bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is IL-6 an appropriate target to treat spondyloarthritis patients refractory to anti-TNF therapy? a multicentre retrospective observational study
Authors: Lekpa Fernando Kemta , Poulain Cécile , Wendling Daniel , Soubrier Martin , De Bandt Michel , Berthelot Jean Marie , Gaudin Philippe , Toussirot Eric , Goupille Philippe , Pham Thao , Sellam Jérémie , Bruckert Rémy , Paul Muriel , Farrenq Valérie , Claudepierre Pascal ,   the Club Rhumatismes et Inflammation
Published: March 2012

Abstract
Introduction
The aim of this study was to evaluate, under real-life conditions, the safety and efficacy of tocilizumab in patients having failed anti-TNFα therapy for spondyloarthritis.

Methods
French rheumatologists and internal-medicine practitioners registered on the Club Rhumatismes et Inflammations website were asked to report on patients given tocilizumab (4 or 8 mg/kg) to treat active disease meeting Assessment of SpondyloArthritis International Society (ASAS) criteria for axial or peripheral spondyloarthritis, after anti-TNFα treatment failure. Safety and efficacy after 3 and 6 months were assessed retrospectively using standardised questionnaires.

Results
Data were obtained for 21 patients, 13 with axial spondyloarthritis (46% men; median age, 42 years; disease duration, 11 years; HLA-B27-positive, 92.3%) and eight with peripheral spondyloarthritis (25% men; median age, 40 years; disease duration, 10 years; HLA-B27-positive, 62.5%). No patients with axial disease had at least a 20 mm decrease in the BASDAI, nor a BASDAI50 response or major ASAS-endorsed disease activity score improvements after 3 or 6 months; an ASAS-endorsed disease activity score clinically important improvement was noted at month 3 in five of 13 patients and at month 6 in one of four patients. A good DAS28 response was achieved in four patients with peripheral disease, including one in EULAR remission at month 3. Four patients were still taking tocilizumab at month 6, including one in EULAR remission and one with a good DAS28 response. Tocilizumab was well tolerated, with no serious adverse events. Initially elevated acute-phase reactants declined during tocilizumab therapy.

Conclusion
In patients having failed anti-TNFα therapy, tocilizumab decreased acute-phase reactants but failed to substantially improve axial spondyloarthritis and was inconsistently effective in peripheral spondyloarthritis.
Immunohistochemical detection of Polo-like kinase-1 (PLK1) in primary breast cancer is associated with TP53mutation and poor clinical outcome
Authors: King Sharon I , Purdie Colin A , Bray Susan E , Quinlan Philip R , Jordan Lee B , Thompson Alastair M , Meek David W 
Published: March 2012

Abstract
Introduction
Polo-like kinase-1 (PLK1) is a crucial driver of cell cycle progression and its down-regulation plays an important checkpoint role in response to DNA damage. Mechanistically, this is mediated by p53 which represses PLK1 expression through chromatin remodelling. Consistent with this model, cultured cells lacking p53 fail to repress PLK1 expression. This study examined PLK1 expression, p53 mutation and clinical outcome in breast cancer.

Methods
Immunohistochemistry was performed using antibodies to PLK1, MDM2 and Ki67 on Tissue Micro-Array (TMA) slides of a cohort of 215 primary breast cancers. The TP53 gene (encoding p53) was sequenced in all tumour samples. Protein expression scored using the "Quickscore" method was compared with clinical and pathological data, including survival.

Results
Staining of PLK1 was observed in 11% of primary breast tumours and was significantly associated with the presence of TP53 mutation (P = 0.0063). Moreover, patients with both PLK1 expression and TP53 mutation showed a significantly worse survival than those with either PLK1 expression or TP53 mutation alone. There was also a close association of elevated PLK1 with triple negative tumours, considered to be poor prognosis breast cancers that generally harbour TP53 mutation. Further association was observed between elevated PLK1 levels and the major p53 negative regulator, MDM2.

Conclusions
The significant association between elevated PLK1 and TP53 mutation in women with breast cancer is consistent with escape from repression of PLK1 expression by mutant p53. Tumours expressing elevated PLK1, but lacking functional p53, may be potential targets for novel anti-PLK1-targeted drugs.
Aromatase inhibitors, estrogens and musculoskeletal pain: estrogen-dependent T-cell leukemia 1A (TCL1A) gene-mediated regulation of cytokine expression
Authors: Liu Mohan , Wang Liewei , Bongartz Tim , Hawse John R , Markovic Svetomir N , Schaid Daniel J , Mushiroda Taisei , Kubo Michiaki , Nakamura Yusuke , Kamatani Naoyuki , Goss Paul E , Ingle James N , Weinshilboum Richard M 
Published: March 2012

Abstract
Introduction
Arthralgias and myalgias are major side effects associated with aromatase inhibitor (AI) therapy of breast cancer. In a recent genome-wide association study, we identified SNPs - including one that created an estrogen response element near the 3' end of the T-cell leukemia 1A (TCL1A) gene - that were associated with musculoskeletal pain in women on adjuvant AI therapy for breast cancer. We also showed estrogen-dependent, SNP-modulated variation in TCL1A expression and, in preliminary experiments, showed that TCL1A could induce IL-17RA expression. In the present study, we set out to determine whether these SNPs might influence cytokine expression and effect more widely, and, if so, to explore the mechanism of TCL1A-related AI-induced side effects.

Methods
The functional genomic experiments performed included determinations of TCL1A, cytokine and cytokine receptor expression in response to estrogen treatment of U2OS cells and lymphoblastoid cell lines that had been stably transfected with estrogen receptor alpha. Changes in mRNA and protein expression after gene knockdown and overexpression were also determined, as was NF-κB transcriptional activity.

Results
Estradiol (E2) increased TCL1A expression and, in a TCL1A SNP-dependent fashion, also altered the expression of IL-17, IL-17RA, IL-12, IL-12RB2 and IL-1R2. TCL1A expression was higher in E2-treated lymphoblastoid cell lines with variant SNP genotypes, and induction of the expression of cytokine and cytokine receptor genes was mediated by TCL1A. Finally, estrogen receptor alpha blockade with ICI-182,780 in the presence of E2 resulted in greatly increased NF-κB transcriptional activity, but only in cells that carried variant SNP genotypes. These results linked variant TCL1A SNP sequences that are associated with AI-dependent musculoskeletal pain with increased E2-dependent TCL1A expression and with downstream alterations in cytokine and cytokine receptor expression as well as NF-κB transcriptional activity.

Conclusions
SNPs near the 3' terminus of TCL1A were associated with AI-dependent musculoskeletal pain. E2 induced SNP-dependent TCL1A expression, which in turn altered IL-17, IL-17RA, IL-12, IL-12RB2, and IL-1R2 expression as well as NF-κB transcriptional activity. These results provide a pharmacogenomic explanation for a clinically important adverse drug reaction as well as insights into a novel estrogen-dependent mechanism for the modulation of cytokine and cytokine receptor expression.
Use of second-person pronouns and schizophrenia
Authors: Watson Andrew R. , Defteralı Çaǧla , Bak Thomas H. , Sorace Antonella , McIntosh Andrew M. , Owens David G. C. , Johnstone Eve C. , Lawrie Stephen M. 
Published: March 2012

SummaryA masked analysis of videotaped assessments of people at high genetic risk of schizophrenia revealed that those who subsequently went on to develop schizophrenia used significantly more second-person pronouns. This was evident before diagnosis, at two separate assessments approximately 18 months apart. This supports the view that people who go on to develop schizophrenia may have an abnormality in the deictic frame of interpersonal communication – that is, the distinction between concepts being self-generated or from elsewhere may be blurred prior to the onset of a diagnosis of schizophrenia.
Suicide and non-suicide mortality after self-harm in Taipei
City, Taiwan
Authors: Kuo Chian-Jue , Gunnell David , Chen Chiao-Chicy , Yip Paul S. F. , Chen Ying-Yeh 
Published: March 2012

BackgroundMost previous studies of long-term mortality risk following self-harm
have been conducted in Western countries with few studies from Asia.AimsTo investigate suicide and non-suicide mortality after non-fatal
self-harm in Taipei City, Taiwan.MethodProspective cohort study (median follow-up 3.3 years) of 7601 individuals
presenting to hospital with self-harm (January 2004 to December 2006).
Standardised mortality ratios (SMRs) for suicide and non-suicide
mortality were calculated.ResultsSuicide risk in the year following self-harm was over 100 times higher
than in the general population (SMR = 119.6, 95% CI 99.6–142.5). Males
and middle-aged and older adults had the highest subsequent risk of
suicide. Compared with people who took an overdose, individuals who used
hanging or charcoal burning in their index episode had the highest risk
of suicide. For non-suicide mortality the SMRs were 6.7 (95% CI 5.7–7.8)
in the first year and 4.4 (95% CI 3.9–4.9) during the whole follow-up
period.ConclusionsPatterns of increased all-cause and suicide mortality following an
episode of self-harm are similar in Taipei City to those seen in Western
countries. Designing better aftercare following non-fatal self-harm,
particularly for those with underlying physical disorders or who have
used lethal self-harm methods, should be a priority for suicide
prevention programmes in Asia.
Parent psychopathology and offspring mental disorders: Results from the WHO World Mental Health Surveys
Authors: McLaughlin Katie A. , Gadermann Anne M. , Hwang Irving , Sampson Nancy A. , Al-Hamzawi Ali , Andrade Laura Helena , Angermeyer Matthias C. , Benjet Corina , Bromet Evelyn J. , Bruffaerts Ronny , Caldas-de-Almeida José Miguel , de Girolamo Giovanni , de Graaf Ron , Florescu Silvia , Gureje Oye , Haro Josep Maria , Hinkov Hristo Ruskov , Horiguchi Itsuko , Hu Chiyi , Karam Aimee Nasser , Kovess-Masfety Viviane , Lee Sing , Murphy Samuel D. , Nizamie S. Haque , Posada-Villa José , Williams David R. , Kessler Ronald C. 
Published: March 2012

BackgroundAssociations between specific parent and offspring mental disorders are likely to have been overestimated in studies that have failed to control for parent comorbidity.AimsTo examine the associations of parent with respondent disorders.MethodData come from the World Health Organization (WHO) World Mental Health Surveys (n = 51 507). Respondent disorders were assessed with the Composite International Diagnostic Interview and parent disorders with informant-based Family History Research Diagnostic Criteria interviews.ResultsAlthough virtually all parent disorders examined (major depressive, generalised anxiety, panic, substance and antisocial behaviour disorders and suicidality) were significantly associated with offspring disorders in multivariate analyses, little specificity was found. Comorbid parent disorders had significant sub-additive associations with offspring disorders. Population-attributable risk proportions for parent disorders were 12.4% across all offspring disorders, generally higher in high- and upper-middle- than low-/lower-middle-income countries, and consistently higher for behaviour (11.0–19.9%) than other (7.1–14.0%) disorders.ConclusionsParent psychopathology is a robust non-specific predictor associated with a substantial proportion of offspring disorders.
The usefulness of combined measurements of squamous cell carcinoma antigens 1 and 2 in diagnosing atopic dermatitis
Authors: Ohta Shoichiro , Shibata Rumiko , Nakao Yoshifumi , Azuma Yoshinori , Taniguchi Kazuto , Arima Kazuhiko , Suzuki Shoichi , Shiraishi Hiroshi , Iwasaka Tsuyoshi , Izuhara Kenji 
Published: March 2012

Background The squamous cell carcinoma antigen (SCCA) is widely used as a serological biomarker for various cancers. There are two known SCCA molecules, SCCA1 and SCCA2. We previously found that interleukin-4 or interleukin-13, two related Th2-type cytokines that play an important role in allergic diseases, induce expression of SCCA1 and SCCA2. In this study, we examined whether combined measurements of SCCA1 and SCCA2 are useful for diagnosing atopic dermatitis (AD). Methods We established new enzyme-linked immunosorbent assays (ELISAs) to specifically detect SCCA1 or SCCA2. We applied serum samples from AD patients with food allergies and from cervical cancer patients to these ELISAs. We performed receiver operating characteristic analyses to diagnose AD and to distinguish AD from cervical cancer. Results Serum concentrations of both SCCA1 and SCCA2 were elevated in AD patients. The serum concentrations of SCCA1 and SCCA2 positively correlated with the clinical severity of AD, showing high specificity (0.86–0.88) and sensitivity (0.86) against control donors. The serum concentrations of SCCA1 and SCCA2 were elevated in cervical cancer patients; however, the SCCA2/SCCA1 ratios clearly distinguished AD patients from cervical cancer patients with high specificity (0.87) and sensitivity (0.87). Expression of SCCA2 was predominant in AD patients, whereas cervical cancer patients showed a predominance of SCCA1. Conclusions Combined measurements of SCCA1 and SCCA2 are very useful in estimating the severity of allergic diseases, making it possible to distinguish allergic diseases from cancers.
Recommendations for standardized reporting of protein electrophoresis in Australia and New Zealand
Authors: Tate Jillian , Caldwell Grahame , Daly James , Gillis David , Jenkins Margaret , Jovanovich Sue , Martin Helen , Steele Richard , Wienholt Louise , Mollee Peter 
Published: March 2012

Background Although protein electrophoresis of serum (SPEP) and urine (UPEP) specimens is a well-established laboratory technique, the reporting of results using this important method varies considerably between laboratories. The Australasian Association of Clinical Biochemists recognized a need to adopt a standardized approach to reporting SPEP and UPEP by clinical laboratories. Methods A Working Party considered available data including published literature and clinical studies, together with expert opinion in order to establish optimal reporting practices. A position paper was produced, which was subsequently revised through a consensus process involving scientists and pathologists with expertise in the field throughout Australia and New Zealand. Results Recommendations for standardized reporting of protein electrophoresis have been produced. These cover analytical requirements: detection systems; serum protein and albumin quantification; fractionation into alpha-1, alpha-2, beta and gamma fractions; paraprotein quantification; urine Bence Jones protein quantification; paraprotein characterization; and laboratory performance, expertise and staffing. The recommendations also include general interpretive commenting and commenting for specimens with paraproteins and small bands together with illustrative examples of reports. Conclusions Recommendations are provided for standardized reporting of protein electrophoresis in Australia and New Zealand. It is expected that such standardized reporting formats will reduce both variation between laboratories and the risk of misinterpretation of results.
Computer-aided detection system performance on current and previous digital mammograms in patients with contralateral metachronous breast cancer
Authors: Kim Seung Ja , Moon Woo Kyung , Cho Nariya , Chang Jung Min 
Published: March 2012

Background The computer-aided detection (CAD) system is widely used for screening mammography. The performance of the CAD system for contralateral breast cancer has not been reported for women with a history of breast cancer. Purpose To retrospectively evaluate the performance of a CAD system on current and previous mammograms in patients with contralateral metachronous breast cancer. Material and Methods During a 3-year period, 4945 postoperative patients had follow-up examinations, from whom we selected 55 women with contralateral breast cancers. Among them, 38 had visible malignant signs on the current mammograms. We analyzed the sensitivity and false-positive marks of the system on the current and previous mammograms according to lesion type and breast density. Results The total visible lesion components on the current mammograms included 27 masses and 14 calcifications in 38 patients. The case-based sensitivity for all lesion types was 63.2% (24/38) with false-positive marks of 0.71 per patient. The lesion-based sensitivity for masses and calcifications was 59.3% (16/27) and 71.4% (10/14), respectively. The lesion-based sensitivity for masses in fatty and dense breasts was 68.8% (11/16) and 45.5% (5/11), respectively. The lesion-based sensitivity for calcifications in fatty and dense breasts was 100.0% (3/3) and 63.6% (7/11), respectively. The total visible lesion components on the previous mammograms included 13 masses and three calcifications in 16 patients, and the sensitivity for all lesion types was 31.3% (5/16) with false-positive marks of 0.81 per patient. On these mammograms, the sensitivity for masses and calcifications was 30.8% (4/13) and 33.3% (1/3), respectively. The sensitivity in fatty and dense breasts was 28.6% (2/7) and 33.3% (3/9), respectively. Conclusion In the women with a history of breast cancer, the sensitivity of the CAD system in visible contralateral breast cancer was lower than in most previous reports using the same CAD system probably due to the relatively small size, subtlety of the lesion findings, and dense parenchymal pattern.
Transcatheter renal artery embolization with N-butyl cyanoacrylate
Authors: Kim Jinoo , Shin Ji Hoon , Yoon Hyun-Ki , Ko Gi-Young , Gwon Dong II , Kim Eun-Young , Sung Kyu-Bo 
Published: March 2012

Background Despite its long history, the application of N-butyl cyanoacrylate (NBCA) has been limited compared to other materials such as particulate agents and coils. This possibly owes to a widespread misconception that NBCA is difficult to handle and carries a high risk of complications due to its liquid nature and rapid polymerization time. However, recent reports have shown that, with knowledge and experience, NBCA is safe and effective to use in visceral arteries. Purpose To review the outcome of transcatheter embolization of the renal artery using NBCA for varied etiologies in the kidney. Material and Methods Fourteen patients with varied etiologies in the kidney underwent renal artery embolization using NBCA as the sole embolic agent (64%) or in combination with an additional embolic material (36%). A review of medical charts and images were performed to gather information regarding underlying etiologies, clinical presentation, and outcome of embolization. Results Technical success was achieved in all patients (100%) while clinical success was achieved in 12 (85.7%). One failed case was managed by repeat embolization using microcoils, while the other underwent partial nephrectomy after failed reattempt at embolization. Three patients with recurrent bleeding after previously having undergone embolization using microcoils or gelatin sponge particles were successfully managed the second time using NBCA. NBCA embolization was also effective in three patients with hemostatic abnormality. Complications attributable to NBCA embolization were renal atrophy in one patient and microcatheter tip fracture in another. Conclusion The application of NBCA for transcatheter embolization of varied etiologies involving the renal artery is feasible and safe in the hands of an experienced interventional radiologist. It offers immediate and effective occlusion of the pathologic vessel and, while it can be used exclusively on its own, it can also be used to complement other embolic materials.
Mosquirix (RTS,S): A Novel Vaccine for the Prevention of Plasmodium falciparum Malaria
Authors: Wilby Kyle J , Lau Tim TY , Gilchrist Samuel E , Ensom Mary HH 
Published: March 2012

Objective: To summarize and evaluate the literature for Mosquirix (RTS,S) and provide insight into the therapeutic and economic controversies of this novel malaria vaccine candidate. Data Sources: A systematic literature search was performed using the terms Mosquirix; RTS.S; malaria; vaccine; and Plasmodium in MEDLINE (1948–November 2011), EMBASE (1980–November 2011), International Pharmaceutical Abstracts (1970-November 2011), Google, and Google Scholar. Study Selection and Data Extraction: Clinical trials describing vaccine development, pharmacology, pharmacokinetics, efficacy, and safety were reviewed. For efficacy, clinical trials were reviewed that reported acquisition of malarial disease. Information regarding study design, population, study period, baseline characteristics, clinical outcomes, results, and assessors of quality was extracted. Data Synthesis: Five randomized controlled trials and 4 follow-up extension studies were identified. In Phase 2 trials, vaccine efficacy rates were 33–65% in infants and 30–53% in children for preventing the first episode of clinic a) disease. In Phase 3 trials, vaccine efficacy was 56% in children aged 5–17 months. RTS,S reduced (he number of clinical malaria episodes and prevented severe malaria in several studies. The follow-up period for vaccine efficacy ranged from 6 to 45 months. RTS,S 25 μg is administered intramuscularly as 3 injections given 1 month apart for infants and children. RTS,S appears to be generally well tolerated. A few cases of meningitis and seizures (within 7 days of vaccination) have been reported. Conclusions: RTS,S has demonstrated efficacy and safety in Phase 1, 2, and 3 trials, and has the potential to decrease morbidity and mortality from malaria worldwide. Major challenges include determination of the duration of immunity, assessment of its cost-effectiveness, its use in special populations, and its dissemination in endemic regions. Pending further studies, RTS,S has the potential to become the benchmark as the first effective vaccine against malaria.
REVIEWS
Authors: Marlin Demelza , Conway Jay , Yun Ohsoon 
Published: March 2012

HOSTING THE STRANGER: BETWEEN RELIGIONS, RICHARD KEARNEY AND JAMES TAYLOR(EDS) (2011) London and New York: Continuum Press, 196 pp., ISBN: 9781441158086 (pbk), £16.99
POLITICS OF THE GIFT: EXCHANGES IN POSTSRUCTURALISM, GERALD MOORE (2011) Edinburgh: Edinburgh University Press,
224 pp., ISBN: 978-0-7486-4202 (hbk), £65.00
COFFEE CULTURE, DESTINATIONS AND TOURISM, LEE JOLIFFE (2010) Bristol: Channel View Publications, x+235 pp., ISBN 978 1 845411428, p/bk, £24.95
Die kognitive Struktur von Hoffnung. Zwei mittelalterliche Erklärungsmodelle
Authors: Perler Dominik 
Published: March 2012

Abstract
Medieval philosophers took hope to be an emotion with a cognitive content. It is precisely this content, they argued, that makes it an intentional phenomenon. But how is its specific content to be characterized? How is it to be distinguished from the content of other emotions? And what kind of cognitive activities are required to produce it? This paper discusses these questions, focusing on Thomas Aquinas’ and William of Ockham’s explanatory models. It pays particular attention to the role these authors ascribed to intellect and will, the two rational faculties. While Aquinas defended an intellectualist view, claiming that it is the intellect alone that fixes the cognitive content and brings about hope, Ockham subscribed to a voluntarist view, affirming that the will always needs to give its assent to the content presented by the intellect. Given this disagreement, they gave different accounts of the responsibility we have for rational as well as irrational forms of hope.