bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adiponectin may contribute to synovitis and joint destruction in rheumatoid arthritis by stimulating vascular endothelial growth factor, matrix metalloproteinase-1, and matrix metalloproteinase-13 expression in fibroblast-like synoviocytes more than proinflammatory mediators
Authors: Choi Hyun-Mi , Lee Yeon-Ah , Lee Sang-Hoon , Hong Seung-Jae , Hahm Dae-Hyun , Choi Sang-Yun , Yang Hyung-In , Yoo Myung Chul , Kim Kyoung Soo 
Published: November 2009

Abstract
Introduction
The role of adiponectin in the pathogenesis of arthritis is still controversial. This study was performed to examine whether adiponectin is involved in joint inflammation and destruction in rheumatoid arthritis (RA) in relation to the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs).

Methods
Synovial cells from RA patients were treated with adiponectin or interleukin (IL)-1β for 24 hours. The culture supernatant was collected and analyzed for the levels of IL-6, IL-8, prostaglandin E2 (PGE2), VEGF, and MMPs by enzyme-linked immunosorbent assay. The levels of adiponectin, VEGF, MMP-1, and MMP-13 in the joint fluids from 30 RA or osteoarthritis (OA) patients were also measured.

Results
Adiponectin at the concentration of 10 μg/mL stimulated the production of IL-6, IL-8, and PGE2 in RA fibroblast-like synoviocytes (FLSs), although the level of these was much lower than with 1 ng/mL IL-1β. However, adiponectin stimulated the production of VEGF, MMP-1, and MMP-13 at the same level as IL-1β. In addition, the level of adiponectin and MMP-1 in the joint fluid of RA patients was significantly higher than in OA patients. Adiponectin was positively correlated with VEGF in RA patients but not in OA patients, while the level of MMPs in joint fluid was not correlated with adiponectin in either RA or OA patients.

Conclusions
Adiponectin may play a significant role in the pathogenesis of RA by stimulating the production of VEGF and MMPs in FLSs, leading to joint inflammation and destruction, respectively.
Sinus aspergilloma in rheumatoid arthritis before or during tumor necrosis factor-alpha antagonist therapy
Authors: Leboime Ariane , Berthelot Jean-Marie , Allanore Yannick , Khalil-Kallouche Lama , Herman Philippe , Orcel Philippe , Lioté Frédéric 
Published: November 2009

Abstract
Introduction
In 2008, the Food and Drugs Administration required manufacturers of TNFα antagonists to strengthen their warnings about the risk of serious fungal infections in patients with rheumatoid arthritis (RA). Sinus aspergilloma occurs occasionally in RA patients and can progress to invasive Aspergillus disease. The purpose of this study was to describe symptomatic sinus aspergilloma in RA patients treated with TNFα antagonists.

Methods
Retrospective descriptive study of symptomatic cases of sinus aspergilloma in patients with RA followed in three French university hospitals. A systematic literature review was performed.

Results
Among 550 RA patients treated with TNFα antagonists, six (1.1%) had symptomatic maxillary aspergilloma diagnosed by computed tomography before or during TNFα antagonist therapy. None had chronic neutropenia. Aspergilloma treatment was with surgery only in all six patients. In the literature, we found 20 reports of Aspergillus infection in patients with chronic inflammatory joint diseases (including 10 with RA). Only 5/20 patients were treated with TNFα antagonists (invasive lung aspergillosis, n = 3; intracranial aspergillosis, n = 1; and sphenoidal sinusitis, n = 1).

Conclusions
Otorhinolaryngological symptoms must be evaluated before starting or switching TNFα antagonists. Routine computed tomography of the sinuses before starting or switching TNFα antagonists may deserve consideration.
Risk factors for acute respiratory distress syndrome during neutropenia recovery in patients with hematologic malignancies
Authors: Rhee Chin Kook , Kang Ji Young , Kim Yong Hyun , Kim Jin Woo , Yoon Hyung Kyu , Kim Seok Chan , Kwon Soon Suk , Kim Young Kyoon , Kim Kwan Hyung , Moon Hwa Sik , Park Sung Hak , Kim Hee Je , Lee Seok , Song Jeong Sup 
Published: November 2009

Abstract
Introduction
Neutropenia recovery may be associated with deterioration in oxygenation and exacerbation of pre-existing pulmonary disease. However, risk factors for acute respiratory distress syndrome (ARDS) during neutropenia recovery in patients with hematologic malignancies have not been studied.

Methods
We studied critically ill patients with hematologic malignancies with the dual objectives of describing patients with ARDS during neutropenia recovery and identifying risk factors for ARDS during neutropenia recovery. A cohort of consecutive neutropenic patients with hematologic malignancies who were admitted to the intensive care unit (ICU) was studied. During a 6-year period, 71 patients recovered from neutropenia, of whom 38 (53.5%) developed ARDS during recovery.

Results
Compared with non-ARDS patients, patients who experienced ARDS during neutropenia recovery were more likely to have pneumonia, be admitted to the ICU for respiratory failure, and receive mechanical ventilator therapy. The in-ICU mortality was significantly different between the two groups (86.8% versus 51.5%, respectively, for patients who developed ARDS during neutropenia recovery versus those who did not during neutropenia recovery). In multivariate analysis, only occurrence of pneumonia during the neutropenic episode was associated with a marked increase in the risk of ARDS (odds ratio, 4.76).

Conclusions
Patients with hematologic malignancies complicated by pneumonia during neutropenia are at increased risk for ARDS during neutropenia recovery.
Divergence of exonic splicing elements after gene duplication and the impact on gene structures
Authors: Zhang Zhenguo , Zhou Li , Wang Ping , Liu Yang , Chen Xianfeng , Hu Landian , Kong Xiangyin 
Published: November 2009

Abstract
Background
The origin of new genes and their contribution to functional novelty has been the subject of considerable interest. There has been much progress in understanding the mechanisms by which new genes originate. Here we examine a novel way that new gene structures could originate, namely through the evolution of new alternative splicing isoforms after gene duplication.

Results
We studied the divergence of exonic splicing enhancers and silencers after gene duplication and the contributions of such divergence to the generation of new splicing isoforms. We found that exonic splicing enhancers and exonic splicing silencers diverge especially fast shortly after gene duplication. About 10% and 5% of paralogous exons undergo significantly asymmetric evolution of exonic splicing enhancers and silencers, respectively. When compared to pre-duplication ancestors, we found that there is a significant overall loss of exonic splicing enhancers and the magnitude increases with duplication age. Detailed examination reveals net gains and losses of exonic splicing enhancers and silencers in different copies and paralog clusters after gene duplication. Furthermore, we found that exonic splicing enhancer and silencer changes are mainly caused by synonymous mutations, though nonsynonymous changes also contribute. Finally, we found that exonic splicing enhancer and silencer divergence results in exon splicing state transitions (from constitutive to alternative or vice versa), and that the proportion of paralogous exon pairs with different splicing states also increases over time, consistent with previous predictions.

Conclusions
Our results suggest that exonic splicing enhancer and silencer changes after gene duplication have important roles in alternative splicing divergence and that these changes contribute to the generation of new gene structures.
Regulatory interdependence of myeloid transcription factors revealed by Matrix RNAi analysis
Authors: Tomaru Yasuhiro , Simon Christophe , Forrest Alistair RR , Miura Hisashi , Kubosaki Atsutaka , Hayashizaki Yoshihide , Suzuki Masanori 
Published: November 2009

Abstract
Background
With the move towards systems biology, we need sensitive and reliable ways to determine the relationships between transcription factors and their target genes. In this paper we analyze the regulatory relationships between 78 myeloid transcription factors and their coding genes by using the matrix RNAi system in which a set of transcription factor genes are individually knocked down and the resultant expression perturbation is quantified.

Results
Using small interfering RNAs we knocked down the 78 transcription factor genes in monocytic THP-1 cells and monitored the perturbation of the expression of the same 78 transcription factors and 13 other transcription factor genes as well as 5 non-transcription factor genes by quantitative real-time RT-PCR, thereby building a 78 × 96 matrix of perturbation and measurement. This approach identified 876 cases where knockdown of one transcription factor significantly affected the expression of another (from a potential 7,488 combinations). Our study also revealed cell-type-specific transcriptional regulatory networks in two different cell types.

Conclusions
By considering whether the targets of a given transcription factor are naturally up- or downregulated during phorbol 12-myristate 13-acetate-induced differentiation, we could classify these edges as pro-differentiative (229), anti-differentiative (76) or neither (571) using expression profiling data obtained in the FANTOM4 study. This classification analysis suggested that several factors could be involved in monocytic differentiation, while others such as MYB and the leukemogenic fusion MLL-MLLT3 could help to maintain the initial undifferentiated state by repressing the expression of pro-differentiative factors or maintaining expression of anti-differentiative factors.
Leukotriene B4 mediates γδ T lymphocyte migration in response to diverse stimuli
Authors: Costa Maria Fernanda de Souza , de Souza-Martins Raquel , de Souza Mariana C , Benjamim Cláudia F , Piva Bruno , Diaz Bruno L , Peters-Golden Marc , Henriques Maria das Graças , Canetti Cláudio , Penido Carmen 
Published: October 2009

Abstractγδ T cell migration into mouse pleural cavities during inflammatory responses triggered by LPS, Mycobacterium bovis BCG, or ovalbumin depends on leukotriene B4 and BLT1 receptor.Herein, we investigated the involvement of the 5-LO-derived lipid mediator LTB4 in γδ T cell migration. When injected into the i.pl. space of C57BL/6 mice, LTB4 triggered γδ T lymphocyte mobilization in vivo, a phenomenon also observed in in vitro chemotaxis assays. The i.pl. injection of Escherichia coli endotoxin (LPS) triggered increased levels of LTB4 in pleural cavities. The in vivo inhibition of LTB4 biosynthesis by the 5-LO inhibitor zileuton or the FLAP inhibitor MK886 attenuated LPS-induced γδ T cell accumulation into pleural cavities. Accordingly, 5-LO KO mice failed to recruit γδ T cells into the inflammatory site after i.pl. LPS. Antagonists of the high-affinity LTB4 receptor BLT1, CP105,696, and LY292476 also attenuated LPS-induced γδ T cell accumulation in pleural cavities as well as in vitro chemotaxis toward pleural washes obtained from LPS-simulated mice. LTB4/BLT1 also accounted for γδ T cell migration induced by i.pl. administration of Mycobacterium bovis BCG or antigen in sensitized mice. BLT1 was expressed on naïve, resident as well as LPS-recruited γδ T cells. Isolated γδ T cells were found to undergo F-actin cytoskeleton reorganization when incubated with LTB4 in vitro, confirming that γδ T lymphocytes can respond directly to LTB4. In addition to its direct effect on γδ T cells, LTB4 triggered their accumulation indirectly, via modulation of CCL2 production in mouse pleural cavities. These data show that γδ T cell migration into the pleural cavity of mice during diverse inflammatory responses is dependent on LTB4/BLT1.
Antipsychotic long-acting injections: Mind the gap
Authors: Patel Maxine X. , Taylor Mark , David Anthony S. 
Published: October 2009

SummaryLong-acting injections of antipsychotic medication (or depots) were developed specifically to promote treatment adherence and are a valuable option for maintenance medication in psychotic illnesses. Approximately 40–60% of patients with schizophrenia are partially or totally non-adherent to their antipsychotic regimen, but only 30% or less are prescribed a long-acting injection. The use of such injections has declined in recent years after the introduction of second-generation (atypical) oral antipsychotic drugs. Research shows that possible reasons for this decline include concerns that may be based on suboptimal knowledge, as well as an erroneous assumption that one's own patient group is more adherent than those of one's colleagues. Research on attitudes has also revealed that psychiatrists feel that long-acting injections have an ‘image’ problem. This editorial addresses the gaps in knowledge and behaviour associated with possible underutilisation of these formulations, highlighting the role of stigma and the need for more research.
Psychopharmacology and adverse effects of antipsychotic long-acting injections: A review
Authors: Taylor David 
Published: October 2009

BackgroundDepot antipsychotics are widely used in clinical practice. Long-acting formulations of second-generation antipsychotics are now being developed and introduced.AimsTo review the pharmacology, pharmacokinetics and adverse effect profiles of currently available antipsychotic long-acting injections (LAIs).MethodThe psychopharmacological properties of first- and second-generation antipsychotic LAIs are reviewed using data available up to October 2008.ResultsFirst-generation antipsychotic (FGA) LAIs are associated with a high rate of acute and chronic movement disorders. Risperidone LAI is better tolerated in this respect, but is associated with hyperprolactinaemia and weight gain. Olanzapine LAI causes weight gain and other metabolic effects but appears not to be associated with an important incidence of movement disorders.ConclusionsDosing of LAIs is complicated by delayed release of drug, changes in plasma levels without change in dose, and by the lack of data establishing clear dose requirements. All LAIs offer the prospect of assured adherence (although patients may still default on treatment) but their use is complicated by adverse effects, complex pharmacokinetics and confusion over dose–response relationships.
First-generation antipsychotic long-acting injections v. oral antipsychotics in schizophrenia: Systematic review of randomised controlled trials and observational studies
Authors: Haddad Peter M. , Taylor Mark , Niaz Omair S. 
Published: October 2009

BackgroundAntipsychotic long-acting injections (LAIs) are often used in an attempt to improve medication adherence in people with schizophrenia.AimsTo compare first-generation antipsychotic long-acting injections (FGA–LAIs) with first- and second-generation oral antipsychotics in terms of clinical outcome.MethodSystematic literature review.ResultsA meta-analysis of randomised controlled trials (RCTs) showed no difference in relapse or tolerability between oral antipsychotics and FGA–LAIs but global improvement was twice as likely with FGA–LAIs. Four prospective observational studies were identified; two studies reported lower discontinuation rates for FGA–LAIs compared with oral medication and two found that outcome was either no different or better with oral antipsychotics. Mirror-image studies consistently showed reduced in-patient days and admissions following a switch from oral antipsychotics to FGA–LAIs.ConclusionsThe results are variable and inconclusive. Some evidence suggests that FGA–LAIs may improve outcome compared with oral antipsychotics. Methodological issues may partly explain the variable results. Selective recruitment in RCTs and lack of randomisation in observational studies are biases against LAIs, whereas regression to the mean in mirror-image studies favours LAIs. In terms of future research, a long-term pragmatic RCT of an FGA–LAI against an oral antipsychotic, in patients with problematic adherence, would be of value.
Negative parental discipline, conduct problems and callous–unemotional traits: monozygotic twin differences study
Authors: Viding Essi , Fontaine Nathalie M. G. , Oliver Bonamy R. , Plomin Robert 
Published: October 2009

BackgroundNegative parenting practices may be an environmental risk factor for subsequent conduct problems. Research on the association between parenting practices and callous–unemotional traits, a risk factor for conduct problems, has produced mixed findings.AimsTo investigate whether negative parental discipline is a non-shared environmental risk factor for the development of conduct problems and callous–unemotional traits.MethodLongitudinal, multi-informant data from a community sample of twins were analysed using the monozygotic (MZ) twin differences design for 4508 twins (2254 twin pairs).ResultsWithin MZ twin pairs, the twin receiving more negative parental discipline at 7 years had more conduct problems (but not more callous–unemotional traits) at 12 years.ConclusionsDuring the transition to early adolescence, negative parental discipline operates as a non-shared environmental risk factor for development of conduct problems, but not for the development of callous–unemotional traits.
One-Year Outcomes of a Behavioral Therapy Intervention Trial on Sleep Quality and Cancer-Related Fatigue
Authors: Berger Ann M. , Kuhn Brett R. , Farr Lynne A. , Von Essen Susanna G. , Chamberlain Julie , Lynch James C. , Agrawal Sangeeta 
Published: November 2009

Purpose To determine 1-year outcomes of a four-component behavioral therapy (BT) sleep intervention (Individualized Sleep Promotion Plan [ISPP]) versus a healthy eating control (HEC) on cancer-related fatigue in women receiving breast cancer adjuvant chemotherapy treatment (CTX). Patients and Methods A total of 219 participants from 12 oncology clinics were randomly assigned in a clinical trial. Before CTX, research nurses coached intervention participants to develop a BT plan including stimulus control, modified sleep restriction, relaxation therapy, and sleep hygiene. BT plans were revised before each CTX and 30, 60, and 90 days after the last CTX and reinforced 7 to 9 days later. HEC participants received nutritional information and equal attention. Pittsburgh Sleep Quality Index (PSQI), Daily Diary, Wrist Actigraph, and Piper Fatigue Scale measures and Repeated Linear Mixed Model analysis following the Intent to Treat paradigm were used. Results Sleep quality differed over 1 years time (F [4,162] = 7.7, P < .001; by group, F [1,173] = 4.8, P = .029; and over time by group, F [4,162] = 3.3, P = .013). Pairwise comparisons revealed significant differences between groups at 90 days (P = .002) but not at 1 year (P = .052). Seven days of diary and actigraphy data did not corroborate with monthly reflections (PSQI). The night awakenings (Actigraph) pattern was significantly different by group over time (P = .046), with no differences between groups at 90 days or at 1 year. Fatigue was lower at 1 year than before CTX; no group effects were found. Conclusion The BT group, on average, experienced significant improvement on global sleep quality compared with the HEC group, but not on objective sleep or fatigue outcomes.
Clinical Relevance of HER2 Overexpression/Amplification in Patients With Small Tumor Size and Node-Negative Breast Cancer
Authors: Curigliano Giuseppe , Viale Giuseppe , Bagnardi Vincenzo , Fumagalli Luca , Locatelli Marzia , Rotmensz Nicole , Ghisini Raffaella , Colleoni Marco , Munzone Elisabetta , Veronesi Paolo , Zurrida Stefano , Nolè Franco , Goldhirsch Aron 
Published: November 2009

Purpose To assess the prognostic role of HER2 overexpression/amplification in patients with node-negative, pT1a-b breast cancers. Patients and Methods All patients with HER2-positive breast cancer were identified among a population of 2,130 patients whose diseases were staged as pT1a-b, pN0 and who underwent surgery at the European Institute of Oncology from 1999 to 2006. A matched cohort was selected by using variables of hormone receptor status, age, and year of surgery. We estimated rates of local and distant recurrence, disease-free survival (DFS), and overall survival (OS) in the two groups. Results We identified 150 consecutive patients with pT1a-b, pN0, HER2-positive tumors. No patient received adjuvant trastuzumab. The median follow-up was 4.6 years (range, 1.0 to 9.0 years). In the hormone receptor–positive group, 5-year DFS rates were 99% (95% CI, 96% to 100%) for HER2-negative disease and 92% (95% CI, 86% to 99%) for HER2-positive disease. In the hormone receptor–negative group, 5-year DFS rates were 92% (95% CI, 84% to 100%) for HER2-negative disease and 91% (95% CI, 84% to 99%) for HER2-positive disease. Overall, the hazard ratio (HR) associated with HER2 overexpression was 2.4 (95% CI, 0.9 to 6.5; P = .09). After analysis was adjusted for pT1 stage, hormone receptor–positive disease with HER2-positive status was associated with a worse prognosis (HR, 5.1; 95% CI, 1.0 to 25.7). OS in HER2-positive, pT1a-b, pN0 breast cancer was similar irrespective of the hormone receptor status (P = .93). Conclusion Patients with node-negative, HER2 positive, pT1a-b breast cancer have a low risk of recurrence at 5 years of follow-up. In patients with hormone receptor–positive disease and pT1a-b, N0 tumors, HER2 overexpression was associated with a worse DFS.
Understanding the Mechanisms Behind Trastuzumab Therapy for Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer
Authors: Spector Neil L. , Blackwell Kimberly L. 
Published: November 2009

PurposeTargeted therapy with the humanized monoclonal antibody trastuzumab has become a mainstay for human epidermal growth factor receptor 2 (HER2) –positive breast cancer (BC). The mechanisms of action of trastuzumab have not been fully elucidated, and data available to date are reviewed here. The impact of the mechanisms of action on clinical benefit also is discussed.MethodsAn extensive literature review of trastuzumab and proposed mechanisms of action was performed.ResultsAt least five potential extracellular and intracellular antitumor mechanisms of trastuzumab have been identified in the preclinical setting. These include activation of antibody-dependent cellular cytotoxicity, inhibition of extracellular domain cleavage, abrogation of intracellular signaling, reduction of angiogenesis, and decreased DNA repair. These effects lead to tumor cell stasis and/or death. Clinical benefit from trastuzumab-based therapy in both early and advanced BC has been demonstrated. The benefit of trastuzumab use beyond progression has also been shown, which indicates the need for continuous suppression of the HER2 pathway. Targeting both HER2, with various approaches, and other pathways may enhance the clinical benefit observed with trastuzumab and overcome potential resistance. Novel combinations include pertuzumab (a HER2 dimerization inhibitor), lapatinib (a HER1/HER2 tyrosine kinase inhibitor), bevacizumab (an antiangiogenic agent), tanespimycin (a heat shock protein inhibitor), antiestrogen therapies, and an antibody-drug conjugate (trastuzumab-DM1).ConclusionTrastuzumab is the foundation of care for patients with HER2-positive BC. Emerging data from studies of other targeted agents may provide alternative treatment combinations to maximize the clinical benefit from trastuzumab and prevent or delay resistance. The continued development of trastuzumab highlights promising treatment approaches for the future.