bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction of proinflammatory cytokine production in intervertebral disc cells by macrophage-like THP-1 cells requires mitogen-activated protein kinase activity
Authors: Park Jung Jae , Moon Hong Joo , Park Jin Hyun , Kwon Taek Hyun , Park Youn-Kwan , Kim Joo Han 
Published: October 2015

OBJECT
To determine the role played by mitogen-activated protein kinase (MAPK) signaling in the interactions between macrophages and intervertebral disc (IVD) cells, it was hypothesized that MAPK inhibition would modulate the production of the proinflammatory cytokines associated with inflammatory reaction in IVD cells.

METHODS
Human annulus fibrosus (AF) and nucleus pulposus (NP) cells were cocultured with phorbol myristate acetate-stimulated macrophage-like THP-1 cells, with and without SB202190 (a p38-α and -β inhibitor), SP600125 (a c-Jun N-terminal kinase [JNK] inhibitor), and PD98059 (an extracellular signal-regulated kinase [ERK] 1/2 inhibitor). The cytokines in conditioned media from cocultured and macrophage-exposed (nemotic) cells were assayed using enzyme-linked immunosorbent assays (ELISAs).

RESULTS
Interleukin (IL)-6 and IL-8 were secreted in greater quantities by the cocultured cells compared with naive IVD cells and macrophages (MΦ) cultured alone. The tumor necrosis factor (TNF)- α and IL-6 levels produced by the NP cells cocultured with MΦs (NP-MΦ) were significantly lower than those produced by AF cells cocultured with MΦs (AF-MΦ). SB202190 dose-dependently suppressed IL-6 secretion by AF-MΦ and NP-MΦ cocultures, and 10 μM SB202190 significantly decreased IL-6 and IL-8 production in nemotic AF and NP pellets. SP600125 at 10 μM significantly suppressed the production of TNF α IL-6. and IL-8 in AF-MΦ and NP-MΦ cocultures and significantly suppressed IL-1β production in the NP-MΦ coculture. Administration of 10 μM PD98059 significantly decreased IL-6 levels in the AF-MΦ coculture, and decreased the levels of TNF α and IL-8 in both the AF-MΦ and NP-MΦ cocultures.

CONCLUSIONS
The present study shows that inhibitors of p38 MAPK effectively controlled IL-6 production during inflammatory reactions and that JNK and ERK1/2 inhibitors successfully suppressed the production of major proinflammatory cytokines during interactions between macrophages and IVD cells. Therefore, selective blockade of these signals may serve as a therapeutic approach to symptomatic IVD degeneration.
Live-cell imaging to detect phosphatidylserine externalization in brain endothelial cells exposed to ionizing radiation: implications for the treatment of brain arteriovenous malformations
Authors: Zhao Zhenjun , Johnson Michael S. , Chen Biyi , Grace Michael , Ukath Jaysree , Lee Vivienne S. , McRobb Lucinda S. , Sedger Lisa M. , Stoodley Marcus A. 
Published: October 2015

OBJECT
Stereotactic radiosurgery (SRS) is an established intervention for brain arteriovenous malformations (AVMs). The processes of AVM vessel occlusion after SRS are poorly understood. To improve SRS efficacy, it is important to understand the cellular response of blood vessels to radiation. The molecular changes on the surface of AVM endothelial cells after irradiation may also be used for vascular targeting. This study investigates radiation-induced externalization of phosphatidylserine (PS) on endothelial cells using live-cell imaging.

METHODS
An immortalized cell line generated from mouse brain endothelium, bEnd.3 cells, was cultured and irradiated at different radiation doses using a linear accelerator. PS externalization in the cells was subsequently visualized using polarity-sensitive indicator of viability and apoptosis (pSIVA)-IANBD, a polarity-sensitive probe. Live-cell imaging was used to monitor PS externalization in real time. The effects of radiation on the cell cycle of bEnd.3 cells were also examined by flow cytometry.

RESULTS
Ionizing radiation effects are dose dependent. Reduction in the cell proliferation rate was observed after exposure to 5 Gy radiation, whereas higher radiation doses (15 Gy and 25 Gy) totally inhibited proliferation. In comparison with cells treated with sham radiation, the irradiated cells showed distinct pseudopodial elongation with little or no spreading of the cell body. The percentages of pSIVA-positive cells were significantly higher (p = 0.04) 24 hours after treatment in the cultures that received 25- and 15-Gy doses of radiation. This effect was sustained until the end of the experiment (3 days). Radiation at 5 Gy did not induce significant PS externalization compared with the sham-radiation controls at any time points (p > 0.15). Flow cytometric analysis data indicate that irradiation induced growth arrest of bEnd.3 cells, with cells accumulating in the G2 phase of the cell cycle.

CONCLUSIONS
Ionizing radiation causes remarkable cellular changes in endothelial cells. Significant PS externalization is induced by radiation at doses of 15 Gy or higher, concomitant with a block in the cell cycle. Radiation-induced markers/targets may have high discriminating power to be harnessed in vascular targeting for AVM treatment.
Correlation between cervical spine sagittal alignment and clinical outcome after cervical laminoplasty for ossification of the posterior longitudinal ligament
Authors: Lee Chang Kyu , Shin Dong Ah , Yi Seong , Kim Keung Nyun , Shin Hyun Chul , Yoon Do Heum , Ha Yoon 
Published: October 2015

OBJECT
The goal of this study was to determine the relationship between cervical spine sagittal alignment and clinical outcomes after cervical laminoplasty in patients with ossification of the posterior longitudinal ligament (OPLL).

METHODS
Fifty consecutive patients who underwent a cervical laminoplasty for OPLL between January 2012 and January 2013 and who were followed up for at least 1 year were analyzed in this study. Standing plain radiographs of the cervical spine, CT (midsagittal view), and MRI (T2-weighted sagittal view) were obtained (anteroposterior, lateral, flexion, and extension) pre- and postoperatively. Cervical spine alignment was assessed with the following 3 parameters: the C2–7 Cobb angle, C2–7 sagittal vertical axis (SVA), and T-1 slope minus C2–7 Cobb angle. The change in cervical sagittal alignment was defined as the difference between the post- and preoperative C2–7 Cobb angles, C2–7 SVAs, and T-1 slope minus C2–7 Cobb angles. Outcome assessments (visual analog scale [VAS], Oswestry Neck Disability Index [NDI], 36-Item Short-Form Health Survey [SF-36], and Japanese Orthopaedic Association [JOA] scores) were obtained in all patients pre- and postoperatively.

RESULTS
The average patient age was 56.3 years (range 38–72 years). There were 34 male patients and 16 female patients. Cervical laminoplasty for OPLL helped alleviate radiculomyelopathy. Compared with the preoperative scores, improvement was seen in postoperative VAS and JOA scores. After laminoplasty, 35 patients had kyphotic changes, and 15 had lordotic changes. However, cervical sagittal alignment after laminoplasty was not significantly associated with clinical outcomes in terms of postoperative improvement of the JOA score (C2–7 Cobb angle: p = 0.633; C2–7 SVA: p = 0.817; T-1 slope minus C2–7 lordosis: p = 0.554), the SF-36 score (C2–7 Cobb angle: p = 0.554; C2–7 SVA: p = 0.793; T-1 slope minus C2–7 lordosis: p = 0.829), the VAS neck score (C2–7 Cobb angle: p = 0.263; C2–7 SVA: p = 0.716; T-1 slope minus C2–7 lordosis: p = 0.497), or the NDI score (C2–7 Cobb angle: p = 0.568; C2–7 SVA: p = 0.279; T-1 slope minus C2–7 lordosis: p = 0.966). Similarly, the change in cervical sagittal alignment was not related to the JOA (p = 0.604), SF-36 (p = 0.308), VAS neck (p = 0.832), or NDI (p = 0.608) scores.

CONCLUSIONS
Cervical laminoplasty for OPLL improved radiculomyelopathy. Cervical laminoplasty increased the probability of cervical kyphotic alignment. However, cervical sagittal alignment and clinical outcomes were not clearly related.
Fisetin, a dietary flavonoid induces apoptosis via modulating the MAPK and PI3K/Akt signalling pathways in human osteosarcoma (U-2 OS) cells
Authors: Li Jian-Ming , Li Wu-Yin , Huang Man-Yu , Zhang Xiao-Qiang 
Published: October 2015

<p>Human osteosarcoma is the most prevalent primary malignant bone tumor with high frequency of invasion and metastasis. Strong resistance coupled with toxicity of the currently available chemotherapeutic drugs poses challenge in treatment. The study aimed to investigate if fisetin, a dietary flavonoid induced apoptosis in human osteosarcoma (U-2 OS) cells. Fisetin at 20-100 µM effectively reduced the viability of OS cells, and induced apoptosis by significantly inducing the expression of caspases (Caspases- 3,-8 and -9) and pro-apoptotic proteins (Bax and Bad) with subsequent down-regulation of Bcl-xL and Bcl-2. While fisetin inhibited PI3K/Akt pathway and ERK1/2, it caused enhanced expressions of p-JNK, p-c-Jun and p-p38. Fisetin-induced ROS generation and decrease in mitochondrial membrane potential would have also contributed to rise in apoptotic cell counts. The observations suggest that fisetin was able to effectively induce apoptosis of U-2 OS cells through ROS generation and modulation of MAPK and PI3K/Akt signalling cascades. </p><p> </p>
L'exécution forcée d'une obligation de faire
Authors: Ayissi Manga Eugène Bertrand 
Published: October 2015

Cet article consiste en une analyse de l'évolution du droit positif sur l'exécution forcée en nature d'une obligation de faire. En effet, après avoir été largement admis, le principe de l'exécution forcée en nature d'une obligation de faire paraît aujourd'hui remis en cause. Une jurisprudence croissante, revenant à une interprétation rigoriste de l'article 1142 du Code civil et, de ce fait, défavorable à l'effet contraignant des obligations, considère, d'une façon générale, que toute obligation de faire (ou de ne pas faire) se résout en dommages et intérêts, en cas d'inexécution par le débiteur.
Le retour vers l'exclusion de l'exécution forcée, constaté en matière de promesses de contrats tend à se généraliser au point d'embrasser les contrats définitifs dès l'origine (I). Mais la portée du principe nouveau d'exclusion de l'exécution forcée d'une obligation de faire semble, en fin de compte, restreinte en raison de son incohérence sur le plan théorique et de son irréalisme sur le plan pratique (II).
Effect of Urate Lowering Therapy on Renal Disease Progression in Hyperuricemic Patients with Chronic Kidney Disease
Authors: Kim Yoonjin , Shin Sungjoon , Kim Kyungsoo , Choi Sangtae , Lee Kwanghoon 
Published: October 2015

Objective.To determine whether urate lowering therapy (ULT) could delay renal disease progression in hyperuricemic patients with chronic kidney disease (CKD).Methods.We performed a retrospective review of hyperuricemic patients with stage 3 CKD followed from September 2005 to July 2014 in Dongguk University Ilsan Hospital, Goyang, Korea. A total of 158 eligible patients were identified and 65 of them were treated with ULT in addition to the usual CKD management. We divided the patients according to the use of ULT and compared the estimated glomerular filtration rate (eGFR) change from baseline value and the proportion of renal disease progression (decline of eGFR > 30% of the baseline value, initiation of dialysis or eGFR < 15 ml/min/1.73m2) at the time of last followup. Risk factors for renal disease progression were identified by logistic regression analysis.Results.After a median followup of 118.5 weeks (minimum 25, maximum 465), the ULT group showed better outcomes compared to the non-ULT group in terms of eGFR change from baseline (−1.19 ± 12.07 vs −7.37 ± 11.17 ml/min/1.73 m2, p = 0.001) and the proportion of renal disease progression (12.3% vs 27.9%, p = 0.01). Goal-directed ULT showed better clinical outcomes compared to maintaining the initial ULT dose. Actual (area under the SUA-time curve adjusted by total observation time period) serum uric acid was significantly associated with the risk of renal disease progression (p for trend = 0.04) and actual serum uric acid level < 7 mg/dl reduced the risk of renal disease progression by 69.4%.Conclusion.ULT significantly delayed renal disease progression in hyperuricemic patients with CKD. Goal-directed ULT seems to be better than continuing the initial ULT prescription.
Subclinical Atherosclerosis Is Not Accelerated in Patients with Ankylosing Spondylitis with Low Disease Activity: New Data and Metaanalysis of Published Studies
Authors: Arida Aikaterini , Protogerou Athanasios D. , Konstantonis George , Konsta Maria , Delicha Evi M. , Kitas George D. , Sfikakis Petros P. 
Published: October 2015

Objective.Chronic inflammatory rheumatic diseases are associated with accelerated atherosclerosis, but data in ankylosing spondylitis (AS) are limited and the relative contribution of inflammation versus classical cardiovascular (CV) risk factors remains a matter of controversy. We addressed this in an original study and a metaanalysis of previous studies.Methods.Atheromatic plaques in carotid and femoral arteries, carotid hypertrophy [intima-media thickness (IMT), cross-sectional area], and carotid stiffness by ultrasound, as well as aortic stiffness by pulse wave velocity, were examined in consecutive nondiabetic, CV disease (CVD)-free patients with AS. Healthy individuals carefully matched 1:1 with patients for age, sex, smoking habits, hyperlipidemia, and hypertension served as controls. A metaanalysis of original studies that examined subclinical atherosclerosis in patients with AS versus controls with comparable CVD risk factors was also performed.Results.Carotid and femoral atheromatic plaques were slightly less prevalent compared with controls in a contemporary cohort consisting of 67 patients with AS (82% men), aged 47.5 ± 12.5 years (mean ± SD), with a median disease duration of 12 years and a Bath AS Disease Activity Index (BASDAI) of 1.8 (interquartile range 0.4–3.6), of whom 66% were receiving anti-tumor necrosis factor (TNF) treatment. Carotid hypertrophy and stiffness, as well as aortic stiffness, were similar between patients and their matched controls. Metaanalysis of all published studies revealed a significantly increased carotid IMT, but not plaque burden, in AS versus controls. Notably, however, increased IMT was not evident in studies involving patients with low disease activity (mean BASDAI < 4) or in those studies that included > 50% of patients treated with anti-TNF.Conclusion.Low AS disease activity is not associated with accelerated atherosclerosis.
Concomitant Methotrexate Protects Against Total Knee Arthroplasty in Patients with Rheumatoid Arthritis Treated with Tumor Necrosis Factor Inhibitors
Authors: Asai Shuji , Takahashi Nobunori , Funahashi Koji , Yoshioka Yutaka , Takemoto Toki , Terabe Kenya , Asai Nobuyuki , Ishiguro Naoki , Kojima Toshihisa 
Published: October 2015

Objective.To determine the effects of concomitant methotrexate (MTX) on the incidence of total knee arthroplasty (TKA) resulting from the progression of joint destruction in patients with rheumatoid arthritis (RA) during longterm treatment with tumor necrosis factor (TNF) inhibitors.Methods.A total of 155 patients with RA (310 knee joints) received TNF inhibitors at our institute between May 1, 2001, and May 31, 2008. A total of 111 symptomatic (tender and/or swollen) knee joints in 68 patients were retrospectively studied over the course of a minimum of 5 years of followup. The median (interquartile range) followup period was 8.1 (7.0–9.3) years. All data were analyzed using the knee joint as the statistical unit of analysis. TKA during treatment with TNF inhibitors was used as the outcome variable in predictive analyses. The cumulative incidence of TKA was compared by concomitant or no MTX use (MTX±).Results.There were 79 subjects (71%) who received concomitant MTX. According to Kaplan-Meier estimates, the cumulative incidence of TKA for the MTX+ group was significantly lower than that for the MTX− group (24% vs 45% at 5 yrs, respectively, p = 0.035). Multivariate analysis using the Cox proportional hazards model revealed that concomitant MTX (HR 0.44, 95% CI 0.22–0.89), Larsen grade (HR 2.93, 95% CI 1.94–4.41), and older age at baseline (HR 1.04, 95% CI 1.01–1.08) were independent predictors of TKA.Conclusion.Concomitant MTX reduces the incidence of TKA by 56% in patients with RA during longterm treatment with TNF inhibitors.
Arnau de Vilanova adversario de Tomás de Aquino : la polémica sobre la conveniencia de conocer los tiempos finales
Authors: Mensa I Valls Jaume 
Published: October 2015

Cet article a pour objet la synthèse et la critique faites par Arnau de Vilanova, dans le Gladius iugulans thomatistas , des thèses de Thomas d’Aquin sur la possibilité de connaître la fin des temps. De surcroît, nous établirons sa contextualisation dans le cadre de la controverse entre le médecin catalan, Jean Vigorós et Martin d’Ateca. Le fragment mentionné est édité avec trois passages supplémentaires ; une description détaillée du ms. Canon. Misc. 370 (Bodleian Library, Oxford) est également fournie.
From Transition Shock to Competent Practice: Developing Preceptors to Support New Nurse Transition
Authors: Clipper Bonnie , Cherry Barbara 
Published: October 2015

Background:
It is well known that new graduate nurses (NGRNs) are likely to have a difficult transition from nursing school into professional practice and often experience a phenomenon known as transition shock. Evidence suggests using preceptors as an effective method supporting the NGRNs through this difficult transition.

Method:
This project evaluated the effectiveness of a structured preceptor development program by measuring perceptions of transition to practice and first-year retention of two groups of former graduate nurses—the first comprising preceptors trained through a preceptor development program, and the second comprising preceptors who did not participate in structured training.

Results:
Graduate nurses who had well-trained preceptors had higher, more positive perceptions about their ability to render safe and optimal care, as well as higher first-year retention.

Conclusion:
A structured preceptor-training program may contribute to an improved transition to practice and improved first-year retention rates of NGRNs.

J Contin Educ Nurs.
2015;46(10):448–454.
Optical Coherence Tomography Angiography of Diabetic Retinopathy in Human Subjects
Authors: Matsunaga Douglas R. , Yi Jack J. , De Koo Lisa Olmos , Ameri Hossein , Puliafito Carmen A. , Kashani Amir H 
Published: October 2015

BACKGROUND AND OBJECTIVE:
Optical coherence tomography angiography (OCTA) is a novel, non-invasive OCT technique capable of imaging the retinal vasculature. This study aims to evaluate the retinal microvasculature in diabetic human subjects with OCTA and assess potential clinical applications.

PATIENTS AND METHODS:
Cross-sectional study of 33 subjects with diabetic retinopathy. OCTA was performed on 3 mm × 3 mm sections using a swept-source OCTA prototype and a phase- and intensity-based contrasting algorithm. OCT angiograms were studied with corresponding clinical examination and fluorescein angiograms, when available, to assess accuracy and clinical utility.

RESULTS:
OCTA was able to demonstrate most clinically relevant vascular changes in subjects with diabetic retinopathy, including microaneurysms, impaired vascular perfusion, some forms of intraretinal fluid, vascular loops, intraretinal microvascular abnormalities, neovascularization, and cotton-wool spots that were largely consistent with fluorescein angiography.

CONCLUSION:
OCTA generates high-resolution angiograms that illustrate many of the clinically relevant findings in diabetic retinopathy and offers a novel complement or alternative to fluorescein angiography. Although currently an investigational technique, OCTA in combination with standard OCT imaging is at least as good as fluorescein angiography in the evaluation of the macular complications of diabetic retinopathy.

[
Ophthalmic Surg Lasers Imaging Retina.
2015;46:796–805.]
Bevacizumab Versus Ranibizumab in the Treatment of Macular Edema Due to Retinal Vein Occlusion: 6-Month Results of the CRAVE Study
Authors: Rajagopal Rithwick , Shah Gaurav K. , Blinder Kevin J. , Altaweel Michael , Eliott Dean , Wee Raymond , Cooper Blake , Walia Harpreet , Smith Bradley , Joseph Daniel P. 
Published: October 2015

BACKGROUND AND OBJECTIVE:
To compare efficacy of monthly treatment with bevacizumab or ranibizumab for macular edema due to retinal vein occlusion.

PATIENTS AND METHODS:

Randomized, multicenter, comparative trial (
ClinicalTrials.gov
identifier: NCT01428388). Participants were randomized 1:1 to receive monthly treatment with bevacizumab or ranibizumab. The primary outcome was change in central foveal thickness at 6 months compared to baseline.

RESULTS:

The trial randomized 98 patients to treatment with bevacizumab or ranibizumab. At 6 months, there were no differences in change in central foveal thickness between groups (bevacizumab: mean reduction of 212.6 µm, 95% confidence interval [CI], −288.3 to −137.0; ranibizumab: mean reduction of 243.8 µm, 95% CI, −309.6 to −178.0;
P
= .72, analysis of variance [ANOVA]). Both groups showed similar functional outcomes (bevacizumab: 0.33 logMAR gain, 95% CI, −0.47 to −0.18; ranibizumab: 0.34 logMAR gain, 95% CI, −0.45 to −0.23;
P
= .38, ANOVA).

CONCLUSION:
In the treatment of retinal vein occlusion, bevacizumab and ranibizumab have similar effects on reducing macular thickness and improving visual acuity.

[
Ophthalmic Surg Lasers Imaging Retina
. 2015;46:844–850.]
Management of Symptomatic Floaters: Current Attitudes, Beliefs, and Practices Among Vitreoretinal Surgeons
Authors: Cohen Michael N. , Rahimy Ehsan , Ho Allen C. , Garg Sunir J. 
Published: October 2015

BACKGROUND AND OBJECTIVE:
To assess the current attitudes, beliefs, and practice patterns among vitreoretinal surgeons when dealing with symptomatic floaters in patients with otherwise healthy eyes.

PATIENTS AND METHODS:
A cross-sectional, Internet-based anonymous survey of 10 questions was distributed via email to vitreoretinal specialists practicing in the United States.

RESULTS:

The survey response rate was 6.1% (159 of 2,600). Forty of 159 respondents (25%) reported they would perform pars plana vitrectomy (PPV) to reduce symptomatic floaters, and 110 of 159 (69%) had previously performed PPV for this indication. When compared to those unlikely to intervene for symptomatic floaters, 33 of 40 (83%) of those likely to intervene performed more than 100 vitrectomy surgical cases annually (
P
< .05). Between those that had and had not performed PPV for symptomatic floaters in the past, statistically significant differences were observed regarding the likelihood to perform PPV for symptomatic floaters in the future (35% vs. 4%;
P
< .0001) and tendency to elect a procedure if the surgeon’s own vision were impacted by symptomatic floaters (55% vs. 8%;
P
< .001). When compared to those likely to perform surgery for symptomatic floaters, those unlikely to intervene identified three statistically significant barriers: the surgical risks involved with PPV (28% vs. 86%;
P
< .001), unrealistic patient expectations (25% vs 58%;
P
< .001), and the possibility of ridicule from the local retina community (10% vs. 32%;
P
< .01).

CONCLUSION:
Vitreoretinal specialists are more likely to intervene for symptomatic floaters if they have previously done so and if they perform more than 100 surgical cases per year. The major barriers preventing physicians from performing an intervention for floaters are standard risks associated with PPV, the fear of unreasonable patient expectations, and the possibility of ridicule within the local retina community.

[
Ophthalmic Surg Lasers Imaging Retina.
2015;46:859–865.]