bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Biologic Agents With and Without Concomitant Methotrexate and at Reduced Doses in Older Rheumatoid Arthritis Patients
Authors: Zhang Jie , Xie Fenglong , Delzell Elizabeth , Yun Huifeng , Lewis James D. , Haynes Kevin , Chen Lang , Beukelman Timothy , Saag Kenneth G. , Curtis Jeffrey R. 
Published: November 2014

ObjectiveTo examine whether concomitant methotrexate (MTX) use is associated with better biologic persistence and whether self‐administered anti–tumor necrosis factor (anti‐TNF) therapies are used at reduced doses in real‐world clinical care settings, not just clinical trials.MethodsWe conducted a retrospective cohort study among rheumatoid arthritis (RA) patients using Medicare claims data from 2006 to 2012. Subjects were new initiators of etanercept, infliximab, adalimumab, abatacept, and tocilizumab with at least 12 months of continuous medical and pharmacy coverage after treatment initiation. We examined the association between concomitant MTX use and persistence on biologic agents using Cox proportional hazards regression, adjusting for demographics and baseline comorbidities. We further identified a subgroup of patients who initiated and were adherent on etanercept or adalimumab for at least 12 months and examined the proportion of patients who subsequently used these therapies at reduced doses continuously for an additional 12, 18, and 24 months.ResultsOf 26,510 eligible RA patients, 10,511 initiated biologic monotherapy. Overall, patients who initiated biologic monotherapy were 1.4 (95% confidence interval [95% CI] 1.3–1.5) times more likely to discontinue at 1 year compared to those who initiated combination therapy, and 1.8 (95% CI 1.7–2.0) times more likely if starting infliximab monotherapy. Approximately 10–20% of patients who initiated and adhered to etanercept and adalimumab for ≥12 months subsequently received reduced‐dose therapy for an 12 additional months and beyond.ConclusionIn real‐world practice, concomitant MTX was associated with improved persistence on biologic therapy, especially for infliximab users; reduced‐dose injectable anti‐TNF therapy was used by a substantial proportion of RA patients.
Cellular plasticity induced by anti–α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptor encephalitis antibodies
Authors: Peng Xiaoyu , Hughes Ethan G. , Moscato Emilia H. , Parsons Thomas D. , Dalmau Josep , Balice‐Gordon Rita J. 
Published: November 2014

ObjectiveAutoimmune‐mediated anti–α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor (AMPAR) encephalitis is a severe but treatment‐responsive disorder with prominent short‐term memory loss and seizures. The mechanisms by which patient antibodies affect synapses and neurons leading to symptoms are poorly understood.MethodsThe effects of patient antibodies on cultures of live rat hippocampal neurons were determined with immunostaining, Western blot, and electrophysiological analyses.ResultsWe show that patient antibodies cause a selective decrease in the total surface amount and synaptic localization of GluA1‐ and GluA2‐containing AMPARs, regardless of receptor subunit binding specificity, through increased internalization and degradation of surface AMPAR clusters. In contrast, patient antibodies do not alter the density of excitatory synapses, N‐methyl‐D‐aspartate receptor (NMDAR) clusters, or cell viability. Commercially available AMPAR antibodies directed against extracellular epitopes do not result in a loss of surface and synaptic receptor clusters, suggesting specific effects of patient antibodies. Whole‐cell patch clamp recordings of spontaneous miniature postsynaptic currents show that patient antibodies decrease AMPAR‐mediated currents, but not NMDAR‐mediated currents. Interestingly, several functional properties of neurons are also altered: inhibitory synaptic currents and vesicular γ‐aminobutyric acid transporter (vGAT) staining intensity decrease, whereas the intrinsic excitability of neurons and short‐interval firing increase.InterpretationThese results establish that antibodies from patients with anti‐AMPAR encephalitis selectively eliminate surface and synaptic AMPARs, resulting in a homeostatic decrease in inhibitory synaptic transmission and increased intrinsic excitability, which may contribute to the memory deficits and epilepsy that are prominent in patients with this disorder. Ann Neurol 2015;77:381–398
Carbon Monoxide Bonding With BeO and BeCO3: Surprisingly High CO Stretching Frequency of OCBeCO3
Authors: Chen Mohua , Zhang Qingnan , Zhou Mingfei , Andrada Diego M. , Frenking Gernot 
Published: November 2014

AbstractThe complexes OCBeCO3 and COBeCO3 have been isolated in a low‐temperature neon matrix. The more stable isomer OCBeCO3 has a very high CO stretching mode of 2263 cm−1, which is blue‐shifted by 122 cm−1 with respect to free CO and 79 cm−1 higher than in OCBeO. Bonding analysis of the complexes shows that OCBeO has a stronger OCBeY bond than OCBeCO3 because it encounters stronger π backdonation. The isomers COBeCO3 and COBeO exhibit red‐shifted CO stretching modes with respect to free CO. The inverse change of CO stretching frequency in OCBeY and COBeY is explained with the reversed polarization of the σ and π bonds in CO.
Diketopyrrolopyrrole‐Porphyrin Conjugates with High Two‐Photon Absorption and Singlet Oxygen Generation for Two‐Photon Photodynamic Therapy
Authors: Schmitt Julie , Heitz Valérie , Sour Angélique , Bolze Frédéric , Ftouni Hussein , Nicoud Jean‐Francois , Flamigni Lucia , Ventura Barbara 
Published: November 2014

AbstractTwo‐photon photodynamic therapy is a promising therapeutic method which requires the development of sensitizers with efficient two‐photon absorption and singlet‐oxygen generation. Reported here are two new diketopyrrolopyrrole‐porphyrin conjugates as robust two‐photon absorbing dyes with high two‐photon absorption cross‐sections within the therapeutic window. Furthermore, for the first time the singlet‐oxygen generation efficiency of diketopyrrolopyrrole‐containing systems is investigated. A preliminary study on cell culture showed efficient two‐photon induced phototoxicity.
Bifunctional Submicron Colloidosomes Coassembled from Fluorescent and Superparamagnetic Nanoparticles
Authors: Bollhorst Tobias , Shahabi Shakiba , Wörz Katharina , Petters Charlotte , Dringen Ralf , Maas Michael , Rezwan Kurosch 
Published: November 2014

AbstractColloidosomes are microcapsules consisting of nanoparticle shells. These microcarriers can be self‐assembled from a wide range of colloidal particles with selective chemical, physical, and morphological properties and show promise for application in the field of theranostic nanomedicine. Previous studies have mainly focused on fairly large colloidosomes (>1 μm) based on a single kind of particle; however, the intrinsic building‐block nature of this microcarrier has not been exploited so far for the introduction of tailored functionality at the nanoscale. We report a synthetic route based on interfacial shear rheology studies that allows the simultaneous incorporation of different nanoparticles with distinct physical properties, that is, superparamagnetic iron oxide and fluorescent silica nanoparticles, in a single submicron colloidosome. These tailor‐made microcapsules can potentially be used in various biomedical applications, including magnetic hyperthermia, magnetic particle imaging, drug targeting, and bioimaging.
Observations on Fur Development in Echidna (Monotremata, Mammalia) Indicate that Spines Precede Hairs in Ontogeny
Authors: Alibardi Lorenzo , Rogers George 
Published: November 2014

ABSTRACTIn the primitive mammal echidna, the initial 2–3 generations of skin appendages produced from birth forms spines and only later true hairs appear. Microscopy on preserved museum specimens reveals that the morphogenesis of spines and hairs is similar but that a larger dermal papilla is formed in spines. The growing shaft comprises a medulla surrounded by a cortex and by an external cuticle. A thick inner root sheath made of cornified cells surrounds the growing shaft inside the spine canal that eventually exits with a pointed tip. Hairs develop later with the same modality of spines but have a smaller papilla and give rise to a fur coat among spines. Therefore the integument of developing echidnas initially produces spines from large dermal papillae but the reduction in size of the papillae later determines the formation of hairs. Although the morphogenesis of spines and hairs can represent a case of specialization in this species, the primitive mammalian characteristics of echidnas has also inspired new speculations on the evolution of the mammalian hair from mammalian‐like reptiles with a spiny coat. The resemblance in the morphogenesis between spines and hairs has suggested some hypothesis on hair evolution, in particular that hairs might be derived from the reduction of protective large spines present in ancient mammalian‐like reptiles possibly derived from the reduction of pre‐existing pointed scales. The hypothesis suggests that spines became reduced and internalized in the skin forming hairs. Anat Rec, 298:761–770, 2015. © 2014 Wiley Periodicals, Inc.
Brief Report: Distinct Dysregulation of the Small Leucine‐Rich Repeat Protein Family in Osteoarthritic Acetabular Labrum Compared to Articular Cartilage
Authors: Juchtmans Nele , Dhollander Aad A. M. , Coudenys Julie , Audenaert Emmanuel A. , Pattyn Christophe , Lambrecht Stijn , Elewaut Dirk 
Published: November 2014

ObjectiveArticular cartilage is well studied in osteoarthritis (OA). However, the role of supporting structures, such as the acetabular labrum, a sealing structure surrounding the hip joint, has been investigated much less. We recently showed that fibrochondrocytic labrum cells are metabolically active. This study was undertaken to investigate hip OA–associated changes in human acetabular labrum cells.MethodsMicroarray analysis was performed to compare OA labrum cells to healthy labrum cells cultured in a 3‐dimensional alginate bead system. Data were analyzed by cluster analysis using gene set enrichment analysis software and by gene list analysis using PANTHER gene family tools. Selected candidates were validated by quantitative polymerase chain reaction analysis on labrum and cartilage samples and by immunohistochemistry. The functional impacts of the genes identified were investigated by in vitro stimulation experiments in labrum cells.ResultsPathway analysis revealed increased cytokine and chemokine signaling in OA labrum cells, whereas reduced extracellular matrix interactions and transforming growth factor β signaling were observed. Several genes were significantly differentially expressed in OA compared to healthy labrum. We specifically focused on 3 small leucine‐rich repeat proteins (SLRPs), osteomodulin, osteoglycin, and asporin, that appeared to be distinctly regulated in OA labrum compared to OA cartilage. SLRPs were strongly down‐regulated in OA labrum but up‐regulated in OA articular chondrocytes. Moreover, in vitro stimulation with osteomodulin increased aggrecan expression in OA labrum cells.ConclusionOA labrum fibrochondrocytes have several features similar to OA chondrocytes. However, SLRP expression seems to be differentially influenced by degeneration in OA labrum compared to cartilage, suggesting a specific role for this supporting structure in OA. The functional impact of SLRPs on labrum cells makes them interesting targets for further studies in hip OA.
Effects of Glucosamine and Chondroitin Supplementation on Knee Osteoarthritis: An Analysis With Marginal Structural Models
Authors: Yang Shibing , Eaton Charles B. , McAlindon Timothy E. , Lapane Kate L. 
Published: November 2014

ObjectiveThe purpose of this study was to estimate the effectiveness of the combination of glucosamine and chondroitin in relieving knee symptoms and slowing disease progression among patients with knee osteoarthritis (OA).MethodsThe 4‐year followup data from the Osteoarthritis Initiative data set were analyzed. We used a “new‐user” design, for which only participants who were not using glucosamine/chondroitin at baseline were included in the analyses (n = 1,625). Cumulative exposure was calculated as the number of visits when participants reported use of glucosamine/chondroitin. Knee symptoms were measured with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and structural progression was determined by measuring the joint space width (JSW). To control for the time‐varying confounders that might be influenced by previous treatments, we used marginal structural models to estimate the effects on OA of using glucosamine/chondroitin for 3 years, 2 years, and 1 year.ResultsDuring the study period, 18% of the participants initiated treatment with glucosamine/chondroitin. After adjustment for potential confounders with marginal structural models, we found no clinically significant differences between users at all assessments and never‐users of glucosamine/chondroitin in WOMAC pain (β = 0.68 [95% confidence interval (95% CI) −0.16 to 1.53]), WOMAC stiffness (β = 0.41 [95% CI 0 to 0.82]), and WOMAC function (β = 1.28 [95% CI −1.23 to 3.79]) or JSW (β = 0.11 [95% CI −0.21 to 0.44]).ConclusionUse of glucosamine/chondroitin did not appear to relieve symptoms or modify disease progression among patients with radiographically confirmed OA. Our findings are consistent with the results of meta‐analyses of clinical trials and extend those results to a more general population with knee OA.
Effects of Prescription Nonsteroidal Antiinflammatory Drugs on Symptoms and Disease Progression Among Patients With Knee Osteoarthritis
Authors: Lapane Kate L. , Yang Shibing , Driban Jeffrey B. , Liu Shao‐Hsien , Dubé Catherine E. , McAlindon Timothy E. , Eaton Charles B. 
Published: November 2014

ObjectiveThe effect of short‐term and long‐term use of nonsteroidal antiinflammatory drugs (NSAIDs) on structural change is equivocal. The aim of this study was to estimate the extent to which short‐ and long‐term use of prescription NSAIDs relieve symptoms and delay structural progression among patients with radiographically confirmed osteoarthritis (OA) of the knee.MethodsWe applied a new‐user design among participants with confirmed OA not reporting NSAID use at the time of enrollment in the Osteoarthritis Initiative. Participants were evaluated for changes in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) subscales (n = 1,846) and joint space width was measured using serial radiographs and a customized software tool (n = 1,116) over 4 years. We used marginal structural modeling to estimate the effect of NSAIDs.ResultsCompared to participants who never reported prescription NSAID use, those reporting use at 1 or 2 assessments had no clinically important changes, but those reporting prescription NSAID use at all 3 assessments had, on average, 0.88 point improvement over the followup period (95% confidence interval [95% CI] −0.46 to 2.22) in pain, 0.72 point improvement (95% CI −0.12 to 1.56) in stiffness, and 4.27 points improvement (95% CI −0.31 to 8.84) in function. The average change in joint space width was 0.28 mm less among those reporting NSAID use at 3 assessments relative to nonusers (95% CI −0.06 to 0.62). Recent NSAID use findings were not clinically or statistically significant.ConclusionLong‐term, but not short‐term, NSAID use was associated with an a priori–defined minimally important clinical change in stiffness, physical function, and joint space width, but not pain. While showing modest clinical importance, the estimates did not reach statistical significance.
Retrievable inferior vena cava filters can be placed and removed with a high degree of success: Initial experience
Authors: Cohoon Kevin P. , McBride Joseph , Friese Jeremy L. , McPhail Ian R. 
Published: November 2014

ObjectivesEvaluate the success rate of retrievable inferior vena cava filter (IVC) removal in a tertiary care practice.BackgroundRetrievable IVC filters became readily available in the United States following Food and Drug Administration approval in 2003, and their use has increased dramatically. They represent an attractive option for patients with contraindications to anticoagulation who may only need short‐term protection against pulmonary embolism.MethodsAll patients who had undergone placement of a retrievable IVC filter at Mayo Clinic between 2003 and 2005 were retrospectively reviewed to evaluate our initial experience with retrievable inferior vena cava filters at a large tertiary care center. Results: During a three‐year‐period of time, Mayo Clinic, Rochester, MN placed 892 IVC filters of which 460 were retrievable. Of the 460 retrievable filters placed (249 Günther Tulip®, 207 Recovery®, and 4 OptEase®), retrieval was attempted in 223 (48.5%). Of 223 initial attempts, 196 (87.9%) were initially successful and 27 (12.1%) were unsuccessful. Of the 27 unsuccessful initial retrieval attempts, 23 (85.2%) were because of the presence of significant thrombus within the filter and 4 (14.8%) were because of tilting and strut perforation. Of the 23 filters containing significant thrombus, 9 (39.1%) were later retrieved after a period of anticoagulation and resolution of the thrombus.ConclusionsRetrievable IVC filters can be removed with a high degree of success. Approximately one in ten retrievable IVC filter removal attempts may fail initially, usually because of significant thrombus within the filter. This does not preclude possible removal at a later date. © 2015 Wiley Periodicals, Inc.
Position of Edwards SAPIEN transcatheter valve in the aortic root in relation with the coronary ostia
Authors: Katsanos Spyridon , Debonnaire Philippe , van der Kley Frank , van Rosendael Philippe , Joyce Emer , de Graaf Michiel A. , Schalij Martin J. , Scholte Arthur J.H.A. , Bax Jeroen J. , Ajmone Marsan Nina , Delgado Victoria 
Published: November 2014

ObjectivesTo determine the implications of stable coverage of the coronary ostia by the Edwards SAPIEN valve frame in terms of myocardial ischemia and subsequent percutaneous coronary intervention (PCI), following transcatheter aortic valve implantation (TAVI).BackgroundEdwards SAPIEN frame is frequently deployed relatively higher than recommended and may overlap the coronary ostia.MethodsA total of 142 patients (age 81 ± 7 years, male 49%) treated with Edwards SAPIEN valve and with multi‐detector row computed tomography at 1 month follow‐up were evaluated. The position of the frame in relation to the coronary ostia was assessed. Levels of troponin T were measured 12–24 hr after TAVI. PCI events at follow‐up were recorded.ResultsThe left coronary ostium was fully covered in three (2.1%) patients and the right coronary ostium in 11 (7.7%). There were no differences in troponin T levels between patients with fully covered ostia versus patients with partly or non‐covered ostia (0.24 (0.13–0.50) μg/L versus 0.35 (0.15–0.55) μg/L, respectively; P = 0.377). At 30 ± 15 months follow up, 10 (7%) patients underwent successful PCI. Rate of subsequent PCI was similar between patients with any covered ostium and patients with non‐covered ostia [4 (7.8%) vs. 6 (6.5%), P = 0.780, respectively].ConclusionsFull overlap of the coronary ostia by Edwards SAPIEN frame is infrequent and in most cases does not limit subsequent PCI. © 2014 Wiley Periodicals, Inc.
The symptom burden of treatment‐naive patients with head and neck cancer
Authors: Hanna Ehab Y. , Mendoza Tito R. , Rosenthal David I. , Gunn G. Brandon , Sehra Pamela , Yucel Emre , Cleeland Charles S. 
Published: November 2014

BACKGROUNDThe treatment of head and neck cancer (HNC) may cause substantial local and systemic symptomatic morbidities, but many patients have high symptom levels before treatment begins. Knowledge of disease‐related (treatment‐naive) symptom status would aid in the evaluation of the symptomatic benefit or burden of HNC therapies.METHODSThe authors retrospectively examined symptoms, quality of life, and health status reported by patients with HNC who were naive to any treatment. Symptoms were explored by anatomical site and disease factors were correlated with symptom severity and interference. A clustering algorithm was used to identify a subset of highly symptomatic patients, and the effects of disease site, tumor stage, and demographic variables on membership in this high‐symptom group were examined.RESULTSA total of 748 treatment‐naive patients with mucosal (434 patients), nonmucosal (272 patients), or skull base (42 patients) tumors were identified who had rated their symptoms using the MD Anderson Symptom Inventory. The majority of patients were white non‐Hispanic (82%) and male (68%), with a median age of 59 years. Approximately one‐third the patients had a high pretreatment symptom burden. Pain, fatigue, distress, and disturbed sleep were the most severe symptoms reported, regardless of tumor stage or site. Symptom burden was found to be higher among patients with more advanced disease. Predictors of a high symptom burden included having a mucosal tumor and being female.CONCLUSIONSThe high prevalence of moderate to severe symptoms found in the current study demonstrates the importance of assessing patient‐reported symptoms routinely before treatment is initiated and emphasizes the need for symptom management in parallel with disease treatment. Baseline characterization of symptom status should be incorporated into clinical trials that may affect symptom burden. Cancer 2015;121:766–773. © 2014 American Cancer Society.
Latent inhibition and facilitation of conditioned taste aversion in preweanling rats
Authors: Gaztañaga Mirari , Aranda‐Fernández P. Ezequiel , Díaz‐Cenzano Elena , Chotro M. Gabriela 
Published: November 2014

ABSTRACTEarly in ontogeny, taste preexposure has been found to induce latent inhibition as well as produce a facilitation of conditioned taste aversion (CTA). In this study, the effect of taste preexposure on CTA was investigated in 13–14 day old rats as a function of taste preexposure (0, 1, or 3 trials) and unconditioned stimulus intensity (LiCl: 0, 0.15, or 0.30 M). After one conditioning trial, with the low intensity US, an aversion was only observed after taste preexposure (facilitation). When using the strong US, an aversion was found without preexposure while latent inhibition was observed with 3 preexposure trials. In conclusion, stimulus preexposure can either facilitate conditioning or produce latent inhibition in infant rats, depending on the amount of stimulus preexposure and the intensity of the US. © 2014 Wiley Periodicals, Inc. Dev Psychobiol 57: 96–104, 2015.
Application of the cis‐regulatory region of a heat‐shock protein 70 gene to heat‐inducible gene expression in the ascidian Ciona intestinalis
Authors: Kawaguchi Akane , Utsumi Nanami , Morita Maki , Ohya Aya , Wada Shuichi 
Published: November 2014

SummaryTemporally controlled induction of gene expression is a useful technique for analyzing gene function. To make such a technique possible in Ciona intestinalis embryos, we employed the cis‐regulatory region of the heat‐shock protein 70 (HSP70) gene Ci‐HSPA1/6/7‐like for heat‐inducible gene expression in C. intestinalis embryos. We showed that Ci‐HSPA1/6/7‐like becomes heat shock‐inducible by the 32‐cell stage during embryogenesis. The 5′‐upstream region of Ci‐HSPA1/6/7‐like, which contains heat‐shock elements indispensable for heat‐inducible gene expression, induces the heat shock‐dependent expression of a reporter gene in the whole embryo from the 32‐cell to the middle gastrula stages and in progressively restricted areas of embryos in subsequent stages. We assessed the effects of heat‐shock treatments in different conditions on the normality of embryos and induction of transgene expression. We evaluated the usefulness of this technique through overexpression experiments on the well‐characterized, developmentally relevant gene, Ci‐Bra, and showed that this technique is applicable for inferring the gene function in C. intestinalis. genesis 53:170–182, 2015. © 2014 Wiley Periodicals, Inc.