bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relatives Without Rheumatoid Arthritis Show Reactivity to Anti–Citrullinated Protein/Peptide Antibodies That Are Associated With Arthritis‐Related Traits: Studies of the Etiology of Rheumatoid Arthritis
Authors: Young Kendra A. , Deane Kevin D. , Derber Lezlie A. , Hughes‐Austin Jan M. , Wagner Catriona A. , Sokolove Jeremy , Weisman Michael H. , Buckner Jane H. , Mikuls Ted R. , O'Dell James R. , Keating Richard M. , Gregersen Peter K. , Robinson William H. , Holers V. Michael , Norris Jill M. 
Published: June 2013

ObjectiveTo examine reactivity to anti–citrullinated protein/peptide antibodies (ACPAs) and determine associations between ACPAs and other rheumatoid arthritis (RA)–related autoantibodies and clinically assessed swollen or tender joints in unaffected first‐degree relatives of RA patients.MethodsSerum samples were obtained from first‐degree relatives without RA according to the 1987 American College of Rheumatology (ACR) and the 2010 ACR/European League Against Rheumatism classification criteria. A bead‐based assay was used to measure 16 separate ACPAs in sera from 111 antibody‐positive first‐degree relatives who were positive on at least 1 visit for any of 5 RA‐related autoantibodies (rheumatoid factor [RF], anti–cyclic citrullinated peptide 2 [anti–CCP‐2], and RF isotypes), and sera from 99 antibody‐negative first‐degree relatives who were never autoantibody positive. Cutoffs for positivity for each ACPA were determined using receiver operating characteristic curves derived from data on 200 RA patients and 98 blood donor controls, in which positivity for ≥9 ACPAs had 92% specificity and 62% sensitivity for RA. In first‐degree relatives, ACPA reactivity was assessed, and associations between ACPAs (number positive, and positivity for ≥9 ACPAs) and RA‐related characteristics were examined.ResultsFifty‐seven percent of anti–CCP‐2–positive first‐degree relatives and 8% of anti–CCP‐2– negative first‐degree relatives were positive for ≥9 ACPAs. After adjusting for age, sex, ethnicity, and pack‐years of smoking, an increasing number of ACPAs was directly associated with the presence of ≥1 tender joint on examination (odds ratio [OR] 1.18, 95% confidence interval [95% CI] 1.04–1.34), with the greatest risk of having ≥1 tender joint seen in first‐degree relatives positive for ≥9 ACPAs (OR 5.00, 95% CI 1.37–18.18).ConclusionRA‐free first‐degree relatives (even those negative for RF and anti–CCP‐2) demonstrate reactivity to multiple ACPAs, and the presence of an increasing number of ACPAs may be associated with signs of joint inflammation. Prospective evaluation of the relationship between these findings and the progression of classifiable RA is warranted.
Systemic Polyarteritis Nodosa in the Young: A Single‐Center Experience Over Thirty‐Two Years
Authors: Eleftheriou Despina , Dillon Michael J. , Tullus Kjell , Marks Stephen D. , Pilkington Clarissa A. , Roebuck Derek J. , Klein Nigel J. , Brogan Paul A. 
Published: June 2013

ObjectivePolyarteritis nodosa (PAN) is a rare disease of childhood. The aims of this study were to describe the clinical features, treatment, and outcome of systemic childhood PAN and to identify predictors of relapse.MethodsA single‐center retrospective medical records review of children with PAN fulfilling the European League Against Rheumatism (EULAR)/Paediatric Rheumatology European Society (PRES)/Paediatric Rheumatology International Trials Organisation (PRINTO) classification criteria who were seen over a 32‐year period was performed. Data on demographic and clinical features, treatments, relapses (recurrence of clinical signs/symptoms or occurrence of new symptoms after initial remission requiring escalation or resumption of immunosuppressive therapy), and deaths were recorded. A disease activity score was retrospectively assigned using the Paediatric Vasculitis Activity Score (PVAS) instrument. Cox regression analysis was used to identify significant predictors of relapse.ResultsSixty‐nine children with PAN were identified; 55% were male, and their median age was 8.5 years (range 0.9–15.8 years). Their clinical features at presentation were fever (87%), myalgia (83%), skin (88%), renal (19%), severe gastrointestinal (GI) (10%), and neurologic (10%) involvement. The PVAS at presentation was 9 of 63 (range 4–24). Histopathologic analysis of the skin showed necrotizing vasculitis in biopsy samples from 40 of 50 children. Results of selective visceral arteriography suggested the presence of PAN in 96% of patients. Treatment included cyclophosphamide and corticosteroids (83%), plasma exchange (9%), and biologic agents (after 2002; 13%). The relapse rate was 35%, and the mortality rate was 4%. Severe GI involvement was associated with increased risk of relapse (P = 0.031), while longer time to induce remission (P = 0.022) and increased cumulative dose of cyclophosphamide (P = 0.005) were associated with lower relapse risk.ConclusionChildhood PAN is a severe inflammatory disease of insidious onset and variable clinical presentation. Relapses occurred more frequently in those with severe GI involvement. A higher cumulative dose of cyclophosphamide was associated with a lower risk of relapse.
Long‐Term Safety and Efficacy of Rilonacept in Patients With Systemic Juvenile Idiopathic Arthritis
Authors: Lovell Daniel J. , Giannini Edward H. , Reiff Andreas O. , Kimura Yukiko , Li Suzanne , Hashkes Philip J. , Wallace Carol A. , Onel Karen B. , Foell Dirk , Wu Richard , Biedermann Stephanie , Hamilton Jennifer D. , Radin Allen R. 
Published: June 2013

ObjectiveTo determine the long‐term safety and efficacy of rilonacept, an anti–interleukin‐1 fusion protein, in patients with active systemic juvenile idiopathic arthritis (JIA).MethodsIn patients with systemic JIA, ages 4–20 years, the efficacy of rilonacept was evaluated using 30%, 50%, and 70% levels of improvement according to the adapted American College of Rheumatology (ACR) Pediatric 30, 50, and 70 response criteria, respectively. Efficacy and safety were evaluated during 23 months of open‐label treatment (3 phases) after a 4‐week, double‐blind, placebo‐controlled phase. Following double‐blind treatment with 2.2 mg/kg or 4.4 mg/kg of rilonacept, patients were eligible to receive open‐label treatment at their prior dose, with adjustments. Reductions in the median daily dose of oral prednisone and improvements in laboratory parameters of disease activity (i.e., decreased levels of D‐dimer and myeloid‐related proteins [MRPs]) were also evaluated.ResultsTwenty‐four patients entered the double‐blind study and 23 entered the open‐label period. Patients were predominantly white and female, and had a median age of 14.0 years at baseline. No significant differences in efficacy were observed between the rilonacept‐ and placebo‐treated patients during the double‐blind phase, but fever and rash completely resolved by month 3 in all patients during the open‐label treatment period and did not recur. Adapted ACR Pediatric 30, 50, and 70 response rates at 3 months from the start of the study were 78.3%, 60.9%, and 34.8%, respectively; these responses were generally maintained over the study duration. Levels of D‐dimer and MRP‐8/MRP‐14 dramatically improved during the study, and in 22 of 23 patients, the prednisone dose was decreased or prednisone therapy was discontinued. No serious treatment‐related adverse events were observed.ConclusionSustained improvements in clinical and laboratory measures of the articular and systemic manifestations of systemic JIA were achieved in >50% of rilonacept‐treated patients over 2 years. Treatment with rilonacept had a substantial steroid‐sparing effect and was generally well‐tolerated.
Incomplete B Cell Tolerance to Cartilage Oligomeric Matrix Protein in Mice
Authors: Geng Hui , Nandakumar Kutty Selva , Xiong Li , Jie Rui , Dong Jiahui , Holmdahl Rikard 
Published: June 2013

ObjectiveCartilage oligomeric matrix protein (COMP) is a major noncollagenous component of cartilage and is used as a biomarker in rheumatoid arthritis and experimental arthritis. Injection of COMP leads to severe inflammatory joint disease, and antibodies play a critical role in mediating arthritis. The arthritogenicity of COMP might be due to the lack of self tolerance. This study was undertaken to determine the status of COMP‐specific B cell tolerance using COMP‐deficient mice.MethodsArthritis development and antibody responses were compared between COMP‐sufficient and COMP‐deficient littermates after immunization with rat COMP. Serum anti‐COMP antibody levels were measured using a panel of recombinant mouse COMP proteins, and antibody‐secreting cells were enumerated by enzyme‐linked immunospot assays. A novel sandwich enzyme‐linked immunosorbent assay was developed to assess COMP molecules in serum.ResultsCOMP‐sufficient mice, but not COMP‐deficient mice, developed severe arthritis following immunization with rat COMP. However, anti‐COMP antibody titers to native COMP and recombinant protein domains covering the entire mouse COMP sequence, except the less immunodominant type 3 repeat domains, were decreased in COMP‐sufficient mice compared to COMP‐deficient mice. In addition, COMP‐sufficient mice had fewer B cells secreting COMP‐reactive antibodies. Detectable levels of full‐length COMP in arthritic COMP‐sufficient B10.Q NCF‐1*/* and healthy mice suggested systemic availability of COMP to the immune system.ConclusionThe lack of arthritis, together with high levels of COMP‐specific antibodies, in COMP‐deficient mice indicates that susceptibility to arthritis is COMP specific and that endogenous expression of COMP in wild‐type mice tolerizes B cells in vivo.
Letter to the Editor
Authors: Wu Beilei , de Leon Alexander R. 
Published: June 2013

AbstractRegarding Paper“Sample size determination in clinical trials with multiple co‐primary endpoints including mixed continuous and binary variables”by T. Sozu, T. Sugimoto, and T. HamasakiBiometrical Journal (2012) 54(5): 716–729Article: http://dx.doi.org/10.1002/bimj.201100221Authors' Reply: http://dx.doi.org/10.1002/bimj.201300032This paper recently introduced a methodology for calculating the sample size in clinical trials with multiple mixed binary and continuous co‐primary endpoints modeled by the so‐called conditional grouped continuous model (CGCM). The purpose of this note is to clarify certain aspects of the methodology and propose an alternative approach based on latent means tests for the binary endpoints. We demonstrate that our approach is more powerful, yielding smaller sample sizes at powers comparable to those used in the paper.
Generation of Free Oligosaccharides from Bacterial Protein N‐Linked Glycosylation Systems
Authors: Dwivedi Ritika , Nothaft Harald , Reiz Bela , Whittal Randy M. , Szymanski Christine M. 
Published: June 2013

ABSTRACTAll Campylobacter species are capable of N‐glycosylating their proteins and releasing the same oligosaccharides into the periplasm as free oligosaccharides (fOS). Previously, analysis of fOS production in Campylobacter required fOS derivatization or large culture volumes and several chromatography steps prior to fOS analysis. In this study, label‐free fOS extraction and purification methods were developed and coupled with quantitative analysis techniques. Our method follows three simple steps: (1) fOS extraction from the periplasmic space, (2) fOS purification using silica gel chromatography followed by porous graphitized carbon purification and (3) fOS analysis and accurate quantitation using a combination of thin‐layer chromatography, mass spectrometry, NMR, and high performance anion exchange chromatography with pulsed amperometric detection. We applied our techniques to analyze fOS from C. jejuni, C. lari, C. rectus, and C. fetus fetus that produce different fOS structures. We accurately quantified fOS in Campylobacter species that ranged from 7.80 (±0.84) to 49.82 (±0.46) nmoles per gram of wet cell pellet and determined that the C. jejuni fOS comprises 2.5% of the dry cell weight. In addition, a novel di‐phosphorylated fOS species was identified in C. lari. This method provides a sensitive and quantitative method to investigate the genesis, biology and breakdown of fOS in the bacterial N‐glycosylation systems. © 2013 Wiley Periodicals, Inc. Biopolymers 99: 772–783, 2013.
A personal perspective on chemistry‐driven RNA research
Authors: Micura Ronald , Kreutz Christoph , Breuker Kathrin 
Published: June 2013

ABSTRACTIn this mini review, we discuss how our understanding of ribonucleic acid (RNA) properties becomes significantly deepened when a broad range of modern chemical and biophysical methods is applied. We span our perspective from RNA solid‐phase synthesis and site‐specific labeling to single‐molecule fluorescence‐resonance‐energy‐transfer imaging and NMR spectroscopy approaches to explore the dynamics of RNA over a broad timescale. We then move on to Fourier‐transform‐ion‐cyclotron‐resonance mass spectrometry (FT‐ICR‐MS) as a powerful technique for RNA sequencing and modification analysis. The novel methodological developments are discussed for selected biological systems that include the thiamine‐pyrophosphate riboswitch, HIV and ribosomal A‐site RNA, and transfer RNA. © 2013 Wiley Periodicals, Inc. Biopolymers 99: 1114–1123, 2013.
One set system for the synthesis and purification of glycosaminoglycan oligosaccharides reconstructed using a hyaluronidase‐immobilized column
Authors: Suto Shinichiro , Kakizaki Ikuko , Nakamura Toshiya , Endo Masahiko 
Published: June 2013

ABSTRACTUsing the transglycosylation reaction as a reverse reaction for the hydrolysis of hyaluronidase, new artificial oligosaccharides may be synthesized by reconstructing natural glycosaminoglycans (GAGs) according to preliminary planned arrangements. However, as some problems have been associated with the method, including the low yields of reaction products and complicated processes of separation and purification, improvements in this method were investigated. Transglycosylation reactions were carried out using bovine testicular hyaluronidase‐immobilized resin packed in a column. For the transglycosylation reaction, pyridylaminated (PA) GAG hexasaccharides, which were the minimum size for hydrolysis sensitivity and the transglycosylation reaction, were used as acceptors, whereas large size GAGs were used as donors. The reaction mixture was pooled after incubation in the hyaluronidase‐immobilized resin column and was then introduced into continuously joined HPLC columns constructed from three steps: the first step of ion‐exchange HPLC for concentrating newly synthesized GAG oligosaccharides as reaction products, the second step of reverse phase HPLC for separating PA oligosaccharides from non‐PA oligosaccharides, and the third step of size fractionation HPLC for fractionating newly synthesized oligosaccharides. Newly synthesized oligosaccharides were obtained by one complete cycle of the transglycosylation reaction and separation. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 189–196, 2014.
Insight into the redox partner interaction mechanism in cytochrome P450BM‐3 using molecular dynamics simulations
Authors: Verma Rajni , Schwaneberg Ulrich , Roccatano Danilo 
Published: June 2013

ABSTRACTFlavocytochrome P450BM‐3 is a soluble bacterial reductase composed of two flavin (FAD/FMN) and one HEME domains. In this article, we have performed molecular dynamics simulations on both the isolated FMN and HEME domains and their crystallographic complex, with the aim to study their binding modes and to garner insight into the interdomain electron transfer (ET) mechanism. The results evidenced an interdomain conformational rearrangement that reduces the average distance between the FMN and HEME cofactors from 1.81 nm, in the crystal structure, to an average value of 1.41 ± 0.09 nm along the simulation. This modification is in agreement with previously proposed hypotheses suggesting that the crystallographic FMN/HEME complex is not in the optimal arrangement for favorable ET rate under physiological conditions. The calculation of the transfer rate along the simulation, using the Pathways Path method, demonstrated the occurrence of seven ET pathways between the two redox centers, with three of them providing ET rates (KET) comparable with the experimental one. The sampled ET pathways comprise the amino acids N319, L322, F390, K391, P392, F393, A399, C400, and Q403 of the HEME domain and M490 of the FMN domain. The values of KET closer to the experiment were found along the pathways FMN(C7) → F390 → K391 → P392 → HEME(Fe) and FMN(C8) → M490 → F393 → HEME(Fe). Finally, the analysis of the collective modes of the protein complex evidences a clear correlation of the first two essential modes with the activation of the most effective ET pathways along the trajectory. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 197–209, 2014.
Partial hepatectomy for ruptured hepatocellular carcinoma
Authors: Yang T , Sun Y F , Zhang J , Lau W Y , Lai E C H , Lu J H , Shen F , Wu M C 
Published: June 2013

Abstract

Background
Improvements in surgical technique and perioperative care have made partial hepatectomy a safe and effective treatment for hepatocellular carcinoma (HCC), even in the event of spontaneous HCC rupture.

Methods
A consecutive cohort of patients who underwent partial hepatectomy for HCC between 2000 and 2009 was divided into a ruptured group and a non-ruptured group. Patients with ruptured HCC were further divided into emergency and staged hepatectomy subgroups. Mortality and morbidity, overall survival and recurrence-free survival (RFS) were compared. Prognostic factors for overall survival and RFS were identified by univariable and multivariable analyses.

Results
A total of 1233 patients underwent partial hepatectomy for HCC, of whom 143 had a ruptured tumour. The morbidity and mortality rates were similar in the ruptured and non-ruptured groups, as well as in the emergency and staged subgroups. In univariable analyses, overall survival and RFS were lower in the ruptured group than in the non-ruptured group (both P &lt; 0·001), and also in the emergency subgroup compared with the staged subgroup (P = 0·016 and P = 0·025 respectively). In multivariable analysis, spontaneous rupture independently predicted poor overall survival after hepatectomy (hazard ratio 1·54, 95 per cent confidence interval 1·24 to 1·93) and RFS (HR 1·75, 1·39 to 2·22). Overall survival and RFS after hepatectomy for ruptured HCC in the emergency and staged subgroups were not significantly different in multivariable analyses.

Conclusion
Spontaneous rupture predicted poor long-term survival after hepatectomy for HCC, but surgical treatment seems possible, safe and appropriate in selected patients.
Systematic review and meta-analysis of hypothermic machine perfusion versus static cold storage of kidney allografts on transplant outcomes
Authors: O'Callaghan J M , Morgan R D , Knight S R , Morris P J 
Published: June 2013

Abstract

Background
Adequate preservation of renal allografts for transplantation is important for maintaining and improving transplant outcomes. There are two prevalent methods: hypothermic machine perfusion and static cold storage. The preferred method of storage, however, remains controversial. The objective was to review systematically the evidence comparing outcomes from these two modalities.

Methods
A literature search was performed using MEDLINE, Embase, the Cochrane Library, the Transplant Library and the International Clinical Trials Registry Platform. The final date for searches was 30 November 2012. Studies were assessed for methodological quality. Summary effects were calculated as relative risk (RR) with 95 per cent confidence interval (c.i.). Randomized clinical trials (RCTs) and non-RCTs were included, but evaluated separately. Results from RCTs alone were used for meta-analysis.

Results
Eighteen studies met the inclusion criteria, including seven RCTs (1475 kidneys) and 11 non-RCTs (728 kidneys). The overall risk of delayed graft function was lower with hypothermic machine perfusion than static cold storage (RR 0·81, 95 per cent c.i. 0·71 to 0·92; P = 0·002). There was no difference in the rate of primary non-function (RR 1·15, 0·46 to 2·90; P = 0·767). There was a faster initial fall in the level of serum creatinine with hypothermic machine perfusion in two RCTs, but not in another. There was no relationship between rates of acute rejection or patient survival and the method of preservation.

Conclusion
Data from the included studies suggest that hypothermic machine perfusion reduces delayed graft function compared with static cold storage. There was no difference in primary non-function, acute rejection, long-term renal function or patient survival. A difference in renal graft survival is uncertain.
Proximal margin length with transhiatal gastrectomy for Siewert type II and III adenocarcinomas of the oesophagogastric junction
Authors: Mine S , Sano T , Hiki N , Yamada K , Kosuga T , Nunobe S , Yamaguchi T 
Published: June 2013

Abstract

Background
A gross proximal oesophageal margin greater than 5 cm is considered to be necessary for curative surgery of adenocarcinoma of the oesophagogastric junction. This study investigated whether a shorter proximal margin might suffice in the context of total gastrectomy for Siewert type II and III tumours.

Methods
The gross proximal margin was measured on stretched specimens just after resection. Relationships between gross proximal margin lengths and clinicopathological features were investigated in patients with Siewert type II and III adenocarcinoma of the oesophagogastric junction treated by R0–1 surgical resection. For survival analyses, only patients who had undergone R0 resection for pathological (p) T2–4 N0–3 M0 tumour via a transhiatal approach were evaluated.

Results
Of the 140 patients, 120 had a total gastrectomy. Two patients (1·4 per cent) had histologically positive proximal margins and another two (1·4 per cent) developed anastomotic recurrence. Of 100 patients with pT2–4 N0–3 M0 tumours who underwent gastrectomy via a transhiatal approach, those with gross proximal margins larger than 20 mm appeared to have better survival than those with shorter margins (P = 0·027). Multivariable analysis demonstrated that a gross proximal margin of 20 mm or less was an independent prognostic factor (hazard ratio (HR) 3·56, 95 per cent confidence interval 1·39 to 9·14; P = 0·008), as was pathological node status (HR 1·76, 1·08 to 2·86; P = 0·024).

Conclusion
Gross proximal margin lengths of more than 20 mm in resected specimens seem satisfactory for patients with type II and III adenocarcinoma of the oesophagogastric junction treated by transhiatal gastrectomy.