinblatt, Michael E.
Burmester, Gerd R.
Kremer, Joel
Miranda, Pedro
Sinibaldi, Dominic
Guo, Xiang
Opis:
Objectives Despite the therapeutic value of current rheumatoid arthritis (RA) treatments, agents with alternative modes of action are required. Mavrilimumab, a fully human monoclonal antibody targeting the granulocyte–macrophage colony-stimulating factor receptor-α, was evaluated in patients with moderate-to-severe RA. Methods In a phase IIb study (NCT01706926), patients with inadequate response to ≥1 synthetic disease-modifying antirheumatic drug(s), Disease Activity Score 28 (DAS28)−C reactive protein (CRP)/erythrocyte sedimentation rate ≥3.2, ≥4 swollen joints despite methotrexate (MTX) were randomised 1:1:1:1 to subcutaneous mavrilimumab (150, 100, 30 mg), or placebo every other week (eow), plus MTX for 24 weeks. Coprimary outcomes were DAS28−CRP change from baseline to week 12 and American College of Rheumatology (ACR) 20 response rate (week 24). Results 326 patients were randomised (150 mg, n=79; 100 mg, n=85; 30 mg, n=81; placebo, n=81); 305 completed the study (September 2012–June 2013). Mavrilimumab treatment significantly reduced DAS28−CRP scores from baseline compared with placebo (change from baseline (SE); 150 mg: −1.90 (0.14), 100 mg: −1.64 (0.13), 30 mg: −1.37 (0.14), placebo: −0.68 (0.14); p<0.001; all dosages compared with placebo). Significantly more mavrilimumab-treated patients achieved ACR20 compared with placebo (week 24: 73.4%, 61.2%, 50.6% vs 24.7%, respectively (p<0.001)). Adverse events were reported in 43 (54.4%), 36 (42.4%), 41 (50.6%) and 38 (46.9%) patients in the mavrilimumab 150, 100, 30 mg eow and placebo groups, respectively. No treatment-related safety signals were identified. Conclusions Mavrilimumab significantly decreased RA disease activity, with clinically meaningful responses observed 1 week after treatment initiation, representing a novel mechanism of action with persuasive therapeutic potential.
Dostawca treści:
Repozytorium Uniwersytetu Jagiellońskiego
Artykuł

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