bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics Predicting Tuberculosis Risk under Tumor Necrosis Factor-α Inhibitors: Report from a Large Multicenter Cohort with High Background Prevalence
Authors: Kisacik Bunyamin , Pamuk Omer Nuri , Onat Ahmet Mesut , Erer Sait Burak , Hatemi Gulen , Ozguler Yesim , Pehlivan Yavuz , Kilic Levent , Ertenli Ihsan , Can Meryem , Direskeneli Haner , Keser Gökhan , Oksel Fahrettin , Dalkilic Ediz , Yilmaz Sedat , Pay Salih , Balkarli Ayse , Cobankara Veli , Cetin Gözde Yildirim , Sayarlioglu Mehmet , Cefle Ayse , Yazici Ayten , Avci Ali Berkant , Terzioglu Ender , Ozbek Suleyman , Akar Servet , Gul Ahmet 
Published: January 2016

Objective.Screening strategies for latent tuberculosis (TB) before starting tumor necrosis factor (TNF)-α inhibitors have decreased the prevalence of TB among patients who are treated with these agents. However, despite vigilant screening, TB continues to be an important problem, especially in parts of the world with a high background TB prevalence. The aim of this study was to determine the factors related to TB among a large multicenter cohort of patients who were treated with anti-TNF.Methods.Fifteen rheumatology centers participated in this study. Among the 10,434 patients who were treated with anti-TNF between September 2002 and September 2012, 73 (0.69%) had developed TB. We described the demographic features and disease characteristics of these 73 patients and compared them to 7695 patients who were treated with anti-TNF, did not develop TB, and had complete data available.Results.Among the 73 patients diagnosed with TB (39 men, 34 women, mean age 43.6 ± 13 yrs), the most frequent diagnoses were ankylosing spondylitis (n = 38) and rheumatoid arthritis (n = 25). More than half of the patients had extrapulmonary TB (39/73, 53%). Six patients died (8.2%). In the logistic regression model, types of anti-TNF drugs [infliximab (IFX), OR 3.4, 95% CI 1.88–6.10, p = 0.001] and insufficient and irregular isoniazid use (< 9 mos; OR 3.15, 95% CI 1.43–6.9, p = 0.004) were independent predictors of TB development.Conclusion.Our results suggest that TB is an important complication of anti-TNF therapies in Turkey. TB chemoprophylaxis less than 9 months and the use of IFX therapy were independent risk factors for TB development.
Improvement in Psoriasis Signs and Symptoms Assessed by the Psoriasis Symptom Inventory with Brodalumab Treatment in Patients with Psoriatic Arthritis
Authors: Mease Philip J. , Genovese Mark C. , Mutebi Alex , Viswanathan Hema N. , Chau Dina , Feng Jingyuan , Erondu Ngozi , Nirula Ajay 
Published: January 2016

Objective.To evaluate the effect of brodalumab on psoriasis signs and symptoms assessed by the Psoriasis Symptom Inventory (PSI) in patients with psoriatic arthritis (PsA).Methods.This prespecified analysis of a phase II study (NCT01516957) evaluated patients with active PsA and psoriasis-affected body surface area ≥ 3%, randomized to brodalumab (140 or 280 mg) or placebo every 2 weeks (Q2W) for 12 weeks with loading dose at Week 1. At Week 12, patients entering an open-label extension received brodalumab 280 mg Q2W. The PSI measures 8 psoriasis signs and symptoms: itch, redness, scaling, burning, stinging, cracking, flaking, and pain. PSI response is defined as total PSI ≤ 8 (range 0–32), each item ≤ 1 (range 0–4). PSI scores were assessed at weeks 12 and 24.Results.There were 107 eligible patients. At Week 12, mean improvement in PSI scores was 7.8, 11.2, and 1.5 in brodalumab 140 mg, 280 mg, and placebo groups, respectively; by Week 24, improvement was 10.2, 12.4, and 11.7. At Week 12, 75.0%, 81.8%, and 16.7% of patients receiving brodalumab 140 mg, 280 mg, and placebo, respectively, achieved PSI response; improvement was sustained through Week 24, when 83.9% of prior placebo recipients achieved response. At Week 12, 25.0%, 36.4%, and 2.8% of patients receiving brodalumab 140 mg, 280 mg, and placebo, respectively, achieved PSI 0. Percentages improved through Week 24: 40.0% brodalumab 140 mg, 42.9% brodalumab 280 mg, and 48.4% placebo.Conclusion.Significantly more brodalumab-treated patients with PsA achieved patient-reported improvements in psoriasis signs and symptoms than did those receiving placebo. Improvements were comparable between brodalumab groups.
Longterm Efficacy of an Antipneumococcal Polysaccharide Vaccine among Patients with Autoimmune Inflammatory Rheumatic Diseases
Authors: Broyde Adi , Arad Uri , Madar-Balakirski Noa , Paran Daphna , Kaufman Ilana , Levartovsky David , Wigler Irena , Caspi Dan , Elkayam Ori 
Published: January 2016

Objective.To estimate the longterm humoral response of an antipneumococcal polysaccharide vaccine (PPSV23) in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), or inflammatory bowel disease (IBD)-associated spondyloarthropathy (SpA), and the effect of demographic and clinical factors and treatment on the longterm efficacy of the vaccine.Methods.A total of 145 consecutive patients treated with biologics [tumor necrosis factor-α (TNF-α) or interleukin 6 (IL-6) receptor inhibitors] or methotrexate (MTX) participated in this study. Fifteen were excluded because of absent information regarding their vaccination status (n = 9) or because of technical problems in obtaining their serum sample (n = 6). They were diagnosed with RA (n = 63, 48.5%), PsA (n = 29, 22.3%), AS (n = 28, 21.5%), or IBD-associated SpA (n = 3, 2.3%). Their mean age was 54.6 years, and 61.5% were women. Data were collected on the timing of vaccination, demographic and clinical characteristics, and treatment, and patients’ serum antipneumococcal antibody levels were tested.Results.Two-thirds of the patients (67.7%) had received PPSV23 45 months (mean) earlier. Treatment included TNF-α inhibitors (73.9%), IL-6 receptor inhibitors (13.1%), or MTX without a biological treatment (13%). The uptake of vaccination was significantly higher in the older population (> 65 yrs). Vaccinated patients had significantly higher antibody levels compared with vaccine-naive patients. The antibody levels had been preserved after 10 years. MTX use, but not biologics, was associated with significantly lower antibody levels.Conclusion.The longterm efficacy of the PPSV23 vaccination seems to be preserved among patients with RA, PsA, AS, and IBD-associated SpA for at least 10 years. Efficacy is slightly impaired by MTX, but it is not affected by biologics. These findings suggest that revaccination after 5 years might not be needed for all, and testing the antibody titers should be considered to identify those who may benefit from revaccination.
Physical and Mental Functioning in Patients with Established Rheumatoid Arthritis over an 11-year Followup Period: The Role of Specific Comorbidities
Authors: van den Hoek Joëlle , Roorda Leo D. , Boshuizen Hendriek C. , Tijhuis Gerard J. , van den Bos Geertrudis A. , Dekker Joost 
Published: January 2016

Objective.To investigate the longterm association of a wide range of comorbidities with physical and mental functioning in patients with rheumatoid arthritis (RA).Methods.Longitudinal data over a period of 11 years were collected from 882 patients with RA. Somatic comorbidity and comorbid depression were measured at baseline, with a questionnaire including 20 chronic diseases and with the Center for Epidemiologic Depression Scale, respectively. Physical functioning was measured at 5 timepoints with a disease-specific measure [Health Assessment Questionnaire (HAQ)] and a generic measure [physical scales of the Medical Outcomes Study Short Form-36 (SF-36)]. Mental functioning was measured with the mental scales of the SF-36. To determine the association of baseline-specific comorbidities with functioning over time, we performed longitudinal analyses.Results.At baseline, 72% percent of the patients were women, mean age ± SD was 59.3 ± 14.8 years, median RA disease duration was 5.0 years, and 68% had ≥ 1 comorbid condition. The effect of comorbid conditions was more apparent when physical functioning was measured with SF-36, a disease-generic measure, compared with the HAQ, a disease-specific measure. Circulatory conditions and depression were associated (p < 0.05) with worse physical functioning according to the HAQ. Respiratory conditions, musculoskeletal conditions, cancer, and depression were associated (p < 0.05) with worse physical functioning according to the SF-36. Respiratory conditions and depression were associated with worse mental functioning.Conclusion.Patients with specific comorbid conditions have an increased risk of low functioning in the long term. Targeted attention for these specific comorbid conditions by clinicians is recommended.
Path Analysis Identifies Receptor Activator of Nuclear Factor-κB Ligand, Osteoprotegerin, and Sclerostin as Potential Mediators of the Tophus-bone Erosion Relationship in Gout
Authors: Chhana Ashika , Aati Opetaia , Gamble Gregory D. , Callon Karen E. , Doyle Anthony J. , Roger Mark , McQueen Fiona M. , Horne Anne , Reid Ian R. , Cornish Jillian , Dalbeth Nicola 
Published: January 2016

Objective.To determine the relationship between tophus, erosion and bone remodeling factors in gout.Methods.Computed tomography bone erosion and circulating bone factors were measured in adults with tophaceous gout. Multiple regression modeling and path analysis were used to determine predictors of erosion.Results.Tophus number, Māori or Pacific ethnicity, creatinine, receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), and sclerostin were independently associated with erosion. Path analysis showed a direct effect of tophus number on erosion, partially mediated through OPG, RANKL, and sclerostin.Conclusion.Tophus number is strongly associated with bone erosion in gout. Circulating RANKL, OPG, and sclerostin are potential mediators of tophus-related erosion.
Mycophenolate Mofetil in Nonrenal Manifestations of Systemic Lupus Erythematosus: An Observational Cohort Study
Authors: Tselios Konstantinos , Gladman Dafna D. , Su Jiandong , Urowitz Murray B. 
Published: January 2016

Objective.Mycophenolate mofetil (MMF), along with corticosteroids, is considered as the standard of care in lupus nephritis (LN); however, little is known regarding its efficacy in extrarenal manifestations of systemic lupus erythematosus (SLE). We aimed to determine its effectiveness in nonrenal SLE.Methods.One hundred seventy-seven patients with SLE were enrolled; 105 for whom MMF was introduced for active LN (mean age 35.6 ± 10.7 yrs, mean disease duration 8.9 ± 7.8 yrs) and 72 for extrarenal manifestations (mean age 38.6 ± 11.7 yrs, mean disease duration 11.7 ± 9.2 yrs). The main indication for MMF initiation was based on the respective SLE Disease Activity Index element that was present at that time. Patients were subdivided according to the major nonrenal manifestation. Improvement was defined as the absence of the initial clinical or laboratory manifestation after 6 and 12 months.Results.Cumulatively, the initial clinical manifestation or hematological abnormality was resolved in 42/72 nonrenal patients (58.3%) after 6 months and in 45/72 (62.5%) after 12 months. Corticosteroid dose was reduced in 44/72 patients (61.1%, p < 0.001, mean dose 18.4 ± 12.6 mg/day at baseline to 12.1 ± 9.0 mg/day after 12 mos, p < 0.05). In renal patients, 40 (38.1%) had complete resolution of the extrarenal manifestation after 6 months, while 53 (50.5%) achieved complete response after 12 months. Prednisone dose was reduced in 73/105 patients (69.5%) after 12 months (mean dose 29.2 ± 16.6 mg/day at baseline to 15.3 ± 9.7 mg/day, p < 0.001).Conclusion.MMF seems to be an efficacious alternative in refractory to standard of care nonrenal manifestations of SLE in the long term, allowing for disease activity control and significant reduction in corticosteroid dose.
Genetic Variants That Are Associated with Neuropsychiatric Systemic Lupus Erythematosus
Authors: Ho Roger C. , Ong Huiyi , Thiaghu Chandra , Lu Yanxia , Ho Cyrus S. , Zhang Melvyn W. 
Published: January 2016

Objective.While genetic risks have been implicated in systemic lupus erythematosus (SLE), the involvement of various genotypes in neuropsychiatric SLE (NPSLE) remains uncertain. The present metaanalysis aimed to combine data from different studies and evaluate the association between each genotype and the risk of developing NPSLE.Methods.Studies were searched and retrieved from online databases (PubMed, EMBASE, BIOSIS, and ScienceDirect). Case-control studies were chosen if they reported genotype frequencies of the γ Fc region (FCγR) receptors II-A, III-A, and III-B; tumor necrosis factor–α (TNF-α); mannan-binding lectin (MBL); integrin alpha M (ITGAM); interleukin (IL) 1, IL-1β, and IL-6; IL-10 promoter; and vitamin D genes. The OR were used to assess the strength of this association between patients with NPSLE and SLE.Results.A total of 33 studies were considered in this metaanalysis. The results suggest that these genotypes demonstrated a significant association with NPSLE: the homozygous FCγR IIIa 158 FF genotype (OR 1.89, p = 0.03 for FF vs VV + FV), heterozygous FCγR IIIb NA1/2 genotype (OR 2.14, p = 0.03 for NA1/2 vs NA1/1; OR 1.81, p = 0.04 for NA1/2 vs NA1/1 + NA2/2), and homozygous ITGAM rs1143679 HH genotype (OR 3.39, p = 0.04 for HH vs RH; OR 3.11, p = 0.048 for HH vs RR + RH). Polymorphisms of the TNF-α, MBL2, IL-1, IL-1β, IL-6, IL-10 promoter, and vitamin D receptor genes did not show a statistically significant association with the risk of developing NPSLE (p > 0.05).Conclusion.This metaanalysis indicates that polymorphisms in the pathways of immune complex clearance, such as the FcγRIIIa, FcγRIIIb, and ITGAM genotypes, are potential susceptibility genes for NPSLE.
Une rhétorique sacrée au service de la République profane
Authors: Schröer Christina 
Published: January 2016

Dès 1789 la Révolution s’est caractérisée par le désir d’un renouveau de l’être humain qui impliquait l’idée d’éducation. Ce projet se radicalise encore avec l’avènement de la République. En plus de la nécessité d’une nouvelle organisation du système scolaire, les républicains songeaient aussi aux possibilités d’une « éducation morale étatique », destinée à convaincre le citoyen des avantages du nouveau régime et à lui faire aimer l’ordre républicain. Le discours politique a été complété par de nouvelles pratiques inspirées largement de sémantique sacrée. Contrairement à ce que l’on pense, l’apogée de ces changements n’a pas été atteint avec le règne des Jacobins, mais sous la République directoriale. C’est surtout grâce aux initiatives du directeur La Révellière-Lépeaux que le projet d’instruction civique républicaine reprend avec vigueur après le 18 fructidor an V. Dans ce contexte « l’art d’argumenter et de convaincre » connut une profonde rupture.
Les sédations en fin de vie
Authors: Copel Laure , Poisson Dominique 
Published: January 2016

La proposition de loi Claeys-Leonetti sur les sédations en fin de vie, en débat au Parlement, a été au cœur de bien des controverses. Qu’entend-on par phase terminale ? Quel contenu donner à la collégialité ? Existe-t-il un risque de détournement de la sédation ? La frontière entre une sédation a priori profonde et continue, avec arrêt de la nutrition et de l’hydratation, et l’euthanasie, est-elle claire ? Les auteurs proposent une réflexion nourrie de leur expérience en soins palliatifs.
Repères éthiques en service de psychiatrie
Authors: Richa Sami , Choueifati Doris , Scheuer Michel 
Published: January 2016

Tous les paramètres à retenir pour élaborer une éthique du soin en psychiatrie ne sont pas propres à cette spécialité : certains tiennent à la personne du patient et au respect de ses droits, rejoignant en cela toute pratique médicale ou soignante. Ils n’en revêtent pas moins, dans le cadre de l’exercice psychiatrique, une dimension particulière qui doit être prise en compte. D’autres repères concernent des situations propres à la psychiatrie, lesquelles requièrent une approche éthique spécifique.
Résistance
Authors: Sauret Marie-Jean 
Published: January 2016

Résumé	Ce titre, « Résistance », équivoque entre la résistance au sens de la psychanalyse, qui est le fait d’un réel, et la résistance politique, qui suppose que le sujet y mette du sien. De l’une à l’autre il y a un point commun : le symptôme qui témoigne de la première, auquel le sujet est conduit par l’analyse à s’identifier, et qui constitue le levier de la seconde, de son inscription dans le lien social… Pour quelles conséquences ?
Loss of Peripheral Protection in Pancreatic Islets by Proteolysis-Driven Impairment of VTCN1 (B7-H4) Presentation Is Associated with the Development of Autoimmune Diabetes
Authors: Radichev Ilian A. , Maneva-Radicheva Lilia V. , Amatya Christina , Salehi Maryam , Parker Camille , Ellefson Jacob , Burn Paul , Savinov Alexei Y. 
Published: January 2016

Abstract
Ag-specific activation of T cells is an essential process in the control of effector immune responses. Defects in T cell activation, particularly in the costimulation step, have been associated with many autoimmune conditions, including type 1 diabetes (T1D). Recently, we demonstrated that the phenotype of impaired negative costimulation, due to reduced levels of V-set domain–containing T cell activation inhibitor 1 (VTCN1) protein on APCs, is shared between diabetes-susceptible NOD mice and human T1D patients. In this study, we show that a similar process takes place in the target organ, as both α and β cells within pancreatic islets gradually lose their VTCN1 protein during autoimmune diabetes development despite upregulation of the VTCN1 gene. Diminishment of functional islet cells’ VTCN1 is caused by the active proteolysis by metalloproteinase N-arginine dibasic convertase 1 (NRD1) and leads to the significant induction of proliferation and cytokine production by diabetogenic T cells. Inhibition of NRD1 activity, alternatively, stabilizes VTCN1 and dulls the anti-islet T cell responses. Therefore, we suggest a general endogenous mechanism of defective VTCN1 negative costimulation, which affects both lymphoid and peripheral target tissues during T1D progression and results in aggressive anti-islet T cell responses. This mechanism is tied to upregulation of NRD1 expression and likely acts in two synergistic proteolytic modes: cell-intrinsic intracellular and cell-extrinsic systemic. Our results highlight an importance of VTCN1 stabilization on cell surfaces for the restoration of altered balance of immune control during T1D.
γδ T Cells Protect the Liver and Lungs of Mice from Autoimmunity Induced by Scurfy Lymphocytes
Authors: Ujiie Hideyuki , Shevach Ethan M. 
Published: January 2016

Abstractγδ T cells have been shown to have immunoregulatory functions in several experimental autoimmune models. A mutation of the Foxp3 gene leads to the absence of regulatory T cells (Tregs) and a fatal systemic autoimmune disease in scurfy mice. Transfer of scurfy lymphocytes to RAG deficient (RAG−/−) recipients reproduces the inflammatory phenotype of the scurfy donor, including hepatitis and pneumonitis. In this study, we show that TCRα−/− recipients, which lack αβ T cells but have γδ T cells and B cells, are significantly protected from the hepatitis and pneumonitis, but not the dermatitis, induced by adoptive transfer of scurfy lymphocytes. Cotransfer of γδ T cells, but not B cells, prevented hepatitis and pneumonitis in RAG−/− recipients of scurfy lymphocytes. γδ T cells in the TCRα−/− recipients of scurfy cells markedly expanded and expressed a highly activated (CD62LloCD44hi) phenotype. The activated γδ T cells expressed high levels of CD39 and NKG2D on their cell surface. A high frequency of scurfy T cells in TCRα−/− recipients produced IL-10, suggesting that γδ T cells may enhance suppressor cytokine production from scurfy T cells in TCRα−/− recipients. This study indicates that γδ T cells may contribute to the maintenance of immunological homeostasis by suppressing autoreactive T cells in liver and lung.
Phosphatidylinositol 4-Phosphate 5-Kinase β Controls Recruitment of Lipid Rafts into the Immunological Synapse
Authors: Kallikourdis Marinos , Trovato Anna Elisa , Roselli Giuliana , Muscolini Michela , Porciello Nicla , Tuosto Loretta , Viola Antonella 
Published: January 2016

Abstract
Phosphatidylinositol 4,5-biphosphate (PIP2) is critical for T lymphocyte activation serving as a substrate for the generation of second messengers and the remodeling of actin cytoskeleton necessary for the clustering of lipid rafts, TCR, and costimulatory receptors toward the T:APC interface. Spatiotemporal analysis of PIP2 synthesis in T lymphocytes suggested that distinct isoforms of the main PIP2-generating enzyme, phosphatidylinositol 4-phosphate 5-kinase (PIP5K), play a differential role on the basis of their distinct localization. In this study, we analyze the contribution of PIP5Kβ to T cell activation and show that CD28 induces the recruitment of PIP5Kβ to the immunological synapse, where it regulates filamin A and lipid raft accumulation, as well as T cell activation, in a nonredundant manner. Finally, we found that Vav1 and the C-terminal 83 aa of PIP5Kβ are pivotal for the PIP5Kβ regulatory functions in response to CD28 stimulation.
Inducible Expression of CXCL1 within the Central Nervous System Amplifies Viral-Induced Demyelination
Authors: Marro Brett S. , Grist Jonathan J. , Lane Thomas E. 
Published: January 2016

AbstractThe functional role of the ELR+ chemokine CXCL1 in host defense and disease following infection of the CNS with the neurotropic JHM strain of mouse hepatitis virus (JHMV) was examined. Mice in which expression of CXCL1 is under the control of a tetracycline-inducible promoter active within glial fibrillary acidic protein–positive cells were generated and this allowed for selectively increasing CNS expression of CXCL1 in response to JHMV infection and evaluating the effects on neuroinflammation, control of viral replication, and demyelination. Inducible expression of CNS-derived CXCL1 resulted in increased levels of CXCL1 protein within the serum, brain, and spinal cord that correlated with increased frequency of Ly6G+CD11b+ neutrophils present within the CNS. Elevated levels of CXCL1 did not influence the generation of virus-specific T cells, and there was no difference in control of JHMV replication compared with control mice, indicating that T cell infiltration into the CNS is CXCL1-independent. Sustained CXCL1 expression within the CNS resulted in increased mortality that correlated with elevated neutrophil infiltration, diminished numbers of mature oligodendrocytes, and an increase in the severity of demyelination. Neutrophil ablation in CXCL1-transgenic mice reduced the severity of demyelination in mice, arguing for a role for these cells in white matter damage. Collectively, these findings illustrate that sustained CXCL1 expression amplifies the severity of white matter damage and that neutrophils can contribute to this process in a model of viral-induced neurologic disease.