bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and Testing of New Candidate Psoriatic Arthritis Screening Questionnaires Combining Optimal Questions From Existing Tools
Authors: Coates Laura C. , Walsh Jessica , Haroon Muhammad , FitzGerald Oliver , Aslam Tariq , Al Balushi Farida , Burden A. D. , Burden‐Teh Esther , Caperon Anna R. , Cerio Rino , Chattopadhyay Chandrabhusan , Chinoy Hector , Goodfield Mark J. D. , Kay Lesley , Kelly Stephen , Kirkham Bruce W. , Lovell Christopher R. , Marzo‐Ortega Helena , McHugh Neil , Murphy Ruth , Reynolds Nick J. , Smith Catherine H. , Stewart Elizabeth J. C. , Warren Richard B. , Waxman Robin , Wilson Hilary E. , Helliwell Philip S. 
Published: January 2014

ObjectiveSeveral questionnaires have been developed to screen for psoriatic arthritis (PsA), but head‐to‐head studies have found limitations. This study aimed to develop new questionnaires encompassing the most discriminative questions from existing instruments.MethodsData from the CONTEST study, a head‐to‐head comparison of 3 existing questionnaires, were used to identify items with a Youden index score of ≥0.1. These were combined using 4 approaches: CONTEST (simple additions of questions), CONTESTw (weighting using logistic regression), CONTESTjt (addition of a joint manikin), and CONTESTtree (additional questions identified by classification and regression tree [CART] analysis). These candidate questionnaires were tested in independent data sets.ResultsTwelve individual questions with a Youden index score of ≥0.1 were identified, but 4 of these were excluded due to duplication and redundancy. Weighting for 2 of these questions was included in CONTESTw. Receiver operating characteristic (ROC) curve analysis showed that involvement in 6 joint areas on the manikin was predictive of PsA for inclusion in CONTESTjt. CART analysis identified a further 5 questions for inclusion in CONTESTtree. CONTESTtree was not significant on ROC curve analysis and discarded. The other 3 questionnaires were significant in all data sets, although CONTESTw was slightly inferior to the others in the validation data sets. Potential cut points for referral were also discussed.ConclusionOf 4 candidate questionnaires combining existing discriminatory items to identify PsA in people with psoriasis, 3 were found to be significant on ROC curve analysis. Testing in independent data sets identified 2 questionnaires (CONTEST and CONTESTjt) that should be pursued for further prospective testing.
Herzregeneration: Chancen und Aufgaben für die Wirkstoff‐Forschung mit neuartigen chemischen und therapeutischen Methoden oder Agentien
Authors: Plowright Alleyn T. , Engkvist Ola , Gill Adrian , Knerr Laurent , Wang Qing‐Dong 
Published: January 2014

AbstractInfolge eines Herzinfarkts kann mehr als eine Milliarde Herzmuskelzellen (Kardiomyozyten) abgetötet werden, was zu Herzinsuffizienz und plötzlichem Tod führt. Heute konzentriert sich die Forschung in diesem Zusammenhang verstärkt auf die Regeneration von Herzgewebe durch die Differenzierung von Stammzellen, die Proliferation vorhandener Kardiomyozyten und Herzprogenitorzellen sowie die Umprogrammierung von Fibroblasten zu Kardiomyozyten. Hierfür gibt es eine Reihe möglicher Lösungsansätze, vom Einsatz niedermolekularer Verbindungen und RNA (einschließlich Mikro‐RNA und Anti‐Mikro‐RNA) bis hin zur Verwendung modifizierter Peptide und Proteine. Wir stellen in diesem Aufsatz aktuelle Entwicklungen in diesem Bereich vor und beschreiben dabei sowohl die jeweilige Methode und ihre Fortschritte, einschließlich neuartiger Screening‐Strategien zur Identifizierung von Treffern, als auch ihre Perspektiven für die Weiterentwicklung dieser Treffer hin zu Medikamenten, wobei die Chemie eine Schlüsselrolle spielt.
DNA‐Hybrid‐Gated Multifunctional Mesoporous Silica Nanocarriers for Dual‐Targeted and MicroRNA‐Responsive Controlled Drug Delivery
Authors: Zhang Penghui , Cheng Fangfang , Zhou Ri , Cao Juntao , Li Jingjing , Burda Clemens , Min Qianhao , Zhu Jun‐Jie 
Published: January 2014

AbstractThe design of an ideal drug delivery system with targeted recognition and zero premature release, especially controlled and specific release that is triggered by an exclusive endogenous stimulus, is a great challenge. A traceable and aptamer‐targeted drug nanocarrier has now been developed; the nanocarrier was obtained by capping mesoporous silica‐coated quantum dots with a programmable DNA hybrid, and the drug release was controlled by microRNA. Once the nanocarriers had been delivered into HeLa cells by aptamer‐mediated recognition and endocytosis, the overexpressed endogenous miR‐21 served as an exclusive key to unlock the nanocarriers by competitive hybridization with the DNA hybrid, which led to a sustained lethality of the HeLa cells. If microRNA that is exclusively expressed in specific pathological cell was screened, a combination of chemotherapy and gene therapy should pave the way for a targeted and personalized treatment of human diseases.
Emerging Applications of Phase‐Change Materials (PCMs): Teaching an Old Dog New Tricks
Authors: Hyun Dong Choon , Levinson Nathanael S. , Jeong Unyong , Xia Younan 
Published: January 2014

AbstractThe nebulous term phase‐change material (PCM) simply refers to any substance that has a large heat of fusion and a sharp melting point. PCMs have been used for many years in commercial applications, mainly for heat management purposes. However, these fascinating materials have recently been rediscovered and applied to a broad range of technologies, such as smart drug delivery, information storage, barcoding, and detection. With the hope of kindling interest in this incredibly versatile range of materials, this Review presents an array of aspects related to the compositions, preparations, and emerging applications of PCMs.
Rheumatoid Factor as a Potentiator of Anti–Citrullinated Protein Antibody–Mediated Inflammation in Rheumatoid Arthritis
Authors: Sokolove Jeremy , Johnson Dannette S. , Lahey Lauren J. , Wagner Catriona A. , Cheng Danye , Thiele Geoffrey M. , Michaud Kaleb , Sayles Harlan , Reimold Andreas M. , Caplan Liron , Cannon Grant W. , Kerr Gail , Mikuls Ted R. , Robinson William H. 
Published: January 2014

ObjectiveThe co‐occurrence of rheumatoid factor (RF) and anti–citrullinated protein antibody (ACPA) positivity in rheumatoid arthritis (RA) is well described. However, the mechanisms underlying the potential interaction between these 2 distinct autoantibodies have not been well defined. The aim of this study was to evaluate the epidemiologic and molecular interaction of ACPAs and RF and its association with both disease activity and measures of RA‐associated inflammation.MethodsIn a cohort of 1,488 US veterans with RA, measures of disease activity and serum levels of cytokines and multiplex ACPAs were compared between the following groups of patients: double‐negative (anti–cyclic citrullinated peptide [anti‐CCP]−/RF−), anti‐CCP+/RF−, anti‐CCP−/RF+, or double‐positive (anti‐CCP+/RF+). Additional studies were performed using an in vitro immune complex (IC) stimulation assay in which macrophages were incubated with ACPA ICs in the presence or absence of monoclonal IgM‐RF, and tumor necrosis factor α production measured as a readout of macrophage activation.ResultsCompared with the double‐negative subgroup (as well as each single‐positive subgroup), the double‐positive subgroup exhibited higher disease activity as well as higher levels of C‐reactive protein and inflammatory cytokines (all P < 0.001). In vitro stimulation of macrophages by ACPA ICs increased cytokine production, and the addition of monoclonal IgM‐RF significantly increased macrophage tumor necrosis factor α production (P = 0.003 versus ACPA ICs alone).ConclusionThe combined presence of ACPAs and IgM‐RF mediates increased proinflammatory cytokine production in vitro and is associated with increased systemic inflammation and disease activity in RA. Our data suggest that IgM‐RF enhances the capacity of ACPA ICs to stimulate macrophage cytokine production, thereby providing a mechanistic link by which RF enhances the pathogenicity of ACPA ICs in RA.
Poor Sleep Quality Is Strongly Associated With Subsequent Pain Intensity in Patients With Acute Low Back Pain
Authors: Alsaadi Saad M. , McAuley James H. , Hush Julia M. , Lo Serigne , Lin Chung‐Wei Christine , Williams Christopher M. , Maher Christopher G. 
Published: January 2014

ObjectiveRecent research suggests that sleep quality and pain intensity are intimately linked. Although sleep problems are common in patients with low back pain, the effect of sleep quality on the levels of pain intensity is currently unknown. The aim of this study was to investigate the effect of sleep quality on subsequent pain intensity in patients with recent‐onset low back pain.MethodsData on 1,246 patients with acute low back pain were included in the analysis. Sleep quality was assessed using the sleep quality item of the Pittsburgh Sleep Quality Index, scored on a 0–3‐point scale, where 0 = very good sleep quality and 3 = very bad sleep quality. Pain intensity was assessed on a numerical rating scale (range 0–10). A generalized estimating equation (GEE) analysis modeled with an exchangeable correlation structure was used to examine the relationship between sleep quality and pain intensity. The model further controlled for symptoms of depression and prognostic factors for low back pain.ResultsThe GEE analysis demonstrated a large effect of poor sleep on subsequent pain intensity, such that for every 1‐point decrease in sleep quality (based on a 0–3‐point scale), pain intensity (based on a 0–10‐point scale) increased by 2.08 points (95% confidence interval 1.99−2.16). This effect was independent of depression and common prognostic factors for low back pain.ConclusionSleep quality is strongly related to subsequent pain intensity in patients with acute low back pain. Future research is needed to determine whether targeting sleep improvement contributes to pain reduction.
Ankylosing Spondylitis, Psoriatic Arthritis, and Risk of Malignant Lymphoma: A Cohort Study Based on Nationwide Prospectively Recorded Data From Sweden
Authors: Hellgren K. , Smedby K. E. , Backlin C. , Sundstrom C. , Feltelius N. , Eriksson J. K. , Baecklund E. , Askling J. 
Published: January 2014

ObjectiveData on lymphoma risk in ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are scarce. This study was undertaken to assess the risk of lymphoma in AS and PsA overall and in relation to therapies, including tumor necrosis factor inhibitor (TNFi), for which lymphoma risks are a concern.MethodsThrough the Swedish National Patient Register we assembled nationwide prevalence cohorts of patients with AS (n = 8,707) and patients with PsA (n = 19,283) for whom data were obtained between 2001 and 2010. Each cohort member was matched to 5 population comparator subjects. Linkage with the nationwide Cancer Register identified all lymphomas recorded from 2001 to 2010. Through the Swedish Biologics Register (Anti‐Rheumatic Therapy in Sweden [ARTIS]), we identified patients exposed to TNFi in the AS cohort (n = 1,908) and the PsA cohort (n = 2,605) before lymphoma diagnosis. Hazard ratios (HRs) for lymphoma were estimated by Cox regression. Crude incidences of lymphoma in TNFi‐exposed and TNFi‐naive patients were compared.ResultsFor AS patients, the HR of having lymphoma versus the general population was 0.9 (95% confidence interval [95% CI] 0.5–1.6) (14 lymphomas). For PsA patients, the corresponding HR was 1.2 (95% CI 0.9–1.7) (45 lymphomas). For PsA patients treated with methotrexate and/or sulfasalazine, the HR of having lymphoma was 1.7 (95% CI 1.0–3.1). The numbers and incidence of lymphoma were not materially different in TNFi‐exposed versus TNFi‐naive AS and PsA patients, although the numbers of lymphomas were small.ConclusionIn contrast to rheumatoid arthritis, the average risks of lymphoma in AS or PsA are not elevated, although increased risks in a subset of PsA patients cannot be excluded. Our findings indicate that TNFi does not affect the risk of lymphoma in AS or in PsA.
Brief Report: Etanercept Inhibits the Tumor Necrosis Factor α–Driven Shift of Th17 Lymphocytes Toward a Nonclassic Th1 Phenotype in Juvenile Idiopathic Arthritis
Authors: Maggi Laura , Cimaz Rolando , Capone Manuela , Santarlasci Veronica , Querci Valentina , Simonini Gabriele , Nencini Francesca , Liotta Francesco , Romagnani Sergio , Maggi Enrico , Annunziato Francesco , Cosmi Lorenzo 
Published: January 2014

ObjectiveTo evaluate the effects of etanercept on the phenotype of CD4+ T helper lymphocytes from patients with juvenile idiopathic arthritis (JIA).MethodsWe compared the proportions of various Th cell subsets in peripheral blood (PB) from etanercept‐treated and untreated JIA patients. An in vitro study was performed on PB mononuclear cells (PBMCs) from 15 children with untreated JIA, in which we evaluated the proliferative response of these cells, as well as their cytokine production profile, in the presence of various stimuli with or without etanercept.ResultsWe found lower proportions of CD4+ CD161+ (nonclassic) Th1 lymphocytes in the PB of patients treated with etanercept than in untreated patients. In vitro, etanercept inhibited the proliferative response induced by either polyclonal or recall antigen stimulation of PBMCs. Moreover, etanercept increased the proportion of CD4+CD161+ Th17/Th1 and Th17 cells in vitro while decreasing the proportions of nonclassic Th1 cell subsets, leaving CD4+CD161− (classic) Th1 cells unaffected. We also found that tumor necrosis factor α (TNFα) was able to induce transition of Th17 lymphocytes toward the nonclassic Th1 phenotype in vitro, probably due to the high expression of TNF receptor type II observed in Th17 cells.ConclusionWe have previously demonstrated the occurrence of a shifting of CD4+CD161+ Th17 cells to the nonclassic Th1 phenotype in children with JIA. The present findings suggest that etanercept can exert its disease‐modifying action by interfering with this shifting.
Early Response of Mouse Joint Tissue to Noninvasive Knee Injury Suggests Treatment Targets
Authors: Wu P. , Holguin N. , Silva M. J. , Fu M. , Liao W. , Sandell L. J. 
Published: January 2014

ObjectiveJoint trauma can lead to a spectrum of acute lesions, including cartilage degradation, ligament or meniscus tears, and synovitis, all potentially associated with osteoarthritis (OA). This study was undertaken to generate and validate a murine model of knee joint trauma following noninvasive controlled injurious compression in vivo.MethodsThe right knees of 8‐week‐old mice were placed in a hyperflexed position and subjected to compressive joint loading at 1 of 3 peak forces (3N, 6N, or 9N) for 60 cycles in a single loading period and harvested on days 5, 9, and 14 after loading (n = 3–5 for each time point and for each loading). The left knees were not loaded and were used as the contralateral control. Histologic, immunohistochemical, and enzyme‐linked immunosorbent assay analyses were performed to evaluate acute pathologic features in chondrocyte viability, cartilage matrix metabolism, synovial reaction, and serum cartilage oligomeric matrix protein (COMP) levels.ResultsAcute joint pathology was associated with increased injurious loads. All loading regimens induced chondrocyte apoptosis, cartilage matrix degradation, disruption of cartilage collagen fibril arrangement, and increased levels of serum COMP. We also observed that 6N loading induced mild synovitis by day 5, whereas at 9N, with tearing of the anterior cruciate ligament, severe posttraumatic synovitis and ectopic cartilage formation were observed.ConclusionWe have established a murine model of knee joint trauma with different degrees of overloading in vivo. Our results suggest that immediate therapies particularly targeted to apoptosis and synovial cell proliferation could affect the acute posttraumatic reaction to potentially limit chronic consequences and OA.
Cyclin‐Dependent Kinase 9 Inhibition Protects Cartilage From the Catabolic Effects of Proinflammatory Cytokines
Authors: Yik Jasper H. N. , Hu Zi'ang , Kumari Ratna , Christiansen Blaine A. , Haudenschild Dominik R. 
Published: January 2014

ObjectiveCyclin‐dependent kinase 9 (CDK‐9) controls the activation of primary inflammatory response genes. The purpose of this study was to determine whether CDK‐9 inhibition protects cartilage from the catabolic effects of proinflammatory cytokines.MethodsHuman chondrocytes were challenged with different proinflammatory stimuli (interleukin‐1β [IL‐1β], lipopolysaccharides, and tumor necrosis factor α) in the presence or absence of either the CDK‐9 inhibitor flavopiridol or small interfering RNA (siRNA). The expression of messenger RNA (mRNA) for inflammatory mediator genes, catabolic genes, and anabolic genes were determined by real‐time quantitative reverse transcription–polymerase chain reaction (qRT‐PCR) analysis. Cartilage explants were incubated for 6 days with IL‐1β in the presence or absence of flavopiridol. Cartilage matrix degradation was assessed by the release of glycosaminoglycan (GAG) and cleaved type II collagen (COL2A) peptides.ResultsCDK‐9 inhibition by flavopiridol or knockdown by siRNA effectively suppressed the induction of mRNA for inducible nitric oxide synthase by all 3 proinflammatory stimuli. Results from NF‐κB–targeted PCR array analysis showed that flavopiridol suppressed IL‐1β induction of a broad range of inflammatory mediator genes (59 of 67 tested). CDK‐9 inhibition also suppressed the induction of catabolic genes (matrix metalloproteinase 1 [MMP‐1], MMP‐3, MMP‐9, MMP‐13, ADAMTS‐4, and ADAMTS‐5), but did not affect the basal expression of anabolic genes (COL2A, aggrecan, and cartilage oligomeric matrix protein) and housekeeping genes. Flavopiridol had no apparent short‐term cytotoxicity, as assessed by G6PDH activity. Finally, in IL‐1β–treated cartilage explants, flavopiridol reduced the release of the matrix degradation product GAG and cleaved COL2A peptides, but did not affect long‐term chondrocyte viability.ConclusionCDK‐9 activity is required for the primary inflammatory response in chondrocytes. Flavopiridol suppresses the induction of inflammatory mediator genes and catabolic genes to protect cartilage from the deleterious effects of proinflammatory cytokines, without affecting cell viability and functions.
Cost-effectiveness and cost–utility of endovascularversusopen repair of ruptured abdominal aortic aneurysm in the Amsterdam Acute Aneurysm Trial
Authors: Kapma M R , Dijksman L M , Reimerink J J , de Groof A J , Zeebregts C J , Wisselink W , Balm R , Dijkgraaf M G W , Vahl A C 
Published: January 2014

AbstractBackgroundMinimally invasive endovascular aneurysm repair (EVAR) could be a surgical technique that improves outcome of patients with ruptured abdominal aortic aneurysm (rAAA). The aim of this study was to analyse the cost-effectiveness and cost–utility of EVAR compared with standard open repair (OR) in the treatment of rAAA, with costs per 30-day and 6-month survivor as outcome parameters.MethodsResource use was determined from the Amsterdam Acute Aneurysm (AJAX) trial, a multicentre randomized trial comparing EVAR with OR in patients with rAAA. The analysis was performed from a provider perspective. All costs were calculated as if all patients had been treated in the same hospital (Onze Lieve Vrouwe Gasthuis, teaching hospital).ResultsA total of 116 patients were randomized. The 30-day mortality rate was 21 per cent after EVAR and 25 per cent for OR: absolute risk reduction (ARR) 4·4 (95 per cent confidence interval (c.i.) –11·0 to 19·7) per cent. At 6 months, the total mortality rate for EVAR was 28 per cent, compared with 31 per cent among those assigned to OR: ARR 2·4 (−14·2 to 19·0) per cent. The mean cost difference between EVAR and OR was €5306 (95 per cent c.i. –1854 to 12 659) at 30 days and €10 189 (−2477 to 24 506) at 6 months. The incremental cost-effectiveness ratio per prevented death was €120 591 at 30 days and €424 542 at 6 months. There was no significant difference in quality of life between EVAR and OR. Nor was EVAR superior regarding cost–utility.ConclusionEVAR may be more effective for rAAA, but its increased costs mean that it is unaffordable based on current standards of societal willingness-to-pay for health gains.
Expertise-based randomized clinical trial of laparoscopic versus small-incision open cholecystectomy (Br J Surg 2013; 100: 886–894)
Authors: Naraynsingh V , Singh Y , Dan D , Maharaj R 
Published: January 2014

Abstract
The Editors welcome topical correspondence from readers relating to articles published in the Journal. Responses should be sent electronically via the BJS website (www.bjs.co.uk). All letters will be reviewed and, if approved, appear on the website. A selection of these will be edited and published in the Journal. Letters must be no more than 250 words in length.
A phase II study of preoperative capecitabine in women with operable hormone receptor positive breast cancer
Authors: Tolaney Sara M. , Jeong Joon , Guo Hao , Brock Jane , Morganstern Daniel , Come Steven E. , Golshan Mehra , Bellon Jennifer , Winer Eric P. , Krop Ian E. 
Published: January 2014

AbstractConventional preoperative chemotherapy regimens have only limited efficacy in hormone receptor positive (HR+) breast cancer and new approaches are needed. We hypothesized that capecitabine, which is effective in metastatic breast cancer, may be an active preoperative treatment for HR+ breast cancer. Women with HR+, HER2‐negative operable breast cancer received capecitabine, 2000 mg/m2 daily in divided doses for 14 days, followed by a 7‐day rest period. Treatment was repeated every 21 days for a total of four cycles. The primary endpoint of the study was to determine the rate of pathological complete response (pCR). Because of slow accrual, the study was closed after 24 patients were enrolled. Three patients had a complete clinical response, and eight patients had a partial clinical response, for an overall clinical response rate of 45.8%. There were no cases of pCR. Of the 22 patients who had pathological response assessment by the Miller–Payne grading system, there were six grade 3 responses, and no grade 4 or 5 responses. Toxicity was manageable: the only grade 3 toxicities observed were one case each of diarrhea, palmar plantar erythrodysesthesia, hypokalemia, and mucositis. There was no association between baseline levels, or change in level from baseline to cycle 1, or from baseline to time of surgery, of thymidine phosphorylase (TYMP), thymidylate synthase (TYMS), dihydropyrimidine dehydrogenase (DPYD), or Ki67 and pathological, clinical, or radiographic response. Preoperative capecitabine is a well‐tolerated regimen, but appears not lead to pCR when used as monotherapy in HR+ breast cancer.