bluuebunny/crossref_metadata_2025_split huggingface dataset:
CCN1 (Cyr61) Is Overexpressed in Human Osteoarthritic Cartilage and Inhibits ADAMTS‐4 (Aggrecanase 1) Activity
Authors: Chijiiwa Miyuki , Mochizuki Satsuki , Kimura Tokuhiro , Abe Hitoshi , Tanaka Yukie , Fujii Yutaka , Shimizu Hidenori , Enomoto Hiroyuki , Toyama Yoshiaki , Okada Yasunori 
Published: February 2015

ObjectiveADAMTS‐4, also called aggrecanase 1, is considered to play a key role in aggrecan degradation in human osteoarthritic (OA) cartilage, but information about regulators of ADAMTS‐4 aggrecanase activity remains limited. We undertook this study to search for molecules that modulate ADAMTS‐4 activity.MethodsMolecules copurified with ADAMTS‐4 from ADAMTS‐4–transfected chondrocytic cells were sequenced by nanoscale liquid chromatography tandem mass spectrometry. Binding activity was determined by immunoprecipitation and solid‐phase binding assay. Effects on ADAMTS‐4 activity were examined by aggrecan digestion assay. Expression of the binding molecule in OA cartilage and chondrocytes was examined by immunohistochemistry and reverse transcription–polymerase chain reaction.ResultsWe identified CCN1 (Cyr61) as an ADAMTS‐4–binding protein and showed specific binding to the ADAMTS‐4 cysteine‐rich domain. Aggrecanase activity of ADAMTS‐4 was inhibited by interaction with CCN1. Expression of messenger RNA for CCN1 was significantly higher in human OA cartilage than in normal cartilage. CCN1 was immunolocalized to chondrocytes in OA cartilage, showing direct correlations of immunoreactivity with the Mankin score of cartilage lesions and chondrocyte cloning. CCN1 and ADAMTS‐4 were commonly coexpressed in clustered chondrocytes. CCN1 expression in OA chondrocytes was down‐regulated by interleukin‐1α (IL‐1α) and up‐regulated by transforming growth factor β (TGFβ). ADAMTS‐4 expression was induced by treatment with IL‐1α or TGFβ, but aggrecanase activity was detected only under stimulation with IL‐1α. TGFβ‐treated chondrocytes exhibited aggrecanase activity when CCN1 expression was knocked down.ConclusionOur findings provide the first evidence that CCN1 suppresses ADAMTS‐4 activity and that CCN1 overexpression is directly correlated with chondrocyte cloning in OA cartilage. Our results suggest that the TGFβ/CCN1 axis plays a role in chondrocyte cluster formation through inhibition of ADAMTS‐4.
Pathogenicity of Lupus Anti–Ribosomal P Antibodies: Role of Cross‐Reacting Neuronal Surface P Antigen in Glutamatergic Transmission and Plasticity in a Mouse Model
Authors: Segovia‐Miranda Fabián , Serrano Felipe , Dyrda Agnieszka , Ampuero Estibaliz , Retamal Claudio , Bravo‐Zehnder Marcela , Parodi Jorge , Zamorano Pedro , Valenzuela David , Massardo Loreto , van Zundert Brigitte , Inestrosa Nibaldo C. , González Alfonso 
Published: February 2015

ObjectiveTo assess whether autoantibodies against ribosomal P (anti‐P), which are possibly pathogenic in neuropsychiatric systemic lupus erythematosus (NPSLE), alter glutamatergic synaptic transmission and to what extent the cross‐reacting neuronal surface P antigen (NSPA) is involved.MethodsWe analyzed glutamatergic transmission and long‐term potentiation (LTP) mediated by AMPA receptor (AMPAR) and N‐methyl‐d‐aspartate receptor (NMDAR) by field excitatory postsynaptic potential (EPSP) at the CA3–CA1 synapse. AMPAR activation by patch‐clamp recordings in primary ventral spinal cord neurons was analyzed. In primary hippocampal neurons, NSPA distribution was assessed by double immunofluorescence, and intracellular calcium changes were evaluated using Fura‐2 AM. NSPA‐LacZ reporter–knockin mice expressing a truncated NSPA were used to assess NSPA expression pattern and function in the brain using β‐galactosidase staining and comparative electrophysiology, calcium responses, and water maze memory tests.ResultsNSPA was expressed in the brain in hippocampal CA1, dentate gyrus and ventral, but not dorsal, CA3 regions, encompassing postsynaptic regions and partial colocalization with NMDAR. Notably, NSPA‐LacZ reporter–knockin mice showed impaired memory, and decreased NMDAR activity and LTP, with neurons insensitive to anti‐P autoantibodies. Anti‐P autoantibodies enhanced CA1 postsynaptic transmission, increasing AMPAR and NMDAR activity and leading to LTP abrogation after prolonged (20‐minute) incubation.ConclusionOur findings indicate that the neuronal cell surface target of anti‐P, NSPA, is involved in glutamatergic synaptic transmission and plasticity related to memory in the hippocampus, and mediates the deleterious effects of anti‐P on these processes. Cognitive impairment, as well as other diffuse NPSLE manifestations, may develop when anti‐P autoantibodies have access to brain regions coexpressing NSPA, AMPAR, and NMDAR.
Brief Report: Responses to Rituximab Suggest B Cell–Independent Inflammation in Cutaneous Systemic Lupus Erythematosus
Authors: Vital Edward M. , Wittmann Miriam , Edward Sara , Md Yusof Md Yuzaiful , MacIver Helen , Pease Colin T. , Goodfield M. , Emery Paul 
Published: February 2015

ObjectiveThe immunopathogenesis of systemic lupus erythematosus (SLE) is heterogeneous, and responses of skin to rituximab are variable. This study was undertaken to determine the phenotype of rituximab‐responsive disease.MethodsEighty‐two patients with SLE who were receiving rituximab were prospectively studied. Of these patients, 32 had significant skin involvement before or after treatment. Disease activity was assessed using the British Isles Lupus Assessment Group (BILAG) index 2004. Cutaneous lupus subtype was classified by a dermatologist as acute cutaneous lupus erythematosus (ACLE), subacute cutaneous lupus erythematosus (SCLE), chronic cutaneous lupus erythematosus (CCLE), or other skin diseases, with supportive photographs or biopsies where necessary.ResultsOf 26 patients with skin disease at baseline, 9 (35%) had a beneficial mucocutaneous response to rituximab at 6 months, with good responses in ACLE (6 of 14 patients [43%]), and poor responses in CCLE (0 of 8 patients) (P = 0.034). Clinical response was associated with anti‐RNP negativity (P = 0.024) and anti‐Ro negativity (P = 0.031). Flares of SCLE and CCLE occurred in 12 patients who either had no skin disease or had ACLE at baseline (i.e., a switch in subtype). Concomitant antimalarials or conventional immunosuppressants were not associated with response or flare rate. Posttreatment biopsies confirmed typical active SLE histology in lesions occurring during B cell depletion.ConclusionOur findings indicate that the clinical response to rituximab in cutaneous manifestations of SLE depends on subtype. None of the CCLE patients responded, and new CCLE lesions were observed during B cell depletion, suggesting that initiation and activity of these lesions is not B cell dependent. Flares of a range of skin diseases after B cell depletion may indicate a change in immune regulation following B cell–targeted therapy.
Orthogonal Translation Meets Electron Transfer: In Vivo Labeling of Cytochrome c for Probing Local Electric Fields
Authors: Völler Jan , Biava Hernan , Koksch Beate , Hildebrandt Peter , Budisa Nediljko 
Published: February 2015

AbstractCytochrome c (cyt c), a redox protein involved in diverse fundamental biological processes, is among the most traditional model proteins for analyzing biological electron transfer and protein dynamics both in solution and at membranes. Studying the role of electric fields in energy transduction mediated by cyt c relies upon appropriate reporter groups. Up to now these had to be introduced into cyt c by in vitro chemical modification. Here, we have overcome this restriction by incorporating the noncanonical amino acid p‐cyanophenylalanine (pCNF) into cyt c in vivo. UV and CD spectroscopy indicate preservation of the overall protein fold, stability, and heme coordination, whereas a small shift of the redox potential was observed by cyclic voltammetry. The C≡N stretching mode of the incorporated pCNF detected in the IR spectra reveals a surprising difference, which is related to the oxidation state of the heme iron, thus indicating high sensitivity to changes in the electrostatics of cyt c.
Mental disorder, imprisonment and reduced life expectancy – A nationwide psychiatric inpatient cohort study
Authors: Steingrimsson Steinn , Sigurdsson Martin I. , Gudmundsdottir Hafdis , Aspelund Thor , Magnusson Andres 
Published: February 2015

AbstractBackgroundThere is a strong correlation between severe mental illness and criminality, but little is known about how these two problem areas together may affect health outcomes.AimThe objective of this paper is to compare survival rates of male psychiatric inpatients over a 25‐year period who have and have not been subject to imprisonment, allowing for nature of psychiatric morbidity.MethodsA nationwide cohort of men who had ever been psychiatric inpatients was identified from Icelandic data‐registers, and their diagnoses after first discharge, cumulative incidence of imprisonment, and mortality established from records. Using a nested case‐control design, survival differences were determined between those ever imprisoned and those never imprisoned.ResultsBetween January 1983 and March 2008, 7665 men were admitted to psychiatric wards in Iceland, of whom 812 (10.6%) had served a prison sentence during that time. Cumulative incidence of imprisonment was highest in the youngest age group (21%). Substance use and personality disorders were more common amongst those imprisoned. All‐cause mortality, adjusted for diagnosis, age, and year of admission, was twice as high amongst those imprisoned as those not imprisoned (Hazard ratio = 2.0, 95% CI 1.5–2.6, p < 0.001).Clinical implicationsOur findings indicate that psychiatric inpatients with criminal records should receive special attention with respect to all aspects of their health, not only within psychiatric services but also through more collaboration between the healthcare and judicial systems. Copyright © 2015 John Wiley & Sons, Ltd.
Synthesis and Composition‐Dependent Visible Photocatalysis of Ag/AgBr Necklace‐Like Heterostructures
Authors: Li Xiaoyu , Zhang Xiao , Jia Changchao , Matras‐Postolek Katarzyna , Yang Ping 
Published: February 2015

AbstractA two‐step synthesis was developed to fabricate Ag/AgBr necklace‐like nano‐heterostructures at room temperature. Multiple crystalline Ag nanowires were used as templates following an oxidation route in situ from CuBr2 to create Ag/AgBr heterostructures. Polyvinylpyrrolidone can govern the formation of one‐dimensional Ag/AgBr necklace‐like nano‐heterostructures. The composition of the heterostructures was adjusted by changing the amount of CuBr2. Experimental conditions were optimized. In particular, the concentration and injection rate of copper bromide solution play an important role in controlling the oxidation of the Ag nanowires for the purpose of adjusting the morphology of the Ag/AgBr heterostructures. As a result, the heterostructures with 40 mol % AgBr displayed a regular necklace‐like morphology. Under visible‐light irradiation, Ag/AgBr necklace‐like heterostructures with AgBr molar ratios of 10 to 50 % exhibited enhanced plasmonic photocatalytic performance for the degradation of organic pollutants (methyl orange, methylene blue, and rhodamine B).
Room Temperature Organocatalyzed Reductive Depolymerization of Waste Polyethers, Polyesters, and Polycarbonates
Authors: Feghali Elias , Cantat Thibault 
Published: February 2015

AbstractThe reductive depolymerization of a variety of polymeric materials based on polyethers, polyesters, and polycarbonates is described using hydrosilanes as reductants and metal‐free catalysts. This strategy enables the selective depolymerization of waste polymers as well as bio‐based polyesters to functional chemicals such as alcohols and phenols at room temperature. Commercially available B(C6F5)3 and [Ph3C+,B(C6F5)4−] catalysts are active hydrosilylation catalysts in this procedure and they are compatible with the use of inexpensive and air‐stable polymethylhydrosiloxane and tetramethyldisiloxane as reductants. A significant advantage of this recycling method is derived from its tolerance to the additives present in waste plastics and its ability to selectively depolymerize mixtures of polymers.
Loss in body weight is an independent prognostic factor for mortality in chronic heart failure: insights from the GISSI‐HF and Val‐HeFT trials
Authors: Rossignol Patrick , Masson Serge , Barlera Simona , Girerd Nicolas , Castelnovo Angelo , Zannad Faiez , Clemenza Francesco , Tognoni Gianni , Anand Inder S. , Cohn Jay N. , Anker Stefan D. , Tavazzi Luigi , Latini Roberto ,   on the behalf of GISSI‐HF and Val‐HeFT Investigators
Published: February 2015

AimsUncertainties remain on the biological and prognostic significance and therapeutic implications of loss in body weight (W‐LOSS) in chronic heart failure (HF) patients. We assessed whether W‐LOSS added additional prognostic value to classical clinical risk factors in two separate and large cohorts of patients with chronic HF. The factors associated with W‐LOSS were studied.Methods and resultsW‐LOSS and estimated plasma volume changes were measured serially in the GISSI‐HF (n = 6820) and Val‐HeFT trials (n = 4892). In both studies, experiencing at least one episode of ≥5% W‐LOSS during the first year of follow‐up was considered a sign of wasting. In GISSI‐HF, self‐reported unintentional W‐LOSS ≥2 kg between two consecutive clinical visits within 1 year was also considered a sign of wasting. W‐LOSS occurred in 16.4% and 15.7% of the patients enrolled in GISSI‐HF and Val‐HeFT, respectively (unintentional ≥2 kg W‐LOSS occurred in 18.9% in GISSI‐HF). In multivariable analyses adjusting for a number of baseline covariates as well as for plasma volume changes, W‐LOSS was found to be independently associated with mortality and adverse cardiovascular and non‐cardiovascular outcomes, with a significant net reclassification improvement (cfNRI) and an increase in integrated discrimination improvement (IDI). W‐LOSS was independently associated with several features representing the severity of HF, including baseline NT‐proBNP and high sensitivity C‐reactive protein (hsCRP) in Val‐HeFT.ConclusionsW‐LOSS was a frequent finding in the GISSI‐HF and Val‐HeFT trials, associated with multiple patient features, and added additional prognostic information beyond clinical variables of HF severity, including estimated plasma volume changes.
Resveratrol‐loaded liposomes: Interaction of resveratrol with phospholipids
Authors: Balanč Bojana D. , Ota Ajda , Djordjević Verica B. , Šentjurc Marjeta , Nedović Viktor A. , Bugarski Branko M. , Ulrih Nataša Poklar 
Published: February 2015

The influence of resveratrol encapsulated into liposomes (prepared with a commercial lipid mixture of phospholipids, phospolipon 90NG, using the thin film and proliposome methods) on the structural properties of the liposome membrane was investigated by electron paramagnetic resonance (EPR) spectroscopy, fluorescence spectroscopy, and differential scanning calorimetry. Two fluorophores and two spin probes were used to monitor the characteristics of membranes made from a commercial mixture of phosphatidylcholine. Resveratrol was positioned rather in the inner part of the liposome membranes causing reduction in membrane fluidity. Moreover, resveratrol induced a concentration‐dependent decrease in the gel‐to‐liquid crystalline phase transition temperature (from 41.3 to 38.3°C, for a saturated 1,2‐dipalmitoyl‐sn‐glycero‐3‐phospatidylcholine bilayer). The antioxidant activity of resveratrol was confirmed by its 95% inhibition of lipid peroxidation, compared to liposomes without resveratrol exposed to the same conditions. Similarly, EPR spectroscopy spin trapping showed an 87% reduction in the spectra intensity of the hydroxyethyl radical, which indicates the efficiency of resveratrol for inhibition of OH radical production.Practical applications: Resveratrol is in the limelight all over the world as a health‐beneficial compound widely investigated as natural antioxidant suitable for prevention of human cardiovascular diseases and inhibition of low‐density lipoproteins oxidation. Public interest in prevention of diseases through enriched staple foods grows each day. Nonetheless, addition of antioxidants to aqueous‐based food can be limited due to their troublesome characteristics. Liposomes are nanocarriers that may be used to overcome the disadvantages and they can be used for food applications. Liposomes could be prepared using only natural components and therefore the new formulations could be quickly implemented. Still, the application of liposomes in food systems is not widespread due to time consuming manufacturing processes and high costs. The presented results provide marks and suggestions to food manufacturers and scientists on how to make broader use of resveratrol‐loaded liposomes which add value and improve the quality of existing food products.The influence of resveratrol encapsulated into liposomes (prepared using the thin film and proliposome methods) on the structural properties of the liposome membrane was investigated by electron paramagnetic resonance spectroscopy, fluorescence spectroscopy, and differential scanning calorimetry. The antioxidant activity of resveratrol was confirmed by its inhibition of lipid peroxidation and by spin trapping.
Contradiction between the C‐property and mass conservation in adaptive grid based shallow flow models: cause and solution
Authors: Liang Qiuhua , Hou Jingming , Xia Xilin 
Published: February 2015

SummaryWhen performing shallow flow simulations on adaptive grids, the C‐property (i.e. conservation property) and the mass conservation may not be simultaneously preserved, that is, either C‐property or mass conservation is likely to be violated following grid refining or coarsening. The cause of such a contradiction is analyzed in detail in this work, which essentially links to the reconstruction of bed and flow information in those newly created cells during grid adaptation. An effective approach is subsequently proposed to resolve the contradiction by locally modifying the bed elevation in certain problematic cells when reconstructing flow information using linear interpolation as part of the grid adaptation procedure. Copyright © 2015 John Wiley & Sons, Ltd.
A robust and well‐balanced scheme for the 2D Saint‐Venant system on unstructured meshes with friction source term
Authors: Duran A. 
Published: February 2015

SummaryIn the following lines, we propose a numerical scheme for the shallow‐water system supplemented by topography and friction source terms, in a 2D unstructured context. This work proposes an improved version of the well‐balanced and robust numerical model recently introduced by Duran et al. (J. Comp. Phys., 235, 565–586, 2013) for the pre‐balanced shallow‐water equations, accounting for varying topography. The present work aims at relaxing the robustness condition and includes a friction term. To this purpose, the scheme is modified using a recent method, entirely based on a modified Riemann solver. This approach preserves the robustness and well‐balanced properties of the original scheme and prevents unstable computations in the presence of low water depths. A series of numerical experiments are devoted to highlighting the performances of the resulting scheme. Simulations involving dry areas, complex geometry and topography are proposed to validate the stability of the numerical model in the neighbourhood of wet/dry transitions. Copyright © 2015 John Wiley & Sons, Ltd.
Assessments of antibody biodistribution
Authors: Glassman Patrick M. , Abuqayyas Lubna , Balthasar Joseph P. 
Published: February 2015

AbstractMonoclonal antibody (mAb) therapeutics are in use for several disease conditions, and have generally shown excellent clinical benefit, in large part due to their high specificity and affinity for target proteins. As this therapeutic class continues to grow in size, improved understanding of the mechanisms controlling mAb biodistribution and protein binding may be expected to allow better prediction of safety and efficacy. Due to the large size and polarity of antibodies, rates of mAb distribution and elimination are typically much slower than those reported for small molecule drugs. Additionally, high affinity interaction with target proteins will often influence mAb pharmacokinetics, leading to complex, nonlinear tissue distribution and elimination. In this report, we summarize key determinants of mAb disposition, methods for assessing antibody exposure and protein binding, and model‐based approaches that may be utilized to predict mAb pharmacokinetics.
Dashboard systems: Pharmacokinetic/pharmacodynamic mediated dose optimization for monoclonal antibodies
Authors: Mould Diane R. , Dubinsky Marla C. 
Published: February 2015

AbstractMany marketed drugs exhibit high variability in exposure and response. While these drugs are efficacious in their approved indications, finding appropriate dose regimens for individual patients is not straightforward. Similar dose adjustment problems are also seen with drugs that have a complex relationship between exposure and response and/or a narrow therapeutic window. This is particularly true for monoclonal antibodies, where prolonged dosing at a sub‐therapeutic dose can also elicit anti‐drug antibodies which will further compromise safety and efficacy. Thus, finding appropriate doses quickly would represent a substantial improvement in healthcare. Dashboard systems, which are decision‐support tools, offer an improved, convenient means of tailoring treatment for individual patients. This article reviews the clinical need for this approach, particularly with monoclonal antibodies, the design, development, and testing of such systems, and the likely benefits of dashboard systems in clinical practice. We focus on infliximab for reference.
Pharmacokinetics of anti‐TNF monoclonal antibodies in inflammatory bowel disease: Adding value to current practice
Authors: Vande Casteele Niels , Gils Ann 
Published: February 2015

AbstractSince anti‐tumor necrosis factor (TNF) antibodies were introduced to treat patients with inflammatory bowel diseases, short‐ and long‐term clinical and endoscopic endpoints can be achieved that were unreachable with conventional anti‐inflammatory agents. Although a large proportion of patients (70–90%) initially respond to the treatment, remission rates after induction are still low (20–50%) and patients are at risk to lose response to the drug over time. This inter‐individual variability in response is likely to be influenced by the observed inter‐individual variability in pharmacokinetics. By extensively reviewing the literature, we evaluated the potential role of therapeutic drug monitoring to optimize dosing of anti‐TNF drugs. Thereby we emphasize some of the pharmacokinetic cornerstones that can help to understand the observed concentration–effect relationship. After discussing some of the most commonly used assays to measure anti‐TNF drug and anti‐drug antibody concentrations, we reviewed the application of those tests and their potential clinical value in retrospective and prospective studies.
Ultrasound diagnosis of serous surface papillary borderline ovarian tumor: A case series with a review of the literature
Authors: Ludovisi Manuela , Foo Xulin , Mainenti Sara , Testa Antonia Carla , Arora Rupali , Jurkovic Davor 
Published: February 2015

ABSTRACTSerous surface papillary borderline ovarian tumors (SSPBOTs) are a rare morphologic variant of serous ovarian tumors that are typically confined to the ovarian surface, while the ovaries themselves tend to appear normal in size and shape. In this report, we describe the findings from five premenopausal women diagnosed with SSPBOTs, in whom ultrasound showed grossly normal ovaries that were partially or wholly covered with irregular solid tumors. In all five cases, histologic examination showed evidence of borderline serous tumors. These findings demonstrate that SSPBOTs can be diagnosed on a preoperative sonographic examination, which could facilitate conservative, fertility‐sparing surgery in young women affected by this condition. © 2015 Wiley Periodicals, Inc. J Clin Ultrasound 43:573–577, 2015