bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adult Primary Central Nervous System Vasculitis Treatment and Course: Analysis of One Hundred Sixty‐Three Patients
Authors: Salvarani Carlo , Brown Robert D. , Christianson Teresa J. H. , Huston John , Giannini Caterina , Miller Dylan V. , Hunder Gene G. 
Published: February 2015

ObjectiveTo describe the treatment and outcomes of patients with primary central nervous system (CNS) vasculitis.MethodsWe retrospectively studied a cohort of 163 consecutive patients with primary CNS vasculitis who were seen at the Mayo Clinic over a 29‐year period. We analyzed treatments, treatment responses, and factors predictive of outcomes.ResultsA favorable response was observed in 85% of patients treated with prednisone alone and in 80% of patients treated with prednisone and cyclophosphamide. Relapses were observed in 27% of patients, and 25% of patients had discontinued therapy by the time of the last followup visit. Treatment with prednisone alone was associated with more frequent relapses (odds ratio [OR] 2.90), while large vessel involvement (OR 6.14) and cerebral infarcts at the time of diagnosis (OR 3.32) were associated with a poor response to treatment. Prominent gadolinium‐enhanced cerebral lesions or meninges were linked with continued treatment at the last followup encounter (OR 2.28). Higher disability scores at the last followup visit were associated with increasing age at the time of diagnosis (OR 1.44) and cerebral infarctions (OR 3.74), while lower disability scores were associated with gadolinium‐enhanced cerebral lesions or meninges (OR 0.35) and cerebral amyloid angiopathy (OR 0.24). Increased mortality was associated with increasing age at diagnosis (hazard ratio [HR] 1.39), diagnosis by angiography (HR 3.28), cerebral infarction (HR 4.44), and large vessel involvement (HR 4.98), while reduced mortality was associated with gadolinium‐enhanced cerebral lesions or meninges (HR 0.20).ConclusionThe majority of patients with primary CNS vasculitis responded to treatment. Recognition of findings at diagnosis that predict the course or outcome may aid in decision‐making regarding therapy.
The Relationship of Autophagy Defects to Cartilage Damage During Joint Aging in a Mouse Model
Authors: Caramés Beatriz , Olmer Merissa , Kiosses William B. , Lotz Martin K. 
Published: February 2015

ObjectiveAging is a main risk factor for osteo arthritis (OA), the most prevalent musculoskeletal disorder. Defects in autophagy, an essential cellular homeostasis mechanism, have recently been observed in OA articular cartilage. The objectives of this study were to establish the constitutive level of autophagy activation in normal cartilage and to monitor the temporal relationship between changes in autophagy and aging‐related degradation of cartilage in a mouse model.MethodsIn GFP‐LC3–transgenic mice, green fluo rescent protein (GFP)–light chain 3 (LC3) is ubiquitously expressed, and the accumulation of GFP puncta, repre senting autophagosomes, was quantified by confocal microscopy as a measure of autophagy activation. Expression of the autophagy proteins autophagy‐related protein 5 (ATG‐5) and microtubule‐associated protein 1 light chain 3 (LC3) was analyzed by immunohistochemistry. Cartilage cellularity, apoptotic cell death, and cartilage structural damage and changes in synovium and bone were examined by histology and immunohistochemistry.ResultsBasal autophagy activation was detected in liver and knee articular cartilage from young (6‐month‐old) mice, with higher levels in cartilage than in liver in the same animals. In 28‐month‐old mice, there was a statistically significant reduction in the total number of autophagic vesicles per cell (P < 0.01) and in the total area of vesicles per cell (P < 0.01) in the articular cartilage as compared to that from young 6‐month‐old mice. With increasing age, the expression of ATG‐5 and LC3 decreased, and this was followed by a reduction in cartilage cellularity and an increase in the apoptosis marker poly(ADP‐ribose) polymerase p85. Cartilage structural damage progressed in an age‐dependent manner subsequent to the autophagy changes.ConclusionAutophagy is constitutively activated in normal cartilage. This is compromised with aging and precedes cartilage cell death and structural damage.
Calcitonin Gene‐Related Peptide–Expressing Sensory Neurons and Spinal Microglial Reactivity Contribute to Pain States in Collagen‐Induced Arthritis
Authors: Nieto Francisco R. , Clark Anna K. , Grist John , Chapman Victoria , Malcangio Marzia 
Published: February 2015

ObjectiveTo evaluate the contribution of sensory neurons in ankle joints and adjacent tissue to the development of pain in collagen‐induced arthritis (CIA), and to determine the relationship between pain and the appearance of clinical signs.MethodsMechanical and heat hypersensitivity and hind paw swelling were assessed in Lewis rats before and until 18 days following collagen immunization. We examined the effect of intrathecal administration of a calcitonin gene‐related peptide (CGRP) antagonist (CGRP8–37) from day 11 to day 18 postimmunization on CIA‐induced hypersensitivity. During CIA development, CGRP and p‐ERK immunoreactivity was quantified in lumbar dorsal root ganglia in which sensory neurons innervating the ankle joint were identified by retrograde labeling with Fluoro‐Gold. Microgliosis in the lumbar dorsal horn was assessed by immunohistochemistry, and release of CGRP evoked by activity of primary afferent fibers was measured using a preparation of isolated dorsal horn with dorsal roots attached.ResultsCIA was associated with mechanical hypersensitivity that was evident before hind paw swelling and that was exacerbated with the development of swelling. Heat hyperalgesia developed along with swelling. Concomitant with the development of mechanical hypersensitivity, joint innervating neurons exhibited enhanced CGRP expression and an activated phenotype (increased p‐ERK expression), and significant microgliosis became evident in the dorsal horn; these peripheral and central changes were augmented further with disease progression. CGRP release evoked by dorsal root stimulation was higher in the dorsal horn on day 18 in rats with CIA compared to control rats. Prolonged intrathecal administration of CGRP8–37 attenuated established mechanical hypersensitivity and reduced spinal microgliosis.ConclusionSensory neuron–derived CGRP sustains mechanical hypersensitivity and spinal microglial reactivity in CIA, suggesting that central mechanisms play critical roles in chronic inflammatory pain. Blockade of these central events may provide pain relief in rheumatoid arthritis patients.
Efficacy and Safety of Anti–Interleukin‐20 Monoclonal Antibody in Patients With Rheumatoid Arthritis: A Randomized Phase IIa Trial
Authors: Šenolt Ladislav , Leszczynski Piotr , Dokoupilová Eva , Göthberg Marie , Valencia Xavier , Hansen Brian Bekker , Cañete Juan D. 
Published: February 2015

ObjectiveInterleukin‐20 (IL‐20) is implicated in the pathogenesis of rheumatoid arthritis (RA). The efficacy, safety, and tolerability of NNC0109‐0012, a selective anti–IL‐20 recombinant human monoclonal antibody (mAb), were assessed in patients with active RA who had an inadequate response to methotrexate therapy.MethodsSixty‐seven patients with RA were enrolled and randomized (2:1) to receive NNC0109‐0012 (3 mg/kg per week, subcutaneously) or placebo in a phase IIa, double‐blind, 12‐week trial with a 13‐week followup. The primary end point was change in the Disease Activity Score in 28 joints based on C‐reactive protein level (DAS28‐CRP) from baseline to week 12.ResultsIn patients treated with NNC0109‐0012, the primary end point, improvement in the DAS28‐CRP at week 12, was achieved (estimated difference −0.88; P = 0.02), with significant improvement starting at week 1. A greater response was observed in seropositive patients (estimated difference −1.66; P < 0.001), which was sustained through 13 weeks of followup, whereas no improvement was noted in patients with seronegative RA. A significant proportion of patients with seropositive RA receiving NNC0109‐0012, compared to those receiving placebo, achieved treatment responses according to the American College of Rheumatology 20% (ACR20) (59% versus 21%), ACR50 (48% versus 14%), and ACR70 (35% versus 0%) levels of improvement, and showed greater improvements in the Health Assessment Questionnaire disability index (P = 0.047). The most frequent adverse events reported with NNC0109‐0012 were injection site reactions and infections (e.g., herpes, nasopharyngitis, respiratory, and urinary). No serious infections or discontinuations associated with NNC0109‐0012 were observed.ConclusionIn this phase IIa trial, treatment with NNC0109‐0012 (anti–IL‐20 mAb) was effective in patients with seropositive RA as early as week 1, with further improvements to week 12. No safety or tolerability concerns were identified with weekly NNC0109‐0012 administration.
Lubricin/Proteoglycan 4 Binding to CD44 Receptor: A Mechanism of the Suppression of Proinflammatory Cytokine–Induced Synoviocyte Proliferation by Lubricin
Authors: Al‐Sharif Afnan , Jamal Maha , Zhang Ling X. , Larson Katherine , Schmidt Tannin A. , Jay Gregory D. , Elsaid Khaled A. 
Published: February 2015

ObjectiveTo evaluate the binding of recombinant human proteoglycan 4 (rhPRG4) to CD44 receptor and its consequences on cytokine‐induced synoviocyte proliferation.MethodsThe binding of rhPRG4 to CD44 and competition with high molecular weight (HMW) hyaluronic acid (HA) was evaluated using a direct enzyme‐linked immunosorbent assay (ELISA) and surface plasmon resonance. Sialidase A and O‐glycosidase digestion of rhPRG4 was performed, and CD44 binding was evaluated using ELISA. Rheumatoid arthritis (RA) fibroblast‐like synoviocytes (FLS) were stimulated with interleukin‐1β (IL‐1β) or tumor necrosis factor α (TNFα) for 48 hours in the presence or absence of rhPRG4 or HMW HA at 20, 40, and 80 μg/ml, and cell proliferation was measured. The contribution of CD44 was assessed by coincubation with a CD44 antibody (IM7). The antiproliferative effect of rhPRG4 was investigated following treatment of PRG4–/– mouse synoviocytes with IL‐1β or TNFα in the presence or absence of IM7.ResultsRecombinant human PRG4 bound CD44 and interfered with the binding of HMW HA to CD44. Removal of sialic acid and O‐glycosylations significantly increased CD44 binding by rhPRG4 (P < 0.001). Both rhPRG4 and HMW HA at 40 and 80 μg/ml significantly suppressed IL‐1β–induced proliferation of RA FLS (P < 0.05). Recombinant human PRG4 at 20, 40, and 80 μg/ml significantly suppressed TNFα‐induced RA FLS proliferation (P < 0.05). CD44 neutralization reversed the effect of rhPRG4 on IL‐1β– and TNFα‐stimulated RA FLS and the effect of HMW HA on IL‐1β–stimulated RA FLS. Recombinant human PRG4 inhibited cytokine‐induced proliferation of PRG4–/– synoviocytes, which could be prevented by blocking CD44.ConclusionPRG4 (lubricin) is a novel putative ligand for CD44 and may control synoviocyte overgrowth in inflammatory arthropathies via a CD44‐mediated mechanism.
Brief Report: Ultrasonographic Assessment of Salivary Gland Response to Rituximab in Primary Sjögren's Syndrome
Authors: Jousse‐Joulin Sandrine , Devauchelle‐Pensec Valérie , Cornec Divi , Marhadour Thierry , Bressollette Luc , Gestin Simon , Pers Jacques Olivier , Nowak Emmanuel , Saraux Alain 
Published: February 2015

ObjectiveTo evaluate changes in salivary gland echostructure and vascularization after rituximab treatment in patients with primary Sjögren's syndrome (SS).MethodsTwenty‐eight patients with primary SS included in the multicenter, randomized, double‐blind, placebo‐controlled Tolerance and Efficacy of Rituximab in Primary Sjögren's Syndrome (TEARS) trial underwent salivary gland ultrasonography before the first placebo or rituximab infusion and then 6 months later. Trial inclusion criteria were scores of ≥50 mm on at least 2 of 4 visual analog scales (VAS) evaluating dryness, pain, fatigue, and global disease; and recent‐onset (<10 years) biologically active primary SS and/or systemic primary SS. Patients were randomly assigned (1:1) to rituximab (1 gm at weeks 0 and 2) or placebo. Ultrasonography of both parotid and submandibular glands was performed to assess echostructure (using a semiquantitative score of 0–4, with improvement defined as a ≥1‐point decrease), size of each gland, and vascularization based on the resistive index of the transverse facial artery of the parotid gland before and after lemon juice stimulation.ResultsOf the 28 patients, 5 (18%; 3 in the placebo group and 2 in the rituximab group) had clinically detectable bilateral parotid gland enlargement at baseline. Parotid parenchyma echostructure improved in 50% of the rituximab‐treated patients versus 7% of the placebo‐treated patients (P = 0.03). In the submandibular glands, echostructure also improved in a larger proportion of rituximab‐treated patients, although the difference was not significant (36% versus 7% of placebo‐treated patients; P = 0.16). Gland sizes and resistive index remained unchanged.ConclusionUltrasonography showed improved salivary gland echostructure in patients with primary SS receiving rituximab, with no changes in salivary gland size or vascularization, 6 months after the first infusion.
Pharmacokinetic modeling of tranexamic acid for patients undergoing cardiac surgery with normal renal function and model simulations for patients with renal impairment
Authors: Yang Qi Joy , Jerath Angela , Bies Robert R. , Wąsowicz Marcin , Pang K. Sandy 
Published: February 2015

AbstractTranexamic acid (TXA), an effective anti‐fibrinolytic agent that is cleared by glomerular filtration, is used widely for cardiopulmonary bypass (CPB) surgery. However, an effective dosing regimen has not been fully developed in patients with renal impairment. The aims of this study were to characterize the inter‐patient variability associated with pharmacokinetic parameters and to recommend a new dosing adjustment based on the BART dosing regimen for CPB patients with chronic renal dysfunction (CRD). Recently published data on CPB patients with normal renal function (n = 15) were re‐examined with a two‐compartment model using the ADAPT5® and NONMEMVII® to identify covariates that explain inter‐patient variability and to ascertain whether sampling strategies might affect parameter estimation. A series of simulations was performed to adjust the BART dosing regimen for CPB patients with renal impairment. Based on the two‐compartmental model, the number of samples obtained after discontinuation of TXA infusion was found not to be critical in parameter estimation (p > 0.05). Both body weight and creatinine clearance were identified as significant covariates (p < 0.005). Simulations showed significantly higher than normal TXA concentrations in CRD patients who received the standard dosing regimen in the BART trial. Adjustment of the maintenance infusion rate based on the percent reduction in renal clearance resulted in predicted plasma TXA concentrations that were safe and therapeutic (~100 mg·L−1). Our proposed dosing regimen, with consideration of renal function, is predicted to maintain effective target plasma concentrations below those associated with toxicity for patients with renal failure for CPB. Copyright © 2015 John Wiley & Sons, Ltd.
Effects of Maternal and Lactational Exposure to 2‐Hydroxy‐4‐Methoxybenzone on Development and Reproductive Organs in Male and Female Rat Offspring
Authors: Nakamura Noriko , Inselman Amy L. , White Gene A. , Chang Ching‐Wei , Trbojevich Raul A. , Sephr Estatira , Voris Kristie L. , Patton Ralph E. , Bryant Matthew S. , Harrouk Wafa , McIntyre Barry S. , Foster Paul M.D. , Hansen Deborah K. 
Published: February 2015

BACKGROUND2‐Hydroxy‐4‐methoxybenzophenone (HMB) is an ultraviolet (UV) absorbing compound used in many cosmetic products as a UV‐protecting agent and in plastics for preventing UV‐induced photodecomposition. HMB has been detected in over 95% of randomly collected human urine samples from adults and from premature infants, and it may have estrogenic potential.METHODSTo determine the effects of maternal and lactational exposure to HMB on development and reproductive organs of offspring, time‐mated female Harlan Sprague‐Dawley rats were dosed with 0, 1000, 3000, 10,000, 25,000, or 50,000 ppm HMB (seven to eight per group) added to chow from gestation day 6 until weaning on postnatal day (PND) 23.RESULTS AND CONCLUSIONExposure to HMB was associated with reduced body and organ weights in female and male offspring. No significant differences were observed in the number of implantation sites/litter, mean resorptions/litter, % litters with resorptions, number and weights of live fetuses, or sex ratios between the control and HMB dose groups. Normalized anogenital distance in male pups at PND 23 was decreased in the highest dose group. Spermatocyte development was impaired in testes of male offspring in the highest dose group. In females, follicular development was delayed in the highest dose group. However, by evaluating levels of the compound in rat serum, the doses at which adverse events occurred are much higher than usual human exposure levels. Thus, exposure to less than 10,000 ppm HMB does not appear to be associated with adverse effects on the reproductive system in rats
Camelina as a sustainable oilseed crop: Contributions of plant breeding and genetic engineering
Authors: Vollmann Johann , Eynck Christina 
Published: February 2015

AbstractCamelina is an underutilized Brassicaceae oilseed plant with a considerable agronomic potential for biofuel and vegetable oil production in temperate regions. In contrast to most Brassicaceae, camelina is resistant to alternaria black spot and other diseases and pests. Sequencing of the camelina genome revealed an undifferentiated allohexaploid genome with a comparatively large number of genes and low percentage of repetitive DNA. As there is a close relationship between camelina and the genetic model plant Arabidopsis, this review aims at exploring the potential of translating basic Arabidopsis results into a camelina oilseed crop for food and non‐food applications. Recently, Arabidopsis genes for drought resistance or increased photosynthesis and overall productivity have successfully been expressed in camelina. In addition, gene constructs affecting lipid metabolism pathways have been engineered into camelina for synthesizing either long‐chain polyunsaturated fatty acids, hydroxy fatty acids or high‐oleic oils in particular camelina strains, which is of great interest in human food, industrial or biofuel applications, respectively. These results confirm the potential of camelina to serve as a biotechnology platform in biorefinery applications thus justifying further investment in breeding and genetic research for combining agronomic potential, unique oil quality features and biosafety into an agricultural production system.
Meta-analysis of prognostic factors for amputation following surgical repair of lower extremity vascular trauma
Authors: Perkins Z B , Yet B , Glasgow S , Cole E , Marsh W , Brohi K , Rasmussen T E , Tai N R M 
Published: February 2015

AbstractBackgroundLower extremity vascular trauma (LEVT) is a major cause of amputation. A clear understanding of prognostic factors for amputation is important to inform surgical decision-making, patient counselling and risk stratification. The aim was to develop an understanding of prognostic factors for amputation following surgical repair of LEVT.MethodsA systematic review was conducted to identify potential prognostic factors. Bayesian meta-analysis was used to calculate an absolute (pooled proportion) and relative (pooled odds ratio, OR) measure of the amputation risk for each factor.ResultsForty-five studies, totalling 3187 discrete LEVT repairs, were included. The overall amputation rate was 10·0 (95 per cent credible interval 7·4 to 13·1) per cent. Significant prognostic factors for secondary amputation included: associated major soft tissue injury (26 versus 8 per cent for no soft tissue injury; OR 5·80), compartment syndrome (28 versus 6 per cent; OR 5·11), multiple arterial injuries (18 versus 9 per cent; OR 4·85), duration of ischaemia exceeding 6 h (24 versus 5 per cent; OR 4·40), associated fracture (14 versus 2 per cent; OR 4·30), mechanism of injury (blast 19 per cent, blunt 16 per cent, penetrating 5 per cent), anatomical site of injury (iliac 18 per cent, popliteal 14 per cent, tibial 10 per cent, femoral 4 per cent), age over 55 years (16 versus 9 per cent; OR 3·03) and sex (men 7 per cent versus women 8 per cent; OR 0·64). Shock and nerve or venous injuries were not significant prognostic factors for secondary amputation.ConclusionA significant proportion of patients who undergo lower extremity vascular trauma repair will require secondary amputation. This meta-analysis describes significant prognostic factors needed to inform surgical judgement, risk assessment and patient counselling.
Comparative Analysis of Different Control Strategies for a Train of Cryogenic 13C Separation Columns
Authors: Muresan Cristina I. , Dulf Eva H. , Both Roxana 
Published: February 2015

AbstractCarbon isotopes are widely used in numerous industries, especially in medicine. The advantage of using 13C‐labeled products is only shadowed by the difficulty of increasing the natural concentration. One method available is a train of cryogenic distillation columns. This paper presents a preliminary analysis of three different control strategies for a unit comprising three 7‐m‐high isotope separation columns: a decentralized multivariable proportional‐integral controller and two decoupling control algorithms. For the first one, a single controller is designed for the entire distillation column train, whereas for the second decoupling approach, three separate controllers are designed for each of the three columns. Simulation results show that the last approach provides significantly improved results when compared to the other two control strategies.
Application of Sorbents for Industrial Waste Water Purification
Authors: Matejkova Martina , Soukup Karel , Kastanek Frantisek , Capek Pavel , Grabowski Jacek , Stanczyk Krzysztof , Solcova Olga 
Published: February 2015

AbstractA sorption technique was tested for decontamination of post‐processing underground coal gasification (UCG) water contaminated by a variety of organic and inorganic substances. Four sorbents (two zeolites and two activated carbons) with nanoiron were chosen for laboratory and pilot sorption experiments. Four main phenol contaminants typical for UCG water served as markers for sorption efficiency. Axial dispersion was evaluated for three pilot channel positions filled with gravel, sand, and sand with stones. Both activated carbons revealed the best sorption efficiency in laboratory as well as in pilot experiments for organic and inorganic contaminants. A sandwich structure of different sorbents was suggested as the optimal design of a reactive bed suitable for tests in the experimental mine.
Energiespeicher – Es gibt keinen Königsweg, aber auch keine Alternative
Authors: Stiller Christoph , Göke Volker , Würtenberger Uwe 
Published: February 2015

AbstractDer steigende Anteil erneuerbarer Energien erschwert die Regulierung von Angebot und Nachfrage in Stromnetzen. Hier werden Möglichkeiten zur Integration von erneuerbaren Energien in das Energiesystem diskutiert. Denkbare Lösungen sind der überregionale Lastausgleich, die zeitliche Verschiebung von Lasten, die Abregelung von Übererzeugung und insb. die Speicherung von Strom, z. B. in Stromspeichern oder chemischen Produkten. Die Komplexität des Problems und der Lösungsmöglichkeiten sind zugleich Herausforderung und Chance für die Technologiewirtschaft, insb. auch für die Chemiebranche.