bluuebunny/crossref_metadata_2025_split huggingface dataset:
Symptomatic Efficacy of Etanercept and Its Effects on Objective Signs of Inflammation in Early Nonradiographic Axial Spondyloarthritis: A Multicenter, Randomized, Double‐Blind, Placebo‐Controlled Trial
Authors: Dougados Maxime , van der Heijde Désirée , Sieper Joachim , Braun Jürgen , Maksymowych Walter P. , Citera Gustavo , Miceli‐Richard Corinne , Wei James Cheng‐Chung , Pedersen Ron , Bonin Randi , Rahman Mahboob U. , Logeart Isabelle , Wajdula Joseph , Koenig Andrew S. , Vlahos Bonnie , Alvarez Daniel , Bukowski Jack F. 
Published: May 2014

ObjectiveTo assess the efficacy of etanercept in the treatment of early active nonsteroidal antiinflammatory drug (NSAID)–refractory nonradiographic axial spondyloarthritis (SpA).MethodsThe study population consisted of patients who met the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial SpA but not the modified New York radiographic criteria for ankylosing spondylitis (as assessed by a radiologist at the central trial site), had a symptom duration of >3 months but <5 years, had a score of ≥4 on the Bath Ankylosing Spondylitis Disease Activity Index, and had been treated unsuccessfully with ≥2 NSAIDs. Patients were randomized to receive etanercept 50 mg/week or placebo and continued background NSAID treatment for 12 weeks (double‐blind study); during the subsequent open‐label period, all patients received etanercept 50 mg/week. The primary study end point was meeting the ASAS criteria for 40% improvement (ASAS40) at week 12. Magnetic resonance imaging (MRI) of the sacroiliac joints and spine was performed at baseline and week 12.ResultsOne hundred six patients were randomized to the etanercept group and 109 to the placebo group. Of the 215 patients, the mean ± SD age at baseline was 32.0 ± 7.8 years, 154 (72%) were HLA–B27 positive, and 174 (81%) had MRI‐confirmed sacroiliitis. At 12 weeks, the proportion of patients with improvement according to the ASAS40 was significantly higher in the etanercept group than in the placebo group (34 of 105 [32%] versus 17 of 108 [16%]; P = 0.006). Patients who received etanercept exhibited a greater reduction in MRI‐based scores for sacroiliac joint inflammation (−46.9% versus −10.9%; P < 0.001) and spinal inflammation (−45.4% versus −33.4%; P = 0.04) compared with placebo‐treated patients at week 12. Post hoc analyses suggested a possible association between higher baseline C‐reactive protein levels or MRI sacroiliac joint inflammation scores and higher rates of ASAS40 response to etanercept. At week 24, patients in the placebo group who had switched to etanercept at 12 weeks exhibited improvement similar to that observed in patients who had received etanercept for 24 weeks.ConclusionIn patients with nonradiographic axial SpA, etanercept treatment was associated with rapid, significant improvement in symptomatic disease activity, function, and systemic and skeletal inflammation over 12 weeks; clinical/functional improvement was sustained over 24 weeks.
Contribution of Transient Receptor Potential Ankyrin 1 to Chronic Pain in Aged Mice With Complete Freund's Adjuvant–Induced Arthritis
Authors: Garrison Sheldon R. , Stucky Cheryl L. 
Published: May 2014

ObjectiveTo investigate age‐related differences in mechanical sensitivity to inflammatory pain and determine the contribution of transient receptor potential ankyrin 1 (TRPA1) to mechanical hypersensitivity during chronic inflammation in young and aged mice with complete Freund's adjuvant (CFA)–induced arthritis.MethodsMechanical sensitivity in young (3‐month‐old) and aged (24‐month‐old) wild‐type (TRPA1+/+) mice and TRPA1‐deficient (TRPA1−/−) mice was measured behaviorally for 8 weeks following injection of CFA into the plantar hind paw. The severity of inflammation was evaluated by histologic analyses and hind‐paw measurements. Ex vivo preparations of the skin saphenous nerve from mice were assessed for C‐fiber sensitivity.ResultsAmong naive (uninjured) wild‐type mice, aged animals were less sensitive than young animals to mechanical stimuli. Afferent recordings of C‐fibers from TRPA1−/− mice indicated that TRPA1 contributes to the normal mechanical sensitivity in both age groups. Following injection of CFA, both young and aged TRPA1+/+ mice exhibited mechanical hypersensitivity. In young TRPA1−/− mice injected with CFA, peak development of mechanical hypersensitivity was delayed until week 4, when they exhibited a sharp decrease (9‐fold) in the mechanical paw withdrawal threshold, whereas aged TRPA1−/− mice did not exhibit mechanical hypersensitivity at any time during the 8 weeks after CFA injection. Recordings of C‐fibers from the saphenous nerve supported these findings, with results indicating that both young and aged TRPA1+/+ mice exhibited increased action potential firing at 8 weeks after CFA injection (increases of 25% and 60%, respectively). Interestingly, among TRPA1−/− mice injected with CFA, mechanical firing was increased markedly in the C‐fibers of young mice (increase of 80%) but not in the C‐fibers of aged mice.ConclusionThese findings reveal marked differences in the long‐term mechanical behavioral sensitivity of aged and young mice, and suggest that TRPA1 may be a key contributor to the transition from acute to chronic inflammatory pain in response to mechanical stimuli as well as to the development of nociceptor sensitization selectively in aged mice.
Brief Report: Involvement of TNFRSF11A Molecular Defects in Autoinflammatory Disorders
Authors: Jéru Isabelle , Cochet Emmanuelle , Duquesnoy Philippe , Hentgen Véronique , Copin Bruno , Mitjavila‐Garcia Maria Teresa , Sheykholeslami Shayan , Le Borgne Gaëlle , Dastot‐Le Moal Florence , Malan Valérie , Karabina Sonia , Mahevas Mathieu , Chantot‐Bastaraud Sandra , Lecron Jean‐Claude , Faivre Laurence , Amselem Serge 
Published: May 2014

ObjectiveAutoinflammatory disorders are caused by a primary dysfunction of the innate immune system. Among these disorders are hereditary recurrent fevers, which are characterized by recurrent episodes of fever and inflammatory manifestations affecting multiple tissues. Hereditary recurrent fevers often lack objective diagnostic criteria, thereby hampering the identification of disease‐causing genes. This study was undertaken to identify a gene responsible for hereditary recurrent fevers.MethodsCopy number variations and point mutations were sought by array‐comparative genomic hybridization and polymerase chain reaction sequencing, respectively. Serum cytokine levels were measured using Luminex technology. The effect of TNFRSF11A molecular defects on NF‐κB signaling in cells expressing wild‐type and mutated forms of the receptor was evaluated by luciferase assay.ResultsA patient with multiple congenital anomalies and hereditary recurrent fever was found to carry a de novo heterozygous complex chromosomal rearrangement encompassing a duplication of TNFRSF11A, a gene known to regulate fever in rodents. We also identified a heterozygous frameshift mutation (p.Met416Cysfs*110) in TNFRSF11A in a mother and daughter with isolated hereditary recurrent fever. This mutation was associated with increased secretion of several inflammatory cytokines (tumor necrosis factor α [TNFα], interleukin‐18 [IL‐18], IL‐1 receptor antagonist, interferon‐γ) and altered the biologic effects of the receptor on NF‐κB signaling. The disease in the patients described herein exhibits striking clinical similarities to TNF receptor–associated periodic syndrome, another hereditary recurrent fever involving a gene of the same family (TNFRSF1A).ConclusionThe involvement of TNFRSF11A in hereditary recurrent fever highlights the key role of this receptor in innate immunity. The present results also suggest that TNFRSF11A screening could serve as a new diagnostic test for autoinflammatory disorders.
Emerging roles of metal solute carriers in cancer mechanisms and treatment
Authors: Jong Nancy N. , McKeage Mark J. 
Published: May 2014

ABSTRACTThe literature concerning the roles of metal transporting solute carriers in the development and progression of human cancer, and in the delivery of metal‐containing anticancer drugs, chemical carcinogens and imaging agents, is reviewed. A range of different solute carrier families, including members from the SLC2A, SLC11A, SLC22A, SLC25A, SLC30A, SLC31A, SLC39A, SLC40A, SLC47A and SLCO1B families, and various metal substrates, including arsenic, copper, gadolinium, iron, platinum and zinc, have been implicated in these cancer‐related transport processes. For example, the transport of platinum‐based anticancer drugs has been reported to be influenced by the expression and activities of OCT1‐3 (SLC22A1‐3), OCTN1/2 (SLC22A4/5), CTR1/2 (SLC31A1/2) and MATE1/2 (SLC47A1/2) solute carriers. As another example, solute carriers mediate control over the availability of endogenous metal ions, such as copper, iron and zinc, may have key roles in regulating tumour angiogenesis, cell proliferation, epithelial‐to‐mesenchymal transition and aberrant MAPK and STAT‐3 signal transduction in cancer. In conclusion, emerging mechanisms involving metal transporting solute carriers are being defined and seem likely to make major contributions to cancer development and progression, and to the delivery of anticancer and tumour imaging agents. Copyright © 2014 John Wiley & Sons, Ltd.
Induction of ganoderic acid biosynthesis by Mn2+ in static liquid cultivation of Ganoderma lucidum
Authors: Xu Yi‐Ning , Xia Xiao‐Xia , Zhong Jian‐Jiang 
Published: May 2014

ABSTRACTMetal ions affect cell physiology and metabolism significantly, but the role of Mn2+ in the secondary metabolism of mushrooms is yet unclear. In static liquid cultivation of Ganoderma lucidum for producing antitumor ganoderic acids (GAs), the Mn2+ addition was performed. Addition of 10 mM Mn2+ at the start of the static liquid cultivation resulted in 2.2‐fold improvement of total GAs production. The expression levels of GA biosynthetic and Ca2+ sensors' genes were up‐regulated with Mn2+ induction while down‐regulated by adding cyclosporin A (calcineurin inhibitor), suggesting that higher GA production might result from calcineurin signal regulation. Intracellular Ca2+ imaging and calcineurin inhibitor study revealed that addition of Mn2+ led to Ca2+ influx from medium to the cells to trigger calcineurin signals. Mn2+ addition was therefore an efficient induction strategy for improving GAs production, whose regulation mechanism was via calcineurin signaling transduction. Biotechnol. Bioeng. 2014;111: 2358–2365. © 2014 Wiley Periodicals, Inc.
Social Contexts and Building Social Capital for Collective Action: Three Case Studies of Volunteers in the Context of HIV and AIDS in South Africa
Authors: Gibbs Andrew , Campbell Catherine , Akintola Olagoke , Colvin Christopher 
Published: May 2014

AbstractSocial capital is increasingly conceptualised in academic and policy literature as a panacea for a range of health and development issues, particularly in the context of HIV. In this paper, we conceptualise social capital as an umbrella concept capturing processes including networks, norms, trust and relationships that open up opportunities for participation and collective action that allow communities to address issues of common concern. We specifically outline social capital as comprising three distinct forms: bonding, bridging and linking social capital. Rather than presenting original data, we draw on three well‐documented and previously published case studies of health volunteers in South Africa. We explore how social contexts shape the possibility for the emergence and sustainability of social capital. We identify three cross‐cutting contextual factors that are critical barriers to the emergence of social capital: poverty, stigma and the weakness of external organisations' abilities to support small groups. Our three case studies suggest that the assumption that social capital can be generated from the ground upwards is not reasonable. Rather, there needs to be a greater focus on how those charged with supporting small groups—non‐governmental organisations, bureaucracies and development agencies—can work to enable social capital to emerge. Copyright © 2014 John Wiley & Sons, Ltd.
Asymmetric Stereodivergent Strategy Towards Aminocyclitols
Authors: Trost Barry M. , Malhotra Sushant 
Published: May 2014

AbstractA concise asymmetric synthesis of aminocyclitols, such as diastereomeric 2‐deoxystreptamine analogues and conduramine A, is described. The Pd‐catalyzed asymmetric desymmetrization of meso 1,4‐dibenzolate enables the synthesis of highly oxidized cyclohexane architectures. These scaffolds can potentially be used to access new aminoglycoside antibiotics and enantiomerically pure α‐glucosidase inhibitors.
Phytol Derivatives as Drug Resistance Reversal Agents
Authors: Upadhyay Harish C. , Dwivedi Gaurav R. , Roy Sudeep , Sharma Ashok , Darokar Mahendra P. , Srivastava Santosh K. 
Published: May 2014

AbstractPhytol was chemically transformed into fifteen semi‐synthetic derivatives, which were evaluated for their antibacterial and drug resistance reversal potential in combination with nalidixic acid against E. coli strains CA8000 and DH5α. The pivaloyl (4), 3,4,5‐trimethoxybenzoyl (9), 2,3‐dichlorobenzoyl (10), cinnamoyl (11), and aldehyde (14) derivatives of phytol ((2E,7R,11R)‐3,7,11,15‐tetramethyl‐2‐hexadecen‐1‐ol) were evaluated by using another antibiotic, tetracycline, against the MDREC‐KG4 clinical isolate of E. coli. Derivative 4 decreased the maximal inhibitory concentration (MIC) of the antibiotics by 16‐fold, while derivatives 9, 10, 11, and 14 reduced MIC values of the antibiotics up to eightfold against the E. coli strains. Derivatives 4, 9, 10, 11, and 14 inhibited the ATP‐dependent efflux pump; this was also supported by their in silico binding affinity and down‐regulation of the efflux pump gene yojI, which encodes the multidrug ATP‐binding cassette transporter protein. This study supports the possible use of phytol derivatives in the development of cost‐effective antibacterial combinations.
Development of Novel Selective Peptidomimetics Containing a Boronic Acid Moiety, Targeting the 20S Proteasome as Anticancer Agents
Authors: Scarbaci Kety , Troiano Valeria , Ettari Roberta , Pinto Andrea , Micale Nicola , Di Giovanni Carmen , Cerchia Carmen , Schirmeister Tanja , Novellino Ettore , Lavecchia Antonio , Zappalà Maria , Grasso Silvana 
Published: May 2014

AbstractThis paper describes the design, synthesis, and biological evaluation of peptidomimetic boronates as inhibitors of the 20S proteasome, a validated target in the treatment of multiple myeloma. The synthesized compounds showed a good inhibitory profile against the ChT‐L activity of 20S proteasome. Compounds bearing a β‐alanine residue at the P2 position were the most active, that is, 3‐ethylphenylamino and 4‐methoxyphenylamino (R)‐1‐{3‐[4‐(substituted)‐2‐oxopyridin‐1(2H)‐yl]propanamido}‐3‐methylbutylboronic acids (3 c and 3 d, respectively), and these derivatives showed inhibition constants (Ki) of 17 and 20 nM, respectively. In addition, they co‐inhibited post glutamyl peptide hydrolase activity (3 c, Ki=2.57 μM; 3 d, Ki=3.81 μM). No inhibition was recorded against the bovine pancreatic α‐chymotrypsin, which thus confirms the selectivity towards the target enzyme. Docking studies of 3 c and related inhibitors into the yeast proteasome revealed the structural basis for specificity. The evaluation of growth inhibitory effects against 60 human tumor cell lines was performed at the US National Cancer Institute. Among the selected compounds, 3 c showed 50 % growth inhibition (GI50) values at the sub‐micromolar level on all cell lines.
Synthesis and Antisense Properties of 2′‐O‐(2S‐Methoxypropyl)‐RNA‐Modified Gapmer Antisense Oligonucleotides
Authors: Yu Jinghua , Pandey Sanjay K. , Khatri Hetal , Prakash Thazha P. , Swayze Eric E. , Seth Punit P. 
Published: May 2014

AbstractTo ascertain whether increasing hydrophobicity can enhance the activity of second‐generation antisense oligonucleotides (ASOs) in muscle, we investigated the antisense properties of 2′‐O‐(2S‐methoxypropyl)‐RNA (2S‐MOP)‐modified ASOs. Synthesis of the 2S‐MOP 5‐methyl uridine phosphoramidite was accomplished on a multi‐gram scale by Lewis‐acid‐catalyzed ring opening of 5′‐O‐tert‐butyldiphenylsilyl ether‐protected 2,2′‐anhydro‐5‐methyl uridine with 2S‐methoxy‐1‐propanol. Synthesis of the 2S‐MOP 5‐methyl cytidine nucleoside from the corresponding 5‐methyl uridine nucleoside was accomplished by formation and displacement of a 4‐triazolide intermediate with aqueous ammonia. 2S‐MOP‐modified oligonucleotides were prepared on an automated DNA synthesizer and showed similar enhancements in duplex thermal stability as 2′‐O‐methoxyethyl RNA (MOE)‐modified oligonucleotides. 2S‐MOP‐containing antisense oligonucleotides were evaluated in Balb‐c mice and showed good activity for decreasing the expression levels of scavenger receptor B1 (Srb1) and phosphatase and tensin homologue (PTEN) mRNA in liver and muscle tissue.
Comparison of younger and older breast cancer survivors and age‐matched controls on specific and overall quality of life domains
Authors: Champion Victoria L. , Wagner Lynne I. , Monahan Patrick O. , Daggy Joanne , Smith Lisa , Cohee Andrea , Ziner Kim W. , Haase Joan E. , Miller Kathy D. , Pradhan Kamnesh , Unverzagt Frederick W. , Cella David , Ansari Bilal , Sledge George W. 
Published: May 2014

BACKGROUNDYounger survivors (YS) of breast cancer often report more survivorship symptoms such as fatigue, depression, sexual difficulty, and cognitive problems than older survivors (OS). This study sought to determine the effect of breast cancer and age at diagnosis on quality of life (QoL) by comparing 3 groups: 1) YS diagnosed at age 45 years or before, 2) OS diagnosed between 55 and 70, and 3) for the YSs, age‐matched controls (AC) of women not diagnosed with breast cancer.METHODSUsing a large Eastern Cooperative Oncology Group (ECOG) database, 505 YS were recruited who were aged 45 years or younger when diagnosed and 622 OS diagnosed at 55 to 70 years of age. YS, OS, and AC were compared on physical, psychological, social, spiritual, and overall QoL variables.RESULTSCompared to both AC and to OS, YS reported more depressive symptoms (P = .005) and fatigue (P < .001), poorer self‐reported attention function (P < .001), and poorer sexual function (P < .001) than either comparison group. However, YS also reported a greater sense of personal growth (P < .001) and perceived less social constraint (P < .001) from their partner than AC.CONCLUSIONSYS reported worse functioning than AC relative to depression, fatigue, attention, sexual function, and spirituality. Perhaps even more important, YS fared worse than both AC and OS on body image, anxiety, sleep, marital satisfaction, and fear of recurrence, indicating that YS are at greater risk for long‐term QoL problems than survivors diagnosed at a later age.Cancer2014;120:2237–2246.©2014 American Cancer Society.
Treatment‐related amenorrhea and sexual functioning in young breast cancer survivors
Authors: Rosenberg Shoshana M. , Tamimi Rulla M. , Gelber Shari , Ruddy Kathryn J. , Bober Sharon L. , Kereakoglow Sandra , Borges Virginia F. , Come Steven E. , Schapira Lidia , Partridge Ann H. 
Published: May 2014

BACKGROUNDSexual dysfunction is a known complication of adjuvant therapy for breast cancer and an important determinant of quality of life. However, few studies have explored how treatment and other factors affect sexual functioning in young breast cancer survivors.METHODSFour hundred sixty‐one premenopausal women with stage 0 through III breast cancer were surveyed an average of 1 year after diagnosis as part of a prospective cohort study of women who were aged ≤40 years at diagnosis. Sexual interest and dysfunction were assessed using the Cancer Rehabilitation Evaluation System (CARES). Mean CARES scores were compared and multiple regression models were fit to assess treatment and a range of menopausal and somatic symptoms in relation to sexual functioning.RESULTSMean CARES sexual interest and dysfunction scores were both highest (indicating poorer functioning) among women who received chemotherapy and were amenorrheic from treatment. After accounting for menopausal and somatic symptoms, treatment‐associated amenorrhea remained associated with decreased interest but was no longer an independent predictor of dysfunction. In the multivariable analysis, independent predictors of dysfunction included vaginal pain symptoms, poorer body image, and fatigue. Sexual interest was associated with vaginal pain symptoms, body image, and weight problems.CONCLUSIONSFactors associated with decreased sexual functioning in young breast cancer survivors can often be ameliorated. The current findings have implications for premenopausal women with other types of cancer who might be experiencing amenorrhea because of chemotherapy or surgery. Increased awareness and early intervention is essential to help improve sexual functioning and associated quality of life for all young cancer survivors. [See editorial on pages 000‐000, this issue.] Cancer 2014;120:2264–2271. © 2014 American Cancer Society.
Physical, emotional, and social health differences between posttreatment young adults with cancer and matched healthy controls
Authors: Salsman John M. , Garcia Sofia F. , Yanez Betina , Sanford Stacy D. , Snyder Mallory A. , Victorson David 
Published: May 2014

BACKGROUNDYoung adults (YAs; ages 18‐39 years) with cancer face interrupted developmental milestones and increased stressors that can adversely influence psychosocial adjustment. Transitioning from active treatment to posttreatment survivorship can be particularly challenging. The purpose of this study is to describe the health‐related quality of life (HRQL) and psychological adaptation of YAs after treatment, relative to young adults without cancer.METHODSThree cohorts of YAs of mixed cancer diagnoses (N = 120, 0‐12 months after treatment; N = 102, 13‐24 months after treatment; and N = 113, 25‐60 months after treatment; combined M = 31.8 years old, combined sex = 68% women) and an age‐, education‐, sex‐, and partner status–matched group of healthy control participants (HCs; N = 335) were recruited via an online research panel. All participants completed measures assessing demographic and clinical characteristics, HRQL (physical, emotional, social, and spiritual), and psychological adaptation (anxiety, depression, positive affect, posttraumatic growth). Measure content was slightly modified for applicability to HCs without a cancer history.RESULTSMultivariate analysis of covariance found a significant main effect for group (YAs versus HCs) and a significant group‐by‐cohort interaction. YAs reported poorer physical (P = .005, d = .22) and emotional well‐being (P = .011, d = .20) but better social well‐being (P < .001, d = .49). YAs reported comparatively stable scores (P = .74) for posttraumatic growth compared to HCs, who reported greater posttraumatic growth across cohorts (P = .01, d = 16).CONCLUSIONSFindings underscore the negative and positive sequelae for YAs and highlight the need for comprehensive assessment among YA survivors of cancer. A matched, HC group allows the HRQL and psychological adaptation of YAs to be placed in context, enabling a more precise determination of the impact of cancer on YAs. Cancer 2014;120:2247–2254. © 2014 American Cancer Society.