bluuebunny/crossref_metadata_2025_split huggingface dataset:
Importance of Contextual Factors When Measuring Work Outcome in Ankylosing Spondylitis: A Systematic Review by the OMERACT Worker Productivity Group
Authors: Stolwijk Carmen , Castillo‐Ortiz José‐Dionisio , Gignac Monique , Luime Jolanda , Boonen A. ,   for the OMERACT Worker Productivity Group
Published: March 2015

ObjectiveTo review the literature on contextual factors (CoFas) and their relationship to work outcomes in individuals with ankylosing spondylitis (AS).MethodsArticles that quantified the relationship between CoFas and employment status, sick leave, or presenteeism in individuals with AS were systematically identified. CoFas were classified into 5 domains for personal factors and 8 domains for environmental factors. We defined criteria for best‐evidence synthesis for each CoFa domain based on the number of studies exploring that domain, and the quality of evidence of individual studies based on the risk of bias, adjustment of multivariable analyses for disease activity and physical function, and sample size.ResultsTwenty‐five studies met our inclusion criteria: 20 addressed employment status, 6 examined sick leave, and 3 presenteeism. For employment, there was strong evidence for the role of age, moderate evidence for related skills/abilities, the absence of work accommodations, the nature of work and absence of workplace support, and poor evidence for the role of marital status. Evidence was insufficient for sex, education, and physical environment. For sick leave and presenteeism there were too few studies to perform a best‐evidence synthesis for the role of CoFas.ConclusionUsing a newly proposed set of criteria for determining the best‐evidence of the association between CoFa domains and work outcome, the following factors emerged: age, related skills/abilities, work accommodations, nature of work, and workplace support. In addition to disease‐related variables, these CoFa domains seem important to include when designing and interpreting studies on work outcomes.
Glucocorticoid Use in Patients With Systemic Lupus Erythematosus: Association Between Dose and Health Care Utilization and Costs
Authors: Chen Shih‐Yin , Choi Chan‐Bum , Li Qian , Yeh Wei‐Shi , Lee Yuan‐Chi , Kao Amy H. , Liang Matthew H. 
Published: March 2015

ObjectiveTo investigate the determinants of health care utilization and costs with use of glucocorticoid (GC) drugs among adult systemic lupus erythematosus (SLE) patients.MethodsThis cross‐sectional study analyzed established SLE patients identified by International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes from a large US insurance claims database in 2007–2011. Five patient groups were defined by their oral GC use during a 1‐year period: non‐GC users, <60 days of GC use, and ≥60 days of GC use in low dosage (≤7.5 mg/day), medium dosage (>7.5 to ≤15 mg/day), or higher dosage (>15 mg/day). Annual health care utilization and costs were compared across these groups. Incremental costs of GC groups, calculated as the difference in total health care costs compared with those of the non‐GC group, were estimated from multivariable regressions adjusting for demographic/clinical characteristics and stratified by concomitant immunosuppressant use.ResultsA total of 50,230 SLE patients were identified (52% non‐GC users, 20% <60 days of GC use, and 10% low dose, 10% medium dose, and 8% higher dose of ≥60 days of GC use). GC users had higher health care utilization and costs. Incremental costs were significant (all P < 0.01) for medium‐dose ($5,319 and $6,913) and higher‐dose ($12,517 and $15,019) GC groups, regardless of concomitant immunosuppressant use. The incremental costs for the low‐dose GC group with concomitant immunosuppressants ($1,285; P = 0.04) were smaller than the incremental costs for the low‐dose GC group without concomitant immunosuppressants ($2,514; P < 0.01).ConclusionGC use, especially at higher doses, was associated with higher health care utilization and costs. Findings in users with concomitant immunosuppressants suggest that therapies with a GC‐sparing effect may be associated with lower economic burden in SLE treatment.
Endoscopic vidian neurectomy: a prospective case series
Authors: Zhang Han , Micomonaco Damian C. , Dziegielewski Peter T. , Sowerby Leigh J. , Weis Ezekiel , Wright Erin D. 
Published: March 2015

BackgroundChronic refractory vasomotor rhinitis (VMR) is a debilitating condition that causes significant impairment of quality of life. The purpose of this study is to investigate the efficacy and potential side effects of endoscopic vidian neurectomy as treatment for patients with VMR.MethodsThis study was a prospective, intent‐to‐follow case series. Inclusion criteria were as follows: (1) patients with debilitating VMR refractory to medical therapy and with significant impact on quality of life; (2) negative allergy history and skin testing; and (3) negative computed tomography (CT) scan to rule out skull‐base defect or cerebrospinal fluid (CSF) fistula. Patients underwent bilateral vidian neurectomy via a pterygomaxillary approach. Prior to surgery all patients underwent formal ophthalmologic testing to quantify preoperative ocular and lacrimal function. Ophthalmologic testing was repeated postoperatively at approximately 3 months. Patients also completed surveys regarding rhinologic outcomes including the Sinusitis Symptom Questionnaire (SSQ) and the 22‐item Sino‐Nasal Outcome Test (SNOT‐22) at the following time points: preoperatively, and 1 week, 4 weeks, 12 weeks, 6 months, 1 year, and 2 years postsurgery. Descriptive statistics and analysis of variance (ANOVA) were undertaken.ResultsEleven patients (22 sides) underwent bilateral vidian neurectomy with pathologic confirmation of nerve section in all cases. Average follow‐up was 19.4 months. Statistically and clinically significant improvement was measured for both the SSQ and the SNOT‐22 and compared with the patients’ baseline scores (p < 0.0001). Subscores for rhinorrhea and nasal congestions were also statistically significantly improved (p < 0.05). No incidence of permanent or measureable dry eye has been reported.ConclusionThe data suggests that vidian neurectomy is an effective, safe, and definitive treatment for most patients with VMR refractory to medical treatment.
Effects of titanate treatment on morphology and mechanical properties of graphene nanoplatelets/high density polyethylene nanocomposites
Authors: Pokharel Pashupati , Bae Hyunmin , Lim Jung‐Gyu , Lee Kyoung Yong , Choi Sunwoong 
Published: February 2015

ABSTRACTThe effect of graphene nanoplatelets (GNPs) and titanate coupling agent on morphology and mechanical properties of high density polyethylene (HDPE) nanocomposites was investigated. The titanate has a tendency to link chemically with the two dissimilar species GNPs and HDPE via proton coordination to generate a complete continuous phase for stress/strain transfer via the elimination of air voids and hydrophobicity. The interaction of titanate with GNPs and HDPE was effective to improve the dispersion of GNPs in HDPE composites. At constant weight (1 wt %) of titanate treatment for 2 and 5 wt % HDPE composites, we clearly observed a significantly high value of tensile strength and elongation at break than untreated composites. Particularly, composite containing 2 wt % GNPs in HDPE with titanate showed 66.5% improvement of the ultimate tensile strength and an enormously high value of elongation at break. The effect of GNPs dispersion and orientation in HDPE for the mechanical reinforcement was also evaluated based on the experimental modulus data to theoretical predictions made using the Halpin‐Tsai model. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42073.
Helios Enhances Treg Cell Function in Cooperation With FoxP3
Authors: Takatori Hiroaki , Kawashima Hirotoshi , Matsuki Ayako , Meguro Kazuyuki , Tanaka Shigeru , Iwamoto Taro , Sanayama Yoshie , Nishikawa Natsuko , Tamachi Tomohiro , Ikeda Kei , Suto Akira , Suzuki Kotaro , Kagami Shin‐ichiro , Hirose Koichi , Kubo Masato , Hori Shohei , Nakajima Hiroshi 
Published: March 2015

ObjectiveHelios+FoxP3+CD4+ (Helios+) Treg cells are believed to be involved in the regulation of various autoimmune diseases; however, the regulatory mechanisms underlying the development of Helios+ Treg cells remain uncertain. This study was undertaken to elucidate the regulatory mechanisms of Helios expression in CD4+ T cells and its roles in transforming growth factor β (TGFβ)–induced Treg cell function.MethodsWe examined the expression of Helios in CD4+ T cells in patients with rheumatoid arthritis by DNA microarray analysis before and after treatment with biologic agents. We also examined the effect of interleukin‐6 (IL‐6) and TGFβ on Helios expression in CD4+ T cells in humans and mice. The effect of forced expression of Helios on murine induced Treg cell function was also examined. The role of FoxP3 in the induction and function of Helios was assessed by using CD4+ T cells from FoxP3‐deficient scurfy mice.ResultsTocilizumab, but not tumor necrosis factor (TNF) inhibitors or abatacept, increased Helios expression in CD4+ T cells in patients with a good response. IL‐6 inhibited the TGFβ‐induced development of Helios+ induced Treg cells in both humans and mice. Both cell‐intrinsic FoxP3 expression and TGFβ signaling were required for Helios induction in murine induced Treg cells. The forced expression of Helios enhanced the expression of various Treg cell–related molecules and the suppressive function in murine induced Treg cells. Helios‐mediated enhancement of the suppressive function of induced Treg cells was obvious in FoxP3‐sufficient CD4+ T cells but not in FoxP3‐deficient CD4+ T cells.ConclusionOur findings indicate that Helios enhances induced Treg cell function in cooperation with FoxP3.
Suppression of Peripheral Pain by Blockade of Voltage‐Gated Calcium 2.2 Channels in Nociceptors Induces RANKL and Impairs Recovery From Inflammatory Arthritis in a Mouse Model
Authors: Baddack Uta , Frahm Silke , Antolin‐Fontes Beatriz , Grobe Jenny , Lipp Martin , Müller Gerd , Ibañez‐Tallon Ines 
Published: March 2015

ObjectiveA hallmark of rheumatoid arthritis (RA) is the chronic pain that accompanies inflammation and joint deformation. Patients with RA rate pain relief as the highest priority; however, few studies have addressed the efficacy and safety of therapies directed specifically toward pain pathways. The ω‐conotoxin MVIIA (ziconotide) is used in humans to alleviate persistent pain syndromes, because it specifically blocks the voltage‐gated calcium 2.2 (CaV2.2) channel, which mediates the release of neurotransmitters and proinflammatory mediators from peripheral nociceptor nerve terminals. The aims of this study were to investigate whether blockade of CaV2.2 can suppress arthritis pain, and to examine the progression of induced arthritis during persistent CaV2.2 blockade.MethodsTransgenic mice expressing a membrane‐tethered form of MVIIA under the control of a nociceptor‐specific gene (MVIIA‐transgenic mice) were used in the experiments. The mice were subjected to unilateral induction of joint inflammation using a combination of antigen and collagen.ResultsCaV2.2 blockade mediated by tethered MVIIA effectively suppressed arthritis‐induced pain; however, in contrast to their wild‐type littermates, which ultimately regained use of their injured joint as inflammation subsided, MVIIA‐transgenic mice showed continued inflammation, with up‐regulation of the osteoclast activator RANKL and concomitant joint and bone destruction.ConclusionTaken together, our results indicate that alleviation of peripheral pain by blockade of CaV2.2‐ mediated calcium influx and signaling in nociceptor sensory neurons impairs recovery from induced arthritis and point to the potentially devastating effects of using CaV2.2 channel blockers as analgesics during inflammation.
Rissbreitenberechnung bei Flächentragwerken mit beliebig orientierter Bewehrung
Authors: Krakowski Waldemar , Empelmann Martin 
Published: March 2015

AbstractDie Berechnung der Rissbreite von Stabtragwerken entsprechend DIN EN 1992‐1‐1 in Verbindung mit dem nationalen Anhang führt auf den bekannten und bewährten Ansatz der DIN 1045‐1. Der Nachweis gilt gleichermaßen für Bauteile unter Zug‐ als auch unter Biegebeanspruchung. Wesentliche Kenngrößen wie z. B. die Betonzugfestigkeit, der Stabdurchmesser und der Bewehrungsgrad werden mechanisch konsistent und ausreichend genau berücksichtigt. Für die Anwendung bei Flächentragwerken mit beliebig orientierter Bewehrung (Platten und Scheiben) sind die Angaben in DIN EN 1992‐1‐1 jedoch nicht ausreichend. Daher wurde im Rahmen von zwei Forschungsvorhaben ein verallgemeinerter Ansatz zur Berechnung der Rissbreiten entwickelt, der die bisherigen Regelungen auch auf Flächentragwerke mit beliebig orientierter Bewehrung erweitert. Im Beitrag werden die Grundlagen der Rissbreitenberechnung bei Flächentragwerken erläutert, ein neuer Ansatz vorgestellt sowie mit zur Verfügung stehenden Versuchsdaten abgeglichen und die Anwendung anhand eines typischen Ingenieurbauwerks aufgezeigt.Crack width calculation for shell elementsThe crack width calculation given in DIN EN 1992‐1‐1 is based on a tension strut model. Influenced by the main parameters as concrete tensile strength, diameter of reinforcement and reinforcement ratio this approach shows good agreement with test data. But application to shell elements like plates or panels is not possible without modification especially for arbitrary reinforcement orientation to the tensile direction. Therefore an extended approach has been developed for calculating crack widths of shell elements in any case. Based on tests this new approach allows variable application for the analysis of plates in bending and panels in tension. The approach has been checked against test data and other models known from literature. The application is demonstrated on a typical construction.
Bacteriophage therapy for membrane biofouling in membrane bioreactors and antibiotic‐resistant bacterial biofilms
Authors: Bhattacharjee Ananda Shankar , Choi Jeongdong , Motlagh Amir Mohaghegh , Mukherji Sachiyo T. , Goel Ramesh 
Published: February 2015

AbstractTo demonstrate elimination of bacterial biofilm on membranes to represent wastewater treatment as well as biofilm formed by antibiotic‐resistant bacterial (ARB) to signify medical application, an antibiotic‐resistant bacterium and its lytic bacteriophage were isolated from a full‐scale wastewater treatment plant. Based on gram staining and complete 16 S rDNA sequencing, the isolated bacterium showed a more than 99% homology with Delftia tsuruhatensis, a gram‐negative bacterium belonging to β‐proteobacteria. The Delftia lytic phage's draft genome revealed the phage to be an N4‐like phage with 59.7% G + C content. No transfer RNAs were detected for the phage suggesting that the phage is highly adapted to its host Delftia tsuruhatensis ARB‐1 with regard to codon usage, and does not require additional tRNAs of its own. The gene annotation of the Delftia lytic phage found three different components of RNA polymerase (RNAP) in the genome, which is a typical characteristic of N4‐like phages. The lytic phage specific to D. tsuruhatensis ARB‐1 could successfully remove the biofilm formed by it on a glass slide. The water flux through the membrane of a prototype lab‐scale membrane bioreactor decreased from 47 L/h m2 to ∼15 L/h m2 over 4 days due to a biofilm formed by D. tsuruhatensis ARB‐1. However, the flux increased to 70% of the original after the lytic phage application. Overall, this research demonstrated phage therapy's great potential to solve the problem of membrane biofouling, as well as the problems posed by pathogenic biofilms in external wounds and on medical instruments. Biotechnol. Bioeng. 2015;112: 1644–1654. © 2015 Wiley Periodicals, Inc.
High throughput screening of particle conditioning operations: I. System design and method development
Authors: Noyes Aaron , Huffman Ben , Godavarti Ranga , Titchener‐Hooker Nigel , Coffman Jonathan , Sunasara Khurram , Mukhopadhyay Tarit 
Published: February 2015

ABSTRACTThe biotech industry is under increasing pressure to decrease both time to market and development costs. Simultaneously, regulators are expecting increased process understanding. High throughput process development (HTPD) employs small volumes, parallel processing, and high throughput analytics to reduce development costs and speed the development of novel therapeutics. As such, HTPD is increasingly viewed as integral to improving developmental productivity and deepening process understanding. Particle conditioning steps such as precipitation and flocculation may be used to aid the recovery and purification of biological products. In this first part of two articles, we describe an ultra scale‐down system (USD) for high throughput particle conditioning (HTPC) composed of off‐the‐shelf components. The apparatus is comprised of a temperature‐controlled microplate with magnetically driven stirrers and integrated with a Tecan liquid handling robot. With this system, 96 individual reaction conditions can be evaluated in parallel, including downstream centrifugal clarification. A comprehensive suite of high throughput analytics enables measurement of product titer, product quality, impurity clearance, clarification efficiency, and particle characterization. HTPC at the 1 mL scale was evaluated with fermentation broth containing a vaccine polysaccharide. The response profile was compared with the Pilot‐scale performance of a non‐geometrically similar, 3 L reactor. An engineering characterization of the reactors and scale‐up context examines theoretical considerations for comparing this USD system with larger scale stirred reactors. In the second paper, we will explore application of this system to industrially relevant vaccines and test different scale‐up heuristics. Biotechnol. Bioeng. 2015;112: 1554–1567. © 2015 Wiley Periodicals, Inc.
Modified amelogenin is a new and versatile nanomaterial for biomedical applications
Authors: Imhof Thomas , Gruenewald Nora , Schwarz Guenter , Noack Michael J. , Koch Manuel 
Published: February 2015

ABSTRACTAmelogenin self‐assembly is crucial for tooth biomineralization and crystallite enamel orientation. Amelogenin forms stable nanoparticles under physiological conditions. Here, we tested whether the surface properties and binding characteristics of these particles could be modified to enhance amelogenin function as a biomaterial. We evaluated different amelogenin fusion proteins for their ability to form hybrid nanoparticles. As a proof‐of‐concept, the integrin‐binding tripeptide Arg–Gly–Asp (RGD) sequence from fibronectin was integrated into mouse amelogenin (rM179) at three different positions. Dynamic light scattering (DLS) measurements revealed that these amelogenin fusion proteins still form nanospheres. Additional DLS and isothermal titration calorimetry measurements showed that the mixtures of RGD‐modified amelogenin and wild‐type amelogenin form stable particles. We determined that insertion of the RGD‐loop at the amelogenin C‐terminus converts the nanoparticle into a cell‐binding substrate. Calvarial osteoblasts efficiently attached and spread on modified amelogenin, whereas almost no binding was observed on wild‐type amelogenin. These results establish amelogenin as a new versatile biomaterial that can be easily modified to add additional functions. Biotechnol. Bioeng. 2015;112: 1708–1713. © 2015 Wiley Periodicals, Inc.
Hi‐Fi SELEX: A high‐fidelity digital‐PCR based therapeutic aptamer discovery platform
Authors: Ouellet Eric , Foley Jonathan H. , Conway Edward M. , Haynes Charles 
Published: February 2015

ABSTRACTCurrent technologies for aptamer discovery typically leverage the systematic evolution of ligands by exponential enrichment (SELEX) concept by recursively panning semi‐combinatorial ssDNA or RNA libraries against a molecular target. The expectation is that this iterative selection process will be sufficiently stringent to identify a candidate pool of specific high‐affinity aptamers. However, failure of this process to yield promising aptamers is common, due in part to (i) limitations in library designs, (ii) retention of non‐specific aptamers during screening rounds, (iii) excessive accumulation of amplification artifacts, and (iv) the use of screening criteria (binding affinity) that does not reflect therapeutic activity. We report a new selection platform, High‐Fidelity (Hi‐Fi) SELEX, that introduces fixed‐region blocking elements to safeguard the functional diversity of the library. The chemistry of the target‐display surface and the composition of the equilibration solvent are engineered to strongly inhibit non‐specific retention of aptamers. Partition efficiencies approaching 106 are thereby realized. Retained members are amplified in Hi‐Fi SELEX by digital PCR in a manner that ensures both elimination of amplification artifacts and stoichiometric conversion of amplicons into the single‐stranded library required for the next selection round. Improvements to aptamer selections are first demonstrated using human α‐thrombin as the target. Three clinical targets (human factors IXa, X, and D) are then subjected to Hi‐Fi SELEX. For each, rapid enrichment of ssDNA aptamers offering an order‐nM mean equilibrium dissociation constant (Kd) is achieved within three selection rounds, as quantified by a new label‐free qPCR assay reported here. Therapeutic candidates against factor D are identified. Biotechnol. Bioeng. 2015;112: 1506–1522. © 2015 Wiley Periodicals, Inc.
Determinants of psychological resistance and recovery among women exposed to assaultive trauma
Authors: Rusch Heather L. , Shvil Erel , Szanton Sarah L. , Neria Yuval , Gill Jessica M. 
Published: February 2015

AbstractIntroductionWomen exposed to potentially traumatic events (PTEs) are at high risk for developing psychiatric disorders, including posttraumatic stress disorder (PTSD), general anxiety disorder (GAD), major depressive disorder (MDD), and substance‐related disorders. However, this risk is not universal. Most women are resistant (i.e., remain asymptomatic), or recover following a brief symptomatic period. This study examined the psychological factors associated with resistant and recovered outcomes in a sample of high‐risk women exposed to assault‐related PTEs.MethodOne hundred and fifty‐nine women completed the Life Events Checklist and were administered the Structured Clinical Interview for DSM‐IV Axis I Disorders. This resulted in three groups: (1) no diagnosis (no past or current psychiatric disorder diagnosis; n = 56), (2) past diagnosis (a past psychiatric disorder diagnosis, but none currently; n = 31), and (3) current diagnosis (a current diagnosis of one or more psychiatric disorders; n = 72). Groups were compared on sociodemographics, PTE exposure, psychopathology, health‐related quality of life (HRQOL), and psychological resilience‐related factors.ResultsThe majority of respondents (79%) did not develop chronic PTSD following assault exposure, and the most common psychiatric outcome was MDD (30%). High endorsement of mastery and social support were associated with the no diagnosis group; and greater reports of mastery and posttraumatic growth were associated with recovery from a past psychiatric disorder. Furthermore, both resilient groups (i.e., no diagnosis and past diagnosis) scored higher on HRQOL measures compared with the current diagnosis group (P < 0.001).ConclusionPsychological resilience has ramifications to health and well‐being, and identifying these factors has potential to inform preventive strategies and treatment interventions for assault exposed women.